Here - CHU Sainte

Program
2ND EDITION
Canadian National
Photo © Alexandra Côté
Perinatal Research Meeting
February 24 – 27, 2015
Montebello, Québec
WELCOME
I would like to welcome each and every one of you to the 2nd annual Canadian National Perinatal Research Meeting!
This new format of annual gathering is bringing together researchers and trainees as well as families under the
common aim to rapidly advance knowledge in the diverse areas of perinatal research and translate our findings to
better care. I hope you will enjoy the meeting as much as we have enjoyed taking on this ambitious task of putting
together the program and organize this meeting for you.
With participants and guest speakers from all Canadian provinces, U.S. and Europe, please take advantage of this
national gathering to exchange and discuss science for the benefit of all: trainees, experienced researchers, babies,
mothers and families. We hope you will go home with novel ideas, new research avenues and break through
concepts to explore, as well as new collaborators and friends. Investing in the next-generation of scientists, we have
followed the tradition of supporting the attendance of trainees and provided them many opportunities for
presenting their results; we are especially grateful to our sponsors to allowing this to happen.
We thank all our guest speakers and attendees, who have travelled from far to join us and wish you all a memorable
stay,
Anne Monique Nuyt
Organizer and Scientific committee Chair
On behalf of all members of the Organizing and Scientific Committee
CNPRM 2015
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CNPRM 2015
TABLE OF CONTENTS
WELCOME
1
TABLE OF CONTENTS
3
PROGRAM AT A GLANCE
5
ORGANIZING COMMITTEE MEMBERS 2015
11
ORGANIZING AND SCIENTIFIC COMMITTEE CHAIR
SCIENTIFIC COMMITTEE MEMBERS
ADMINISTRATIVE SUPPORT AND ORGANIZING LOGISTICS
PHOTOGRAPHIC CREDITS
VENUE
11
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GUEST SPEAKERS BIOPROFILES
13
PLENARY SESSIONS SPEAKERS
THEMATIC SESSION SPEAKERS
BANQUET & HONORARY SPEAKERS
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16
25
SPONSORS
27
MORNING PLENARY SESSIONS ABSTRACTS
35
WEDNESDAY MORNING, FEBRUARY 25 [ROOM OUTAOUAIS]
THURSDAY MORNING, FEBRUARY 26TH [ROOM OUTAOUAIS]
FRIDAY MORNING, FEBRUARY 27TH [ROOM OUTAOUAIS]
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37
40
CONCURRENT THEMATIC SESSIONS ABSTRACTS
43
WEDNESDAY AFTERNOON, FEBRUARY 25TH
DEVELOPMENTAL/TRANSGENERATIONAL ORIGINS OF HEALTH AND DISEASES [ROOM LE CLUB]
PERINATAL BRAIN INJURY
[ROOM QUÉBEC]
FAMILY CENTERED CARE – DEVELOPMENTAL OUTCOMES AND INTERVENTIONS [ROOM MONTEBELLO]
CANADIAN MATERNAL FETAL MEDICINE SOCIETY [ROOM CANADA]
MEDICAL TEACHING AND NEONATAL RESUSCITATION RESEARCH [ROOM ONTARIO]
THURSDAY AFTERNOON, FEBRUARY 26TH
CHRONIC LUNG DISEASE OF PREMATURITY [ROOM MONTEBELLO]
NEONATAL NUTRITION [ROOM QUÉBEC]
PERINATAL EPIDEMIOLOGY AND RANDOMIZED TRIALS [ROOM CANADA]
PREECLAMPSIA AND PLACENTA DEVELOPMENT [ROOM LE CLUB]
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POSTER SESSIONS ABSTRACTS
65
TUESDAY EVENING, FEBRUARY 24TH
DEVELOPMENTAL/TRANSGENERATIONAL ORIGINS OF HEALTH AND DISEASES
PERINATAL BRAIN INJURY
FAMILY CENTERED CARE – DEVELOPMENTAL OUTCOMES AND INTERVENTIONS
CANADIAN MATERNAL FETAL MEDICINE SOCIETY
MEDICAL TEACHING AND NEONATAL RESUSCITATION RESEARCH
CHRONIC LUNG DISEASE OF PREMATURITY
PERINATAL EPIDEMIOLOGY AND RANDOMIZED TRIALS
PREECLAMPSIA AND PLACENTA DEVELOPMENT
NEWBORN HEALTH
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CNPRM 2015
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TH
WEDNESDAY EVENING, FEBRUARY 25TH
DEVELOPMENTAL/TRANSGENERATIONAL ORIGINS OF HEALTH AND DISEASES
PERINATAL BRAIN INJURY
FAMILY CENTERED CARE – DEVELOPMENTAL OUTCOMES AND INTERVENTIONS
CANADIAN MATERNAL FETAL MEDICINE SOCIETY
CHRONIC LUNG DISEASE OF PREMATURITY
NEONATAL NUTRITION
PERINATAL EPIDEMIOLOGY AND RANDOMIZED TRIALS
PREECLAMPSIA AND PLACENTA DEVELOPMENT
NEWBORN HEALTH
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137
NOTES
141
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CNPRM 2015
PROGRAM AT A GLANCE
Tuesday afternoon, February 24th
13:00 -17:00
Welcome
[HOTEL LOBBY]
18:30-21:30
Dinner : Restaurant aux Chantignoles
Poster Session I – Mezzanine
Author attendance from 19:30 to 21:00
19:30-21:30
Sponsored by:
CIHR - Institute of Human Development, Child and Youth Health (IHDCYH)
CNPRM 2015
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Wednesday morning, February 25th
SCIENTIFIC PLENARY SESSION [ROOM OUTAOUAIS]
8h00-8h15
Opening remarks:
Dr. Anne Monique Nuyt - Organizing Committee Chair
MODERATORS: Drs. THUY MAI LUU & MARILYN BALLANTYNE
8:15-8:h55
Mrs. Katharina Staub - Canadian Premature Babies Foundation
The long shadow of the NICU: the impact of trauma for NICU infants and families
8:55-9:35
Dr. Cindy-Lee Dennis - University of Toronto
Can We Prevent Postpartum Depression? Results from a Systematic Review and a Clinical Trial
9:35-9:50
Amy Metcalfe
Does Maternal Chorioamnionitis Increase or Decrease Neonatal Respiratory Morbidity? (#238)
9:50-10:05
Emma G Duerden
Effect of Midazolam on Hippocampal Growth and Neurodevelopment
in very preterm born neonates (#455)
10:05-10:20 Issaka Yougbare
Pathology Of Placenta In Fetal And Neonatal Immune Thrombocytopenia: Roles Of Th17 Immune
Responses, Anti-Platelet Antibodies And Angiogenic Factors (#370)
10:20-10:50
Refreshment Break
MODERATOR: Dr. ROBERT JANKOV
10:50-11:05 Denise Harrison
Are There Too Many Rcts Of Sweet Solutions For Pain Management In Babies? (#323)
11:05-11:20 Marianne Bertagnolli
Treatment With Losartan Prevents The Developmental Programming Of Cardiac Dysfunction
Caused By Neonatal High Oxygen Exposure In Rats (#388)
11:20-11:35 Siwen Yang
Oral Lactobacillus rhamnosus GR-1/ L. reuteri RC-14 does not change the vaginal microbiota or
cervico-vaginal cytokines in low risk pregnant women with an abnormal Nugent score. (#303)
11:35-12:15 Dr. Bernard Thebaud - University of Ottawa
Prevention/repair of organ injury while promoting normal organ development in extreme
premature infants: possible with cell therapy?
12:15-13:30
Lunch : Restaurant Aux Chantignoles
17:30–19:30
Wednesday afternoon, February 25th
CONCURRENT THEMATIC SESSIONS [13:30 – 17:00]
see detailed schedule next page
Dinner : Restaurant Aux Chantignoles
Poster Session II– Mezzanine
19:30–21:30
6
Author attendance from 19:30 to 21:00
Sponsored by
CIHR- Institute of Human Development, Child and Youth Health (IHDCYH)
CNPRM 2015
Wednesday, February 25th
CONCURRENT THEMATIC SESSIONS
Developmental / Transgenerational Origins of Health and Diseases [ROOM LE CLUB]
MODERATORS: Drs. TC TAI & SANDRA DAVIDGE
13:30 Dr. Deborah Sloboda
15:00 Refreshment Break
15:30 Dr.Gerlinde Metz
Early life nutritional impacts on offspring
reproductive function
14:00
Ancestral Exposure to Stress Programs Preterm Birth
Risk and Adverse Maternal and Newborn Outcomes
Dr.Tim Regnault
16:00
The good, the bad and the ugly outcomes of
adverse pre and postnatal environments
14:30
14:45
Dr. Cathy Vaillancourt
In utero exposure to antidepressant alters placental
serotonin and estrogen system: Role in fetal
programming
Kaitlyn Chan (#283)
Stephanie-May Ruchat (#305)
16:30
16:45
Kristyn Dunlop (#350)
Kelsey Dancause (#486)
Perinatal Brain Injury [ROOM QUÉBEC]
MODERATORS:
Drs GREGORY LODYGENSKY & BRYAN RICHARDSON
13:30 Dr. Sylvie Girard
Targeting inflammation to achieve
neuroprotection in neonates
14:00
Refreshment Break
Dr. Pia Wintermark
Injury and repair in perinatal brain injury: insights
from bedside, imaging and bench
16:00
16:15
16:30
16:45
Pr. Olivier Baud
Oxygen is a toxic gas not a therapy: effects of
oxygen exposure on the developing brain
14:30
14:45
15:00
15:30
Issaka Yougbare (#327)
Vanessa R Kay (#341)
Loredana-Sorina Truica (#409)
Clara Lee (#418)
Nasser Al-Shafouri (#254)
Rani Bashir (#260)
Family Centered Care [ROOM MONTEBELLO]
Sponsored by BLES BIOCHEMICALS INC.
MODERATORS:
Drs. JENNIFER TOYE & MARIE-NOELLE SIMARD
13:30 Mrs Katharina Staub
15:00
15:30
An educational program of developmentallysupportive care for parents of preterm infants
Prematurity does not end when you go home
14:00
16:00
Dr. Marilyn Ballantyne
Dr. Paige Terrien Church
Little Nomads: the behavioral outcomes of
prematurity and potential interventions
Family experiences with transitions in care
14:30
14:45
Refreshment Break
Dr.Thuy Mai Luu
Timothy Disher (#364)
Britney Benoit (#403)
16:30
16:45
Chantalle Clarkin (#414)
J. Keiko McCreary (#422)
Canadian Maternal Fetal Medicine Society [ROOM CANADA]
MODERATOR: Dr. AHMED MOUSSA
13:30 Dr. Wendy Robinson
What does the maternity care provider need to
know about epigenetics
14:00
14:15
Stephane Bourque (#343)
Craig Olmstead(#345)
14:30
14:45
15:00
15:30
15:45
16:00
Alex Pittini (#463)
Nir Melamed (#467)
Refreshment Break
Nir Melamed (#468)
Sonia Grandi (#471)
GROUP DISCUSSION
Medical Teaching and Neonatal Resuscitation Research [ROOM ONTARIO]
Sponsored by IKARIA
MODERATORS: Drs AMANDA SKOLL & LINE LEDUC
13:30 Dr. Ahmed Moussa & Dr. Emer Finan
15:00
15:30
Procedural Skills Training in the NIC. // Caring For
the High-risk Newborn: the role of simulationbased training
14:15
14:30
14:45
Elliot S. Li (#235)
Gregory Moore (#247)
Gregory Moore (#264)
Refreshment Break
Dr. Georg Schmölzer
Monitoring in the delivery room: Understanding
physiological changes to improve neonatal
outcomes
16:00
16:15
16:30
CNPRM 2015
Anne Lee Solevåg (#329)
Ahmed Bakry (#428)
David Pogorzelski (#439)
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Thursday morning, February 26th
SCIENTIFIC PLENARY SESSION – [ROOM OUTAOUAIS]
MODERATOR: Dr. THIERRY LACAZE
8:15-8:55
Prof. Olivier Baud - Paris-Diderot University
Early Low-Dose Hydrocortisone to improve Survival without Bronchopulmonary Dysplasia in
Extremely Preterm Infants: rationale and PREMILOC randomized controlled trial
8:55-9:35
Prof. Paul Leeson - University of Oxford
Preeclampsia, Prematurity and Offspring Cardiovascular Health in Later Life
9:35-9:50
Amir Elmekkawi
Impact Of A Stewardship Program On Inhaled Nitric Oxide (Ino) Use In A Quaternary Neonatal
Intensive Care Unit (Nicu). (#420)
9:50-10:05
Matthew Ratsep
Impact Of Placental Growth Factor On Brain Development, Cognition And Behavior (#359)
10:05-10:h45
Refreshment Break
MODERATOR: Dr. BERNARD THEBAUD
10:45-11:00
Maureen Heaman
Evaluation Of The Partners In Inner-City Integrated Prenatal Care (Piipc) Project: Perspectives Of
Women And Care Providers (#375)
11:00-11:15
Seungmi Yang
Perinatal Outcomes By Immigration Status In Canada: Similarities And Differences Across
Outcomes, Provinces And Duration Of Residence (#335)
11:15-11:55
Dr. Stephen Lye - University of Toronto
Maternal Immune Cells: Mediators of Reproductive Function and Tools to Monitor Pregnancy
Health
Ikaria Young Investigator Research Fund and Forum
11:55-12:30
12:30-13:30
17:15-18:00
19:00-21:00
21:30-
8
Dr. AMIT MUKERJI – McMaster University
Non-Invasive High Frequency Oscillatory Ventilation (Nihfov) Versus Bi-Phasic Continuous
Positive Airway Pressure (Bp-Cpap) Following Cpap Failure In Infants <1,250 Grams: Preliminary
Results From A Pilot Randomized Controlled Trial
Dr. ANNE DIOS - CHU Erasme Brussels, Belgium
Impact Of Transient Neonatal High Oxygen Exposure On Right Ventricular Tissue And Function
In Rats
Dr. LANNAE STRUEBY - University of Saskatchewan
Paracrine Effect Of Mesenchymal Stromal Cells On Multifactorial Lung Injury In Neonatal Mice
Lunch : Restaurant Aux Chantignoles
Thursday afternoon, February 26th
CONCURRENT THEMATIC SESSIONS [13:30 – 17:00]
see detailed schedule next page
Business Meeting [ROOM CANADA]
*Open to all*
Reception & Banquet [ROOM OUTAOUAIS]
Guest Speaker: Mr. Vincent Dumez
Faculty Office of the Patient Partner Expertise,
Faculty of Medicine, University of Montreal
Live Music
CNPRM 2015
Thursday, February 26th
CONCURRENT THEMATIC SESSIONS
Chronic Lung Disease of Prematurity [ROOM MONTEBELLO]
MODERATOR: Dr. SHYAMALA DAKSHINAMURTI
13:30 Dr. Martin Post
15:00
15:30
Lung Development, Injury and Repair
14:00
Building Foundations to Study Long-term CardioRespiratory Health of Extremely Pre-term Infants
Dr. Robert Jankov
16:00
Dr. Amish Jain
16;15
The concept of pulmonary heart disease in chronic 16:30
neonatal lung disease in preterms
16:45
Dr. Anne Monique Nuyt
The Pulmonary Circulation in BPD
14:20
14:40
Refreshment Break
Dr. Theo Moraes / Dr. Sherri Katz
Anurag Singh Sikarwar (#331)
Anna-Maria Preziosi (#338)
Jennifer J.P. Collins(#466)
Megan O'Reilly (#492)
Vascular impact of preterm birth: beyond the
lungs
Neonatal Nutrition [ROOM QUEBEC]
Sponsored by MEDELA
MODERATOR: Dr. BRUNO PIEDBOEUF
13:30 Dr. Jean-Claude Lavoie
Oxidative stress in neonatology, there is time to
improve antioxidant defenses of premature
newborn
14:00
14 :30
14 :45
15:00
15:30
Postnatal Growth Restriction and Individualized
Fortification
Dr. Isabelle Marc
Omega-3 in neonatology: RCT/Meta-analyses
Ebtihal Ali (#231)
Hai Lun Liu (#267)
Refreshment Break
Dr. Christopher Fusch
16:00
16:15
Gerhard Fusch (#412)
Niels Rochow(#449)
Perinatal Epidemiology [ROOM CANADA]
MODERATOR: Dr. MICHAEL KRAMER
13:30 Dr. Martin Offringa
15:00
15:30
Research tools to facilitate interoperability in
neonatal drug research
BEST ABCs: Benefits and Effectiveness of Support
offered Through A Breastfeeding Clinic study: A
Randomized Controlled Trial
14h:00 Dr. Suzanne Tough
The All Our Babies Cohort: What we can Learn
from Longitudinal Follow-up
14:30
14:45
Marc Beltempo (#233)
Alison L. Park (#250)
Refreshment Break
Dr. Thierry Lacaze
16:00
16:15
16:30
16:45
Andrea Lanes (#284)
Deshayne Fell (#307)
Neda Razaz (#377)
Britt McKinnon (#430)
Preeclampsia and Placenta Development [ROOM LE CLUB]
MODERATORS:
Drs. DENISE HEMMINGS & FRANÇOIS AUDIBERT
13:30 Pr. Benoit Barbeau
14:45
15:00
15:30
Association between Human Endogenous
Retrovirus proteins, placenta development and
pre-eclampsia
14:00
14:30
Waiha Gohir (#293)
Refreshment Break
Mrs. Malia Murphy
Examining non-traditional markers of cardiovascular
risk after pre-eclampsia
16:00
16:15
Death by Sphingolipids: Preeclampsia versus IUGR 16:30
Anne-Sophie Morisset (#246)
16:45
Dr. Isabella Caniggia
CNPRM 2015
Kevin Sinclair (#346)
Jacqueline Cohen (#362)
Brian Cox (#376)
Daniel Kerage (#447)
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Friday morning, February27th
SCIENTIFIC PLENARY SESSION – [ROOM OUTAOUAIS]
MODERATOR: Dr. SUZANNE KING
8:15-8:55
Dr. Richard Oster - University of Alberta
Disparities in diabetes in pregnancy and other perinatal outcomes according to ethnicity in
Alberta
8:55-9:35
Dr. Wendy Robinson - University of British Columbia
DNA methylation in the human placenta: what can it tell us about normal and abnormal
development?
9:35-9:50
Dr. Mathieu Nadeau-Vallée
Characterization Of A Selective Interleukin (Il) -1 Receptor Antagonist Effective In Preventing
Preterm Birth (#278)
9:50-10:05
Dr. Liz Darling
Association Of Hyperbilirubinemia Guidelines With Newborn Follow-Up Care And
Socioeconomic Disparities In Follow-Up (#465)
10:05-10:20
Dr. Laura M. Reyes
The effect of aerobic exercise training in the gastrocnemius muscle arteries from intrauterine
growth restricted offspring. (#318)
10:20-10:50
Refreshment Break
MODERATOR: Dr. DEBORAH SLOBODA
10:50-11:35
Dr. Kjersti Aagaard - Baylor College of Medicine
Birth and Bacteria: Seeding the Future
Sponsored by Molly Towell Perinatal Research Foundation
11:35-12:15
Trainee Awards-Closing Remarks
Dr. Shoo Lee, Scientific Director of the Institute of Human Development, Child and Youth Health
(IHDCYH), CIHR.
& Dr. Anne Monique Nuyt, 2015 CNPRM meeting organizer
12:30-13:30
Lunch: Restaurant Aux Chantignoles
SEE YOU IN 2016!
Check out our website for
update on our 2016 program
www.cnprm.org
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CNPRM 2015
ORGANIZING COMMITTEE MEMBERS 2015
The Canadian National Perinatal Research Meeting relies on the excellent guidance and assistance provided by our
Organizing Committee. Representing a wide variety of fields within perinatal research, medicine and care, it ensures
the conference provides a well-rounded perspective.
ORGANIZING AND SCIENTIFIC COMMITTEE CHAIR
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Anne Monique Nuyt, CHU Sainte-Justine, Université de Montréal
SCIENTIFIC COMMITTEE MEMBERS
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François Audibert, CHU Sainte-Justine, Université de Montréal
Jean-Francois Bilodeau, CHU de Québec, Université Laval
Angela Bowen, College of Nursing, University of Saskatchewan
Martin Frasch, CHU Sainte-Justine, Université de Montréal
Wendy Hall, School of Nursing, University of British Columbia
Robert Jankov, The Hospital for Sick Children, University of Toronto
Michael Kramer, Montreal Children’s Hospital, McGill University
Thierry Lacaze-Masmonteil, Children’s Hospital of Eastern Ontario, University of Ottawa
Pascal Lavoie, BC Children’s Hospital and BC Women’s Hospital & Health Centre University of British Columbia
Line Leduc, CHU Sainte-Justine, Université de Montréal
Gregory Lodygensky, CHU Sainte-Justine, Université de Montreal
Thuy Mai Luu, CHU Sainte-Justine, Université de Montréal
Bruno Piedboeuf, CHU de Québec, Université Laval
Bryan Richardson, Children’s Health Research Institute Western University
Georg Schmöelzer, Royal Alexandra Hospital Edmonton
Deborah Slobada, Department of Biochemistry and Biomedical Sciences, McMaster University
Graeme Smith, Queen’s University
Bernard Thebaud, Ottawa Hospital Research Institute, University of Ottawa
ADMINISTRATIVE SUPPORT AND ORGANIZING LOGISTICS
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Evelyne Clerc, Administrative Assistant, CHU Sainte-Justine
Viki Rivière, Conference & Training Services, CHU Sainte-Justine
Joelle Fortier, Conference & Training Services, CHU SainteJustine
Marise Daigle, Strategic Development, University Affairs &
Communications, CHU Sainte-Justine
Maude Hoffmann-Bélisle, Strategic Development, University
Affairs & Communications, CHU Sainte-Justine
Caroline Nuyt, Consultant
CNPRM 2015
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PHOTOGRAPHIC CREDITS
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Cover photo by Alexandra Côté © [email protected], taken at CHU Sainte-Justine
3-D photo of fetus from Département de Gynécologie-Obstétrique, CHU Sainte-Justine.
VENUE
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Fairmont Le Château Montebello
392 Notre Dame, Montebello, J0V 1L0 Quebec, Canada
TEL + 1 819 423 6341
FAX + 1 819 423 1133
[email protected]
www.fairmont.com/montebello
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CNPRM 2015
GUEST SPEAKERS BIOPROFILES
PLENARY SESSIONS SPEAKERS
Kjersti Aagaard
Baylor College of Medicine
Birth and Bacteria: Seeding the Future
[Friday morning, February 27th]
Dr. Aagaard is board certified in Obstetrics and Gynecology and Maternal-Fetal Medicine and a Fellow
of the American College of Obstetrician Gynecologists. She specializes in the field of Maternal-Fetal
Medicine, and has specialty clinical interests in preterm birth, stillbirth, maternal obesity and cardiac
disorders, ultrasound diagnosis and testing for fetal anomalies and genetic disorders, and
management of pregnancies complicated by infections. Dr. Aagaard’s research interests include both
basic science investigations and translation into clinical research. She is internationally recognized for
her work on maternal obesity and nutrition, genomics, the “microbiome” and prevention of preterm
birth. Dr. Aagaard also actively conducts clinical research related to both cause and management of
common perinatal fetal conditions (preterm birth, stillbirth and fetal growth abnormalities), alongside
research in the implications of parallel maternal conditions and behavior (obesity, smoking, and nutrition). In addition to the Aagaard labs
research on epigenetics, they are leading the way in unraveling secrets about our “microbiome.” Of the 100 trillion cells in our body, 90 trillion
are microbial. This includes viruses, bacteria, parasites, and other microbes and are collectively referred to as our “microbiome.” Each of these
has their own genomic codes, which regulate not only their metabolism but ours. For example, without bacteria we could not make Vitamin K,
or convert most of our B vitamins to useable forms. We have recently demonstrated that the pregnancy microbiome is distinct, and in fact with
98% certainty we can actually tell if someone is pregnant simply by sequencing their vaginal microbiome. With respect to pregnancy, the
Aagaard lab is funded to understand the microbiome and pregnancy complications leading to later in life diseases. Throughout her career and
training she has raised three children on her own and remained an active member in the community. She is a recipient of the Houston
Women’s Magazine “Maximum Mom” Award which is awarded “to a woman who has been an extraordinary mother to her children and
mentor to others in providing strong moral character and serving as a role model.”
Olivier Baud
Université Paris-Diderot, Sorbonne Paris Cité
Early Low-Dose Hydrocortisone to improve Survival without Bronchopulmonary Dysplasia
in Extremely Preterm Infants: rationale and PREMILOC randomized controlled trial
[Thursday morning, February 26th]
Oxygen is a toxic gas, not a therapy. Effect of oxygen exposure on the developping brain
[Wednesday afternoon, February 25th]
Professor Olivier Baud is a neuroscientist and head of a translational research team shared between INSERM Unit
1141 and NICU at Robert Debré children’s hospital, all members of “Département Hospitalo-Universitaire”
PROTECT. He is also the head of the Neonatal Intensive Care Unit of the Robert Debré Children’s Hospital, one of
the premier paediatric hospitals in Europe. He is full professor of Paediatrics at Paris-Diderot University. He
founded his own research team in 2006 (INSERM “AVENIR program”), a team that is emerging as a leader in
preclinical research on neuroprotection and brain repair. He’s now team leader of the biggest team within INSERM U1141 including more than
30 researchers, doctoral students and postdoctoral fellows. Olivier Baud was research coordinator both in clinical and experimental research
fields in perinatal neuroscience and other hot topics in the field of perinatal medicine. Olivier Baud directed translational clinical works on
several neuroprotectant agents including melatonin and therapeutic evaluation of corticosteroids therapy during the perinatal period. He is the
author of 115 research papers (h index = 25).
Cindy-Lee Dennis
University of Toronto
Can We Prevent Postpartum Depression?
Results from a Systematic Review and a Clinical Trial
[Wednesday morning, February 25th]
Dr. Cindy-Lee Dennis is a Professor in the Faculty of Nursing and the Faculty of Medicine, Department of
Psychiatry at the University of Toronto. She holds a Canada Research Chair in Perinatal Community Health and
was further appointed the Shirley Brown Chair in Women’s Mental Health at Women’s College Research Institute.
She is currently the principal investigator of four large, multi-site studies related to the prevention and treatment
of postpartum depression. She is also examining the relationship between maternal and paternal postpartum
depression and early child development and analyzing why immigrant women are at higher risk to develop
postpartum depression. She is a co-investigator on twelve other research projects concerning maternal and
paternal health outcomes. She has over $6 million in funding from the Canadian Institutes of Health Research (CIHR) as a principal investigator
and has completed six Cochrane systematic reviews as the lead author. She is an expert advisor for the Ontario Ministry of Children and Youth
Services, the Provincial Council for Maternal and Child Health, and numerous other maternal health organizations.
CNPRM 2015
13
Paul Leeson
University of Oxford
Preeclampsia, Prematurity and Offspring Cardiovascular Health in Later Life
[Thursday morning, February 26th]
Paul Leeson is Professor of Cardiovascular Medicine at the University of Oxford and head of the Oxford
Cardiovascular Clinical Research Facility. He is also a Consultant Cardiologist at the John Radcliffe
Hospital in Oxford, where he provides expertise in cardiovascular imaging and hypertension. His
research group is focused on why certain individuals, in particular those born following pregnancy
complications such as preeclampsia and prematurity, develop hypertension in early life. The work
combines novel cardiovascular imaging approaches with laboratory and epidemiological investigations
in both observational studies and clinical trials. He is also the National Lead for Cardiovascular
Prevention within the UK NIHR Clinical Research Network, Chair-Elect of the Translational Research
Nucleus of the European Association for Cardiovascular Prevention and Rehabilitation as well as a Member of the British Hypertension Society
Collaborative Research Working Group and UK Biobank Imaging Enhancement Expert Working Group.
Stephen J. Lye
University of Toronto
Maternal Immune Cells: Mediators of Reproductive Function
and Tools to Monitor Pregnancy Health
[Thursday morning, February 26th]
Professor Stephen Lye is the Executive Director of the Fraser Mustard Institute
for Human Development and Vice-Chair, Research of the Department of
Obstetrics and Gynaecology at the University of Toronto. He is also Associate
Director of the Samuel Lunenfeld Research Institute of Mount Sinai Hospital
and Professor within the Departments of Physiology, of Medicine and of
Applied Psychology and Human Development at the University of Toronto. Dr.
Lye is an expert in women’s and infants’ health and pioneered investigations
into the mechanisms underlying preterm birth. Dr. Lye has led numerous largescale, peer-review funded, research programs at the local, national and international level. His research has integrated discovery, clinical and
translational studies including the commercialization of discoveries in partnership with industry. He has published over 220 research papers on
pregnancy and maternal-child health and holds a Canada Research Chair in Improved Health and Function. He has received numerous awards
and honours, including the President’s Scientific Achievement Award from the Society for Gynecologic Investigation, Fellowship of the Canadian
Academy of Health Sciences and Fellowship (Ad Eundem) of the Royal College of Obstetrics and Gynaecology.
Richard Oster
University of Alberta
Disparities in diabetes in pregnancy and other perinatal outcomes according to ethnicity
in Alberta
[Friday morning, February 27th]
Dr Richard Thomas Oster is a Senior Research Coordinator with the Believing we can Reduce the Aboriginal
Incidence of Diabetes (BRAID) research group at the University of Alberta, Canada. In this position he uses
mixed methods approaches (including community-based methods) to address Indigenous health concerns
related to diabetes and other chronic diseases, pregnancy and maternal health outcomes, and the social
determinants of health. His interests lie in diminishing the health disparities between Indigenous and nonIndigenous people. Richard completed his PhD in Experimental Medicine in 2013 (dissertation title: “Diabetes
in pregnancy among First Nations women in Alberta: a multiphase mixed methods approach”). Richard is also a
graduate of the University of Guelph Masters in Nutrition and Metabolism program and attained a Bachelors of Science degree from the
University of Alberta (BSc in Nutrition).
14
CNPRM 2015
Wendy Robinson
University of British Columbia
DNA methylation in the human placenta: what can it tell us about normal
and abnormal development?
[Friday morning, February 27th]
What does the maternity care provider need to know about epigenetics
[Wednesday afternoon, February 25th]
Wendy Robinson earned a PhD in Genetics at the University of California, Berkeley CA USA in 1989, specializing in
population genetics and genetic epidemiology. From 1989-1994 she worked as a postdoctoral fellow at the
Medical Genetics Institute at the University of Zurich, Switzerland focusing on chromosomal disorders. Since
1994, Dr. Robinson has been a faculty member of the Department of Medical Genetics, University of British
Columbia in Vancouver, Canada, where she is currently full professor. She is also a senior scientist at the Child &
Family Research Institute also in Vancouver, where she has chaired the Reproduction and Healthy Pregnancy Research Cluster tfrom 2002-2007
and 2012-present. Her research interests involve many areas, including genetic and epigenetic aspects of reproduction and early human
development. She has an interest in genetic and environmental causes underlying placental causes of pregnancy complication, including
preeclampsia, growth restriction and preterm birth. More recently, Dr. Robinson has become involved with whole genome evaluation of DNA
methylation as an approach to understand developmental processes in both placenta and fetus.
Katharina Staub
Canadian Premature Babies Foundation
The long shadow of the NICU: the impact of trauma for NICU infants and families
[Wednesday morning, February 25th]
Prematury does not end when you go home
[Wednesday afternoon, February 25th]
Katharina’s professional training is in language education. She holds a B. Ed. from the University of Alberta
in Edmonton and a B.A. in Primary Education from the University of Zurich, Switzerland. Katharina has
worked in an international setting for many years and has expertise in the areas of international recruitment
and communications. She speaks German, French and English. Most importantly though, Katharina is the
mother of twins born at 27 weeks gestation in 2008 in Edmonton, Alberta. This experience left Katharina
convinced that there needed to be an increase in public awareness about prematurity and better
information and education of parents during pregnancy and long term consequences of prematurity. In 2009, Katharina met Silke Mader, the
founder of the European Foundation for the Care of Newborn Infants, EFCNI. After having seen their great work across Europe, Katharina knew
there was a need for a national Canadian organisation for Premature Babies. Québec was the only province in Canada that had a professional
association for premature babies. Préma-Québec led by Ginette Mantha, has supported families for 10 years across the province. CPBF- FBPC
was founded in 2012 by Katharina together with experts and stakeholders. Many staff, families and industry have helped along the way and
have supported the creation of this foundation.
Bernard Thébaud
University of Ottawa
Prevention/repair of organ injury while promoting normal organ development
in extreme premature infants: possible with cell therapy?
[Wednesday morning, February 25th]
Dr. Bernard Thébaud is a clinician-scientist recruited to Ottawa from Edmonton in 2012 to
accelerate the translation of stem cell-based therapies for lung diseases. Dr. Thébaud is a
neonatologist with the Children’s Hospital of Eastern Ontario (CHEO) and a senior scientist with the
Ottawa Hospital Research Institute and CHEO Research Institute. He is also a Professor of Pediatrics
at the University of Ottawa. Dr. Thébaud obtained his MD, PhD, and clinical training in France before
completing a postdoctoral fellowship at the University of Alberta in 2002. From 2002 to 2012, he
worked as a staff neonatologist with the Northern Alberta Neonatal Program and established his
research laboratory. He studies the mechanisms underlying lung development, injury and repair in
order to develop new treatments for incurable lung diseases. Over the past 10 years, his lab’s research contributions include: (i) the discovery
of the role of angiogenesis for normal lung development and repair, and (ii) the demonstration of the therapeutic potential of stem cells in
experimental bronchopulmonary dysplasia (BPD), asthma, COPD and pulmonary hypertension. Over the coming 5 years, his goal is to translate
safe and effective cell-based therapies into the clinic.
CNPRM 2015
15
THEMATIC SESSION SPEAKERS
Marilyn Ballantyne
University of Toronto
Family experiences with transitions in care
[Wednesday afternoon, February 25th]
Marilyn Ballantyne is Chief Nurse Executive at Holland Bloorview Kids Rehabilitation Hospital, and Clinician
Investigator in the Bloorview Research Institute in Toronto. She obtained her PhD from the University of
Toronto, followed by postdoctoral studies at the University of Calgary. Marilyn’s research focuses on ways to
improve outcomes for children and parents, from infancy through to early childhood. Her interest in child and
parenting research arose from her experiences as a nurse practitioner in Neonatal Intensive Care, Neonatal
Follow-Up (NFU) and Complex Care Child Development settings. Marilyn’s doctoral research (funded by CIHR)
addressed factors that predict attendance at NFU programs. Building on this work, her post-doctoral fellowship
(funded by Preterm Birth and Healthy Outcomes Team [PreHOT] and ACHRI/CIHR) delved into the barriers and
facilitators to NFU programs from the perspectives of mothers and health care providers. Her current research focuses on addressing gaps in
health services and supporting transitions for infants and parents following the diagnosis of a developmental disability. Through this research,
she is developing linkages among parents, knowledge-users, policy-makers and researchers.
Benoit Barbeau
University of Quebec in Montreal (UQAM)
Association between Human Endogenous Retrovirus proteins, placenta
development and pre-eclampsia
[Thursday afternoon, February 26th]
Pr Barbeau has obtained his Ph.D. at Université de Montreal and has been trained in virology as a
postdoctoral fellow in the Infectious Disease Center at the CHUL hospital. His research expertise is
mainly focussed on human retroviruses, such as HIV-1, Human T-cell Leukemia Viruses (HTLVs) and
human Endogenous Retroviruses (ERV). Over past years, his team has examined the role of ERV
proteins termed Syncytin-1 and -2 in placental development. More recently, results from his
laboratory has demonstrated that these proteins were incorporated on the surface of extracellular
vesicles, known as exosomes. Such a demonstration has important implication in the role that
Photo: Émilie Tournevache, UQAM
these proteins could be playing in functions associated to the placenta but could also lead to the
development of an early diagnostic tool for disorders associated to pregnancy. Pr. Barbeau holds a
Canada Research Chair (tier 2) and his research efforts are currently supported by funding from CIHR, NSERC, March of Dimes and CFI. He is the
director of the UQAM-based BioMed Research Center, which regroups over 40 researchers from various institutions. Although his research is
mostly fundamental in nature, some of his projects have a strong potential to bring new potential application at the diagnostic levels.
Isabella Caniggia
University of Toronto
Death by Sphingolipids: Preeclampsia versus IUGR
[Thursday afternoon, February 26th]
Dr. Isabella Caniggia MD, PhD is a Senior Investigator at the Lunenfeld-Tanenbaum Research Institute of
Mt. Sinai Hospital and a Professor of Obstetrics and Gynaecology and Physiology at the University of
Toronto. Dr. Caniggia received her MD cum laude from the University of Siena, Italy and completed her
residency training in Pediatrics at the University of Perugia, Italy. Following research training at the
Hospital for Sick Children, Toronto, she obtained her PhD degree from the University of Parma, Italy. Dr.
Caniggia is internationally recognized for her work on molecular mechanisms regulating normal placental
development and diseases including preeclampsia and IUGR. She was the first to discover the importance
of proper HIF-1a and TGFb3 signaling in preeclampsia and identified a novel splice variant of the proapoptotic BOK protein. She has received numerous honors and awards including the Ontario Women’s Health CIHR/IGR Mid-Career Award, the
Castellucci Award from the International Federation of Placental Associations that recognizes outstanding research achievements in human
placental development and preeclampsia, and the National Bank Business Excellence Award in Arts, Science and Culture from the Italian
Chamber of Commerce of Ontario for her innovative research. Her work is funded by CIHR and she holds 4 patents related to discovery of
diagnostic markers for preeclampsia and IUGR.
16
CNPRM 2015
Emer Finan
University of Toronto
Procedural Skills Training in the NIC.
Caring For the High-risk Newborn: the role of simulation-based training.
[Wednesday afternoon, February 25th]
Emer Finan is a Staff Neonatologist at Mount Sinai Hospital and Neonatal-Perinatal Program Director at the
University of Toronto. She obtained her medical degree and undertook paediatric training in Ireland before
completing Neonatal-Perinatal training at the University of Toronto (2008). She obtained her Masters in
Education from the University of Toronto in 2009. Dr. Finan’s research and academic interests are in medical
education, particularly in relation to neonatal resuscitation and procedural skills training. Dr Finan is ViceChair of the Canadian NRP Steering Committee and Chair of the NRP Education Subcommittee.
Christoph Fusch
McMaster University
Postnatal Growth Restriction and Individualized Fortification
[Thursday afternoon, February 26th]
Dr. Christoph Fusch obtained his M.D. (1984) and pediatric education (1989) at the University of Tübingen,
Germany. In 1997, he obtained his Ph.D. upon completing his training in MR research (1992) and Neonatology
in Zurich and Berne, Switzerland. From 1997–2008, Dr. Fusch was Professor and Chair of Neonatology at the
Ernst-Moritz-Arndt University Greifswald, Germany and was the Acting Medical Director and President of the
Executive Board, University Hospital at Greifswald (2003-2005). He is the first to hold the Jack Sinclair Chair in
Neonatology at McMaster University. He authors more than 120 scientific papers in international journals. Dr.
Fusch has received continuous funding from government and private sectors for his research. In Canada, he
was awarded an infrastructure award by the CFI as well as a start-up grant by McMaster University.
Additionally, he has been awarded a Canadian Institutes of Health Research (CIHR) Operating Grant, a
Collaborative Health Research Project (CHRP) grant, and a Hamilton Academic Health Sciences Organization (HAHSO) Innovation Fund grant. He
is a member of several international Pediatric and Neonatal Societies in Canada, Switzerland and Germany. Dr. Fusch’s main areas of research
focus on developing an artificial placenta in collaboration with Biomedical Engineering here at McMaster; optimizing nutrition and growth of
neonates and its impact on overall outcomes.
Sylvie Girard
University of Montreal
Targeting inflammation to achieve neuroprotection in neonates
[Wednesday afternoon, February 25th]
Sylvie Girard, PhD, is an assistant research professor at the Sainte-Justine Hospital Research Centre
(Fetomaternal and Neonatal Pathologies research axis) and is part of the Department of Obstetrics &
Gynecology at the University of Montreal. She obtained her PhD in immunology, focused on neuroscience,
from the University of Sherbrooke, Qc, in 2010 followed by postdoctoral studies at the University of
Manchester, UK. During the latter, her work was directed towards inflammation in both brain injury (with
Profs Nancy Rothwell and Stuart Allan) and pathological pregnancies (with Prof Colin Sibley and Dr
Rebecca Jones). She also worked at Yale University (with Dr Vikki Abrahams) on the prenatal effects of
inflammation. In 2014 she began her independent research program in Montreal, which combines
immunology, obstetrics and neuroscience in order to get a better understanding of how prenatal
inflammation leads to brain injury in neonates, and develop new therapeutic strategies targeting inflammation in order to protect the
developing brain.
CNPRM 2015
17
Amish Jain
University of Toronto
The concept of pulmonary heart disease in chronic neonatal lung disease in preterms
[Thursday afternoon, February 26th]
Established and leading the targeted neonatal echocardiography program in the NICU since 2011. Holds
Clinician-Scientist Program’s Doctoral Award and is pursuing aPhD in cardiovascular physiology at the
University of Toronto. Current research focuses on right heart function and pulmonary haemodynamics.
Robert Jankov
University of Toronto
The Pulmonary Circulation in BPD
[Thursday afternoon, February 26th]
Dr. Robert Jankov completed his medical studies at the University of Melbourne, Australia and trained in
Paediatrics at the Royal Children’s Hospital, also in Melbourne. He subsequently completed a Clinical Fellowship
in Neonatal-Perinatal Medicine at the University of Toronto (1996-1999), which was followed by a PhD (20012004) examining mechanisms underlying pulmonary hypertension in experimental chronic neonatal lung injury.
Dr. Jankov has been the recipient of a number of training, support and infrastructure awards, including a Career
Development Award from the Canadian Child Health Clinician Scientist Program, a Canadian Institutes of Health
Research (CIHR) New Investigator Award. Currently, Dr. Jankov is an Associate Professor in the Departments of
Paediatrics and Physiology at the University of Toronto and is a Clinician-Scientist at the Hospital for Sick Children.
Dr. Jankov’s research interests include the cellular and molecular mechanisms of vasoconstriction, vascular
remodeling and right-ventricular dysfunction in chronic neonatal pulmonary hypertension. The overall goal of his research is to develop new
therapeutic approaches, which might allow for improvements in quality of life and survival. Specific mechanisms under study in both the lung
and heart include the roles of inflammatory cells, free radicals, nitric oxide and its metabolites and growth factors, using both in vitro and in
vivo models. His work is funded by the CIHR.
Sherri Katz
University of Ottawa
Building Foundations to Study Long-term Cardio-Respiratory Health
of Extremely Pre-term Infants
[Thursday afternoon, February 26th]
Dr. Sherri Katz is a Pediatric Respirologist and Director of the Sleep Laboratory at the Children’s Hospital of
Eastern Ontario, as well as an Assistant Professor of Medicine at the University of Ottawa. She is a Clinical
Investigator at the Children’s Hospital of Eastern Ontario Research Institute. She attended medical school at
McGill University and went on to complete residency training in Pediatrics, as well as Fellowship training in
Pediatric Respirology and Pediatric Sleep Medicine at Sick Kids in Toronto. She then completed a Masters of
Science and the Clinician-Investigator Program of the Royal College of Physicians and Surgeons of Canada, at the
University of Toronto. She has been on staff at CHEO since September, 2003. Her clinical interests include
complex respiratory care, sleep disordered breathing, respiratory aspects of chronic diseases and technology
dependent children. She is the principal investigator of several research studies evaluating respiratory technologies, including non-invasive
ventilation and lung volume recruitment, in children with chronic diseases. She is currently leading a national initiative on the “Long-Term
Cardio-Respiratory Outcomes of Extremely Preterm Infants.
18
CNPRM 2015
Thierry Lacaze
CHEO Research Institute
BEST ABCs: Benefits and Effectiveness of Support offered Through A Breastfeeding Clinic
study: A Randomized Controlled Trial
[Thursday afternoon, February 26th]
Neonatologist trained in Paris and Professor of Pediatrics at the University Paris Sud, Dr. Thierry Lacaze
immigrated to Canada and moved to Edmonton in 2003. During his first years in Alberta, he led the planning for
the Women and Children’s Health Research Institute (WCHRI) of which he became the inaugural Director in
2006. In 2010, he moved to Ottawa to become the Regional Newborn Lead of the Champlain MaternalNewborn Regional Program and the Divisional Chief for Neonatology at the Children’s Hospital of Eastern
Ontario (CHEO) and the Ottawa Hospital. He joined the CHEO-Research Institute in 2010 as a senior scientist
and became the Scientific Director of the CHEO Clinical Research Unit (CRU) in 2011. Building on the CRU and
CHEO-Research Institute strengths, and with colleagues at SickKids and CHEO, he played an instrumental role in the creation of the Ontario
Child Health SPOR SUPPORT Unit (OCHSU). The overall vision for OCHSU is to build a world-class clinical research infrastructure in Ontario to
optimize child health outcomes. Dr. Lacaze is committed to expand provincial and national infrastructure to foster high-quality clinical trials in
infants and children. Dr. Lacaze is also the Chair of the Fetus and Newborn Committee of the Canadian Pediatric Society.
Jean-Claude Lavoie
University of Montreal
Oxidative stress in neonatology, there is time to improve antioxidant
defenses of premature newborn
[Thursday afternoon, February 26th]
Ph.D. degree in Biomedical Sciences in 1998 from Université de Montréal. Associate
professor in department of Nutrition and of Paediatrics, Université de Montréal.
Scientist researcher affiliated to the neonatal unit of the CHU Sainte-Justine. Expert in
oxidative stress, especially in preterm newborns. Scientific interests in parenteral
nutrition as source of oxidant and, possibly, antioxidant molecules affecting health of
preterm newborns, of which bronchopulmonary dysplasia. Researches essentially
supported by operative grants from CIHR. In the last 5 years, his team has published 22
articles (on total of 83), principally on oxidative stress in neonatal model of parenteral
nutrition or in premature infants, mainly in biochemical journal such as Free Radical Biology and Medicine or in Paediatric journals. In the last
years, his lab has tracked molecules as well as biochemical pathways implied in development of bronchopulmonary dysplasia. With animal
model of neonatal parenteral nutrition, and corresponding data from preterm infants, his team has documented that, as prepared and
administered, parenteral nutrition is contaminated by oxidant molecules that are biologically active, inducing a reduction of alveolar
development.
Thuy Mai Luu
University of Montreal
An educational program of developmentally-supportive care for parents of preterm infants
[Wednesday afternoon, February 25th]
Dr Luu is a general paediatrician and clinician-scientist with a clinical and research interest in long-term follow-up
of preterm born children. She obtained her medical degree at McGill University and trained in pediatrics at CHU
Sainte-Justine before completing a fellowship in neonatal follow-up at the Warren Alpert School of Medicine of
Brown University in Providence. She holds a master degree in epidemiology. She currently works at the Neonatal
Follow-Up Clinic of CHU Sainte-Justine and is an executive member of the Canadian Neonatal Follow-Up Network
(CNFUN). Dr Luu is a principal investigator of a CIHR-funded study on long-term health of adults born preterm.
Her research, which is supported by the Fonds de recherche en santé du Québec and the SickKids’ Foundation,
also focuses on developmental screening strategies and educational interventions to promote developmentallysupportive care.
CNPRM 2015
19
Isabelle Marc
Laval University
Omega-3 in neonatology: RCT/Meta-analyses
[Thursday afternoon, February 26th]
Dr Isabelle Marc obtained her MD (1983) and completed her residency in paediatrics (1986) at the
University Pierre and Marie Curie in Paris, France. In 1986, she completed one year of clinical and research
training in neonatology in the department of Paediatrics at Laval University, Quebec, Canada. She obtained
a PhD in epidemiology in 2007. She is an associate professor at Laval University, and a clinical scientist
supported by the Fonds de recherche du Quebec_ Santé. Her research interests focus on maternal life
habits and their impact on fetal growth and development. Dr Marc has received funding for infrastructure
development from the Canadian Foundation for Innovation, and clinical research development funding from
the Federal and Provincial governments as well as various foundations. She was recently awarded a large
grant by the CIHR to conduct a multi-centric randomized controlled trial across Canada. This RCT is designed
to determine whether a high dose dietary supplementation of omega-3 lipids taken by mothers providing breast-milk to their babies during the
neonatal period reduces the incidence of bronchopulmonary dyplasia (BPD) in at-risk preterm babies.
Gerlinde Metz
University of Lethbridge
Ancestral Exposure to Stress Programs Preterm Birth Risk and Adverse Maternal and
Newborn Outcomes
[Wednesday afternoon, February 25th]
Gerlinde A.S. Metz is a Professor of Neuroscience and an AHFMR Senior Scholar at the Canadian Centre for
Behavioural Neuroscience at the University of Lethbridge. Dr. Metz completed her undergraduate studies
in Biology at the University of Giessen, Germany, and graduate studies in Neuroscience at the ETH Zurich,
Switzerland. She habilitated in Medicine at the University of Jena, Germany. Dr. Metz’ research program
focuses on the influence of experience and environment on brain plasticity and behaviour. Her work in
animal models was the first to show that stress affects motor system function, risk of Parkinson’s disease
and recovery from stroke. More recently, her laboratory has developed animal models to explore
transgenerational inheritance of stress responses. This work showed that through mechanisms of
epigenetic programming, experience in parents, grandparents and beyond can influence behaviour, health and disease from early development
to old age.
Theo Moraes
University of Toronto
Building Foundations to Study Long-term Cardio-Respiratory Health of Extremely Preterm Infants
[Thursday afternoon, February 26th]
Dr. Theo Moraes is a Pediatric Respirologist and Clinician Scientist at the Hospital for Sick Children in Toronto.
He completed medical training at the University of Toronto, Pediatrics Residency at Queen’s University in
Kingston and a Respirology Fellowship at SickKids. He has a PhD from the University of Toronto and
subsequently completed a Postdoctoral Fellowship. His current research focuses on Respiratory Syncytial Virus.
His clinical responsibilities include the Complex Respiratory Care Clinic which takes in all NICU graduates
requiring home oxygen in the Toronto area.
20
CNPRM 2015
Ahmed Moussa
University of Montreal
Procedural Skills Training in the NIC.
Caring For the High-risk Newborn: the role of simulation-based training.
[Wednesday afternoon, February 25th]
Ahmed Moussa completed his medical degree (2004) and paediatric training at University de Montreal, QC
and his Neonatal-Perinatal Medicine training (2009) at University of British-Columbia in Vancouver, BC. He
is currently completing a Masters in Medical Education in Dundee, Scotland. Dr Moussa is a neonatologist,
educator and medical education researcher at CHU Sainte-Justine. He is the program director of the
Neonatal-Perinatal Medicine training program at University of Montreal and the research director at the
Mother-Child Simulation Center at CHU Sainte-Justine. He is an active member of national and international
simulation networks (Canadian Paediatric Simulation Network, International Network for Simulation-based
Pediatric Innovation, Research and Education). His research focuses on simulation-based training,
procedural skills and communication training.
Malia Murphy
Queen’s University
Examining non-traditional markers of cardiovascular risk after pre-eclampsia
[Thursday afternoon, February 26th]
Malia Murphy is a Ph.D. Candidate with the Department of Biomedical and Molecular Sciences at Queen’s
University at Kingston, Ontario. She received her undergraduate degree from the Life Sciences Program at
Queen’s University where she completed her undergraduate thesis in the Department of Epidemiology,
exploring the effect of mercury exposure on the development of pervasive developmental disorders. Malia
is currently enrolled in a Ph.D. program under the supervision of Dr. Graeme Smith, MD, Ph.D., Head of
Obstetrics and Gynecology at Kingston General Hospital, with whom she is studying complications in
pregnancy and their impact on maternal outcomes. The Smith laboratory uses both clinical and basic science
research to explore the mechanisms underlying the development and recovery after pre-eclampsia. The
theme of Malia’s thesis is centered on the characterization of maternal postpartum cardiovascular
dysfunction and risk after pregnancies complicated by pre-eclampsia. This research is funded by the Ontario Graduate Scholarship program.
Anne Monique Nuyt
University of Montreal
Vascular impact of preterm birth: beyond the lungs
[Thursday afternoon, February 26th]
Anne Monique Nuyt is a neonatologist at CHU Ste-Justine, Université de
Montréal. She received her medical degree (88) and pediatric residency training
at the Université de Sherbrooke (QC, Canada), and her subspecialty in neonatalperinatal medicine from McGill University (93). Supported by the Medical
Research Council of Canada, she pursued a research fellowship at the University
of Iowa (93-96) and at the College de France-INSERM-U36 (now U-691) (96-98).
She was appointed as clinician-scientist at the CHU Ste Justine – Université de
Montréal in 1998, where she is currently full professor, associate head of the
Division of Neonatology and head of the Feto-maternal and Neonatal Research
Axis of the CHU Ste Justine Research Center.
Dr Nuyt studies mechanisms of developmental programming of hypertension and cardiovascular dysfunction in children and adults, with
emphasis on the role of oxidative stress and of adverse conditions during neonatal life such as preterm birth. Her translational research
program spans from experimental animal work, to clinical as well as epidemiological studies.
CNPRM 2015
21
Martin Offringa
University of Toronto
Research tools to facilitate interoperability in neonatal drug research
[Thursday afternoon, February 26th]
Martin Offringa is a neonatologist and a clinical trialist. He is Programme Head, Clinical Health Evaluative
Sciences (CHES), Hospital for Sick Children Toronto and Chair, International Forum for Standards for
Research with Children. After graduation from medical school he trained in epidemiology and clinical
decision analysis at the Rotterdam Centre for Clinical Decision Analysis, and completed his training in
paediatrics and neonatology. He developed an interest in evidence-based practice and clinical drug
research in 1995 while working as a neonatologist in the University of Amsterdam Academic Medical
Center. Motivated by the increased focus on clinical research in children and the deficiencies in knowledge
about optimum ways to tackle methodological and practical challenges of research in children, Martin
created StaR Child Health with a team of like-minded. This initiative aims to enhance the design, conduct,
and reporting of clinical trials in children. He received a partner grant in the European consortium Global Research in Paediatrics. GRiP aims to
create consensus on international standards, methodologies and interoperability tools for paediatric research. In 2012, Dr. Offringa was
appointed as Senior Scientist and Head of the Child Health Evaluative Science Program at The Hospital for Sick Children. He holds a clinical
appointment in the Department in Neonatology at SickKids and is a Professor in the Department of Paediatrics at the University of Toronto.
Martin Post
University of Toronto
Lung Development, Injury and Repair
[Thursday afternoon, February 26th]
Dr. Martin Post received his PhD from the University of Utrecht, The Netherlands, in
1982. Following postdoctoral research training at Harvard Medical School, he was
appointed as an Assistant Professor at Harvard in 1985. This was followed by a move to
SickKids in 1986. Here he is the Head and Senior Scientist of the Physiology and
Experimental Medicine Program at the Hospital for Sick Children and Professor of
Physiology, Pediatrics and Pathology and Medicine at the University of Toronto. His
discovery research is focused on pulmonary development, injury and repair. He has
authored more than 280 scientific papers, reviews and book chapters and holds a
Canada Research Chair in Fetal, Neonatal and Maternal Health. He directs the Centre for
Study of Complex Childhood Diseases, a CFI-funded translational research initiative, supporting interventional studies in preclinical models and
in patients. He is also the Scientific Director of the Analytical Facility for Bioactive Molecules enabling metabolic research in Toronto and
beyond. He has received numerous awards, including the distinguished CIHR Lectureship in Respiratory Sciences for life-time achievement in
respiratory sciences in 2013.
Tim Regnault
Western University, London Ontario
The good, the bad and the ugly outcomes of adverse pre and postnatal
environments
[Wednesday afternoon, February 25th]
Tim Regnault received his undergraduate degree in Rural Science (Hons) from the University
England in Armidale, Australia. Following graduation he undertook positions as a District
agronomist and then a District livestock officer at Goodwindi and Hay, Australia respectively.
He commenced and completed his PhD studies through a CSIRO/University of Western Sydney
scholarship at CSIRO Prospect, studying the role of litter size and nutrition upon placental
lactogen actions. He then moved to Denver, Colorado in the US to undertake postdoctoral
training, and subsequent faculty positions, with Drs. Battaglia, Meschia, Wilkening and
Anthony. During his time in Denver, his investigations focused on areas such as placental angiogenesis, fetal hypertension, fetal oxygenation
and placental nutrient transport, in the IUGR sheep model. In 2005 he moved London, Ontario in Canada, to join the Perinatal Research group
there led by Drs. Richardson, Gagnon and Han. While continuing aspects of sheep work with a focus on cardiovascular perturbations in IUGR,
he commenced abnormal pregnancy and postnatal outcome studies using the guinea pig and cell culture systems where the laboratories focus
has been on the in utero origins and postnatal dietary interactions resulting in the development of insulin resistance and non alcoholic fatty
liver disease (NAFLD).
22
CNPRM 2015
Georg Schmölzer
University of Alberta
Monitoring in the delivery room:
Understanding physiological changes to improve neonatal outcomes
[Wednesday afternoon, February 25th]
Dr. Georg Schmölzer is a clinician-scientist recruited to Edmonton in 2012 to continue his research around
neonatal resuscitation. Dr. Schmölzer is a neonatologist at the Royal Alexandra Hospital and the inaugural
Heart and Stroke Foundation/University of Alberta Professor of Neonatal Resuscitation. He is currently the
director of CSAR (Center for the Studies on Asphyxia and Resuscitation) in Edmonton. Dr. Schmölzer obtained
his MD, PhD and clinical training in Austria and Australia. In 2014 he completed his Banting Postdoctoral
Fellowship at the University of Alberta. His research group studies physiological changes during fetal to
neonatal transition, improve mask ventilation techniques, and new approaches during chest compression. The
main contribution of the last years include i) improved mask ventilation techniques using respiratory function
monitoring, ii) using exhaled CO2 to guide lung aeration at birth, and iii) improved chest compression techniques.
Deborah Sloboda
McMaster University
Early life nutritional impacts on offspring reproductive function
[Wednesday afternoon, February 25th]
Dr Sloboda holds a Canada Research Chair in Perinatal Programming and is an Associate Professor in the Dept of
Biochemistry and Biomedical Sciences at McMaster University. She is an Associate member to the Depts of
Obstetrics & Gynecology and Pediatrics at McMaster and maintains an Honorary Research Fellow appointment at
the Liggins Institute in New Zealand. She completed her PhD training at the University of Toronto, Dept of
Physiology following which she was a Research Fellow at the University of Western Australia. In 2006 she was
recruited to the Liggins Institute at the University of Auckland in New Zealand where in 2008 she was the Deputy
Director of the National Research Centre for Growth and Development at the University of Auckland. In 2009 she
held the position of Acting Director of the Centre for one year. Dr Sloboda’s laboratory investigates the impact of
poor maternal nutrition on the developing fetus and how it influences the risk of non-communicable disease later
in life. Her experimental studies investigate the effects of maternal nutrient manipulation combined with a changing postnatal diet on pubertal
onset, ovarian development and maturation, metabolic function as well as maternal nutritional impacts on the placenta. Dr Sloboda is the
Secretary of the International Society for the Developmental Origins of Health and Disease (DOHaD) and is an Associate Editor for the Journal of
Developmental Origins of Health and Disease. Dr Sloboda has published over 75 papers in leading scientific journals and contributed to over 10
books on the concept of Early life origins of health and disease.
Paige Terrien Church
Sunnybrook Health Sciences Centre
Little Nomads: the behavioral outcomes of prematurity and potential interventions
[Wednesday afternoon, February 25th]
Dr. Paige Terrien Church is an Assistant Professor of Paediatrics at the University of Toronto. She is the
director of the Neonatal Follow Up Clinic at Sunnybrook Health Sciences Centre and the Developmental
Behavioral Physician Lead in the Spina Bifida clinic at Holland Bloorview Kids Rehabilitation Hospital. Dr.
Church is board certified through the American Board of Pediatrics in Neonatology, and Developmental
Behavioral Pediatrics and is interested in long-term functional outcomes of infants with neurologic
conditions.
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Suzanne Tough
University of Calgary
The All Our Babies Cohort: What we can Learn from
Longitudinal Follow-up
[Thursday afternoon, February 26th]
Suzanne Tough is a Professor with the Departments of Paediatrics and
Community Health Sciences in the Faculty of Medicine at the University of
Calgary and a Health Scholar supported by the Alberta Innovates – Health
Solutions. She is also the Scientific Director of the Maternal, Newborn, Child
and Youth Strategic Clinical Network and of the Alberta Centre for Child, Family
and Community Research, an organization whose vision is to improve child,
family and community well-being through applied research. Her research
program focuses on improvinghealth and well-being of women during
pregnancy to achieve optimal maternal, birth and early childhood outcomes. Suzanne is the Principal Investigator of the All Our Babies Study, a
cohort with 3,200 mother-child pairs that is investigating the impact of genetic and environmental factors on maternal-child health. The
underlying aim of her research program is to optimize birth and childhood outcomes by creating evidence that informs the development of
community and clinical programs and influences policy.
Cathy Vaillancourt
Institut national de la recherche scientifique
In utero exposure to antidepressant alters placental serotonin
and estrogen system: Role in fetal programming
[Wednesday afternoon, February 25th]
Pr. Vaillancourt obtained her M.Sc. and Ph.D. degrees in biomedical sciences
from the CHU-Saint-Justine, University of Montreal followed by postdoctoral
studies in Psychiatry at the Douglas Mental Health University Institute, and in
Neurosciences at the University of Reading (UK). She is a placentologist. Her
research focuses on the effect of maternal prenatal stress, depression,
pharmaceutical drugs, and contaminants on placental development and
function, which may have short- and long-term consequences on the
development and programming of the fetus. Her group had recently
demonstrated the production of serotonin and melatonin by the human placenta which act as a local regulator in trophoblast cells and play a
protective role in pregnancy and fetal development. Pr. Vaillancourt research is supported by March of Dimes Foundation (US), NSERC, and
CIHR. She is the treasurer of the International Federation of Placenta Association, and on the steering committee of the BioMed research
center, the Club de recherche clinique du Québec, and the International Groupe de la francophonie placentaire. She sits on grant committees
at the provincial, federal, and international levels. She currently supervises ten graduate students and one post-doctoral researcher and her
group ultimate goal is to contribute to the improvement of the quality of the life of the fetus and the newborn through to adulthood.
Pia Wintermark
McGill University
Injury and repair in perinatal brain injury: insights from bedside, imaging and bench
[Wednesday afternoon, February 25th]
Dr. Pia Wintermark is a pediatrician and neonatologist, with a research interest in neonatal neurology, currently
working at the Montreal Children’s Hospital, McGill University. Before joining the Montreal Children’s Hospital
and opening the NeoBrainLab in 2010, Dr. Pia Wintermark worked at the Children’s Hospital Boston (Harvard
Medical School) in Boston, USA, and at the Lausanne University Hospital (University of Lausanne) in Lausanne,
Switzerland. Her research is devoted to the understanding of the causes and consequences of brain and eyes
damages in sick babies. The main goals of the lab are to develop innovative strategies to prevent or repair these
brain and eyes damages, and thus to improve the future of these babies. The laboratory uses both clinical
research and basic science techniques to understand mechanisms underlying these brain and eyes damages.
24
CNPRM 2015
BANQUET & HONORARY SPEAKERS
Vincent Dumez
Université de Montréal
[Thursday evening, February 26th]
Mr. Vincent Dumez holds a finance degree and a master in science of management from Montreal’s
international business school Hautes Études Commerciales (HEC). Up until 2010, Mr. Dumez was an
associate in one of Montreal’s most influential consulting firm where he acted as a senior strategic
consultant.
Suffering from severe chronic diseases for more than three decades, M. Dumez has been actively
involved in the thinking and the promotion of the ‘patient partner’ concept at Montreal University.
This involvement has come forward over the recent years through the completion of his masters
dissertation on patient-doctor relationship, his contribution to the training of patients, his work on
various boards of community organizations and his involvement as a speaker in forums and
workshops addressed to healthcare professionals.
In the past years, Mr. Dumez has been a key collaborator for the Education Centre (CPASS) of the Faculty of medicine of the University of
Montreal. From October 2010 to June 2013, he had founded and leaded the Faculty Office of the Patient Partner Expertise. He is now codirector with Dr Paule Lebel of a larger unit, which integrates inter professional collaboration and patient partnership competencies
development.
Shoo K. Lee
MBBS, PhD, FRCPC
[Friday morning, February 27th]
Dr. Shoo Lee is a neonatologist and health economist. He is Scientific Director of the Institute of Human
Development, Child and Youth Health (IHDCYH) at the Canadian Institutes of Health Research; Professor of
Paediatrics, Obstetrics & Gynaecology and Public Health; Paediatrician-in-Chief and Director of the MaternalInfant Care (MICare) Research Centre at Mt. Sinai Hospital and Associate Member of the Samuel Lunenfeld
Research Institute.
Dr. Lee received his medical degree from the University of Singapore, completed his paediatric training at the
Janeway Children's Hospital in Newfoundland and neonatal fellowship training at Boston’s Children’s Hospital,
and received his PhD in Health Policy (Economics) from Harvard University.
As the founder and Director of the Canadian Neonatal NetworkTM and the International Neonatal Collaboration,
Dr Lee fosters collaborative research, and he leads the CIHR Team in Maternal-Infant Care. His research focuses
on improving quality of care, patient outcomes and health care services delivery.
Awards for his work include the CIHR Knowledge Translation Award, the Aventis Pasteur Research Award and the Distinguished Neonatologist
Award from the Canadian Paediatric Society, and the Premier Member of Honour Award from the Sociedad Iberoamericana de Neonatologia
and Magnolia Award from the Shanghai government.
CNPRM 2015
25
26
CNPRM 2015
SPONSORS
THE CANADIAN PERINATAL RESEARCH MEETING ORGANIZING COMMITTEES GREATLY
APPRECIATE THE CONTRIBUTIONS FROM ALL OF OUR 2015 SPONSORS
CNPRM 2015
27
BLES Biochemicals Inc., the market leader for pulmonary
surfactant in Canada, manufactures and distributes BLES®, a
pulmonary surfactant for use in the treatment of premature
infants suffering from NRDS. BLES® is manufactured from a
lung lavage process; there is no generic form of this product.
BLES Biochemicals Inc. is a privately owned Canadian
controlled pharmaceutical company.
28
CNPRM 2015
The Molly Towell Perinatal Research Foundation provides
funding to support basic biomedical research concerning fetalneonatal health. The Foundation considers applications for
matched funding of 2-year Fellowships and for 2-year operating
grants to support newly-appointed investigators in this
research area. This year’s application deadline is April 15, 2015.
For further info, please go to mtprf.org
I also have attached a copy of the Foundation’s new logo. It
hasn’t been officially approved yet and may change a bit but
please feel free to use it in your program.
Please visit our website at: MTPRF.org
CNPRM 2015
29
Medela Canada caters to both parents and healthcare
professionals. Parents have made Medela the market leader in
breastpumps and breastmilk feeding products due to the
company’s high quality research based products and relentless
support of breastmilk feeding mothers.
Healthcare professionals rely on Medela’s research based
solutions to improve patient care and outcomes while reducing
length of stay, saving the provincial healthcare systems money.
30
CNPRM 2015
CIHR-IHDCYH is happy to support the attendance of trainees
as well as provide awards for their presentations.
CNPRM 2015
31
Prolacta Bioscience is a life sciences company developing clinically proven, high-quality products
derived from human milk that are designed to meet the needs of extremely premature infants in the
NICU. Prolacta’s first commercial product, Prolact+ H2MF®, is a Human Milk Fortifier made
exclusively with 100 percent donor breast milk.
The university hospital center CHU Sainte-Justine (SainteJustine) is affiliated with the Université de Montréal, and
fosters close collaborations with many other institutions of
higher learning at the local, national, and international
levels.
Sainte-Justine nurtures the vision of a Quebec where mother,
child and adolescent health ranks among the best in the
world. With this in mind, it is intent on fulfilling its mission
Axe pathologies foetomaternelles et néonatales
of advancing knowledge and applying new findings with faster and
less invasive methods and devices aimed at disease prevention,
prognosis, treatment, and long-term follow-up starting at conception and gestation and continuing
right through to adulthood.
32
CNPRM 2015
DIVISION OF NEONATOLOGY, DEPARTMENT OF
PAEDIATRICS, HOSPITAL FOR SICK CHILDREN


DEPARTMENT OF PAEDIATRICS, DIVISION
OF NEONATOLOGY
DEPARTMENT OF OBSTETRICS AND
GYNECOLOGY


CNPRM 2015
33
AXE MALADIES VIRALES,
IMMUNITAIRES ET CANCERS
NEONATOLOGY SERVICE
34
CNPRM 2015
MORNING PLENARY SESSIONS ABSTRACTS
WEDNESDAY MORNING, FEBRUARY 25TH
[ROOM OUTAOUAIS]
Mrs. Katharina Staub
Canadian Premature Babies Foundation
The long shadow of the NICU: the impact of trauma
for NICU infants and families
Dr. Cindy-Lee Dennis - University of Toronto
Can We Prevent Postpartum Depression?
Results from a Systematic Review and a Clinical Trial
[238]
DOES MATERNAL CHORIOAMNIONITIS INCREASE OR DECREASE
NEONATAL RESPIRATORY MORBIDITY? Amy Metcalfe1, Sarka
Lisonkova2, Yasser Sabr2, KS Joseph2
1University of Calgary/Obstetrics and Gynecology, 2University of
British Columbia/Obstetrics and Gynecology.
Introduction: There are conflicting results in the literature on the
impact of chorioamnionitis on fetal lung development. Some
authors have suggested that antenatal inflammation promotes
lung maturation in the premature infant, thus reducing the risk of
respiratory distress syndrome (RDS) and simultaneously causing an
acute injury thus increasing the risk of bronchopulmonary
dysplasia (BPD). Objective: This study aimed to determine
whether chorioamnionitis affects the incidence of RDS and BPD
after accounting for the increased risk of death. Methods:
Retrospective cohort study using linked infant birth, death and
hospitalization records from Washington State between 20072010 (n=320, 648 singleton infants). Logistic regression models
based on the fetuses-at-risk approach were used to model two
composite outcomes namely RDS, stillbirth or neonatal death and
BPD, stillbirth or neonatal death. Confounders adjusted in the
models included maternal age, race, diabetes, hypertension,
corticosteroid prophylaxis, mode of delivery and infant sex.
Results: Chorioamnionitis lead to a shift in the gestational age
distribution, with an increased rate of preterm birth. Crude models
indicated that chorioamnionitis was associated with an increased
odds of RDS, stillbirth or neonatal death (OR=1.33, 95% CI: 1.121.58); however, this association was attenuated following
adjustment for other confounders (OR=0.92, 95% CI: 0.76-1.13).
Crude and adjusted models showed that chorioamnionitis
increased the odds of BPD, stillbirth or neonatal death (crude
OR=1.13, 95% CI: 0.84-1.54; adjusted OR=1.54, 95% CI: 1.07-2.23).
Conclusion: The fetuses-at-risk approach models the causal impact
of maternal chorioamnionitis on the development of the fetal lung
and shows an increased risk of respiratory morbidity and perinatal
mortality and morbidity associated with such maternal infection.
Acknowledgements: This study was funded by a CIHR Team Grant
on Severe Maternal Morbidity (MAH-115445). Contact
information: [email protected]
[455]
EFFECT OF MIDAZOLAM ON HIPPOCAMPAL GROWTH AND
NEURODEVELOPMENT IN VERY PRETERM BORN NEONATES.
Emma G. Duerden1, Lorin Dodbiba1, Ruth E. Grunau2, Vann Chau1,
Anne Synnes2, Ting Guo1, M. Mallar Chakravarty3, Steven P. Miller1
1Paediatrics, Hospital for Sick Children, 2Pediatrics, University of
British Columbia, 3Psychiatry, McGill University.
Introduction: Concerns are prevalent that analgesia and sedation
for pain management in the neonatal intensive care unit may be
associated with widespread alterations in metabolic and
microstructural brain development in very preterm neonates (2432 weeks gestation). The hippocampus is a stress-sensitive region
that mediates memory processes and may be vulnerable to the
effects of procedural pain and analgesic/sedatives therapies and
underlie poor neurodevelopmental outcome. Objective: 1. To
determine the association with pain and analgesics/sedative
exposure on slower hippocampal growth in very preterm
neonates. 2. To assess the relationship between hippocampal
changes and 18-month (corrected age) neurodevelopmental
outcomes. Methods: Hippocampal volumes were measured in 94
neonates on MRI early in life and at term-equivalent age.
Generalized Estimating Equation (GEE) analyses were used to
determine factors predicting hippocampal size. Infants were
assessed at 18 months corrected age using the cognitive, language
and motor measures of the Bayley Scales of Infant DevelopmentIII. Models testing the association of Midazolam exposure and the
number of painful procedures with hippocampal volumes
accounted for the following clinical factors: gestational age at
birth, sex, postmenstrual age at MRI, dose of analgesics/sedatives
(Fentanyl, Morphine, Midazolam), days of mechanical ventilation,
hypotension, and dose of steroids. Results: Midazolam exposure
(total dose, mg) affected hippocampal size (p=0.02) while the
number of painful procedures did not (p = 0.5), even when
accounting for other clinical factors. Smaller hippocampal volumes
predicted significantly lower cognitive and language outcome
scores (p<0.05), but not motor scores (p>0.05). Conclusion:
Hippocampal growth disturbances in early preterm neonates are
associated with Midazolam exposure and predict
neurobehavioural impairments at 18 months. Further research is
needed to understand the effects of Midazolam and its use in
preterm born infants is cautioned. Acknowledgements: Funding
for this research was provided by the Canadian Institutes of Health
Research and NeuroDevNet. Contact Information:
[email protected]
[370]
PATHOLOGY OF PLACENTA IN FETAL AND NEONATAL IMMUNE
THROMBOCYTOPENIA: ROLES OF TH17 IMMUNE RESPONSES,
ANTI-PLATELET ANTIBODIES AND ANGIOGENIC FACTORS. Issaka
Yougbare1,2, Wei-She Tai1,2, Darko Zdravich1,2,3, Brian Vasdaz2,3,
Alexandra Marshall1,2, Pingguo Chen1,2, Guangheng Zhu1,2, Heyu
Ni1,2,3,4
1Canadian Blood Services; 2Toronto Platelet Immunobiology
Group, Keenan Research Centre for Biomedical Science, St.
Michael's Hospital, University of Toronto; 3Department of
Laboratory Medicine and Pathobiology; 4Departments of Medicine
and Physiology.
Introduction: Fetal and neonatal alloimmune thrombocytopenia
(FNAIT) occurs in 0.5 to 1.5 per 1000 live born neonates and often
leads to intracranial hemorrhage, severe bleeding diathesis,
and/or miscarriage. FNAIT occurred when the mother mounts an
alloimmune response against fetal platelet antigens (especially
glycoproteins GPIIbIIIa and GPIb). Pregnancy success is critically
dependent on the type of maternal immune response to fetal
allogenic cells. T helper (Th)1 and Th17 pro-inflammatory response
have been associated with recurrent miscarriages. Objective: We
investigated whether Th17 cells and anti-beta 3 integrin antibodies
in FNAIT target alphaV beta3 integrin of invasive trophoblast cells
to impair placental function. Methods: To model FNAIT as
observed in human patients, beta3 integrin (GPIIIa) deficient
female mice were immunized with wild-type (WT) platelets and
then bred with WT males. Placenta function was investigated by
CNPRM 2015
35
Doppler and contrast-enhanced ultrasound. Placenta
vascularisation was assessed by perfusion of casting compound
and micro-computered tomography. Placental pathology was
investigated by H&E staining, immunohistochemistry, and
electronic microscopy study. The maternal immune response was
investigated using cytokine arrays, immune cell
immunophenotyping, and ELISA. Placental angiogenesis was
investigated by measuring placenta growth factor (PlGF) and fmslike tyrosine receptors (Flt-1) by ELISA and angiogenesis cytokine
array kit. Results: Miscarriage occurred in anti-beta3-mediated
FNAIT, while no fetal death was reported in the naïve control
group. Placenta from anti-beta3-mediated FNAIT had significantly
reduced vessel development and poor materno-placental
perfusion. Th17 polarized immune response increased circulating
IL-23 and MCP-1 levels. Subsequently, angiogenic inhibitors
(Endoglin, thrombospondin-1) were up-regulated in the placenta.
Placental Flt-1 over-expression significantly decreased plasma
PlGF/sFlt-1 ratio resulting in impaired pro-angiogenic signalling.
Intravenous biotin injection into the mother further demonstrated
biotin accumulation in the placenta, suggesting impaired placental
blood flow. Hematoxylin and eosin staining also confirmed that
placenta of affected fetuses were ischemic. Interestingly, we also
demonstrated that intravenous immunoglobulin (IVIG), which
induced anti-inflammatory responses, ameliorated placental
angiogenesis, and increased survival of FNAIT fetuses. Conclusion:
Reduced placental angiogenesis and trophoblast cell invasion
caused miscarriage in anti-beta3-mediated FNAIT. IVIG rescued
placental growth and function by inhibiting the Th17 proinflammatory response. Acknowledgements: We thank our
founding institutes: CIHR and CBS. Contact Information:
[email protected]
[323]
ARE THERE TOO MANY RCTS OF SWEET SOLUTIONS FOR PAIN
MANAGEMENT IN BABIES? Denise Harrison1, Catherine
Larocque2, Mariana Bueno3, Jessica Reszel4, Yehudis Stokes5, Li
Tian6, Lucy Turner7, Brian Hutton7, Bonnie Stevens8
1School of Nursing, University of Ottawa and Children's Hospital of
Eastern Ontario, 2School of Nursing, University of Ottawa and
Children's Hospital of Eastern Ontario Research Institute, 3School
of Nursing, University of São Paulo, 4Children's Hospital of Eastern
Ontario Research Institute, 5Children's Hospital of Eastern Ontario,
6Department of Nursing, the First Affiliated Hospital of Soochow
University, 7Ottawa Hospital Research Institute, 8The Hospital for
Sick Children.
Introduction: Sucrose and glucose consistently reduce procedural
pain in newborns (Stevens 2013; Bueno 2013). In 2010, our team
concluded that a state of equipoise no longer exists (Harrison
2010), yet new trials with placebo groups continue to be
published. Objective: Based on an updated search of the
literature, conduct cumulative meta-analyses (CMA) to ascertain
the calendar year/s at which statistically significant treatment
effects were evident. Methods: Search strategies as per methods
of the Cochrane Neonatal Review Group were used with searches
continuing until March 2014. Databases included CINAHL;
Medline; EMBASE; psychINFO; Cochrane library and the major
Chinese databases (Chinese Biomedical Literature Database, China
National Knowledge Infrastructure and WANFANG) using
keywords: sweet (糖) and pain (痛). Risk of bias (RoB) was rated
for additional studies (Higgins 2011) and data was extracted for
crying time and pain scores. CMA of mean differences (MD) using
a random effects model to generate summary measures, with 95%
confidence intervals (CI) were conducted for crying duration, and a
pooled standardized mean difference (SMD) with 95% CI was
conducted for pain scores. All analyses were conducted using
STATA Version 11 and were verified using CMA Version 2.0.
36
Statistical heterogeneity was assessed using the I2 statistic.
Results: There were 202 studies included. ROB was low in most
RCTs. Most procedures were heel lance (42%), venipuncture
(20%), immunization (30%) and 183 (91%) had placebo/notreatment groups. CMA for crying time included 28 trials, 1814
infants. From 2002, there was a significant reduction in mean cry
time for sweet solutions compared to placebo (-26 seconds (95%
CI, -34, -18)). Cumulative meta-analysis for SMD of pain scores
included 53 trials, 3887 infants, and showed a statistically
significant reduction during any painful procedures (-1.1 (95% CI, 1.3, - 0.9)). The directions of effects were consistent but imprecise
trial estimates resulted in wide variability in upper and lower 95%
CIs and significant heterogeneity (I2 (crying time= 94%; pain
scores= 90%)). Conclusion: Evidence of analgesic effects of sweet
solutions during painful procedures in newborns has existed since
early 2000 and it can be argued that a state of equipoise has not
existed since then. Sweet solutions or other effective strategies
(maternal care) should be considered as standard of care in future
RCTs and researchers and clinicians need to prioritize putting
knowledge into action and improving pain management.
Acknowledgements: We acknowledge Shanthi Sembacuttiaratchy
for her assistance with data extraction. Contact Information:
[email protected]
[388]
TREATMENT WITH LOSARTAN PREVENTS THE DEVELOPMENTAL
PROGRAMMING OF CARDIAC DYSFUNCTION CAUSED BY
NEONATAL HIGH OXYGEN EXPOSURE IN RATS. Mariane
Bertagnolli1, Sarah Beland-Bonenfant1, Anne Dios1, Marie-Amélie
Lukaszewski1, Anik Cloutier1, Megan Sutherland1, Denis Deblois1,
Pierre Paradis2, Ernesto L Schiffrin2, Anne Monique Nuyt1
1Sainte-Justine University Hospital Research Center, Université de
Montréal, 2Lady Davis Institute, Jewish General Hospital, McGill
University.
Introduction: Neonatal oxidative stress is a major postnatal
deleterious factor predisposing preterm born infants to classical
complications of prematurity (retinopathy, bronchopulmonary
dysplasia), which are characterized by impaired vascular
development. Our group has previously shown that rats
transiently exposed to high oxygen (O2) as newborns (mimicking
human preterms oxidative stress conditions) develop high blood
pressure (BP), cardiac remodeling and dysfunction later in life, in
part mediated by the renin angiotensin system (RAS). Cardiac RAS
activation is characterized by AT1/AT2 receptors imbalance in rats
exposed to high O2, with increased AT1R at adult age. Objective:
In order to study the role of RAS at early stages of the
developmental programming of cardiac dysfunction caused by
high O2 exposure, we assessed whether an early and short-term
treatment with AT1R blocker, Losartan, prevents cardiac
alterations at young male 4 weeks-old rats (prior to the elevation
of BP in this model). Methods: Sprague-Dawley newborns rats
were kept with their mother in 80% O2 (O2 group, n=9) or room air
(Ctrl, n=9) from days 3-10 of life (P3-P10). Losartan (LOS, n=10, 20
mg/Kg) or water was administered by gavage in O2 rats from P8P10 (last 2 days of O2 to avoid impact on nephrogenesis). Data
presented as mean±SD and statistically different when P<0.05.
Results: At 4 weeks, echocardiography reveals that O2 rats have
decreased fraction of shortening compared to Ctrl (FS: 37 ± 2 vs 42
± 2 %), suggesting impaired systolic function in O2. Cardiac
hypertrophy evaluated by heart/body weight and cardiomyocyte
surface area (CSA) is also increased in O2 vs Ctrl (141 ± 13 vs 118 ±
4 µm2). LOS treatment prevented the impairment of systolic
function in O2 by ameliorating FS (43 ± 2 %) and reducing CSA (121
± 11 µm2). LOS treatment also modulated RAS genes expression
(RT-PCR): LOS restored AT1/AT2 balance in O2 hearts by decreasing
AT1b subunit (O2:0.8 ± 0.2 vs O2+LOS:1.3 ± 0.3 vs Ctrl:0.9±0.2 gene
CNPRM 2015
expression/s16) as well as increasing ACE2 (O2:1.5 ± 0.4 vs
O2+LOS:0.8±0.1 vs Ctrl:1.1±0.4 Ctrl) expressions. Short-term LOS
treatment has not modified glomerular volume compared to Ctrl
and O2 groups, suggesting no impact on nephrogenesis.
Conclusion: In conclusion, a short-term treatment with LOS during
neonatal O2 exposure prevents the impairment of cardiac systolic
function and hypertrophy at young age. This data reinforces the
key role of RAS in the developmental programming of cardiac
dysfunction and reveals LOS as an effective strategy to prevent
early cardiac alterations caused by neonatal high O2 exposure.
Acknowledgements: We thank FQRNT, FRQS, SQHA, HSFC and
CIHR for supporting this study. Contact Information:
[email protected]
[303]
ORAL LACTOBACILLUS RHAMNOSUS GR-1/ L. REUTERI RC-14
DOES NOT CHANGE THE VAGINAL MICROBIOTA OR CERVICOVAGINAL CYTOKINES IN LOW RISK PREGNANT WOMEN WITH AN
ABNORMAL NUGENT SCORE. SW Yang1, JRG Challis2, G Reid3, GB
Gloor3, SL Seney3, MJ Martin4, TM Rocco4, E Asztalos 5, AD
Bocking4
1University of Toronto, 2University of Western Australia, 3Western
University, 4Mount Sinai Hospital, 5Sunnybrook Health Sciences
Center.
Introduction: A decrease in lactobacilli and an overgrowth of
facultative anaerobic bacteria represent a disturbed vaginal
microbiota termed bacterial vaginosis (BV). Probiotic L. rhamnosus
GR-1 and L. reuteri RC-14 (GR-1/RC-14) reduces BV recurrence and
restores the indigenous lactobacilli in non-pregnant women.
Objective: We hypothesized that oral GR-1/RC-14 would modulate
the vaginal microbiota and cervicovaginal cytokines in pregnant
women with an abnormal Nugent score. Methods: Pregnant
women (n=86) with Nugent score >4 at 13 weeks gestation were
randomized to receive orally either GR-1/RC-14 (5x109 CFU
/strain) or placebo for 12 weeks. Vaginal swabs were collected at
13, 28 and 35 weeks gestation. Vaginal microbiota were analyzed
by sequencing the V6 region of 16S rRNA, and 27 cytokines were
measured with a multiplex assay. Significance was assessed with t
test or Two-Way Repeated Measure ANOVA with Holm Sidak test.
Results: Among the 93 distinct bacterial species detected, L. iners,
L. crispatus, Gardnerella (G.) vaginalis and Atopobium (A.) vaginae
were the most abundant vaginal bacterial species. The Nugent
score returned to normal in 30% of the women in both groups by
28 weeks. Compared to 13 weeks gestation, the relative
abundance of 26 species including several Lactobacillus spp and
the BV-associated bacteria, G. vaginalis and A. vaginae decreased
in both groups at 28 and 35 weeks. In contrast, 21 species
including Finegoldia magna and Prevotella micans increased
variably between groups. There was no difference in the vaginal
microbiota and cervicovaginal cytokines between the two groups.
However, the inflammatory cytokines IL-6, CCL3 and CCL 4
decreased and the anti-inflammatory cytokines IL-4 and IL-10
increased by 28 and 35 weeks in the probiotic group but not in the
placebo group. Conclusion: Oral Lactobacillus rhamnosus GR-1/ L.
reuteri RC-14 at 5x109 CFU /strain twice daily for 12 weeks does
not change the vaginal microbiota or cervico-vaginal cytokines
significantly in pregnant women. The vaginal microbiome and the
cervico-vaginal cytokines in pregnant women with an elevated
Nugent score are dynamic across gestation. Acknowledgements:
We thank the research nurses, MJ Martin and TM Rocco, of Mount
Sinai Hospital for the recruitment of participants and collection of
vaginal swabs, as well as for their continuous support throughout
the study. Contact Information: [email protected]
Dr. Bernard Thebaud - University of Ottawa
Prevention/repair of organ injury while promoting
normal organ development in extreme premature
infants: possible with cell therapy?
THURSDAY MORNING, FEBRUARY 26TH
[ROOM OUTAOUAIS]
Prof. Olivier Baud - Paris-Diderot University
Early Low-Dose Hydrocortisone to improve Survival
without Bronchopulmonary Dysplasia in Extremely
Preterm Infants: rationale and PREMILOC
randomized controlled trial
Prof. Paul Leeson - University of Oxford
Preeclampsia, Prematurity and Offspring
Cardiovascular Health in Later Life
[420]
IMPACT OF A STEWARDSHIP PROGRAM ON INHALED NITRIC
OXIDE (INO) USE IN A QUATERNARY NEONATAL INTENSIVE CARE
UNIT (NICU). Amir Elmekkawi MD1, Kiran More MD1, Jennifer
Francis RRT1, Christina Sperling RRT2, Michael Finelli RRT1, Robert P
Jankov MD PhD1
1Division of Neonatology, Hospital for Sick Children, Toronto,
2Department of Critical Care, Hospital for Sick Children, Toronto.
Introduction: iNO remains the “gold standard” therapy for
hypoxaemic respiratory failure (HRF) in newborns. Despite the
availability of high quality evidence to guide the use of iNO in
newborns, we observed considerable practice variation in our
NICU, particularly with respect to timing and manner of weaning.
With the goals of promoting evidence-based practice and of
providing robust data to guide iNO use, an iNO Stewardship
Program was launched at the Hospital for Sick Children NICU
(quaternary outborn unit) in April 2013. Key aspects of the
program include identified physician champions, revision and
dissemination of evidence-based practice guidelines, detailed
prospective data collection, monthly reviews and formalised
interdisciplinary collaboration in decisions relating to iNO use.
Objective: To determine whether institution of iNO Stewardship
was associated with changes in iNO utilisation and weaning
practice. Methods: A comparative analysis of two epochs [Epoch 1
(April 2011-March 2012 - retrospective) and Epoch 2 (April 2013March 2014 - prospective)] was conducted on all infants who
received iNO therapy. Primary outcomes included indication for
iNO, response to iNO (FiO2 decrease ≥0.2 and/or SaO2≥10%) and
number of excess iNO hours attributable to non-progression of
weaning after guideline criteria were met. Patients were
considered “off-label” if iNO was initiated at >14 days age and/or
<35 weeks’ gestation or for an indication other than HRF. Excluded
from analyses of weaning times were patients in whom: 1) iNO
was discontinued from maximum dose (20 ppm), 2) rebound
hypoxaemia necessitated escalation in iNO dose, 3) a deviation
from the weaning guidelines was mandated by physician order, 4)
death occurred whilst on iNO, or 5) ECMO was instituted.
Comparison between groups was conducted using Student’s t-test,
Mann-Whitney U test or Chi Square test, as appropriate, with
p<0.05 considered significant. Results: 51 patients received iNO in
Epoch 1 and 31 in Epoch 2. There were no significant differences
(p>0.05) in patient demographics between Epochs (sex,
gestational age, birthweight), in the proportion of patients
CNPRM 2015
37
receiving iNO “off-label” or in the proportion responding to iNO
(Table). There were significant (p<0.05) reductions in total hours
on iNO per patient and in iNO hours per patient from maximum
dose to initial wean and in hours from initial wean to
discontinuation of iNO (Table). Conclusion: The establishment of
an iNO Stewardship Program was associated with improved
alignment of weaning practices with evidence-based guidelines
and an overall reduction in iNO use. Contact Information: Robert
Jankov [email protected]
[359 ]
IMPACT OF PLACENTAL GROWTH FACTOR ON BRAIN
DEVELOPMENT, COGNITION AND BEHAVIOR. Matthew T.
Rätsep1, Angelina Paolozza2, Bruno Zavan1, Vanessa R. Kay1,
Brandon Maser1, Andrew Hickman1, Patrick W. Stroman2, Graeme
N. Smith1, James N. Reynolds2, Michael A. Adams1, B. Anne Croy1
1Department of Biomedical and Molecular Sciences, Queen's
University, Kingston, ON, Canada, 2Centre for Neuroscience
Studies, Queen's University, Kingston, ON, Canada.
Introduction: In many preeclamptic (PE) pregnancies, maternal
plasma is low in the placentally-produced angiokine “placental
growth factor” (PGF). Offspring of severe PE (PE-F1) compared to
uncomplicated pregnancies are at greater risk for hypertension,
cognitive impairment and stroke. Mechanisms explaining these
risks are not well understood. Pgf-/- mice have less decidual and
placental vascular branching and connectivity than controls and
most experience stroke after unilateral common carotid artery
occlusion. Objective: We hypothesized that PGF deficiency, which
manifests in PE, diminishes brain vascular development and leads
to impaired cognition and elevated stroke risk postpartum.
Methods: Pgf-/- and Pgf+/+ adult mouse brain vasculature and
structural anatomy were examined by polymer casting and
magnetic resonance imaging (MRI), respectively. Cognitive
behaviour was assessed in these mice by five standard paradigms
that tested depression, spatial learning, short and long term
memory, activity and anxiety. Brains of 10 pairs of children aged 810 born to preeclamptic or uncomplicated pregnancies were
analyzed for cognitive functions (psychometrics, eye tracker study)
and brain structure through MRI. Results: Pgf-/- brain vasculature
was deficient (80% incomplete circle of Willis; less capillary
development) and abnormally patterned compared to Pgf+/+
controls. Cognitive behavioural testing revealed impairments in
numerous cognitive domains of Pgf-/- mice, with sexually
dimorphic differences. Preliminary analyses of PE-F1 children
found brain vascular anomalies (narrower vessels and less fine
branching) compared with children born to uncomplicated
38
pregnancies. Analyses of cognitive function tests are ongoing.
Conclusion: This work has uncovered a previously unknown link
between PGF expression, brain vascular development and
cognitive functions in mice. Our data in children suggest that
experience of gestation in a PE pregnancy may also depress brain
vascular development with roles for PGF yet to be defined. While
further analyses are needed to refine and extend our preliminary
data set, these initial data suggest expansion of our approach to
children born to pregnancies complicated by PE, IUGR and
diabetes will have great merit in defining the full impact of these
common gestational pathologies. Acknowledgements: Supported
by NSERC, CIHR, the CRC program and Kingston General Hospital
Foundation. Contact Information: [email protected]
[375]
EVALUATION OF THE PARTNERS IN INNER-CITY INTEGRATED
PRENATAL CARE (PIIPC) PROJECT: PERSPECTIVES OF WOMEN
AND CARE PROVIDERS. Maureen Heaman1, Lynda Tjaden2, Zorina
Marzan Chang1, on behalf of the PIIPC Research Team3.
1College of Nursing, Faculty of Health Sciences, University of
Manitoba, 2Public Health, Winnipeg Regional Health Authority,
3Various partnership sites.
Introduction: Our previous research (1) demonstrated high rates
of inadequate prenatal care (PNC) among women living in innercity community areas in Winnipeg, and (2) identified barriers,
motivators and facilitators related to use of PNC among inner-city
women. Building on these findings, representatives of the
Winnipeg Regional Health Authority (WRHA), Healthy Child
Manitoba (HCM), Manitoba Health, and the Assembly of Manitoba
Chiefs, in collaboration with researchers from the University of
Manitoba, developed the Partners in Inner-city Integrated Prenatal
Care (PIIPC) Project. The goal of PIIPC is to reduce inequities in
access to and use of PNC through the implementation of health
system improvement initiatives. Objective: The objective of this
qualitative component of the larger mixed-methods study was to
explore the perspectives of women and health care providers
about the PIIPC project, its integration of services, and whether
the initiatives reduced barriers to use of PNC. Methods: A
qualitative descriptive design was used. In-depth individual
interviews were conducted with 20 postpartum women and 26
health care providers who participated in the PIIPC project.
Purposeful and maximum variation sampling strategies were used.
Interviews were audio recorded and transcribed verbatim. Content
analysis was used to identify themes and sub-themes arising from
the data. Results: The majority of women participants selfidentified as First Nations or Metis. Women described access to
PNC as convenient and coordinated. They appreciated flexible
scheduling and receiving assistance with transportation (e.g., bus
tickets) and incentives (e.g., food vouchers). They commented on
positive relationships with health care providers, using descriptors
such as helpful, caring, understanding, respectful, reassuring,
available, and non-judgemental. A variety of health care providers
participated in the interviews (e.g., obstetricians, family
physicians, nurses, social workers). Themes included better
understanding of other programs, improved communication
between programs, benefits of teamwork, and changes in service
delivery (e.g., more accessible and convenient; consistent contact
person). Conclusion: The PIIPC program has transformed the way
PNC is provided to inner-city pregnant women at risk of
inadequate PNC, resulting in improved access to and use of PNC by
this population. This project exemplifies how building successful
partnerships involving researchers, clinicians, administrators, and
policy makers can contribute to health system improvements.
Acknowledgements: Funded by a CIHR Partnerships in Health
System Improvement (PHSI) grant, the Manitoba Health Research
CNPRM 2015
Council, WRHA and HCM. Contact Information:
[email protected]
[335]
PERINATAL OUTCOMES BY IMMIGRATION STATUS IN CANADA:
SIMILARITIES AND DIFFERENCES ACROSS OUTCOMES, PROVINCES
AND DURATION OF RESIDENCE. Seungmi Yang1, Tracey Bushnik2,
Russell Willkins2, Jay S. Kaufman3, Michael Tjepkema2, Amanda
Sheppard4, Michael S. Kramer1.
1McGill University/Department of Epidemiology, Biostatistics and
Occupational Health, 2Statistics Canada, 3McGill
University/Departments of Pediatrics and Epidemiology,
Biostatistics and Occupational Health, 4Sick Kids Hospital.
Introduction: In many high-income countries, foreign-born
mothers have been reported to experience different rates of
adverse perinatal outcomes vs those native-born. However,
outcomes in prior studies have been largely limited to preterm
birth and size at birth. In Canada, national data on associations
between maternal nativity and perinatal outcomes has not been
available heretofore. Objective: To assess differences in perinatal
outcomes by maternal nativity in Canada at the national and
regional levels, and by duration of residence among foreign-born
mothers. Methods: We linked the 2006 long-form census data to
the linked live birth, infant death, stillbirth database and identified
maternal nativity status, province of residence at birth, and year of
immigration for each linked birth record among infants born in
May 2004-May 2006. We compared rates of preterm birth (PTB,
<37 weeks of gestation), small-for-gestational age (SGA) birth,
large-for-gestational age (LGA) birth, stillbirth, and neonatal and
postneonatal mortality between Canadian- and foreign-born
mothers overall, by province/region, and by duration of residence
among foreign-born mothers. Results: Overall, foreign-born
mothers had lower rates of PTB (7.7% vs.8.4%), LGA (8% vs 13%),
stillbirth (5.5 vs 5.9 per 1,000 total births), neonatal mortality (2.2
vs 3.0 per 1,000 births), and postneonatal mortality (1.8 vs. 1.0 per
1,000 births) but a higher rate of SGA (11.4% vs 7.6%). For regionspecific analysis, the difference in PTB by maternal nativity was
greater in QC (8.1 vs 7.4) and ON (8.2 vs 7.5) than in the rest of
Canada. The difference in SGA was greater in ON (7.3 vs 12.1) and
BC (5.9 vs 10.4) and lower in QC (8.3 vs 9.8), while differences in
LGA were substantially larger in ON (13.0 vs 7.5), Western Canada
(excluding BC) (13.5 vs 8.5), and BC (14.2 vs 7.6). The difference in
stillbirth rate was larger in Western Canada, but the rates
estimates were imprecise, owing to low numbers of stillbirth. The
infant mortality rate difference was larger in Western Canada
excluding BC (e.g., 7.0 vs 4.7 for neonatal mortality). Among
foreign-born mothers, those who had lived in Canada >5 years had
higher rates of PTB (8.4 vs 6.7), LGA (8.3 vs 7.4), stillbirth (5.7 vs
5.3), neonatal (2.4 vs 1.9) and postneonatal (1.2 vs. 0.7) mortality
but a lower rate of SGA (10.9 vs 12.1) compared to those who had
lived in Canada for <5 years. Conclusion: Foreign-born mothers
had more favorable perinatal outcomes than Canada-born
mothers, except for a higher rate of SGA, However, the longer
their duration of residence in Canada, the more their adverse
outcome rates resembled those of Canada-born mothers,
suggesting an unfavourable effect of acculturation.
Acknowledgements: CIHR. Contact Information:
[email protected]
Dr. Stephen Lye - University of Toronto
Maternal Immune Cells: Mediators of Reproductive
Function and Tools to Monitor Pregnancy Health
Ikaria Young Investigator Research Fund and Forum
Dr. AMIT MUKERJI – McMaster University
Non-invasive high frequency oscillatory ventilation
(nihfov) versus bi-phasic continuous positive airway
pressure (bp-cpap) following cpap failure in infants
<1,250 grams: preliminary results from a pilot
randomized controlled trial
Dr. ANNE DIOS - CHU Erasme Brussels, Belgium
Impact of transient neonatal high oxygen exposure
on right ventricular tissue and function in rats
Dr. LANNAE STRUEBY - University of Saskatchewan
Paracrine effect of mesenchymal stromal cells on
multifactorial lung injury in neonatal mice
CNPRM 2015
39
FRIDAY MORNING, FEBRUARY 27TH
[ROOM OUTAOUAIS]
Dr. Richard Oster - University of Alberta
Disparities in diabetes in pregnancy and other
perinatal outcomes according to ethnicity in Alberta
Dr. Wendy Robinson - University of British Columbia
DNA methylation in the human placenta: what can it
tell us about normal and abnormal development?
[278]
CHARACTERIZATION OF A SELECTIVE INTERLEUKIN (IL) -1
RECEPTOR ANTAGONIST EFFECTIVE IN PREVENTING PRETERM
BIRTH. Mathieu Nadeau-Vallée1, Christiane Quiniou2, Xin Hou2,
Julia Palacios1, Sylvain Chemtob2
1Faculty of medicine/Université de Montréal/Pharmacology
department, 2CHU Sainte-Justine Research Centre/Departments of
Pediatrics, Ophthalmology and Pharmacology.
Introduction: Preterm labor (PTL) is associated with an increased
production of inflammatory cytokines, particularly interleukin (IL) 1β and prostaglandins, in the uterus and in the cervix. These
factors promote the influx of inflammatory cells that release
matrix metalloproteins and other uterine activation proteins
(UAPs), which contribute to the anatomical changes associated
with increased myometrial responsiveness and cervical ripening.
Since IL-1 has been identified as a major actor in those
inflammatory-triggered changes, the host laboratory developed a
small peptide inhibitor of IL-1 receptor, namely rytvela (termed
101.10) eliciting allosteric-like modulatory properties and
functional selectivity toward specific IL-1-driven inflammatory
pathways. Objective: To characterize 101.10 efficacy at
preventing/delaying preterm labor in three different
infection/inflammation-induced PTL models. Methods: Timedpregnant CD-1 mice at gestational day (G) 16.5 were primed with a
single 1µg intrauterine IL-1β injection and then received 101.10
(1mg/Kg/12h) or vehicle subcutaneously twice a day until delivery.
Time of birth was rigorously assessed and myometrium fragments
from the right uterine horn were collected for qPCR analysis.
Results: 101.10 significantly delayed IL-1β-, LTA- and LPS-induced
PTL. In addition, 101.10 decreased the induction of several proinflammatory and/or pro-labor genes in myometrium tissues
collected <2h postpartum. Desirably, 101.10 had no significant
effect on IL-1β-induced NF-κB activation while dose-dependently
inhibiting the phosphorylation of alternative pathways p38, JNK, cjun and ROCK in primary myometrial cells, all of which lead to the
assembly of transcription factor AP-1. Conclusion: It has been
suggested that completely inhibiting IL-1 signalling in pregnant
women to prevent PTL could be harmful for the health of both the
foetus and the mother. We hereby propose a hitherto unexplored
strategy of delaying infection/inflammation-induced PTL by
selectively inhibiting IL-1-induced MAPK and downstream AP-1
pathway, desirably without significant effect on NF-κB.
Acknowledgements: We want to acknowledge GAPPS (Global
Alliance to Prevent Prematurity and Stillbirth, an initiative of
Seattle Children's), CIHR and the Bill and Melinda Gates
Foundation. Contact Information: [email protected]
[465]
ASSOCIATION OF HYPERBILIRUBINEMIA GUIDELINES WITH
NEWBORN FOLLOW-UP CARE AND SOCIOECONOMIC DISPARITIES
IN FOLLOW-UP. Elizabeth Darling1, Doug Manuel2, Timothy
Ramsay2, Ann Sprague3, Mark Walker4, Astrid Guttmann5
40
1Laurentian
University/Midwifery, 2University of
Ottawa/Epidemiology and Community Medicine, 3BORN-Ontario &
University of Ottawa/Nursing, 4University of Ottawa/Obstetrics &
Gynecology, 5Institute for Clinical Evaluative Sciences & University
of Toronto
Introduction: Lack of timely follow-up can result in delays in the
diagnosis and treatment of severe hyperbilirubinemia, which are
established risk factors for long term sequelae. To explore
potential disparities in the degree of benefit derived from
implementation the Canadian Paediatric Society’s 2007
hyperbilirubinemia guidelines, we examined follow-up outcomes
associated with guideline implementation in Ontario.
Objective: To determine whether implementation of universal
bilirubin screening was associated with: 1) an increase in use of
recommended follow-up care for eligible newborns, and 2) a
differential effect between material deprivation quintiles.
Methods: Design: Retrospective population-based cohort study
using survey and health administrative data. Setting: 97 of 100
Ontario hospitals providing maternity care. Population: 733,990
newborns born at 35 or more weeks gestation discharged to home
from hospital within 72 hours of birth between April 1, 2003 and
February 28, 2011. Intervention: Implementation of universal
bilirubin screening which occurred between 2007 and 2011 in 67
hospitals. Main outcome measures: Recommended follow-up care
(physician visit within one calendar day after discharge for babies
discharged <24 hours after birth, or one or two calendar days after
discharge for babies discharged between 24-72 hours after birth).
Results: Implementation of the guidelines was associated with a
modest increase in recommended follow-up from 29.9 % to 35.0%
(n=711,242, adjusted relative risk: 1.11, 95% confidence interval
1.00 to 1.22, p=0.047), but the majority of babies still do not
receive follow-up within the timeframe recommended by the
guidelines. There was a striking socioeconomic gradient in the
crude percentage increase in recommended follow-up associated
with guideline implementation (ranging from 0.3% in the lowest
quintile to 29.0% in the highest quintile), with a significant
interaction between guideline implementation and material
deprivation status. Disparity in recommended follow-up increased
following guideline implementation, with 40% of the crude
increase attributable to the highest SES quintile and none to the
lowest SES quintile. Conclusion: Implementation of universal
bilirubin screening has had limited impact in ensuring timely
follow-up for all newborns in Ontario. Lack of timely follow-up
represents an ongoing weakness in efforts to prevent severe
hyperbilirubinemia. The observed widening of the SES disparity in
access to recommended follow-up illustrates that universal
programs which fail to address root causes of disparities may lead
to overall improvements in population outcomes but increased
inequity. Contact Information: [email protected]
[318]
THE EFFECT OF AEROBIC EXERCISE TRAINING IN THE
GASTROCNEMIUS MUSCLE ARTERIES FROM INTRAUTERINE
GROWTH RESTRICTED OFFSPRING. Laura M Reyes1,2,3; Jude S
Morton2,3; Raven Kirschenman2,3, Sandra T Davidge1,2,3.
1Department of Physiology, 2Department of Obstetrics and
Gynecology, 3Women and Children’s Health Research Institute;
University of Alberta.
Introduction Fetal hypoxia is one of the most common
consequences of complicated pregnancies worldwide. We have
demonstrated that prenatal hypoxia leads to intrauterine growth
restriction (IUGR) and impairs later-life endothelial-dependent
vascular function, demonstrating that fetal environment during
early development is important for cardiovascular health.
Alterations in the balance between nitric oxide (NO), endothelialdependent hyperpolarization (EDH) and prostaglandins results in
CNPRM 2015
endothelial dysfunction. Early interventions are needed to
ultimately reduce later life risk for cardiovascular disease. We
tested whether aerobic exercise prevents IUGR-induced
endothelial dysfunction. Objective To determine whether aerobic
exercise training improve vascular function in IUGR offspring.
Methods Pregnant Sprague-Dawley rats were exposed to control
(21% oxygen) or hypoxia (11% oxygen) conditions from gestational
day 15 to 21. Male and female offspring from normoxic (control)
and hypoxic (IUGR) pregnancies were randomized at 10 weeks of
age to either an exercise-trained or sedentary group. After
acclimatization, rats ran on a treadmill for 6 weeks; 5 days/week,
30 min/day at 20 m/min. After a recovery period of 24 hours,
animals were euthanized and gastrocnemius muscle arteries were
mounted on a wire myograph. Response curves to methacholine
were performed in the absence or presence of L-NAME (100μM), a
combination of Apamin (0.1μM) and TRAM-34 (10μM), or
indomethacin (5μM). Results In sedentary males, NO (p<0.01) and
EDH (p<0.05) contributed to vasodilation in control but not IUGR
offspring. Exercise increased EDH-mediated vasodilation (11.9
±32.7 vs. 142.5 ±20.5 delta change area under the curve [AUC],
p<0.05) and enhanced prostaglandin-mediated vasoconstriction in
male IUGR offspring (p<0.01). Being born growth restricted was
associated with impaired maximal vasodilator capacity in female
offspring (93.1 ±0.3% vs. 77.6 ±6.8% Emax, p=0.02). In sedentary
IUGR female offspring, the NO component of vasodilation was
abolished and only EDH contributed to vasodilation (p<0.01).
Exercise increased a prostaglandin-mediated vasoconstriction in
female IUGR offspring (61.5 ±17.1 vs. -30.1 ±19.9 delta change
AUC, p=0.002) and decreased NO-mediated vasodilation (123.7
±14.2 vs. 65.8 ±14.2 delta change AUC, p=0.007). Conclusions The
results from the present study highlight that understanding the
mechanisms by which exercise impacts the cardiovascular system
in a susceptible population, and the consideration of sexual
dimorphism is essential. Exercise may not prove to be a beneficial
therapy for specific vascular pathways affected by prenatal
insults, particularly in female offspring. Contact information : Dr.
Sandra Davidge [email protected]
Dr. Kjersti Aagaard - Baylor College of Medicine
Birth and Bacteria: Seeding the Future
Trainee Awards-Closing Remarks
Drs. Shoo Lee & Anne Monique Nuyt
CNPRM 2015
41
42
CNPRM 2015
CONCURRENT THEMATIC SESSIONS ABSTRACTS
WEDNESDAY AFTERNOON, FEBRUARY 25TH
Developmental/Transgenerational Origins of
Health and Diseases
[ROOM LE CLUB]
Dr. Debbie Sloboda
Early life nutritional impacts on offspring
reproductive function
Dr. Tim Regnault
The good, the bad and the ugly outcomes of adverse
pre and postnatal environments
Dr. Gerlinde Metz
Ancestral Exposure to Stress Programs Preterm Birth
Risk and Adverse Maternal and Newborn Outcomes
Dr. Cathy Vaillancourt
In utero exposure to antidepressant alters placental
serotonin and estrogen system: Role in fetal
programming
[283]
PRENATAL NUTRIENT RESTRICTION INDUCES FETAL GROWTH
RESTRICTION AND REDUCES FEMALE OFFSPRING OVARIAN
FOLLICLE NUMBER. Kaitlyn Chan1, Dr. Deborah Sloboda1
1McMaster University, Department of Biochemistry and
Biomedical Sciences
Introduction: The intrauterine environment induces
developmental adaptations that impact health and disease risk
later in life. Reproductive abnormalities are now included in the
long list of health complications seen in offspring exposed to early
life adversity indicated by low birth weight, including poor
prenatal nutrition. We have shown using a rat model that offspring
born to mothers that were nutrient restricted during pregnancy
are growth restricted, enter puberty early, and as adults, display
characteristics of early ovarian aging. The underlying mechanisms
however remain unclear. Objective: We hypothesize that early
life nutritional adversity impairs key proteins involved in ovarian
follicle recruitment including the PI3K/Akt pathway. Methods:
Pregnant Wistar rats were randomized into one of 2 groups:
mothers fed control diet during pregnancy and lactation (CON),
and mothers fed 50% of control intake during pregnancy (UN) and
then fed a control diet ad libitum during lactation. At 21 days of
life, offspring were weaned to a control diet and reproductive
cyclicity was evaluated at 60 days of age. At 4, 27, and 60 days of
postnatal age (P), offspring ovaries were collected, processed,
sectioned at 4?m, and stained with hematoxylin and eosin in order
to assess follicle numbers. Sections were stained for
immunpositive phosphorylated Akt (pAkt) in order to localize and
semi- quantitatively evaluate ovarian pAkt levels. Results:
Prenatal nutrient restriction resulted in irregular estrous cyclicity
due to persistent estrus. Furthermore, prenatal UN resulted in a
significant decrease in young adult (P60) ovarian antral follicles
(p<0.01), and corpus lutea (p=0.03), and a significant increase in
atretic secondary follicles (p=0.02). These offspring also tended to
have lower primordial follicle numbers (p=0.095). Neonatal (P4),
and prepubertal (P27) follicle numbers were similar between
groups. Immunohistochemical staining for pAkt in P4 and P27
ovaries shows pAkt to be localized in the oocyte, and increased in
P4 UN offspring ovaries. Preliminary analyses suggest no change in
pAkt staining in P27 UN offspring ovaries. Staining of pAkt at P60 is
still to be determined. Conclusion: We show that prenatal UN
impaired offspring reproductive cyclicity and resulted in a loss of
antral follicles in young adulthood. Although follicle numbers are
not different early in neonatal and prepubertal life, it appears that
already in neonates, pAkt mediated primordial follicle recruitment
could be accelerated, contributing to a loss later in life. Studies
investigating accelerated recruitment of primordial follicles as a
mechanism to explain a loss of follicle reserve are ongoing.
Contact Information: [email protected]
[305]
DNA METHYLATION LEVELS AT SEC16B CANDIDATE GENE FOR
CHILDHOOD OBESITY ARE AFFECTED BY AN IN UTERO EXPOSURE
TO LATE MATERNAL GESTATIONAL WEIGHT GAIN. StephanieMay Ruchat 1, Catherine Allard 2, Patrice Perron 2, 3, Luigi Bouchard
3,4, Marie-France Hivert 2, 5, 6
1 Dept of Physical Activity, Université du Québec à Trois-Rivières; 2
Dept of Medicine, Université de Sherbrooke; 3 ECOGENE-21,
Clinical Research Center and Lipid Clinic, Saguenay; 4 Dept of
Biochemistry, Université de Sherbrooke; 5 Dept of Population
Medicine, Harvard Pilgrim Health Care Institute, Boston;6
Massachusetts General Hospital, Boston
Introduction Exposure and timing of exposure to in utero
metabolic insults are associated with adverse health outcomes in
the offspring. Among others, excessive maternal gestational
weight gain (GWG), especially in the 2nd and 3rd trimesters of
pregnancy, has been associated with an increased risk for fetal
overgrowth and childhood obesity. This association might be
mediated by epigenetic adaptations. Objective The objective was
to assess whether maternal GWG in 1st, 2nd and 3rd trimesters of
pregnancy is associated with DNA methylation level changes in
newborns. Methods Maternal metabolic profile and
anthropometry were measured at the end of the 1st (T1) and 2nd
(T2) trimesters of pregnancy in 168 normal glucose tolerant
women. At delivery (T3), cord blood (n=168) and placenta (n=164)
samples and materno-fetal clinical outcomes were collected. DNA
methylation levels were quantified at CpG sites located within or
near by 10 genes previously associated with childhood obesity in
genome-wide association studies (ADCY3, FAIM2, FTO, HOXB5,
MC4R, OLFM4, POMC, SEC16B, TMEM18 and TNNI3K). A total of
160 CpG sites that were identified on the Illumina’s Infinitum
HumanMethylation450 BeadChip Arrays were selected. Regression
analyses were performed, with DNA methylation levels as
dependent variables, and GWG at T1 (T1-prepregnancy maternal
weight), T2 (T2-T1 maternal weight) and T3 (delivery-T2 maternal
weight) and covariates (maternal age, smoking, and prepregnancy
body mass index (BMI), and newborn gestational age and sex) as
independent variables. Results Women had a prepregnancy BMI
of 24.9±5.6 kg/m2 and mean total GWG was 13.8±5.5 kg. Higher
GWG in T3 was associated with lower methylation levels at SEC16B
cg25135333 in both cord blood and placenta (=-0.084, p=.006
and =-0.081, p=.01, respectively). Higher GWG at T3 was also
associated with lower methylation levels at additional CpGs site in
SEC16B (.005≤p≤.01) and in POMC (.02≤p≤.05) in the placenta.
Overall, we observed a higher number of CpG sites that might be
epigenetically affected by T3 GWG (cord blood, n=8 and placenta,
n=16) compared to T1 and T2 GWG (n=3 and 4 respectively in cord
blood; n= 5 both at T1 and T2 in placenta). No CpG overlap was
found between T1 and T2 or tissues. Conclusion We found that
GWG at T3 epigenetically affects SEC16B in both cord blood and
CNPRM 2015
43
placenta tissues. Excessive GWG might influence epigenetic
regulation of obesity gene SEC16B; both genetic and epigenetic
variations at SEC16B may be involved in risk of developing
childhood obesity. Acknowledgements This project was
supported by a Fonds de la Recherche du Québec-Santé (FRQ-S)
operating grant (MFH) and by Diabète Québec (PP). Contact
information: [email protected]
[350]
INDEPENDENT OF A HIGH-ENERGY/HIGH-REFINED
CARBOHYDRATE POSTNATAL DIET, YOUNG LOW BIRTH WEIGHT
MALE GUINEA PIGS ARE AT RISK FOR DEVELOPING MARKERS OF
INSULIN RESISTANCE AND MITOCHONDRIAL OVERLOAD. Kristyn
Dunlop1, Ousseynou Sarr1, Ting-Yim Lee2, Timothy RH Regnault3
1Departments of Physiology & Pharmacology, Obstetrics &
Gynaecology, Western University, 2Lawson Health Research
Institute, Robarts Research Institute, London, ON, 3Departments of
Physiology & Pharmacology, Obstetrics & Gynaecology, Western
University; Lawson Research Institute, Childrens Health Research
Institute, London, ON
Introduction: Low birth weight (LBW) offspring are at increased
risk of developing metabolic syndrome with age, specifically its
precursor, insulin resistance (IR). Adult IR is postulated to arise
from fatty acid-induced phosphorylation changes to insulin
signaling, &/or mitochondrial overload resulting in accumulated
markers of incomplete β -oxidation (medium & long chain
acylcarnitines), which negatively impact insulin signaling
phosphorylation status. The in utero environment is a major
determinant of later life insulin sensitivity; however, how an
adverse in utero environment may program skeletal muscle fatty
acid &/or mitochondrial metabolism and IR progression, remain ill
defined. Interactive effects of a second insult, high-energy/highrefined carbohydrate postnatal diet, and LBW upon accelerated IR
development also remain poorly defined. Objective: To
investigate skeletal muscle insulin signaling and mitochondrial
metabolism following an adverse in utero environment, and
progression towards IR. Methods: Term LBW was induced via
uterine artery ablation at mid-pregnancy. Male pups below the
25th percentile were classified LBW and above the 25th percentile
normal birth weight (NBW). Pups were weaned onto control (CD)
or Western (WD) diets. Hindlimb glucose uptake was measured by
positron-emission tomography/computed tomography (PET/CT) at
days 50 and 110. Ten days later, intraperitoneal glucose tolerance
tests assessed whole body glucose tolerance. Gastrocnemius
muscle was collected at approx. day 145 for immunoblotting,
acylcarnitine analysis by mass spectrometry, and fatty acid
profiling by gas chromatography. Results: Neither whole body
glucose tolerance, nor hindlimb glucose uptake were significantly
altered; however, significantly (p<0.05) reduced muscle insulin
receptor phosphorylation along with reduced AKT Ser-473 and
elevated IRS Ser-307 was observed in WD-fed animals, and
independently in LBW animals. Markers of mitochondrial overload,
including significant (p<0.05) accumulation of medium & long
chain acylcarnitines, was observed with postnatal WD feeding, as
well as independently of postnatal diet in LBW/CD animals. Fatty
acid profile showed reduced (p<0.05) levels of omega-3 & omega6 fatty acids in WD-fed animals, but no effect of in utero
environment. Conclusion: These studies highlight LBW offspring,
independent of postnatal diet, have alterations in muscle insulin
signaling and mitochondrial lipid metabolism. These chronic in
utero programmed changes at this age, resembling a pre-diabetic
state, highlight loss in plasticity of muscle metabolism, which likely
predisposes these offspring to development of IR and later life
diabetes. Acknowledgements: CIHR-FRN-102733 & Ontario
Graduate Scholarship. Contact Information: [email protected]
44
[486]
GENOTYPE MODERATES EFFECTS OF PRENATAL MATERNAL
STRESS DUE TO A NATURAL DISASTER ON GROWTH IN INFANCY
AND EARLY CHILDHOOD: THE IOWA FLOOD STUDY. Kelsey
Needham Dancause1, Lei Cao2, David Laplante2, Kimberly J. Hart3,
Michael W. O'Hara4, Guillaume Elgbeilli2, Aihua Liu5, Alain Brunet6,
Suzanne King6 *These authors contributed equally to this work.
1Université du Québec à Montréal (UQAM), Canada, 2Douglas
Hospital Research Center, Canada, 3University of Illinois at
Chicago, USA, 4University of Iowa, USA, 5Douglas Hospital Research
Center, Canada, 6Douglas Hospital Research Center, McGill
University, Canada
Introduction: Past research suggests that prenatal maternal stress
(PNMS) affects growth in infancy and early childhood. However,
research among humans is limited because of the difficulties of
designing studies of stress during pregnancy. Furthermore, results
are not always consistent and might vary based on type of stress
as well as genotype. We examine prenatal stress due to natural
disasters, which provide an excellent model of stressors unrelated
to potentially confounding maternal and household
characteristics. The present study analyzes child outcomes
following a severe flood in Iowa, USA in 2008. Objective: We
sought to examine relationships between prenatal stress due to
the floods and infant and child growth outcomes, and potential
mediation by child genotype for four genes commonly associated
with growth outcomes: COMT, APOA2, OLFM4, and HOXB5.
Methods: We recruited women exposed to the floods during
pregnancy, assessed their stress levels soon after the floods, and
collected their children's measurements at birth, as well as
detailed anthropometric measurements at ages 2½ and 4 years.
During assessments at age 2½, we collected buccal samples for
genetic analyses. We analyzed genotypes for COMT (rs4680,
n=102), APOA2 (rs5082, n=99), OLFM4 (rs9568856, n=103) and
HOXB5 (rs9299, n=99). We examined relationships between timing
and severity of flood exposure and these body composition
measurements, and potential interactions with child genotype.
Results: We observed significant interactions between PNMS and
COMT, APOA, and HOXB genotypes for children's birth length,
birth weight, and head circumference, as well as between PNMS
and APOA, HOXB, and OLFM genotypes for children's skinfolds,
arm fat index, waist to height ratio, and body mass indices at ages
2½ and 4 years. In general, greater PNMS predicted larger growth
outcomes among children with the COMT AA genotype, but not
GG/AG; smaller growth outcomes among children with APOA GG
genotype, but not AA/AG; and smaller growth outcomes among
children with the HOXB CC genotype, but not TT/CT. Gene by
stress interactions explained up to 10% of the variance in
children's growth outcomes. Conclusion: Our study emphasizes
the importance of PNMS on infant and childhood growth
outcomes, as shown in previous studies. It also highlights the
importance of gene by environment interactions on child growth.
These interactions might underlie inconsistencies in past studies of
PNMS and growth outcomes, and highlight the need for further
research. Acknowledgements: The authors wish to thank all of
the families and children who have participated in the Iowa Flood
Study. Contact Information: [email protected]
CNPRM 2015
Perinatal Brain Injury
[ROOM QUÉBEC]
Dr. Sylvie Girard
Targeting inflammation to achieve neuroprotection
in neonates
Dr. Olivier Baud
Oxygen is a toxic gas not a therapy: effects of oxygen
exposure on the developing brain
Dr. Pia Wintermark
Injury and repair in perinatal brain injury: insights
from bedside, imaging and bench
[254]
HIGH GLUCOSE VARIABILITY IS ASSOCIATED WITH POOR
NEURODEVELOPMENTAL OUTCOMES IN NEONATAL HYPOXIC
ISCHEMIC ENCEPHALOPATHY. Nasser Al-Shafouri1, Michael
Narvey1, Ganesh Srinivasan1, Jeff Vallance2, Gregory Hansen1
1Pediatrics and Child health, University of Manitoba, Winnipeg,
MB, Canada, 2Faculty of Health Disciplines, Athabasca University
Introduction: In neonatal hypoxic ischemic encephalopathy (HIE),
hypoglycemia and hyperglycemia are associated with poor
outcomes. In adult, high glucose variability is predictive of
mortality after subarachnoid hemorrhage and poor long-term
functional outcomes in traumatic brain injury. The impact of
glucose variability in neonate with HIE has not been studied.
Objective: To examine the association between serum glucose
variability within the first 24 hours and adverse
neurodevelopmental outcomes at 2 year follow up in neonates
who received whole body hypothermia for HIE. Methods: In this
retrospective cohort study, clinical and demographic data were
recorded in 23 term newborns treated with whole body
therapeutic hypothermia within 6 hours of age. The children were
assessed at 2 years. Severe poor neurodevelopmental outcome
was defined as the presence of any one of the following: Gross
Motor Function Classification System (GMFCS) levels 3 to 5, Bayley
III Motor Standard Score <70, Bayley III Language Score <70 and
Bayley III Cognitive Standard Score <70. Results: Demographic
and clinical characteristics of gestational age, sex, head
circumference, umbilical artery pH, apgar score at 1 min and 5
min, cardiopulmonary resuscitation and neonatal seizures showed
no significant differences between children with good and poor
neurodevelopmental outcomes. The adverse neurodevelopmental
outcomes in 8 of 23 patients were considered severe. This group
demonstrated a significant increase in mean absolute glucose
(MAG) change (-0.28 to -0.03 mmol/L, 95% CI, p=0.032). There was
no significant difference between outcome groups in regards to
hyperglycemic means, one or more hypo or hyperglycemic
measurements and mean glucose values.Table 1. Conclusion:
High serum glucose variability as demonstrated by MAG changes is
significantly associated with poor neurodevelopmental outcomes
in neonates with HIE who underwent whole body cooling. This
information may be relevant for prognostication and potential
management strategies in neonates with HIE. Contact
Information: [email protected]
[260]
CHORIOAMNIONITIS AND NEURODEVELOPMENTAL OUTCOMES
IN PREMATURE INFANTS WITH BRONCHOPULMONARY
DYSPLASIA. Rani A Bashir1, Vineet Bhandari4, Sakeer
Vayalthrikkovil1, Yacov Rabi1,2, Amuchou Soraisham1,2, Selphee
Tang1, Essa Al Awad5 and Abhay Lodha1,2,3.
1Department of Pediatrics, University of Calgary; 2Alberta
Children's Hospital Research Institute, University of
Calgary; 3Department of Community Health Sciences, University of
Calgary; 4Department of Pediatrics, Yale University School of
Medicine, New Haven, CT, United States and 5Department of
Pediatrics, Peter Lougheed Centre.
Background: Uncertainty exists as to whether chorioamnionitis is a
risk factor for bronchopulmonary dysplasia (BPD). BPD and
chorioamnionitis (C) are independently associated with
neurodevelopmental disability (NDD). However, studies on
neurodevelopmental outcomes for infants with both BPD and
chorioamnionitis (BPDC) are limited. Objective: To compare
preterm infants with no BPD, BPDC and BPD without C (BPDNC) to
determine the association with NDD at 3 years corrected age.
Design/Methods: In this retrospective cohort study, all surviving
infants ≤1250 g BW admitted to a regional NICU from 1995-2007
were eligible for multidisciplinary follow-up at 3 years.
Demographic, neonatal and outcome data were collected on all
infants. The data were compared among children on the basis of
whether they had BPD, chorioamnionitis or both. NDD were
considered present if a child had any evidence of cerebral palsy,
mental retardation, major visual impairment or deafness. Logistic
regression model was used to determine the effects of potential
confounders on severe NDD. BPD was defined as oxygen
dependency at 36 weeks postmenstrual age. Results: 1009
infants were placed into one of three groups - No BPD (n=442),
BPDNC (n=437) and BPDC (n=130). No BPD, BPDNC and BPDC
groups had median (IQR) birth weights of 1070 (930-1180), 840
(700-1030) and 810 (720-1000) g and GA of 29 (27-30), 27 (25-28)
and 26 (25-27) wks respectively (p<0.001). Infants in BPDC group
were of lower BW, GA and had longer length of hospital stay,
duration of mechanical ventilation, blood transfusions and sepsis
compared to BPDNC and no BPD groups (all p<0.001). At age 3,
children with BPDC had more moderate to severe cerebral palsy
(3.2% No BPD, 5.7% BPDNC and 12.3% BPDNC, p<0.001), cognitive
delay (5% No BPD, 11.6% BPDNC, 12.4% BPDC, P<0.001) and any
disability (6.3%No BPD, 16.3% BPDNC, 22.8% BPDC,
p<0.001). After adjusting for various confounders, the odds ratio
of severe NDD in infants with BPDC was not significantly different
than in infants with BPDNC (OR 1.45, 95%CI 0.72-2.92). Infants of
mothers who received intrapartum antibiotics were less likely to
have severe NDD (OR 0.46, 95%CI 0.25-0.85). Conclusions: BPD
with chorioamnionitis does not appear to worsen the odds of NDD
in preterm infants, compared to those with BPD alone. However,
use of intrapartum antibiotics appeared to be a protective factor
for NDD. Contact informations:
[email protected]
[327]
MATERNAL ANTI-PLATELET Β3 INTEGRIN ANTIBODIES TARGET
BLOOD VESSELS AND CAUSE INTRACRANIAL HEMORRHAGE IN
FETAL AND NEONATAL ALLOIMMUNE THROMBOCYTOPENIA.
Issaka Yougbare1,2, Sean Lang1,3, Pingguo Chen2,3, Alexandra
Marshall2, Wei-She Tai1, Conglei Li1,3, Siavash Piran1,3, Guangheng
Zhu2and Heyu Ni1,2,3,4
1Toronto Platelet Immunobiology Group, and Department of
Laboratory Medicine, Keenan Research Centre for biomedical
science, St. Michael's Hospital, Toronto, ON; 2Canadian Blood
Services, Toronto, ON; 3Department of Laboratory Medicine and
Pathobiology, University of Toronto; 4Departments of Physiology,
University of Toronto.
CNPRM 2015
45
Introduction Fetal and neonatal alloimmune thrombocytopenia
(FNAIT) is a severe bleeding disorder that results from fetal
platelet destruction by maternal antibodies. Severe bleeding is
frequent in FNAIT, particularly the occurrence of intracranial
hemorrhage (ICH) leading to neurological impairment or death.
Integrin β3 is an abundant glycoprotein on the platelet and
endothelial cell (EC) surface and is also a major target antigen for
FNAIT allo-antibodies. It has been demonstrated that αVβ3
integrin plays an important role in angiogenesis, impairment of
which may lead to hemorrhage, particularly ICH. Objective We
investigated whether anti-β3 integrin antibodies in FNAIT crossreact with blood vessels of the developing fetus/neonate and
contribute to the pathogenesis of FNAIT. Methods β3 integrin- or
GPIbα-deficient female mice were transfused with wild-type (WT)
platelets and bred with WT male mice to generate heterozygous
fetuses. ICH was investigated by high performance ultrasound in
fetuses and by hematoxylin eosin staining of brain sections. Blood
vessel development was examined by immunostaining for both
brain and retinal vasculature. Results We found that pups in both
groups had thrombocytopenia, but ICH was only observed in some
neonates targeted by anti-β3 antibodies (3/15, 20%). ICH occurred
in utero as shown by high performance ultrasound or after birth.
Anti-β3 antibodies, but not anti-GPIbα, reduced vascularization of
both brain and retina. Pups with anti-β3 antibodies had increased
apoptosis in the brain blood vessel, as determined by TUNEL and
CD31 double-staining. To investigate whether these impairments
were directly due to the antibodies, anti-β3 IgG was injected into
naive β3 integrin heterozygous pups after birth and these pups
developed ICH. In addition, anti-β3 IgG injection into αIIb integrin
deficient neonates caused ICH despite normal platelet counts.
Retinal vascular development which starts postneonately was
reduced in pups injected with anti-β3 sera. To further elucidate
the mechanism of the observed anti-angiogenic events, we
investigated the effects of anti-β3 antibodies on ECs in vitro. Antiβ3 sera inhibited cell adhesion, invasion, proliferation and
capillary-like tube formation on Matrigel. Importantly, maternal
anti-HPA-1a antibodies (against fetal β3 integrin) induced
apoptosis of endothelial cells. We also found that phosphorylation
of Akt were reduced in the brain of anti-β3-mediated FNAIT mouse
pups. Conclusions: Anti-β3 integrin antibodies in FNAIT target
blood vessels of the developing fetus and neonate and impair
angiogenesis in which VEGFR-2/Akt signalling may involve.
Acknowledgements We thank our founding institutes: CIHR, Heart
and Stroke Foundation and CBS. Contact
information [email protected]
[341]
PLACENTA GROWTH FACTOR IS IMPORTANT IN FETAL CENTRAL
NERVOUS SYSTEM VASCULARIZATION. Vanessa R. Kay 1, B. Anne
Croy1
1Department of Biomedical and Molecular Sciences, Queen’s
University, Kingston, ON, Canada
Introduction: In preeclampsia, a human hypertensive disorder of
pregnancy, the angiokine placenta growth factor (PGF) is low in
maternal blood. The placenta drives maternal plasma PGF levels in
pregnancy but information is scant on fetal expression in normal
or in preeclamptic pregnancies. Cohort studies report that seniors
who were born to preeclamptic versus normotensive mothers
have a higher risk of stroke. In preparing to study blood pressure
in PGF null mice, via common carotid probe placement, we found
PGF null mice (>80%) were vulnerable to stroke. Objective: We
hypothesized that PGF has an important role in developmental
vascularization of the central nervous system (CNS), particularly in
the forebrain. Methods: We used fluorescent whole mount
staining to examine vascularization in three CNS areas during
development in control C57BL/6 (B6) and B6-Pgf-/- mice. All
46
tissues were fixed in 4% paraformaldehyde, blocked with a
solution of bovine serum albumin or normal goat serum, and
stained with fluorescently-conjugated isolectin-B4 (IB4) to mark
endothelium. Retinal vascularization was examined at postnatal
day (PND) 5, 8, 15 and adulthood. Fetal hindbrain vascularization
was examined at gestational day (GD) 10.5. Finally, anterior circle
of Willis completeness was determined in GD14.5 fetal and PND 7
forebrains. Photomicrographs were analyzed using ImageJ and
Angiotool. T-test and one way ANOVA analyses were used to
determine significance. Results: Retinal vascularization in Pgf-/mice was comparable to control with respect to vessel density and
sprouting angiogenesis. However, vessels were more frequently
disorganized with more arteriovenous crossovers and abnormal
venous branching patterns. In Pgf-/- fetal hindbrain, greater
numbers of vessel junctions and smaller vessel diameters were
noted. Close examination of the sprouting vessels suggested a
delay in vessel maturation. In GD14.5 and PND7 Pgf-/- forebrains,
the anterior cW was composed of fewer arteries than controls and
often exhibited unilateral stenosis, despite being complete.
Conclusion: Pgf-/- mice have subtle developmental impairments in
CNS vascularization with cW defects that may account for their
increased susceptibility to stroke. In preeclamptic, low maternal
plasma PGF pregnancies, low fetal PFG levels may occur and
disturb human fetal CNS vascularization including cW
development. Further translational studies are essential.
Acknowledgements: Supported by Awards from NSERC, CFI and
CRC. Contact Information: Vanessa Kay [email protected]
[409]
T2 MR RELAXOMETRY STUDY OF BRAIN DEVELOPMENT IN A
VALPROIC ACID MODEL OF AUTISM. Loredana Sorina Truica1,
Sarah Raza1, Keiko McCreary1, Ian Q. Wishaw1, Robbin Gibb1
1Neuroscience, University of Lethbridge, Lethbridge, AB, Canada
Introduction: Human neuroimaging studies have shown abnormal
regulation of brain growth in autism spectrum disorders (ASD),
suggesting that processes governing apoptosis and synaptic
pruning are highly implicated. Brain tissue changes in the valproic
acid (VPA) animal model of ASD and placental transfer of the drug
are investigated using MR T2 relaxometry. Objective: To quantify
brain tissue changes in the VPA animal model of ASD as well as
placental transfer of VPA and its implications. In vivo T2relaxometry measurements were collected for both brain and
placental analysis. Methods: Pregnant Long-Evans rats (n=3) were
exposed orally to VPA (800mg/kg) on gestational day (GA) 12.5.
Long-Evans male and female rats born (n=12) from VPA dams and
(n=12) from control dams were imaged on postnatal (P)day
30,35,40 and 45 with a 4.7 T Oxford magnet. Rats were perfused
(P60) and brains extracted for histology. Study was in accordance
with the CCAC and the U of Lethbridge Animal Welfare Committee.
Localizer images, T2 measurements and T2-weighted images were
obtained. Pregnant dams were imaged at GA=16, 18 and 20 days
with a similar protocol. A region of interest (ROI) based analysis
was done for both studies and mean values extracted from the T2
maps with Image J. A prefrontal cortex (PFC; Figure 1B, 1C and 1D)
ROI was chosen for the pups while the placental ROIs were drawn
on the dams central slice (Figure 1A). T2 values were calculated
with software written in our lab in IDL. Results: T2-Relaxometry:
There was a significant mean difference in the T2 values from P30
to P45 in the VPA [12.157 ± 6.933] and control groups [25.616 ±
6.781], in the PFC (Figure 1C and 1D). This suggests that prenatal
exposure to VPA altered the expected neuronal density in PFC. A
clear trend of altered T2 values was observed across all postnatal
ages (Figure 1C, see significance). A parietal cortex ROI was also
quantified, which produced a trend similar to the PFC. T2 values
for the placental ROIs in the VPA dams were altered from controls
for all GA’s investigated (Figure 1A). Conclusion: Brain and
CNPRM 2015
placental in vivo T2-relaxometry measurements were conducted.
Results showed differences between VPA and control groups in
the prefrontal cortex, suggesting that prenatal exposure to VPA
altered the expected neuronal density. Placental transfer was
evident in the T2 maps. Drug crosses placenta rapidly and is found
in larger concentration in the umbilical cord and fetal villi, hence
the more intense color gradient on the placental T2 VPA maps.
This supports the evidence that VPA impacts fetal development
pre and postnatally. T2-relaxometry offers valuable insight into the
neurobiological abnormalities induced by prenatal VPA exposure.
Contact Information: [email protected]
the Preterm Preschool subgroup suggest that young preterm
children might rely on verbal STM to support visuospatial tasks.
Acknowledgements: This study was supported by the Women and
Children’s Health Research Institute Innovation Grant. Contact
Information: Clara Lee [email protected]
Family Centered Care – Developmental
Outcomes and Interventions
[ROOM MONTEBELLO]
Mrs Katharina Staub
Prematurity does not end when you go home
Dr. Marilyn Ballantyne
Family experiences with transitions in care
[418]
WORKING MEMORY PERFORMANCE IN CHILDREN BORN
EXTREMELY PRETERM. Clara Lee1, Jacqueline Pei1, Kimberly
Kerns2, Gail Andrew3, Carmen Rasmussen4
1University of Alberta/ Department of Educational Psychology,
2University of Victoria/ Department of Psychology, 3Glenrose
Rehabilitation Hospital, 4University of Alberta/ Department of
Pediatrics and Glenrose Rehabilitation Hospital
Introduction: Research shows that children born preterm have
higher risk of working memory (WM) impairments. Some
researchers report deficits in verbal WM, while others find
impairments in visuospatial WM. Inconsistent study findings
cannot guide us to design training. In this study, we want to better
understand the profile of the WM in children born extremely
preterm in order to inform intervention planning. Objective: We
examined the WM profile of preterm children using a modeldriven measure in an effort to identify the developmental pattern
of their WM. Methods: Participants. Two groups of children were
recruited: a Preterm group included 24 children (mean age = 78.75
months, SD = 23.85; mean GA = 27.96 weeks, SD = 1.99; mean BW
= 1106.45 grams, SD = 328.33) and a Control group included 22
children (mean age = 77.18 months, SD = 19.89; mean GA = 39.09
weeks, SD = 1.51; mean BW 3183.93 grams, SD = 603.62).
Measures. The Automated Working Memory Assessment (AWMA)
was administered to measure the WM abilities. Attention was
assessed by the NEPSYII Auditory Attention subtest and the Test of
Variables of Attention (TOVA). Results: The Preterm group
performed worse than the age-matched full-term Control group in
all verbal and visuospatial tests of the AWMA. However, MANOVA
showed that the group difference for either verbal or visuospatial
tests was insignificant(p>.05). To further examine the WM
performance of both groups, each group was divided into two
subgroups based on their education level(i.e., Preschool subgroup
and School subgroup). Significant difference (F (1, 19) = 3.095, p =
.046) between the Preterm and the Control School subgroups in
visuospatial tasks was found. Discriminant function analyses
revealed a significant association between groups and all
visuospatial tests, accounting for 43.56% of the between-group
variability. The standardized canonical coefficients showed that
Dot Matrix (-1.280) and Spatial Recall (1.039) were the two tests
contributed to the group difference. High correlations between
verbal and visuospatial short-term memory (STM) were found in
the Preterm Preschool subgroup (rs ranged from .629 to .781), this
pattern was not found in their full-term peers. Conclusion:
Consistent with previous research, children born extremely
preterm performed worse than full-term peers in their visuospatial
WM. The high correlations between verbal and visuospatial STM in
Dr. Thuy Mai Luu
An educational program of developmentallysupportive care for parents of preterm infants
Dr. Paige Terrien Church
Little Nomads: the behavioral outcomes of
prematurity and potential interventions
[364]
THE BENEFITS OF KANGAROO CARE ACROSS GESTATIONAL AGE
AND GEOGRAPHY. Timothy Disher1, Britney Benoit2, Celeste
Johnston1, Marsha Campbell-Yeo3
1IWK Health Centre, 2Dalhousie University, 3IWK Health
Centre/Dalhousie University
Introduction: Kangaroo Care (KC), holding of a diaper-clad infant in
ventral skin-to-skin contact with a caregiver, has been studied
extensively in both painful and non-painful contexts since its initial
implementation as an alternative to incubator care in resourcepoor environments. Cochrane systematic reviews have been
published that assess outcomes ranging from mortality and
infection, parent-infant attachment, and breastfeeding status. This
review provides a synthesis of the current knowledge in pain and
non-pain contexts across gestational age, in low and higher
resource countries. Objective: To assess the level of evidence for
KC outcomes in existing systematic reviews. Recommendations for
implementation will be provided, and gaps in the literature
highlighted. Methods: Narrative synthesis of Cochrane systematic
reviews of the benefits of skin-to-skin contact. Results: Three
reviews were included, capturing 71 studies spanning pain (n=383
preterm/lbw and 30 term infants in developed Countries; n=275
preterm/lbw and 907 term infants in developing countries) and
non-pain (n=292 preterm/lbw, 8 late preterm, and 1080 term
infants in developed Countries; n=2480 preterm/lbw, 69 late
preterm, and 989 full term infants) contexts. There are no known
harms in both pain and non-pain context across resource rich or
resource poor environments. Benefits across gestational age
include: reduced pain response, more mature sleep, improved
physiological stability, superior growth rates, better breastfeeding
outcomes, and a less adverse outcomes. Continuous KC (Kangaroo
Mother Care, or KMC) was only researched in developing
countries, but was associated with reduced mortality, morbidity,
and infection. In the non-pain context, research conducted in
developed Countries emphasized breastfeeding (BF) and
attachment (20/25 studies vs 11/25 reporting
physiologic/mortality measures). Developing Countries showed an
opposite trend (17/26 BF/attachment, 23/26
physiologic/mortality). Conclusion: Itermittent KC should be
standard care in both term and preterm infants in all units. Dose-
CNPRM 2015
47
response studies are needed in order to recommend optimal daily
duration. As recently published results have shown an association
between improved neuro-behavioural outcomes and KC provided
for one hour per day, all babies should receive at least this amount
of exposure. Morbidity/mortality outcomes remain unknown in
high-resource units when KMC is provided, and would be of
interest to assess. Measurements of attachment and
breastfeeding would benefit from consensus on methods and
tools in order to enable combined analysis. Lastly, future research
should assess economic and intangible burdens to families.
Acknowledgements: Dalhousie University and the IWK. Contact
Information: [email protected]
[403]
BARRIERS AND FACILITATORS TO IMPLEMENTING THE BABY
FRIENDLY HOSPITAL INITIATIVE IN NEONATAL INTENSIVE CARE
UNITS (NICUS): PERSPECTIVES OF NICU MANAGERS, EDUCATORS,
AND CLINICAL LEADERS. Britney Benoit, MScN, RN1, Sonia
Semenic, PhD, RN2
1Dalhousie University School of Nursing; Centre for Pediatric Pain
Research, IWK Health Centre, Halifax, NS, Canada, 2Ingram School
of Nursing, McGill University, Montreal, QC, Canada
Introduction: Although initially developed for regular maternity
units, the Baby Friendly Hospital Initiative “Ten Steps to Successful
Breastfeeding” (Ten Steps) has recently been expanded for
application in Neonatal Intensive Care Units (NICUs). Emerging
research indicates that adoption of the BFHI, or breastfeeding
promotion programs modeled from the BFHI’s Ten Steps, have
positive effects on the rate of exclusive breastfeeding at NICU
discharge. However to date there is little information on factors
influencing the success of implementing Baby-Friendly practices in
the NICUs, that can be used to help plan initiatives to improve
breastfeeding support in the NICU setting. Objective: Guided by
the Promoting Action on Research Implementation in the Health
Services (PARIHS) framework, the purpose of this study was to
explore NICU manager, educator, and clinical leader (e.g.,
advanced practice nurses, lactation consultants) perspectives of
barriers and facilitators influencing implementation of the BFHI in
the NICU. Methods: A qualitative descriptive design using semistructured interviews was utilized. Medical and nursing managers,
nurse educators, lactation consultants, and neonatal nurse
practitioners were purposively sampled (N=10). Interviews were
analyzed using qualitative content analysis. Results: While
participants’ valued breastfeeding and family-centered care, they
identified numerous contextual barriers to Baby-Friendly practices.
These included infant health status/stability, parent infant
separation, staff workloads and work patterns, gaps in staff
knowledge and skills, and lack of continuity of breastfeeding
support. Facilitators of the BFHI included breastfeeding education,
breastfeeding champions, and interprofessional collaboration.
Conclusion: Despite identifying numerous contextual barriers,
participants recognized the potential value of the BFHI adaptation
to the NICU setting. Recommendations include promoting BFHI as
a facilitator of family-centered care, interdisciplinary staff
education, increasing access to lactation consultants, and
establishing a core group of NICU “champions” dedicated to BFHI
implementation. Acknowledgements: Britney Benoit was
supported by fellowship and research project funding from the
Quebec Nursing Intervention Research Network (RRISIQ). The
authors thank Linda Boisvert for assistance with participant
recruitment. Contact Information: [email protected]
[414]
BUT WE'RE NOT LIKE THE PEOPLE ON TV: A QUALITATIVE
EXAMINATION OF THE INFLUENCE OF MEDIA MESSAGES ON THE
LIVES, BELIEFS, AND HEALTH BEHAVIOURS OF PREGNANT AND
PARENTING YOUTH. Chantalle Clarkin1, Kerry Worth2, Kristina
48
Rohde3, Megan Harrison4
1University of Ottawa, Faculty of Education, 2Queen's University,
Department of Obstetrics and Gynecology, 3Children's Hospital of
Eastern Ontario, Research Institute, 4University of Ottawa,
Department of Pediatrics
Introduction: The media has long been established as a powerful
educational and socializing agent for youth. Recently, there has
been an upsurge in broadcast media portraying pregnant and
parenting youth (PPY), such as “Teen Mom” and “Sixteen and
Pregnant”. While this type of programming is generally tailored to
a teenage audience, research has not yet examined the ways in
which PPY deconstruct these media messages. Objective: It
remains unknown whether media depictions of teenage
motherhood shape the meanings PPY construct about health and
well-being, and whether these perceptions influence their health
behaviours. This study explored how PPY experienced and
perceived media messages portraying teen pregnancy, as well as
how media messages influenced their social and health
interactions. Methods: Five focus groups were conducted at two
urban community centres known to service PPY. A convenience
sample of 26 participants was recruited across sites. Focus groups
were moderated by two qualitative researchers, audio recorded
and transcribed verbatim. Transcripts were analyzed thematically
to identify key concepts. To enhance the trustworthiness of the
findings, we triangulated the focus group data, maintained audit
trails and engaged in peer debriefing. Results: Participants were a
mean age of 18.7 years. The majority watched more than 3 hours
of television per day (52%), with another 3 hours of daily Internet
use (57%). Participants discussed teen pregnancy reality television
and the film “Juno”, comparing and contrasting characters and
storylines with their lived experiences. Participants were acutely
aware of the negative impact of media messages on public
perception, noting that they perpetuated negative stereotypes.
They believed healthcare providers (HCPs) were not immune to
media messaging. Perceptions of negative interactions, combined
with value-laden media messaging, contributed to a general sense
of mistrust and social alienation. In fact, several reported
withdrawing from public interaction and delaying access to health
services because of media-fuelled public views. Conclusion: There
is a need for heightened awareness of the influence of popular
media on the construction of notions of teen pregnancy and
parenting. Acknowledging and challenging some of the
stereotypes of teen pregnancy, as well as initiating dialogue about
the impact of the media, could act as a protective factor to
empower PPY to engage with healthcare. HCPs should consider
their own biases when providing care to this vulnerable group, and
reflect on ways to connect with PPY in order to improve the
quality of care provided. Acknowledgements: CHEO RI Resident
Research Grant. Contact Information: [email protected]
[422]
ADVERSE TRANSGENERATIONAL PROGRAMMING OF MENTAL
HEALTH AND EPIGENETIC MARKS IS REVERSED BY
ENVIRONMENTAL ENRICHMENT. J. Keiko McCreary1, Zachary T.
Erickson1, Nasrin Soltanpour1, Erin Falkenberg1, Alena Babenko1,
Yaroslav Ilnytskyy2, Igor Kovalchuk2, Gerlinde A. S. Metz1
1University of Lethbridge/ Neuroscience, 2University of Lethbridge/
Biology
Introduction: Prenatal stress (PS) has been associated with
impaired neurodevelopment and related psychopathologies,
including depression, anxiety and schizophrenia. We have
previously shown in rats that developmental programming by PS
propagates across three generations of the maternal lineage, and
increases the risk of adverse offspring health and development.
Objective: The objectives of this study were 1) to investigate the
effects of a stressful maternal environment across several
CNPRM 2015
generations on behaviour, brain morphology, and the epigenome,
and 2) to determine if consequences linked to ancestral stress can
be reversed by environmental enrichment. Methods: Dams of the
parental F0 generation experienced psychosocial stress from
postnatal day 90 until parturition. Their pregnant daughters (F1)
and grand-daughters (F2) were either stressed (multigenerational
prenatal stress; MPS) or remained unstressed (transgenerational
prenatal stress; TPS, with stress limited to F0 dams). A non-stress
maternal lineage was used for comparison. To test if enriched
environment (EE) serves as an intervention for ancestral stress,
some of the F3 rats were housed in a complex environment from
postnatal days 35-180. In the adult male F3 offspring, anxiety-like
behaviors and fine motor skills were assessed. Histological analysis
and microRNA analysis were also performed. Results: MPS and
TPS resulted in an anxious phenotype and impaired fine motor
function. These results were related to changes in the morphology
of cortical neurons and altered microRNA profiles. EE in all groups
drastically reduced the response to stress across all groups. TPS
and MPS animals raised in an EE showed diminished anxiety-like
behaviour and improved motor function. EE also had beneficial
effects on the stress response, cortical morphology and microRNA
profiles. Conclusion: These findings suggest that ancestral stress
alters neuronal morphology and lead to mood disorders,
psychopathologies, and motor impairments. Overall, EE reversed
the consequences of ancestral stress. Epigenetic modifications via
microRNAs could be a primary mechanism of stress transfer and
reversal by EE, with implications for the discovery of new
therapeutic targets or predictive biomarkers of mental health.
Acknowledgements: This work was funded by the AIHS Preterm
Birth and Healthy Outcomes Team Interdisciplinary Team Grant
#200700595 (GM), Alberta Innovates – Health Solutions (GM), and
the Canadian Institutes of Health Research (GM). JM was
supported by the National Sciences and Engineering Research
Council of Canada CREATE #371155 . Contact Information:
[email protected]
Canadian Maternal Fetal Medicine Society
[ROOM CANADA]
Dr. Wendy Robinson
What does the maternity care provider need to know
about epigenetics
[343]
PRENATAL IRON DEFICIENCY IN THE ABSENCE OF MATERNAL
ANEMIA CAUSES FETAL HYPOXIA. Stephane Bourque1, Yael
Mansour1
1University of Alberta, Department of Anesthesiology & Pain
Medicine
Introduction: Iron deficiency (ID) is the most common nutritional
deficiency in the world, and is particularly prevalent in pregnant
women due to volume expansion as well as demands from the
fetal-placental unit. Fetal ID is associated with pre-term birth and
fetal growth restriction, both of which have important implications
for the long-term health of the offspring. Current assessments for
fetal anemia rely on maternal hematological indices. However, it is
not presently known whether latent ID in mothers (with no overt
anemia) would impact pregnancy outcomes and fetal growth
trajectories. Objective: The objective of the present study was to
determine if a modest iron restriction during pregnancy would
impact growth trajectories and oxygen delivery in the fetus.
Methods: Female Sprague Dawley rats (12 wk of age) were fed a
control diet (70mg/kg iron) or an identical diet with no added iron
(3mg/kg iron) throughout pregnancy. Dams were treated with
pimonidazole (60mg/kg) at gestational day 20 to assess maternal
and fetal hypoxia. Tissues were harvested and fixed in
paraformaldehyde, and adduct formation was quantified by
immunofluorescence. Results: Maternal iron-restriction resulted
in fetal anemia (control: 9.0±0.5 g/dL; iron-restricted: 6.2±1.0
g/dL; P<0.05), but not maternal anemia (control: 13.2±0.5 g/dL;
iron-restricted: 12.2±0.3 g/dL; P=0.13). There was no evidence of
fetal growth restriction. Pimonidazole staining was evident in fetal
tissues in the iron restricted group (including the liver [P=0.01],
kidneys [P=0.01]), but was not observed in maternal tissues nor in
the placenta. Conclusion: These results suggest that modest
prenatal ID compromises oxygen transport in the fetus. In
conclusion, the prevalence of fetal ID anemia may be higher than
previously estimated and therefore, novel diagnostic approaches
independent of maternal hematological indices may be needed.
Acknowledgements: This work is supported by the Women and
Children's Health Research Institute (WCHRI) at the University of
Alberta and the Canadian Institutes of Health Research. YM was
supported by a summer studentship from the WCHRI. Contact
Information: [email protected]
[345]
ASSESSMENT OF FETAL FAT DISTRIBUTION WITH WATER-FAT
MRI. Craig Olmstead1, Lanette Friesen-Waldner2, Abraam
Soliman3, Kevin Sinclair2, Charles McKenzie2, Barbra de Vrijer4
1University of Western Ontario, Schulich School of Medicine and
Dentistry, 2University of Western Ontario, Department of Medical
Biophysics, 3University of Western Ontario, Department of
Biomedical Engineering, 4University of Western Ontario,
Department of Obstetrics and Gynecology
Introduction: Intrauterine growth restriction (IUGR) represents a
significant obstetric pathology, requiring careful management.
IUGR fetuses have elevated perinatal morbidity and mortality, and
are at increased risk of chronic diseases later in life. Current
detection of IUGR involves ultrasound (US) evaluation of fetal size
and Doppler US to assess placental function. However, this
assessment fails to address risk for long term metabolic
disturbances associated with IUGR and is less reliable in high-BMI
patients. Fetal fat distribution may serve as an identifying
characteristic of IUGR, as IUGR infants have reduced subcutaneous
fat. Fetal fat distribution has particular relevance in a high-BMI
population, as such fetuses may have increased intra-abdominal
fat, particularly in the liver. By imaging fetal fat distribution, MRI
could add assessment of metabolic risk to US’s capacity to address
neonatal morbidity. Objective: This study attempts to develop a
tool for in utero fetal fat distribution, by translation of validated
fat imaging techniques for adults to fetal MRI. Methods: Women
in their 2nd or 3rd trimester with singleton pregnancies were
recruited during obstetric clinics. Consenting patients had fetal
MRI performed in a 70 cm diameter 1.5 T MRI. Scout images were
acquired to locate the fetus and determine its orientation. Wateronly and fat-only images were produced during a maternal breath
hold with a 3D LAVA Flex acquisition in a plane axial to the fetal
abdomen. A fat fraction image was calculated (Fat Fraction =
Fat/(Water+Fat)). Images were evaluated for their ability to be
segmented: images were deemed “segmentable” when the
subcutaneous tissue and intra-abdominal cavity could be
delineated or “non-segmentable” when they could not. An ROI
within the fetal liver was also drawn to assess liver fat content.
This study was approved by our institution’s Office of Research
Ethics. Results: 7 patients consented to the study (gestational age
20-32 weeks). Motion free fetal water (Fig 1A) and fat (Fig 1B)
images were successfully obtained using the LAVA Flex sequence
in all 7 patients. In 1 patient, the scan was repeated once for
technical reasons. In all patients, segmentable fat fraction images
(Fig 1C) were obtained. Liver ROIs (green in Fig 1C) demonstrated
CNPRM 2015
49
an average fetal liver fat percentage ranging from 0.35% to 0.97%,
with no voxels within these ROIs registering a fat fraction above
2.0%. Conclusion: Fetal MRI using water-fat separation
techniques allow for the segmentation and quantification of fetal
adipose tissue volume and liver fat in normal-BMI and high-BMI
pregnancy. This has the potential to provide additional diagnostic
information in the evaluation of IUGR in utero. Contact
Information: Craig Olmstead [email protected]
[463]
SERIAL CERVICAL LENGTH MEASUREMENTS IN TWIN GESTATIONS
IMPROVES THE PREDICTIVE ACCURACY FOR PRETERM BIRTH.
Alex Pittini1, Nir Melamed1, Noor Niyar N. Ladhani1, Dini Hui1,
Howard Cohen1, Ori Nevo1, Anne Berndl1, Elizabeth V. Asztalos2,
Jon Barrett1
1Division of Maternal Fetal Medicine, Sunnybrook Health Sciences
Centre, University of Toronto, 2Department of Neonatology,
Sunnybrook Health Sciences Centre, University of Toronto
Introduction: A sonographic short cervix determined by a single
assessment in the midtrimester of pregnancy is a major risk factor
for preterm birth. There is a paucity of evidence about the benefit
of serial cervical length (CL) determinations in twin gestations.
Objective: To determine whether serial measurements of CL
improve the predictive accuracy for preterm birth (PTB).
Methods: This was a retrospective study of all women with twin
pregnancies followed in the Twins Clinic in a tertiary referral
medical center between 2012-2014. All women underwent routine
measurement of CL at mid gestation (18+0 to 21+6 weeks) and
every 2-4 weeks thereafter until 28-32 weeks of gestation.
Pregnancies complicated by any of the following conditions were
excluded: monoamniotic twins, birth weight <500g, gestational
age at delivery <24 weeks, stillbirth of one or both fetuses, genetic
or structural anomalies, less than 4 measurements of CL along
gestation, cervical cerclage or uncertain pregnancy dating. For
each patient, CL measurement was determined at 4 time periods
along gestation: 18+0 to 21+6 weeks (Period 1, routine midgestation exam), 22+0 to 24+6 weeks (Period 2), 25+0 to 27+6
weeks (Period 3) and 28+0 to 32+0 weeks (Period 4). The results of
CL measurement at periods 2, 3 or 4 (expressed as absolute values
(in mm), absolute change in CL from period 1 (in mm), relative
change in CL from period 1 (in %), or rate of CL shortening
(mm/week)) and their impact on the predictive accuracy for PTB
was analyzed. Results: Overall 124 (28.1%) women were
diagnosed with short cervix(<25mm): 11 (8.9%) were diagnosed at
the routine mid-gestation exam(period 1) while all other women
were diagnosed with short cervix for the first time during period
2(18.5%), period 3(40.3%) or period 4(32.3%). The results of CL
measurement at periods 2, 3 or 4 were associated with an
increased risk of PTB irrespective of the results of the routine CL
measurement at period 1 (p<0.001). Importantly, these
measurements had a higher predictive accuracy for PTB than that
achieved with the mid-gestation CL measurement (Table).
Combining mid-gestation CL (period 1) with the information
obtained from the subsequent CL measurements (in the form of
absolute CL, absolute or relative change in CL from period 1,
50
shortening rate between examinations, or combinations of these
variables) improved the overall predictive accuracy for PTB(Table).
Conclusion: Serial measurements of CL in twin pregnancies can
detect pregnancies at risk of PTB that were not detected by the
routine CL measurement at mid-gestation, and increase the overall
predictive accuracy for PTB. Contact Information:
[email protected]
[467]
SONOGRAPHIC WEIGHT ESTIMATION OF SMALL FOR
GESTATIONAL AGE FETUSES: IS THE OPTIMAL MODEL RELATED
TO FETAL BODY PROPORTIONS? Nir Melamed1, John Kingdom2
1Division of Maternal Fetal Medicine, Sunnybrook Health Sciences
Centre, University of Toronto, 2Fetal Medicine, Mount Sinai
Hospital, University of Toronto
Introduction: Most sonographic models for fetal weight
estimation (EFW) do not perform as well in SGA fetuses, possibly
due to to differences in the relative proportions and composition
of the various fetal body parts between SGA and normally grown
fetuses. Objective: To perform a systematic comparison of the
accuracy of different sonographic models for fetal weight
estimation among several subgroups of SGA fetuses. Methods:
We compared the accuracy of 33 different models using a cohort
of 305 SGA fetuses who underwent sonographic EFW within 7 days
of delivery. Models were ranked based on multiple measures of
predictive accuracy within the overall SGA group as well as within
specific subgroups of SGA with distinct fetal body proportion
(small AC,short FL, small HC, symmetrically small fetuses), Doppler
studies, and gestational age. Cluster analysis was used to identify
homogenous subgroups of models based on the systematic and
random errors. Results: There was a wide variation in the
accuracy of the different models (systematic error -11.6% - 15.7%,
random error 7.7% - 15.7%). In the overall SGA group, the most
accurate model was the SGA-specific model by Scott et al (AC- FLHC), followed by models of Hadlock (AC-FL-BPD-HC, AC-FL-BPD,
AC-FL-HC), Woo (AC-BPD) and Warsof (AC-BPD). The optimal
model for weight estimation varied with fetal body proportions,
presence of Doppler abnormalities, and early vs. late SGA. Overall,
the model of Hadlock (AC-FL-BPD-HC) had the best performance
across all subgroups of SGA fetuses, followed by the models of
Hadlock (AC-FL-HC, AC-FL-BPD and AC-FL), and the SGA-specific
models of Scott (AC- FL-HC) and Sabbagha (AC-FL-HC and GA).
Conclusion: The optimal sonographic model for EFW among SGA
fetuses may need to be tailored to the characteristics of the
specific SGA fetus including its body proportions, Doppler
abnormalities and early vs. late SGA. Contact Information:
[email protected]
[468]
THE EFFECT OF ANTENATAL CORTICOSTEROIDS ON OUTCOME OF
PRETERM NEONATES – DOES THE ADMINISTRATION-TODELIVERY INTERVAL MATTER? Nir Melamed1, Jyotsna shah2,
Prakeshkumar Shah3, Kellie E. Murphy4
1Division of Maternal Fetal Medicine, Sunnybrook Health Sciences
Centre, University of Toronto, 2Department of Pediatrics, Mount
Sinai Hospital, University of Toronto, 3Department of Pediatrics,
Mount Sinai Hospital, Maternal-Infant Care Research Centre,
CNPRM 2015
University of Toronto, For the Canadian Neonatal Network,
4Department Obstetrics and Gynecology, Division of MFM, Mount
Sinai Hospital, University of Toronto
Introduction: A better understanding of the duration of the
beneficial effects of antenatal corticosteroids (ACS) is of major
importance since it may affect the decision of care givers to
administer ACS in cases in which the risk of preterm delivery
within the next 7 days is low to moderate. Unfortunately, available
data regarding the duration of the effects of ACS are conflicting.
Objective: To assess the impact of antenatal corticosteroid (ACS)
to delivery interval on neonatal outcome Methods: Data from the
Canadian Neonatal Network were used to obtain a national cohort
of all live-born singleton neonates born between 24-34 weeks in
Canada between 2010–2012. Primary outcome was a composite
defined as one or more of the following: neonatal death,
bronchopulmonary dysplasia (BPD), intraventricular hemorrhage
(IVH) grade III-IV and/or periventricular leukomelacia (PVL), and
severe retinopathy of prematurity (ROP). Using univariate
followed by multivariable logistic regression analysis, controlling
for confounding factors, neonatal outcomes were compared
between four groups based on the ACS to delivery interval
(Figure): 1) No ACS administrated, 2) Partial ACS course
(administration of ACS <24 hours of delivery), 3) Complete ACS
course administrated between 1-7 days from delivery (ACS 1-7d),
and 4) Complete ACS course administrated >7 days before delivery
(ACS >7d). Results: A total of 6,870 neonates were eligible for the
study (Figure). Compared to the ACS 1-7d group, all of the other
groups experienced an increased risk of composite morbidity (No
ACS group: OR 2.1, 95%CI 1.7-2.7, ACS <24h group: OR 1.5, 95%CI
1.2-1.8, and ACS >7d group: OR 1.5, 95%CI 1.2-1.8) and neonatal
death (No ACS group: OR 2.6, 95%CI 1.8-3.6, ACS <24h group: OR
1.6, 95%CI 1.2-2.2, and ACS >7d group: OR 1.4, 95%CI 1.0-2.0). In
the extremely preterm infants (defined as delivery < 28 weeks) the
benefits of the optimal ACS 1-7d window were most pronounced.
In neonates born at >28 weeks, an ACS to delivery interval of more
than 7 days was associated with an increase in the risk of neonatal
death (OR 1.9, 95%CI 1.0-3.6) and necrotizing enterocolitis (NEC)
(OR 1.7, 95%CI 1.0-3.0). Conclusion: The current study provides
support to the observations that the effect of ACS is incomplete at
<24h from administration and may decline after 7 days. This is
especially true in cases of extreme prematurity. Contact
Information: [email protected]
[471]
HYPERTENSIVE DISORDERS IN PREGNANCY AND THE RISK OF
INCIDENT CARDIOVASCULAR DISEASE. Sonia M Grandi, MSc1,
Karine Vallée-Pouliot, RM1, Maria Eberg, MSc2, Robert W. Platt,
PhD3, Roxane Arel, MD4, Kristian B. Filion, PhD5
1McGill University, Dept. Epidemiology, Biostatistics, and
Occupational Health, 2Lady Davis Institute for Medical Research of
the Jewish General Hospital, Division of Clinical Epidemiology,
3McGill University, Department of Epidemiology, Biostatistics and
Occupational Health, 4St. Mary’s Hospital Centre, Department of
Family Medicine, 5Lady Davis Institute for Medical Research of the
Jewish General Hospital, Division of Clinical Epidemiology
Introduction: Despite the different pathophysiological
mechanisms of gestational hypertension and preeclampsia,
hypertensive disorders (HTD) in pregnancy are hypothesized to
increase the risk of incident cardiovascular disease (CVD).
However, previous studies investigating the association between
HTD in pregnancy and incident CVD have not accounted for timevarying confounding. Objective: To investigate the association
between hypertensive disorders in pregnancy and incident
cardiovascular disease accounting for time-varying confounding.
Methods: A retrospective cohort of 156,967 women with a first
recorded pregnancy between the ages of 15-45 years and no prior
history of chronic hypertension or CVD. Exposure was defined as a
composite of: 1) a diagnosis of HTD in pregnancy or new
hypertension; 2) high systolic or diastolic blood pressure readings;
or 3) a prescription for anti-hypertensive agents between 20
weeks gestation and 6 weeks postpartum. Our primary outcome
was incident CVD, defined as a composite endpoint of coronary
artery disease and related procedures, cerebrovascular disease,
and peripheral vascular disease. Our secondary outcome was
chronic hypertension. Marginal structural Cox models were used
to account for important time-varying confounders. In secondary
analyses, exposure was sub-classified as 1) pre-eclampsia or
eclampsia; and 2) other HTD of pregnancy. In sensitivity analyses,
an approach analogous to an intention-to-treat analysis was used.
Results: The mean age at cohort entry was 29 years (SD 6). HTDs in
pregnancy were associated with an approximately 3 times higher
rate of CVD and 7 times higher rate of hypertension (Table).
Similar results were obtained when using an intention-to-treat
approach. The increased rate of incident CVD was greater with
other HTDs in pregnancy than with preeclampsia/eclampsia, while
both groups had a similarly increased rate of hypertension.
Conclusion: Women who are exposed to HTD in pregnancy are at
increased risk of developing future CVD. These results suggest that
a more aggressive approach to management for CVD risk factors
should be taken in women with a history of HTD in pregnancy.
Acknowledgements: Dr. Filion had full access to all the data in the
study and takes responsibility for the integrity of the data and the
accuracy of the data analysis. Mrs. Grandi and Vallée-Pouliot were
responsible for interpretation and drafting of the manuscript. All
other authors contributed equally to the interpretation of data
and critical revision of the manuscript. Contact Information:
[email protected]
Medical Teaching and Neonatal Resuscitation
Research
[ROOM ONTARIO]
Dr. Ahmed Moussa & Dr. Emer Finan
Procedural Skills Training in the NIC. &
Caring For the High-risk Newborn: the role of
simulation-based training
Dr. Georg Schmölzer
Monitoring in the delivery room: Understanding
physiological changes to improve neonatal outcomes
[235]
SUSTAINED INFLATION AND CHEST COMPRESSION VERSUS 3:1
CHEST COMPRESSION:VENTILATION RATIO IN A PORCINE MODEL
OF ASPHYXIA. Elliott S Li1, Po-Yin Cheung2, Min Lu2, Tze-Fun Lee2,
Megan O’Reilly2, Georg M. Schmölzer2
1Faculty of Science, McGill University, 2Centre for the Studies of
Asphyxia and Resuscitation, Neonatal Research Unit, Royal
Alexandra Hospital; Department of Pediatrics, University of
Alberta.
Introduction: Current resuscitation guidelines recommend a 3:1
Compression:Ventilation (C:V) ratio; however, the most effective
C:V ratio in newborns remains controversial. We recently
CNPRM 2015
51
demonstrated that delivering chest compressions (CC) at a rate of
120/min superimposed by sustained inflations (SI) significantly
improved return of spontaneous circulation (ROSC), and reduced
mortality in asphyxiated newborn piglets when compared to
standard coordinated 3:1 resuscitation. Objective: To determine
if CC at a rate of 90/min superimposed with SI reduces time for
ROSC, when compared to coordinated 3:1 C:V resuscitation in
newborn piglets with asphyxia induced bradycardia. Methods:
Newborn piglets were exposed to 50-minutes of normocapnic
hypoxia followed by asphyxia; once bradycardia was achieved,
defined as a heart rate less than 25% of baseline, piglets were
randomized to receive either “3:1 C:V” or “SI+CC”. Piglets
randomized to 3:1 received coordinated CC and ventilation
according to the current resuscitation guidelines. Piglets
randomized to “SI+CC” received uninterrupted CC at a rate of
90/min superimposed by a SI of 30 sec. The default settings for
airway pressures were a peak inflation pressure of 30 cm H2O, and
a positive end expiratory pressure of 6 cm H2O. The primary
outcome was duration of CC to achieve ROSC. Results: Eight
piglets were randomized to each group; the mean (SD) age was 3
(1) weeks vs. 3 (1) weeks in the in the SI+CC and 3:1 group,
(p=0.858) respectively. Mean (SD) weight was 2037 (238) g vs.
2025 (249) g in the SI+CC group and 3:1 group, (p=0.919)
respectively. Mean (SD) arterial pH at bradycardia was 6.87 (0.088)
vs. 6.76 (0.15) in the SI+CC and 3:1 group (P=0.086), respectively.
Mean (SD) blood lactate at bradycardia was 13.7 (1.7) mmol/L vs.
14.4 (1.8) mmol/L in the SI+CC and 3:1 group (p=0.452)
respectively. Survival was 7/8 piglets vs. 4/8 piglets for the SI+CC
and 3:1 groups (p=0.106), respectively. Median (IQR) ROSC was
significantly decreased in the SI+CC group with 34 (28-156) sec vs.
210 (72-300) sec in the 3:1 group (p=0.043). 3/8 in the SI+CC group
and 8/8 in the 3:1 group received oxygen (p=0.007) and 3/8 in the
SI+CC group and 7/8 in the 3:1 group received epinephrine
(p=0.039). Conclusion: ROSC was significantly faster in newborn
piglets resuscitated with CC superimposed by SI compared to 3:1
C:V. Acknowledgements: Heart and Stroke Foundation Canada,
Heart and Stroke Foundation Alberta, Neonatal Resuscitation
Program - Canadian Pediatric Society. Contact Information:
Georg Schmolzer [email protected]
[247]
EFFECT OF AN EDUCATIONAL PRESENTATION ON KNOWLEDGE
AND ATTITUDES TOWARDS MANAGEMENT OF EXTREMELY
PREMATURE INFANTS. Stefani Doucette MD1, Salwa Akiki MSc2,
Brigitte Lemyre MD FRCPC3, Thierry Daboval MD FRCPC3, Sandra
Dunn RN PhD4, Nick Barrowman PhD2, Gregory Moore MD FRCPC3
1University of Ottawa/Children's Hospital of Eastern
Ontario/Department of Pediatrics, 2University of
Ottawa/Children's Hospital of Eastern Ontario/Clinical Research
Unit, 3University of Ottawa/Children's Hospital of Eastern
Ontario/Department of Neonatology, 4University of
Ottawa/Children's Hospital of Eastern Ontario/Research Institute
Introduction: A guideline regarding perinatal management of
extremely premature infants (EPI – 22-25 wks GA) is being
developed in Ottawa. To date, no research has examined the
immediate effect of healthcare providers (HCP) education on
knowledge and attitudes regarding EPI, despite the fact that
assessment of barriers and facilitators is critical to guideline
implementation. Objective: 1) To determine if HCP knowledge of
and attitudes towards EPI changed after attending a presentation
about survival and neurodevelopmental impairment of EPI and
associated ethical issues 2) to explore the correlation between
knowledge and attitudes of HCP. Methods: Local HCP (neonatal
and obstetrical nurses, trainees and consultants; pediatricians)
working with EPI or their parent(s) attended a presentation.
Participants completed a pre/post survey. Changes in knowledge
52
and attitudes were analyzed using the McNemar test and marginal
homogeneity test. Association between knowledge and attitudes
was assessed using Spearman correlation. Results: One hundred
and sixty of 508 potential participants attended a presentation
(attendance rate = 31%); 130 completed both surveys (response
rate = 81%). HCP knowledge for each GA significantly improved
following the presentation (p<0.001). Of the 16 items assessing
HCP attitudes, all but one demonstrated a significant ‘positive’
shift in the modal category (i.e. more likely to consider
resuscitation) (p=0.04 to p<0.001) after the presentation. Based on
post-presentation responses, Spearman correlation between
knowledge and attitudes ranged from 0.04 to 0.40 with a median
of 0.22 (eg. Table). Some attitudes did not significantly correlate
with HCP knowledge (eg. use of epi during resuscitation of 24 wk
infant based on survival knowledge (p=0.16)). Conclusion: The
survey results revealed a statistically significant improvement in
knowledge and alteration in attitudes of HCP after attending a
presentation about EPI. The correlation between knowledge and
attitudes varied but was generally low. Acknowledgements:
Salwa Akiki MSc, Brigitte Lemyre MD FRCPC, Thierry Daboval MD
FRCPC, Sandra Dunn RN PhD, Nick Barrowman PhD, Gregory
Moore MD FRCPC. Contact Information: Dr. Gregory Moore
[email protected]
[264]
MODIFICATION AND FIELD TESTING OF A PATIENT DECISION AID
AND DECISION COACHING FOR COUNSELING PARENTS FACING
THE POTENTIAL BIRTH OF AN EXTREMELY PREMATURE INFANT.
Gregory Moore1, Brigitte Lemyre1, Sandy Dunn2, Thierry Daboval1,
Sharon Ding1, Allyson Shephard1, Margaret Lawson1
1Children's Hospital of Eastern Ontario, 2Better Outcomes Registry
Network (BORN) Ontario
Introduction: Risk of death or neurodevelopmental impairment
(NDI) is relatively high for extremely premature infants (EPI -- 2225 weeks GA). Given the notable prognostic uncertainty about the
outcome, early intensive care and palliative care are both
potentially acceptable options. Use of decision aids (DA) and
decision coaching have been shown to improve decision quality
and patient engagement in the decision making process. Although
DAs have been evaluated in simulated antenatal counseling
sessions for EPI, none have been tested during real life
consultations. Objective: 1) To create a DA specific to our
population; and 2) field test the DA and decision coaching in an at
risk population. Methods: The only published EPI DA was assessed
using the International Patient Decision Aids Standards (IPDAS)
tool. An existing working group for EPI was surveyed to identify
key elements to include in a DA and feedback was sought from the
local family decision services team, neonatologists and parents.
Four neonatologists were trained in decision coaching and alphatested the DA. The revised DA along with decision coaching was
then field tested on women (and partners) at risk of delivering
between 23+0 and 24+6 weeks GA. Usefulness for decision making
and degree of pre/post decisional conflict were assessed. Results:
Deficits were identified in the published DA (IPDAS score 13/35):
need for more information overall, incorporation of local data and
creation of a detailed palliative care description. The EPI working
group identified seven key elements essential for the DA: survival;
moderate/severe NDI rates; quality of life of survivors and their
parents; and maternal risk of death and long term morbidity.
Revisions were made to the DA and to the number and content of
CNPRM 2015
the decision cards (3-options, 6-key elements and 16-GA specific
data). Post-modification IPDAS score was 31/35. Ongoing field
testing (8 parents to date) suggests: neonatologists like using the
DA; average consult is 50 mins; DA presents balanced and clear
information; DA reduces parental decisional conflict (22/40 down
to 4/40). Conclusion: We were able to improve the quality of an
existing yet untested DA using multi-source feedback. Field testing
to date demonstrates our DA’s promise for helping parents engage
in the decision making process at the limit of viability. Contact
Information: [email protected]
[329]
CHANGES OVER TIME IN APPLIED PRESSURE DURING SIMULATED
NEONATAL CHEST COMPRESSION – A RANDOMIZED
CONTROLLED TRIAL. Anne Lee Solevåg1, Po-Yin Cheung1, Elliot Li2,
Khalid Aziz1, Megan O'Reilly2, Bo Fu3, Bin Zheng3, Georg
Schmölzer2
1Department of Pediatrics, University of Alberta, 2Centre for the
Studies of Asphyxia and Resuscitation, Neonatal Research Unit,
Royal Alexandra Hospital, 3Department of Surgery, University of
Alberta
Introduction: Outcomes after prolonged cardiopulmonary
resuscitation in newborn infants are poor. Focused efforts to
standardize chest compressions (CC) might improve survival and
long-term outcomes. Objective: The aim of the study was to
investigate applied pressure during CC throughout five minutes of
simulated neonatal CC. We compared the recommended 3:1
compression to ventilation (C:V) ratio with continuous chest
compression with asynchronous ventilation (CCaV) using two
different rates. Methods: We used the FingerTPS™ system (PPS,
Los Angeles, CA) for wireless tactile pressure measurement. A oneinch (2.5 cm) pressure sensor was placed on the chest of a
ResusciBaby (Laerdal, Stavanger, Norway). Every participant used
the two-thumb method to perform CC. Each participant performed
CC using the 3:1 C:V ratio, CCaV at a rate of 90/min (CCaV 90) or
120/min (CCaV 120). Each intervention was performed for 5 min.
Changes in applied pressure during CC were recorded and
analyzed. Results: Fifty-three Neonatal Resuscitation Program
(NRP) providers were randomized to perform CC on the manikin
with the different techniques. Following an initial rise, the
FingerTPS™ tracings showed a downward trend in applied
pressure. These initial changes were followed by a stable pressure
for the remainder of the duration of CC. [figure1] Mean
percentage of initial decline from baseline and time before
achieving a stable pressure in the different groups are presented
in Table 1. [table1] There was no difference in the parameters
between groups. Conclusion: Both with a 3:1 C:V ratio and CCaV
at two different rates, the pressure per CC changed the first 30-60
seconds of CC, suggesting that the operator needs to acclimatize
to the task of CC. Further studies are needed to assess CC quality
during the important first minutes of CC. Acknowledgements:
We wish to thank the NRP providers who took part in the study.
Contact Information: [email protected]
[428]
EFFECT OF COHORTING PATIENTS BY LEVEL OF ACUITY TO
DESIGNATED AREAS WITHIN A NEONATAL INTENSIVE CARE UNIT
– DESCRIPTION OF THE MICROSYSTEMS PROJECT. Ahmed Bakry1,
Sourabh Dutta, Salhab El-Helou1, Gerhard Fusch1, Lynda Aliberti1,
Carrie-Lynn Meyer1, Christoph Fusch 1, on behalf of the project
group
1Department of Pediatrics, McMaster University, Hamilton, ON
Introduction: There are different organisational models to provide
care in NICU's; however, there is no or limited data on the effect of
cohorting vs. a mixed acuity model on quality and cost of care. Our
plan to switch from the mixed acuity model to one using
cohorting/microsystems model created a unique opportunity to
add scientific evidence to this important question. Objective: To
measure the impact of the introduction of Microsystems in an
NICU on effectiveness, efficacy, and safety thereby testing various
domains Methods: Institution: McMaster University NICU, a 47bed level III unit with approx. 1000 admissions/year and a staff of
300 healthcare providers (HCP); five pods with 4 x 10 and 1 x 7
beds. Intervention: Preparatory phase: 8 months; weekly meetings
of an interdisciplinary group including representatives of all HCP;
Implementation phase of Microsystems: the five-pod NICU was
switched from a model of care with mixed acuity to MS. Before
implementation of Microsystems, there were three teams ’North’,
’South’ and ’Central’ with similar mix of acuity, whereas; after the
start of Microsystems, teams were differently re-arranged as
’Acute-1’, ’Acute-2’ and ’Intermediate Care’ teams. The newly
developed teams were comprised of physicians, nurses, nurse
practitioners, and respiratory therapists. Resources (nurse-topatient ratio e.g.) were allocated according to acuity of sickness
and hence were different between acute and intermediate care.
Time: The data collection was done during three periods: 1. preimplementation phase from Jan to Apr 2014; 2. transition phase
from May to Jul 2014; and 3. post-implementation phase from Aug
to Jun 2015. Outcome measures: The impact of Microsystems was
assessed by 17 sub-projects from 4 domains (patient-, healthcare
personnel-, process of care-, and administrative-related, see Table
1). Results: Meetings (n=40) of the interdisciplinary group started
in summer 2013. We successfully implemented Microsystems on
May 1, 2014. Currently all pre-implementation data are collected
according to plan as well as the transition phase data. First results
of the sub-projects are reported in three separate abstracts during
this conference (Noise levels and Round length). Conclusion: This
unique opportunity will give us the chance to create scientific
bases about the effect of different care models in a NICU setting.
Acknowledgements: The project is funded by HAHSO. The other
members of the working group are: Debborah Barnard, Jennifer
Callen, Joanne Doucette, Sourabh Dutta, Donna LaForce, Michael
CNPRM 2015
53
Marrin, Deb Patterson, David Pogorzelski, Karen Prim, Samira
Samiee, Karen Schatthauer, Sandesh Shivananda, Sumesh Thomas,
Connie Williams . Contact Information: Christoph Fusch
[email protected]
THURSDAY AFTERNOON, FEBRUARY 26TH
Chronic Lung Disease of Prematurity
[ROOM MONTEBELLO]
Dr. Martin Post
Lung Development, Injury and Repair
[439]
INTRODUCTION OF A “MICROSYSTEMS” CARE MODEL IN THE
NICU – IMPACT ON ROUND LENGTH. David Pogorzelski1, Ahmed
Bakry1, Carri-Lynn Meyer2, Lynda Aliberti2, Salhab Elhelou1,
Sourabh Dutta, Christoph Fusch1
1McMaster University, Dept of Pediatrics, 2Hamilton Health
Sciences
Introduction: There are different organisational models to manage
a NICU. We recently introduced “Microsystems” and cohorting of
patients according to acuity in our level III unit. One outcome
parameter to assess the impact of this introduction is the length of
rounds. This implementation will create designated areas with
more and less intensive care within the NICU. We hypothesize that
round length will be shorter after introduction of the new model.
Objective: 1)To assess the round length during weekdays before
and after implementation of Microsystems; 2)To investigate the
effect of implementing microsystems on round length in different
areas of the NICU. Methods: Design: prospective interventional
study Institution: McMaster University NICU, a 47-bed level III; 5
pods with 4 x 10 and 1 x 7 beds. Successful implementation of
Microsystems on May 1st, 2014 after a preparatory phase of 8
months. Data collection: Prospective collection of daily reports of
round lengths (weekdays) for all three teams (T1, T2, T3); Time:
Data was collected during two periods: 1. pre-implementation
phase from Jan- Apr 2014; 2. post-implementation phase from
June - Sept 2014. Descriptive analysis using standard statistical
methods. Results: For the two acute teams rounds started
earlier and more punctual (T1: 10.06 am ± 10min; T2: 10.08 am ±
10min compared to T1: 10:32am ±20min; T2: 10:33 ±15min; T3:
10.28 am ± 20min); the new intermediate care (IMC) team started
later (as planned) and less punctual (not planned) T3: 13:22 ±
30min. Round length decreased in all three teams (12, 6 and 41
min, respectively), on average by 20 min per team. Cumulative
gain in efficiency 1 hour per day. This translates approximately
into 8 hours per day per medical staff. Conclusion: Round length
was impacted by the organisational model applied. The average
reduction in cumulative rounding time with the microsystems
model corresponds to one 100% FTE, or - in other words - would
free up the work time of one FTE, thereby increasing efficiency of
the medical team. Acknowledgements: The project is funded by
HAHSO (Hamilton Academic Health Sciences Organisation).
Contact Information: Dr. Christoph Fusch [email protected]
54
Dr. Robert Jankov
The Pulmonary Circulation in BPD
Dr. Amish Jain
The concept of pulmonary heart disease in chronic
neonatal lung disease in preterms
Dr. Theo Moraes / Dr. Sherri Katz
Building Foundations to Study Long-term CardioRespiratory Health of Extremely Pre-term Infants
Dr. Anne Monique Nuyt
Vascular impact of preterm birth: beyond the lungs
[331]
PULMONARY ARTERIAL ADENYLYL CYCLASE ACTIVITY IS
IMPAIRED IN PPHN. Anurag Singh Sikarwar1, Martha Hinton1,
Shyamala Dakshinamurti2
1University of Manitoba, Department of Physiology, 2University of
Manitoba, Department of Pediatrics and Physiology
Introduction: Persistent pulmonary hypertension of the newborn
(PPHN) is marked by hypoxemia, pulmonary vasoconstriction and
poor cardiac responses to inotropic drugs. The Gαs–adenylyl
cyclase–cAMP pathway is crucial for pulmonary vasodilation and
cardiac contraction. We reported low basal and stimulated cAMP
in hypoxic pulmonary artery smooth muscle cells (PASMC), and in
PASMC from PPHN animals. Objective: We examine pulmonary
arterial adenylyl cyclase (AC) activity and regulation in hypoxic
PPHN. Methods: PPHN was induced in newborn swine by
normobaric hypoxia (FiO2 0.10) for 72h; age- matched normoxic
controls. 2 mm pulmonary arteries rings on isometric myograph
were pre contracted with thromboxane mimetic 3x10-8M U46619,
and relaxation to AC activator forskolin, and non-AC-mediated
relaxant sodium nitroprusside (SNP) studied. Human and neonatal
porcine PASMC (from Day 0 animals, and from PPHN/control
animals) were grown in hypoxia (H, 10% O2) or normoxia (N, 21%
O2) for 72hr in vitro. AC content, isoform expression and catalytic
activity were determined, in presence or absence of Gαs- coupled
receptor agonists or forskolin; ATP content; and cAMP degradation
due to PDE activity. Results: Relaxation to forskolin and SNP were
impaired in PPHN pulmonary arteries. AC specific activity was
diminished in H; AC Vmax in N= 606, H= 408 (p<0.0001), N Km=
5.62x10-8M, H Km= 3.16x10-8M. PASMC from PPHN swine had
reduced AC activity despite prolonged exposure to N in culture;
transient hypoxia in vitro further decreased AC activity. PASMC
mainly expressed AC isoform 6 and 9; total AC content and isoform
profile was unchanged by hypoxia. Basal ATP abundance increased
(p<0.05); cAMP-specific PDE activity was lower in hypoxia (p<0.05).
Prostacyclin receptor ligand affinity was decreased, but its
association with Gαs increased in hypoxia. AC activity upon
stimulation with prostacyclin mimetic iloprost, adenosine A2
agonist NECA, or forskolin, was lower in hypoxic myocytes
(p<0.001). Conclusion: PPHN pulmonary arterial relaxation is
impaired, with decreased forskolin sensitivity. Receptor dependent and -independent AC activity are impaired in
CNPRM 2015
pulmonary arterial hypoxia; AC activity is not corrected by removal
from hypoxia. Substrate ATP availability is not limiting; cAMP
degradation is not accelerated. Hypoxic AC has a catalytic constant
similar to normoxic AC, but a lower velocity of product formation.
These findings may have implications for use of Gαs-coupled
receptor agonists in hypoxic PPHN. Acknowledgements: Funding
from CIHR and HSFC. Contact Information: Dr Shyamala
Dakshinamurti [email protected]
[338]
SUCCESS RATE AND ASSOCIATED CLINICAL FACTORS OF EARLY
EXTUBATION IN THE PRETERM NEONATE BELOW 29 WEEKS OF
GESTATION. Anna-Maria Preziosi MD1, Anne Monique Nuyt MD1,
Keith J. Barrington MD1, Ahmed Moussa MD1
1Division of Neonatology, Department of Pediatrics, Ste-Justine
University Hospital and Research Center
Introduction: Mechanical ventilation in preterm neonates is
associated with adverse health outcomes. Early extubation may
mitigate these risks. Success rate and associated factors of early
extubation are not clearly described. Objective: Assess success
rate of early extubation in infants < 29 weeks gestation and
identify factors associated with extubation outcome. Methods:
Retrospective study in a level 3 NICU (Ste Justine, Montreal,
Canada). Neonates born in 2012 and 2013 at < 29 weeks gestation
intubated in the first 7 days of life and extubated in the following
72 hours were included. Infants with congenital anomaly or that
died before extubation were excluded. Primary outcome was
success of early extubation (not requiring reintubation for > 72
hours). Secondary outcome was to identify factors associated with
extubation success. Chi2 was used for categorical variables,
independent t-test was used for continuous variables and multiple
logistic regression (MLR) was performed to identify factors
contributing to extubation success. Results: Of the 209 patients
born at < 29 weeks gestation during the study period, 75 were
included. Characteristics of infants who remained extubated
(success) vs. were reintubated (failure) are presented. There were
no differences in pre-extubation ventilatory parameters. MLR
identified PDA as a significant contributor to extubation failure: OR
0.05 (95%CI 0.01 – 0.42). Patients failing early extubation had
increased risk of severe ROP or death: OR 0.14 (95%CI 0.03 – 0.66).
(See Table in attached PDF). Conclusion: In our cohort of infants <
29 weeks gestation, early extubation succeeded in 2/3 of patients.
PDA might be a significant contributor to extubation outcome.
Patients failing extubation had increased risk of severe ROP or
death. Acknowledgements: Thank you to Mrs Lucie Lafond for
her help in data compilation. Contact Information: Anna-Maria
Preziosi [email protected]
[466]
IN VIVO HYPEROXIA ALTERS THE REPAIR POTENTIAL AND GENE
EXPRESSION PROFILE OF CD146+ ENDOGENOUS LUNG
MESENCHYMAL STROMAL CELLS. Jennifer J.P. Collins PhD1,
Marissa A. Lithopoulos BSc1, Claudia C. dos Santos MD MSc2,
Marius A. Möbius3, Arul Vadivel PhD4, Shumei Zhong MSc4,
Bernard Thébaud MD PhD 5
1Regenerative Medicine Program, Sinclair Centre for Regenerative
Medicine, Ottawa Hospital Research Institute, University of
Ottawa, 2The Keenan Research Centre of the Li Ka Shing
Knowledge Institute of St. Michael’s Hospital, University of
Toronto, 3Regenerative Medicine Program, Sinclair Centre for
Regenerative Medicine, Ottawa Hospital Research Institute &
Bereich Neonatologie und pädiatrische Intensivmedizin,
Universitätskinderklinikum und Hochschulmedizin “Carl Gustav
Carus”, 4Regenerative Medicine Program, Sinclair Centre for
Regenerative Medicine, Ottawa Hospital Research Institute,
5Regenerative Medicine Program, Sinclair Centre for Regenerative
Medicine, Ottawa Hospital Research Institute, Children's Hospital
of Eastern Ontario Research Institute, University of Ottawa.
Introduction: Bronchopulmonary dysplasia (BPD), one of the most
common adverse outcomes of extreme preterm birth, can be
caused by oxygen-related lung injury and is characterized by an
arrest in alveolar development. Mesenchymal stromal cells (MSCs)
prevent and rescue lung injury when administered exogenously in
animal models of BPD. Given the regenerative potential of MSCs, it
is unclear why resident lung MSCs (L-MSCs) do not support lung
repair and growth in BPD. Objective: We hypothesized that in
vivo hyperoxia exposure perturbs the repair potential and gene
expression in CD146+ endogenous lung MSCs in an oxygeninduced rat model of BPD. Methods: Rat pups were exposed to
21% or 95% oxygen from postnatal day 0 to 10 and sacrificed on
day 12. L-MSCs were isolated by enzymatic digestion, Ficollpurification and plastic adherence. CD146+ L-MSCs were isolated
through magnetic bead selection and characterized according to
the International Society for Cellular Therapy criteria. Epithelial
repair potential was tested by scratch assay, angiogenesis
potential by network formation assay. Microarray analysis was
performed using the Affymetrix Rat Gene 2.1 ST array, significance
analysis of microarrays (SAM) and gene set enrichment analysis
(GSEA) software. Results: Hyperoxia exposure decreased CD73
expression in CD146+ L-MSCs 2-fold, but not colony forming
capacity and other surface marker expression. CD146+ L-MSCs
promoted epithelial wound healing over baseline by 25% over 24
CNPRM 2015
55
hours, regardless of in vivo hyperoxia exposure. Network
formation was decreased by ~25% in endothelial cells exposed to
conditioned media from hyperoxia CD146+ L-MSCs. GSEA analysis
revealed that gene expression of the axonal guidance cue and
CDC42 pathways were most strongly increased after in vivo
hyperoxia. Among the decreased gene sets, most notably
fibroblast growth factor (FGF) signaling and the janus kinase
(JAK)/signal transducer and activator of transcription (STAT)
pathway were decreased. Conclusion: Exposure to hyperoxia in
vivo lowered CD73 and JAK/STAT expression, indicating decreased
immune-regulatory function and repair capacity. Increased axonal
guidance cue signaling and decreased FGF signaling would indicate
a halt in alveolar growth and development signaling from the
mesenchyme. This is further supported by a decrease in
angiogenesis potential. These changes in endogenous L-MSCs
likely reflect both their role in normal lung development, immune
regulation and repair, and possibly their dysfunction in BPD. A
better understanding of endogenous MSCs may lead to improved
effectiveness of exogenous MSC therapy. Acknowledgements:
JJPC is supported by a CIHR postdoctoral fellowship. BT is
supported by CIHR, CTS and SCN. Contact Information: Jennifer
J.P. Collins [email protected]
[492]
ENHANCED HEALING CAPACITY OF MRL/MPJ MICE IN RESPONSE
TO HYPEROXIA-INDUCED NEONATAL LUNG INJURY. Megan
O’Reilly1, Farah Eaton2, John J Greer3, Bernard Thébaud4.
1 Department of Pediatrics, University of Alberta, 2University of
Alberta, 3Department of Physiology, University of Alberta,
4University of Ottawa.
Background: Many preterm infants develop a chronic lung disease
known as bronchopulmonary dysplasia (BPD), which interrupts
lung development and results in long-term pulmonary
complications that reach beyond childhood and into adult life. The
MRL/MPJ strain of mouse has a unique capacity for accelerated
and regenerative wound healing, but it is not known if the same
healing process applies to the neonatal lungs. Objective: To
determine if MRL/MPJ mice are protected from, or capable of
repair, following neonatal exposure to hyperoxic gas compared to
the non-healer C57Bl/6 mouse strain. Methods: Experimental
BPD was achieved by exposing neonatal MRL/MPJ and C57Bl/6
mice to hyperoxic gas (95% O2) from postnatal day (P) 4-10.
Thereafter, mice were raised room air. Controls breathed only
room air from birth. Lung structure was assessed at P10, P28, and
P56. Lung function was assessed at P28 and P56. Results:
Immediately after O2-exposure at P10, both MRL/MPJ and C57Bl/6
mice exhibited lung injury characterized by impaired alveolar
growth with air-space enlargement (p<0.05). In O2-exposed
MRL/MPJ mice at P28, there was no significant difference in lung
structure compared to room air controls. However, O2-exposed
C57Bl/6 mice displayed persistent structural lung injury (p<0.05).
Despite the improvement in lung structure at P28, O2-exposed
MRL/MPJ mice exhibited functional differences (increased
dynamic lung compliance; p<0.05). C57Bl/6 mice also displayed
increased dynamic lung compliance at P28 (p<0.05). Structural
lung injury persisted into adulthood at P56 in O2-exposed C57Bl/6
mice (p<0.05), which was also associated with an increase in
dynamic lung resistance (p<0.05). Conversely, at P56, MRL/MPJ
mice were persistently protected from O2-induced lung injury and
displayed no significant difference in lung structure as well as no
functional differences compared to controls. Conclusions:
MRL/MPJ mice display enhanced healing potential of the lung
following neonatal O2-exposure, which persists into adulthood.
MRL/MPJ mice may be useful to identify new therapeutic
strategies to promote injury resolution in BPD. Contact
information: [email protected]
56
Neonatal Nutrition
[ROOM QUÉBEC]
Dr. Jean-Claude Lavoie
Oxidative stress in neonatology, there is time to
improve antioxidant defenses of premature newborn
Dr. Isabelle Marc
Omega-3 in neonatology: RCT/Meta-analyses
Dr. Christopher Fusch
Postnatal Growth Restriction and Individualized
Fortification
[231]
IS CAFFEINE A RISK FOR OSTEOPENIA OF PREMATURITY. Dr.
Ebtihal Ali1, Dr Depeng Jiang2
1Faculty of Health Sciences/University of Manitoba/Department of
Community Health Sciences, 2Faculty of Health Sciences/university
of Manitoba/Department of Community Health Sciences
Introduction: Osteoporosis in adulthood often has its roots in
childhood. A premature infant likely suffers lifelong decreased
bone mineral density as a result of its early birth and the lack of
adequate mineral stores that are typically present in full-term
infants. Caffeine is now one of the most commonly prescribed
drugs in the NICU to treat apnea of prematurity. Later studies in
preterm infants confirmed the diuretic effect of caffeine, and
revealed a significant increase in osteoclastogenesis and urinary
calcium excretion. The effect of caffeine treatment on bone health
of premature infants was not studied before. Objective: The
primary outcome is 1-To elucidate the effect of the cumulative
dose of caffeine and the duration of caffeine usage on osteopenia
of premturity (OP). As secondary outcome:1- To observe any effect
of steroids and diuretics on bone metabolism, 2-To determine the
effect of Vitamin D intake, 3-To observe any relation or causation
between maternal parity and osteopenia of prematurity.
Methods: This is a quantitative retrospective cohort study, was
conducted at Health Sciences Centre in Winnipeg from October
2007 to June 2012. Cases were defined as premature infants less
than 31 weeks gestational age and birth weight less than 1500
grams, with X-ray evidence of osteopenia. The demographic data
included: gestational age, gender, birth weight and maternal parity
level as categorical data. Laboratory data included serum
phosphate levels. Exclusion criteria;1- Infants born with congenital
anomalies including congenital heart disease.2-Infants
experiencing gut surgery affecting feeding. 3)Infants with non
osteopenic fractures. The statistical analyses was carried out using
SAS 9.3. Results: the cohort had 109 infants who had 12 weeks of
hospital stay.The demographic data in Table 1(file1). We first fitted
generalized linear model to examine each individual variable
associate with the probability of OP.Table 2(file2). Then we fitted
multivariable generalized mixed model with gestational age,
average biweekly weight, cumulative dose of caffeine, cumulative
steroids dose and vitamin D considering the clinical importance
and statistical significance at univariate analysis in Table 3and
Figure 1 (file 3). To examine whether the effect of caffeine dose on
OP differs by duration of treatment, we fitted another generalized
mixed model by including the interaction between caffeine dosage
and duration of therapy, and other covariates File 4 Conclusion:
The Cumulative caffeine dose & duration of therapy and steroids
have a statistical significant positive correlation with OP even
when controlling for the effects of gestational age, weight and
vitamin D. Acknowledgements: I acknowledge my Committee
members. Contact Information: [email protected]
CNPRM 2015
[267]
FETAL GUT MICROBIOME DIVERSITY IS MODULATED BY
SUBCLINICAL ILEUM INFLAMMATION DUE TO SYSTEMIC
ENDOTOXIN EXPOSURE AND BY VAGAL DENERVATION. Hai Lun
Liu1, James Butcher2, Guillaume Romain2, Mingju Cao 3, Lucien D.
Durosier3, Patrick Burns4, P-Y Mulon4, Gilles Fecteau4, André
Desrochers4, Natalie Patey5, Luca Garzoni6, Christophe Faure6,
Alain Stintzi2, Martin G. Frasch7
1OBGYN/Neurosci, Université de Montréal, INP, McGill University,
2Dept. of Biochemistry, Microbiology and Immunology, University
of Ottawa, 3OBGYN/Neurosci, UdeM, Montréal, 4Clinical Sciences,
UdeM, St-Hyacinthe, 5Pathology, UdeM, Montreal, 6Pediatrics,
UdeM, Montréal, 7OBGYN/Neurosci, UdeM, Montréal, CRRA,
UdeM, St-Hyacinthe.
Introduction: The recent discovery of the placental microbiome
has challenged the notion that the fetus develops in a sterile
environment. Intestinal microbiota are an integral part of the gutbrain axis essential for proper intestinal development and the
inflammatory response. The gut is the most extensive vagusinnervated organ. Objective: We aimed to determine if a
microbiome is present in the fetal gut near-term and to test how
brain-gut communication via the vagus nerve influences this
microbiome. We hypothesized that ileal inflammation will result in
reduced α-diversity in the fetal ileal microbiome. Methods: Nearterm fetal sheep were surgically prepared with vascular catheters.
Arterial blood samples were drawn at baseline and seven selected
time points to profile lipopolysaccharide (LPS)-induced
inflammation. At 54h post LPS, necropsy was performed. The
plasma levels of IL-6 (ELISA, pg/ml) and the Iba1+ cell intensity in
terminal ileum were used to quantify the degree of inflammation
and macrophage activation, respectively. Results are reported for
P<0.05 as mean±SD. The microbiome composition was
characterized by high-throughput sequencing of the V6 hypervariable region of the 16S rRNA gene. Results: In the LPS group,
but not in the control and Vx+LPS groups, at 3h post LPS, IL-6, but
not TNF- α, was elevated compared to baseline: 0.6 ± 1.5; 261.7 ±
228.7; 155 ± 200.5; 1.3 ± 3.9 (Controls; LPS; Vx+LPS; mean baseline
across all groups, respectively). IL-6 values were higher at 3h in the
LPS group vs. control, but not vs. Vx+LPS group; Vx+LPS did not
differ from controls. In line with Vx effect on systemic
inflammation, Iba1+ cell intensity was lower in Vx+LPS vs. LPS
group but not different from controls (Fig. 1). The presence of a
fetal ileum microbiome was validated (Fig. 2) and its dependence
on intact vagal innervation revealed (Fig. 3 and 4): α -diversity
decreased in response to LPS, but was higher in more inflamed ilea
after vagal denervation (Spearman R=0.75). We found no
correlation α -diversity and the levels of Iba1+ cells in the ileum
across all groups. However, group-specific analysis revealed a
strong correlation for Vx+LPS group (Spearman R=0.75, p=0.02,
N=9), but not for the LPS treated groups that were not
vagatomized. Conclusion: Late gestation sheep’s fetal gut
contains a full complement of intestinal bacteria whose diversity is
influenced by the exposure to low doses of endotoxin if brain-gut
communication is interrupted. Acknowledgements: Funded by
CIHR, FRQS, Molly Towell Perinatal Research Foundation, QTNPR
A.S. is funded by the Government of Canada through Genome
Canada and the Ontario Genomics Institute (OGI-067), CIHR grant
number GPH-129340, CIHR grant number MOP-114872, the
Ontario Ministry of Economic Development and Innovation (REG14450), the 3C Foundation of Canada and Crohn’s and Colitis of
Canada (CCC). Contact Information: Hai Lun Liu
[email protected]
[412]
VALIDATION OF NIR MILK ANALYZER FOR PASTEURIZED AND
NATIVE MILK. Gerhard Fusch1, Arum Choi1, Celia Kwan1, Dasol
Choi1, Sonia Huang1, Niels Rochow1, Christoph Fusch1
1Department of Pediatrics, McMaster University, Hamilton, ON
Introduction: Reliable milk analysis is a prerequisite to implement
the concept of target fortification in the NICU. We recently
showed that this concept is feasible (Rochow 2013) but that IR
milk analyzers need to be evaluated. We proposed equations to
improve accuracy for fat and protein analysis that need to be
validated (Fusch 2014). Additionally, we study the impact of
pasteurization on milk analysis. Objective: 1) To validate
published correction algorithms for fresh or frozen breast milk 2)
to assess the impact of pasteurization on IR analysis (Unity
SpectraStar) and chemical analysis. Methods: Pooled breast milk
samples (N=50) were divided into control and Holder pasteurized.
1) validation (only fat and protein): correlation analysis of 20
unpasteurized and 10 corresponding pasteurized samples
measured with IR analyzer and chemical reference methods 2) For
pasteurization (F, P and lactose): correlation analysis of
unpasteurized and pasteurized samples measured with (1) IR
analyzer (n=50 each) and (2) chemical reference methods (n=10).
Results: Figure 1: Validation shows reliability of proposed
correction algorithms. Figure 2: pasteurization has no influence on
IR and chemical method readouts. Conclusion: Published
algorithms can be used to correct for fat and protein readouts of
the IR analyzer. Pasteurized milk can be rapidly assessed and
target fortified which is important to identify low protein donor
milk. Acknowledgements: C. Fusch holds the Hamilton Health
Sciences Foundation – Jack Sinclair Chair in Neonatology at
McMaster University. Fusch G et al. Clin Nutr. 2014, doi:
10.1016/j.clnu.2014.05.005 Rochow N et al. J Pediatr. 2013
Oct;163(4):1001-7. Contact Information: Christoph Fusch
[email protected]
[449]
GASTRIC RESIDUALS IN PRETERM INFANTS AS PREDICTOR OF
TOLERANCE TO EARLY ENTERAL FEEDS (GRIP TRIAL). Balpreet
Singh1, Lori Chessell1, Niels Rochow1, Kathy Cunningham1, Jennifer
Wilson1, Prashanth Murthy1, Christoph Fusch1, Sumesh Thomas1
1McMaster Children Hospital, Hamilton, Ontario
Introduction: Evidence is inconsistent to support checking gastric
residual volumes (GRv) in predicting feeding intolerance in
CNPRM 2015
57
preterm infants. Gastric residual volume remains standard practice
in guiding feeding advancement in several neonatal centers. We
hypothesizes that this practice delays establishment of full enteral
feeding with associated complications. Objective: The effect on
time to reach full feeds (120 ml/k/day) with not checking gastric
residual volume in advancing feeds in preterm infants Methods:
Design: Single Centre, unmasked, parallel armed RCT Study site:
Neonatal intensive care unit at McMaster Children Hospital
Inclusion criteria: Infants recruited within 48hrs of birth with birth
weight (BW) 1500 grams <2000 grams. Exclusion criteria: Major
congenital malformations, asphyxia and BW <3rd percentile
Randomization: Variable number blocks stratified by BW Study
Intervention: Gastric residual volume assessed only with bloody
aspirates or with vomiting and abnormal abdominal examination.
Control: Gastric residual volume assessed routinely with feeding
advancement (Please see attached intervention document for
details) Results: 87 infants were enrolled. There was no
difference in time to reach full feeds in both groups.There was no
difference in episodes of feeding interruptions, incidence of sepsis,
reaching BW, and 120% of BW between two groups. However, two
infants in the control group developed NEC. Please see table 1 and
2 for results. Conclusion: There were no adverse events noted.
Time to achieve full enteral feeds was short in both groups. In
VLBW babies, time to reach full enteral feeds is longer and gastric
residuals could be a significant barrier to advancement of feeds.
This study serves as a feasibility trial to do multicenter RCT to
study effect of not checking gastric residual on time to reach full
feeds and incidence of NEC in VLBW babies. Acknowledgements:
We wish to acknowledge the contribution of medical and nursing
staff at Neonatal Intensive Care Unit at McMaster Children
Hospital to conduct the study. Contact Information:
[email protected]
Study Group
Results (Table 2)
Perinatal Epidemiology and Randomized Trials
[ROOM CANADA]
Dr. Martin Offringa
Research tools to facilitate interoperability in
neonatal drug research
Dr. Suzanne Tough
The All Our Babies Cohort: What we can Learn from
Longitudinal Follow-up
Dr. Thierry Lacaze
BEST ABCs: Benefits and Effectiveness of Support
offered Through A Breastfeeding Clinic study: A
Randomized Controlled Trial
Control Group
Baseline Characteristics (Table 1)
58
[233]
NURSING OVERTIME INCREASES THE RISK OF MEDICAL
INCIDENTS IN THE NICU. Marc Beltempo1, Guy Lacroix2, Michèle
Cabot3, Vicky Beauchesne 4, Bruno Piedboeuf3
1McGill University Health Center, Neonatology, 2Economics,
Université Laval, 3CHU de Québec, Neonatology, 4CHU de Québec,
Analyse et performance Clinique
Introduction: Adult studies have shown that increased fatigue in
workers is associated with a higher risk of error. Medical incidents
are preventable causes of adverse events in the hospital setting.
To our knowledge, no study has assessed the impact of nurse
overtime on the risk of medical incidents in the neonatal intensive
care unit (NICU). Objective: The objective of this study was to
assess the impact of nurse overtime on the risk of medical
incidents on all infants hospitalised in the NICU. Methods: We
conducted a retrospective study on all infants (n= 5,976) admitted
in the CHU de Québec NICU (capacity of 51 beds) from April 1st
2009 to March 31st 2013. Administrative data (overtime hours per
day) was obtained from the database Logibec, patient information
was obtained from Med-Echo and information on medical
incidents was obtained from the local incident reporting database
CNPRM 2015
Gesrisk. We assessed the association between administrative data
and patient outcomes by using logit and probit models. Twosample test of proportions and t test were used to assess risk
factors. Results: There were a total of 601 medical incidents that
were reported during the study period. The most common
categories of incidents were related to medication (78.9%),
feeding (7.7%) and treatment (7.1%). On average, incidents
happened on day of life 9.5 ± 1.1. A total of 428 (7.2%) patients
had at least one medical incident. Patients who had a medical
incident had significantly smaller gestational age (32.6 ± 0.25 wk
compared to 36.3 ± 0.1 wk; p<0.001)) and had a smaller birth
weight (2022.2 ± 55.3 g compared to 2786.7 ± 10.7 g; p<0.001)).
The average overtime as percentage of total daily hours of work
was 4.0 ± 3.4%. Days of higher overtime (expressed as percentage
of total worked hours) were significantly associated with an
increased risk of medical incidents (p=0.02). Adjusted risk of
suffering from a medical incident was significantly higher on days
of high overtime (>8% of all hours worked) (OR=1.34; P=0.03). On
days of very high overtime (>12% of all hours worked), the risk of
medical incidents was greatest (OR= 1.62; P=0.045). Conclusion:
In our study, periods of high overtime were significantly associated
with an increased risk of medical incidents in the NICU. This
suggests that re-organising the medical workforce to reduce
nursing overtime should become an integral part in improving
patient care and reducing risk of medical errors in the NICU.
Acknowledgements: We would like to thank the administration of
the hospital for their collaboration in facilitating data collection
and analysis. Contact Information: [email protected]
or late PTB at 34-36 weeks (aOR 0.92, 95% CI 0.89-0.94), but a
higher risk of very PTB < 32 weeks (aOR 1.09, 95% CI 1.04-1.16).
Infants of immigrant couples from Guyana, Trinidad & Tobago, the
Philippines and Jamaica had an increased risk of PTB at < 37 weeks
(Figure 1a), 34-36 weeks (Figure 1b) and < 32 weeks (Figure 1c).
On average, the rate of PTB < 37 weeks was 3% lower for
immigrant mothers in Ontario compared to the published rate for
their native country (Figure 2). This difference was wider for
countries with high native PTB rates (Figure 2). Conclusion:
Parental country of origin influences the risk of PTB, late PTB and
very PTB, especially for couples originating from Guyana, Trinidad
& Tobago, the Philippines and Jamaica. The rate of PTB may
decline after immigration to Canada, and more for parents who
come from countries with a high rate of PTB. Acknowledgements:
This work was supported by a grant from the Canadian Institutes
of Health Research (CIHR). Dr. Ray holds a CIHR Chair in
Reproductive and Child Health Services and Policy Research. Dr.
Urquia holds a CIHR New Investigator Award. Contact
Information: Joel G Ray [email protected]
[250]
MATERNAL AND PATERNAL COUNTRY OF BIRTH AND RISK OF
PRETERM BIRTH. Alison L. Park, MSc1, Marcelo L. Urquia, PhD2,
Joel G. Ray, MD MSc FRCPC3
1St. Michael’s Hospital; Institute for Clinical Evaluative Sciences,
Toronto, Ontario, 2Centre for Research on Inner City Health, St.
Michael’s Hospital; University of Toronto; Institute for Clinical
Evaluative Sciences, Toronto, Ontario, 3Departments of Medicine,
Health Policy Management and Evaluation, and Obstetrics and
Gynecology, St. Michael's Hospital; University of Toronto; Institute
for Clinical Evaluative Sciences, Toronto, Ontario
Introduction: Preterm birth (PTB) is a leading cause of infant
mortality and morbidity worldwide. The contribution of both
maternal and paternal ethnicity to PTB is unknown. Objective: To
examine if PTB rates of infants of immigrant parents originating
from the same country differ from the PTB rate of infants whose
parents are both Canadian-born. Methods: We included all
singleton and twin live births in Ontario from 2002-2011. There
were i) 670,492 infants born to two Canadian-born parents (the
referent), ii) 291,699 to immigrant parents from the same country,
iii) 68,589 to immigrant parents from different countries, iv)
77,537 to an immigrant mother & a Canadian-born father, v)
92,547 to a Canadian-born mother & an immigrant father. Logistic
regression analysis was used to generate adjusted odds ratios
(aORs) and 95% CIs for a) PTB < 37 weeks, b) late PTB 34-36 weeks,
and c) very PTB < 32 weeks gestation. Models were adjusted for
maternal age, paternal age, parity, marital status, income quintile,
newborn sex and twin pregnancy. For the top-50 immigrant
countries contributing births to Ontario, we compared the PTB
rates for infants born to immigrant parents from the same country
to the PTB rate of infants whose parents were both Canadianborn. Finally, we measured the differ ence in the calculated rate of
PTB for infants born in Ontario for each maternal immigrant
country minus the published rate for their native country.
Results: Overall, compared to infants whose parents were both
Canadian-born, those of immigrant parents from the same country
had at lower risk of PTB < 37 weeks (aOR 0.94, 95% CI 0.92-0.96)
CNPRM 2015
59
1D.B.
Fell - BORN Ontario, 2M. Teitelbaum - CHEO, 3A.A. Yuzpe Olive Fertility , 4M. Gysler - ISIS Fertility Clinic, 5M.C. Walker BORN Ontario
Introduction: In 2013, a new web-based register for assisted
reproductive technologies (ART) began collecting data on
treatment cycles from all 35 Canadian clinics providing these
services. Objective: To describe the features of the Canadian
Assisted Reproductive Technologies Register Plus (CARTR Plus), the
types of ART treatments initiated in 2013, and treatment
outcomes. Methods: Data from treatment cycles initiated
between January 1st and December 31st, 2013 were descriptively
summarized. Treatment cycle information included patient
demographics, clinical characteristics of treatment (e.g., method
of oocyte insemination, fresh versus frozen embryo transfer cycle,
number of embryos transferred) and treatment outcomes (e.g.,
whether the treatment resulted in a clinical pregnancy, plurality of
the pregnancy). Data were validated by each clinic prior to
submission. Results: Novel features of the new CARTR Plus
include quarterly data submission, the ability to follow patients
longitudinally to calculate cumulative pregnancy rates, and
automatic linkage of ART pregnancies to the provincial birth
registry to ascertain birth outcomes for Ontario clinics
(representing approximately half of all ART pregnancies). All
Canadian ART clinics participated in this voluntary registry in 2013
and almost all clinics (33/35) submitted 2013 treatment cycle data
in time to be included in this report. There were 25,767 treatment
cycles, over half of which were fresh in vitro fertilization cycles
(IVF) using autologous oocytes (58%), followed by frozen embryo
transfer (FET) cycles using autologous oocytes (30%). The clinical
pregnancy rates per initiated cycle were 28% and 32%,
respectively, for these treatment cycles. Among ongoing viable
pregnancies, the proportion with documentation of more than one
fetal heart be at on ultrasound (i.e., multifetal pregnancy) was 17%
and 15% for IVF and FET cycles using autologous oocytes,
respectively. The proportion of multifetal pregnancies was lower in
Quebec (where ART is publicly-funded) than in the rest of Canada.
Conclusion: This new national ART register has enhanced features
that will support more timely and robust reporting and research
on ART outcomes in Canada. The automatic linkage of ART
pregnancies from Ontario clinics to the provincial birth registry will
ensure more complete and timely follow-up of birth outcomes in
the province and enable longitudinal research on health outcomes
of babies born following this technology. Acknowledgements:
We are grateful to the Canadian ART clinics for their ongoing
participation in this important registry. Contact Information:
Andrea Lanes [email protected]
[284]
ASSISTED REPRODUCTIVE TECHNOLOGY IN CANADA: RESULTS
FROM THE NEW CANADIAN ASSISTED REPRODUCTIVE
TECHNOLOGIES REGISTER PLUS (CARTR PLUS). A. Lanes University of Ottawa/Epidemiology and Community Medicine;
BORN Ontario1, A.E. Sprague - BORN Ontario2, F. Bissonette - OVO
Fertility3, M.C. Leveille - Ottawa Fertility Clinic4, M. Johnson BORN Ontario5
60
[307]
CIRCULATING INFLUENZA VIRUS AND ADVERSE PREGNANCY
OUTCOMES: AN ECOLOGIC TIME-SERIES STUDY. Deshayne B
Fell1, David L Buckeridge1, Robert W Platt1, Jay S Kaufman1, Olga
Basso1, Kumanan Wilson1
1McGill University / Department of Epidemiology and Biostatistics
Introduction: Although pregnant women are considered a highrisk group for severe illness and complications related to influenza,
risks to the fetus are unclear. Since influenza activity affects the
entire population and is routinely measured at the populationlevel through a system of sentinel laboratories, we used an
ecologic time-series approach to assess the association between
influenza and adverse pregnancy outcomes. Objective: To
determine whether weekly variation in population-level influenza
virus circulation is associated with population-level rates of
preterm birth, stillbirth and perinatal death. Methods: We
applied an ecologic time-series design over 10 years,
encompassing seasonal influenza epidemics and the 2009-2010
H1N1 pandemic. Using a province-wide hospitalization database of
CNPRM 2015
linked maternal and newborn records, we assembled a cohort of
all live births and stillbirths delivered in Ontario hospitals between
2003 and 2012. Provincial influenza surveillance data were used to
measure population-level exposure to influenza, defined as the
proportion of specimens testing positive for influenza A or B
viruses in each influenza surveillance week. Counts of preterm
birth, stillbirth, and perinatal death were aggregated into time
series indexed by influenza surveillance week. We assessed
exposure as a continuous variable during three different time
windows (week before birth, month before birth, and first month
of gestation) using Poisson regression models offset by the
number of ongoing gestations at risk for each outcome, and
adjusted for underlying seasonal and long-term temporal patterns
in outcomes, and respiratory syncytial viral co-circulation.
Results: Across the 10 years of the study, there were 11 defined
influenza seasons, including the two waves of the 2009-2010 H1N1
pandemic. The population-level rate of preterm birth was not
associated with the ecologic measure of influenza exposure during
the week before birth (adjusted rate ratio: 1.01, 95% confidence
interval: 0.99-1.02), nor in any of the other exposure time
windows. These findings were robust to alternate specification of
the exposure measure in sensitivity analyses. Stillbirth and
perinatal death rates were similarly not associated with influenza
activity in late pregnancy exposure windows. We were unable to
assess stillbirth and perinatal death in relation to influenza
circulation during the first month of gestation due to data
limitations. Conclusion: In this study, we found no association
between short-term variation in population-level influenza activity
and rates of preterm birth, stillbirth or perinatal death.
Acknowledgements: Ms. Fell was supported by a CIHR Doctoral
Award while conducting this study. Contact Information:
[email protected]
[377]
5-MINUTE APGAR SCORE AS A MARKER FOR DEVELOPMENTAL
VULNERABILITY AT 5 YEARS OF AGE. Neda Razaz1, W. Thomas
Boyce2, Marni Brownell3, Douglas Jutte4, Helen Tremlett5, Ruth
Ann Marrie6, KS Joseph7
1School of Population and Public Health, University of British
Columbia, 2Departments of Pediatrics and Psychiatry, School of
Medicine, University of California, San Francisco, 3Department of
Community Health Sciences, College of Medicine, University of
Manitoba, Winnipeg, Canada , 4School of Public Health, University
of California, Berkeley, California, 5Brain Research Centre and
Department of Medicine (Division of Neurology), Faculty of
Medicine, University of British Columbia, Vancouver, Canada ,
6Departments of Internal Medicine and Community Health
Sciences, College of Medicine, University of Manitoba, Winnipeg,
Canada, 7Department of Obstetrics & Gynaecology, Faculty of
Medicine, University of British Columbia, Vancouver, Canada
Introduction: The Apgar score at birth was initially developed to
assess the immediate condition of the newborn. It has been
examined in relation to various health outcomes, but its
association with childhood developmental outcomes remains
unclear. Objective: We carried out a population-based study to
examine the role of the 5-minute Apgar score as a marker for
developmental vulnerability at 5 years of age. Methods: We
conducted a population-based retrospective cohort study in
Manitoba, Canada. All children born between January 1999 and
December 2006, with a gestational age 37 weeks, a documented
5-minute Apgar score and a completed Early Development
Instrument (EDI) assessment at 5 years of age were included.
Logistic regression was used to assess the association between
Apgar score and vulnerability on each domain of the EDI. The
performance of an Apgar-based prognostic model for identifying
developmental vulnerability was assessed in terms of calibration
ability, stratification capacity, and classification accuracy. Results:
Most (81.5%) children in the study (n=33,883) had a 5-minute
Apgar score of 9; 1% of children scored <7, 11.9% with scores of 7
or 8 and 5.6% had an Apgar score of 10 (Figure 1). Children with
Apgar scores of 7, 8 or 9 had higher odds of vulnerability on the
physical domain compared with those scoring 10 (adjusted odds
ratio [aOR] for an Apgar score of 7=1.45, 95% confidence interval
[CI] 1.10-1.91; aOR for an Apgar score of 8=1.24, 95% CI 1.03-1.49;
and aOR for an Apgar score of 9=1.23, 95% CI 1.05-1.44). Similarly,
those with Apgar scores of 7, 8 and 9 had higher odds of
vulnerability on the emotional domain (aOR for an Apgar score of
7=1.60, 95% CI 1.21-2.10; aOR for an Apgar score of 8=1.24, 95% CI
1.03-1.50; and aOR for an Apgar of 9=1.20, 95% CI 1.03-1.41).
Although the Apgar score-based prognostic model had reasonable
calibration ability and risk-stratification accuracy for identifying
developmentally vulnerable children, classification accuracy was
poor (e.g., sensitivity for physical vulnerability 19%, 95% CI 18%20%). Conclusion: The 5-minute Apgar score across its entire
range was inversely associated with a risk of developmental
vulnerability at 5 years of age, with each incremental worsening in
physiologic dysfunction soon after birth associated with a higher
risk for developmental vulnerability in early childhood. While
Apgar-based prognostic models may not be sufficiently sensitive
for identifying developmentally vulnerable infants for early
intervention programs, the Apgar score at birth might serve as a
population level indicator of developmental risk. Further studies
are warranted. Acknowledgements: This work was supported by
the Canadian Institute of Health Research (MOP-119393).
Contact Information: [email protected]
[430]
THE BLACK-WHITE DISPARITY IN PRETERM BIRTH: A UNIQUELY
AMERICAN PROBLEM?
Britt McKinnon1, Seungmi Yang2, Tracey Bushnik3, Amanda
Sheppard4, Michael S. Kramer5, Jay S. Kaufman2
1McGill University/Institute for Health and Social Policy, 2McGill
University/Epidemiology, Biostatistics and Occupational Health,
3Health Analysis Division, Statistics Canada, 4AboutKidsHealth, The
Hospital for Sick Children, 5McGill University/Pediatrics and
Epidemiology, Biostatistics and Occupational Health
Introduction: A higher risk of preterm birth (PTB) in blacks vs
whites is well established in the United States (US). While Canada
consistently reports lower average rates of PTB than the US,
differences in PTB risk by maternal race/ethnicity have not been
previously reported. Objective: To report nationally
representative rates of PTB and very PTB in black vs white mothers
in Canada in both absolute and relative terms, and to compare the
disparities with those estimated for the US. Methods: We used
data on singleton live births to non-Hispanic black and nonHispanic white mothers in Canada and the US between May 2004
and May 2006. The Canadian data come from a cohort linking
Canadian birth and infant death registrations and a 20% sample
completing the long form of the 2006 Canadian census, while US
CNPRM 2015
61
data were obtained from the National Center for Health Statistics’
linked birth/infant death files. For both countries, gestational age
was based on a clinical/obstetric estimate of gestational duration.
We estimated crude and adjusted risk differences (RD) and risk
ratios (RR) for PTB (<37 weeks vs. 37-41 weeks gestation) and very
PTB (<32 weeks vs. 33-41 weeks) for infants born to black vs white
mothers in each country. Adjusted models for the US were
standardized to the covariate distribution of the Canadian cohort
to facilitate comparability. Results: In Canada, 8.6% and 5.8% of
infants born to black and white mothers were preterm, while
corresponding figures for the US were 12.7% and 8.0%. For PTB,
crude RRs were 1.47 (95% CI: 1.31, 1.63) for Canada and 1.57
(1.56, 1.58) for the US (heterogeneity p-value=0.213), while crude
RDs were 2.75 (1.84, 3.65) for Canada and 4.65 (4.58, 4.72) for the
US (p<0.001). Crude RRs for very PTB were also similar between
the two countries, while RDs were greater in the US. Adjusted RR
estimates for PTB (p=0.066) and very PTB (p=0.005) were slightly
higher in Canada than the US, while adjusted RDs were similar
between the countries. Conclusion: Relative black-white
disparities in PTB and very PTB are similar in magnitude in Canada
and the US. Absolute disparities are smaller in Canada, reflecting
lower overall rates of PTB in Canada vs the US for both blacks and
whites. Contact Information: [email protected]
Preeclampsia and Placenta Development
[ROOM LE CLUB]
Pr. Benoit Barbeau
Association between Human Endogenous Retrovirus
proteins, placenta development and pre-eclampsia
Dr. Isabella Caniggia
Death by Sphingolipids: Preeclampsia versus IUGR
Mrs. Malia Murphy
Examining non-traditional markers of cardiovascular
risk after pre-eclampsia
[246]
DIETARY INTAKES OF IRON AND IRON STATUS IN PREGNANT
CANADIAN WOMEN FROM THE MIREC STUDY: ASSOCIATIONS
WITH MATERNAL CHARACTERISTICS AND PREGNANCY
OUTCOMES. Anne-Sophie Morisset1, Hope A. Weiler2, Lise
Dubois3, Jillian Ashley-Martin4, Linda Dodds4, William D. Fraser1
1Sainte Justine University Hospital Research Center, University of
Montreal, Montreal, Canada, 2School of Dietetics and Human
Nutrition, McGill University, Montreal, Canada, 3Department of
Epidemiology and Community Medicine, Faculty of Medicine,
University of Ottawa, 4Perinatal Epidemiology Research Unit,
Dalhousie University, Halifax, Nova Scotia, Canada
Introduction: To examine iron intake from food and supplements
as well as functional iron status in relationship with maternal
characteristics and pregnancy outcomes. Objective: Iron intake
in the prenatal period is an important determinant of fetal growth
and development. Methods: Data were collected in the
Maternal-Infant Research on Environmental Chemicals (MIREC)
Study, a cohort study of 2001 pregnant women recruited from 10
Canadian sites between 2008 and 2011. Analyses included 1186
mothers who had a singleton live-births, and completed dietary
surveys. Iron intake from diet was estimated using a one-month
semi-quantitative food frequency questionnaire (FFQ) between 16
and 21 weeks. Iron intake from supplements was obtained from a
questionnaire completed between 6 and 13 weeks. Women were
62
divided into 2 groups according to the median total iron intake.
Mean haemoglobin (Hb) was measured at 14.1±7.6 weeks of
pregnancy. Anemia was defined as a Hb value 110 g/L. Results:
Median total iron intake was 33.7 mg (11.9-37.1 mg), with a
median of 74.2% (0-81.3%) of the total from dietary supplements.
67.7% of the women were taking a supplement/multivitamin
containing at least 16 mg iron. Low total iron intake was
associated with age below 30 years, having less than a university
education, family income below $60 000, and BMI over 25 kg/m2
(p<0.001 for all comparisons). Mean Hb was 124.6±9.9 g/L, and 82
cases of anemia (7.8%) were observed. Maternal Hb
concentrations were lower in mothers over 30 years of age
(124.1±9.9 vs. 126.6±9.7 g/L, p=0.0003). No association was
observed between Hb concentration and iron intake (total, diet, or
supplement). No differences were found between women with
low vs. high total iron intake in the prevalence of small-forgestational (SGA) or large-for-gestational age (LGA) birth, preterm
birth or excessive gestational weight gain. A higher prevalence of
glucose intolerance (gestational diabetes mellitus (GDM) and
impaired glucose tolerance (IGT)) was found among women with
lower iron intake from diet only compared to women with higher
dietary iron intake (12.0 vs. 5.4%, p=0.0007); this association was
not observed between women with and without anemia.
Conclusion: No association was found between iron intake (total,
diet, or supplement) and functional iron status as measured by Hb
concentrations. Lower total iron intake was found in heavier,
younger women with lower levels of education and family income.
Our finding that women with lower iron intake from diet had a
higher prevalence of glucose intolerance requires further
investigation. Acknowledgements: Fundings: Chemicals
Management Plan of Health Canada,Canadian Institutes for Health
Research and Ontario Ministry of the Environment. Contact
Information: [email protected]
[293]
PREGNANCY-RELATED CHANGES IN THE MATERNAL GUT
MICROBIOTA AND IMPACTS OF A PERICONCEPTIONAL HIGH FAT
DIET. Waiha Gohir1, Fiona J Whelan 1, Michael G Surette2,
Caroline Moore1, Jonathan Schertzer3, Deborah M Sloboda3
1Department of Biochemistry & Biomedical Sciences, McMaster
University, Hamilton Canada, 2Department of Biochemistry &
Biomedical Sciences, and Department of Medicine, McMaster
University, Hamilton Canada, 3Department of Biochemistry &
Biomedical Sciences, and Department of Pediatrics and Obstetrics
and Gynecology, McMaster University, Hamilton Canada
Introduction: Recent studies have demonstrated pregnancy
associated changes in the maternal gut microbiome. When these
shifts occur and whether pregnancy-associated microbial shifts are
influenced by periconceptional nutrition is unknown. Objective:
Our aim was to investigate maternal gut microbiota changes over
the course of pregnancy and how pregnancy and diet interact to
influence its composition, using a mouse model of diet induced
obesity. Methods: Female C57BL/6 mice were fed either a control
or a high fat diet for 8-10 weeks prior to mating (n=5 per group).
All females were mated and pregnancy confirmed, maternal
weight gain and food intake were recorded, and fecal pellets
collected at 0.5, 5.5, 10.5 and 15.5 days of pregnancy. The
microbial composition and predicted metabolic functionality of the
maternal gut was determined via sequencing of the variable 3
region of the 16S rRNA gene. Results: As early as 0.5 days of
gestation, shifts in the pregnant microbiome were observed when
compared to non-pregnant mice; shifts that were modulated by
advancing gestation. We observed a significant diet x pregnancy
interaction where, in some bacterial species, pregnancy-induced
changes in microbial abundance were dependent upon the
maternal preconception diet. Compared to control fed pregnant
CNPRM 2015
mice, high fat fed pregnant mice demonstrated significantly
greater shifts in their gut microbiota as indicated by beta diversity
metrics and statistically significant taxonomic differences. Using
Picrust analysis, we observed significant elevations in sequences
mediating fatty acid and sulfur-containing amino acid metabolism,
glycolysis and gluconeogenesis, cysteine and methionine
metabolism, unsaturated fatty acid biosynthesis, and in the
synthesis and degradation of ketone bodies in high fat versus
control fed pregnant mice. Conclusion: Our results demonstrate
that diet and pregnancy have interactive effects on the
composition of the female gut microbiota in mice. We show that
pregnancy-induced changes in the gut microbiota occur
immediately at the onset of pregnancy, and are vulnerable to
modulation by diet. Future studies are required to determine
whether these shifts result in changes in maternal nutrient
absorption and how maternal dietary induced shifts in the gut
microbiota impact fetal growth and placental function.
Acknowledgements: I would like to members of the Sloboda Lab
for their assistance. Contact Information:
[email protected]
[346]
MAGNETIC RESONANCE IMAGING OF GROWTH RESTRICTED
FETAL GUINEA PIGS DUE TO PLACENTAL INSUFFICIENCY. Kevin J
Sinclair1, Lanette J Friesen-Waldner1, Colin M McCurdy1, Curtis N
Wiens2, Trevor P Wade1, Barbra de Vrijer3, Timothy RH Regnault3,
Charles A McKenzie1
1Medical Biophysics, Western University, London, Ontario, Canada,
2Radiology, University of Wisconsin, Madison, Wisconsin, United
States, 3Obstetrics and Gynaecology, Western University, London,
Ontario, Canada
Introduction: Intrauterine growth restricted (IUGR) fetuses are at
an increased risk for later life metabolic and cardiovascular
disease. IUGR caused by placental insufficiency reduces nutrient
and oxygen transport to the developing fetus. Brain growth is
often prioritized at the expense of abdominal organs and muscle
tissue, leading to asymmetrical growth restriction. Adaptations to
this suboptimal in utero environment, such as altered fat storage,
can progress into postnatal life, setting up the offspring for later
life disease. Magnetic resonance imaging (MRI) is a useful tool for
studying fetal anatomy due to its excellent soft tissue contrast. It is
especially useful in studying fat deposition as its ability to separate
water from fat signals allows for analysis of adipose tissue volumes
as well as organ fat content. Objective: To utilize MRI to observe
developmental abnormalities such as asymmetrical growth and
altered fat deposition in utero. Methods: Pregnant guinea pigs
were anaesthetized and scanned ~60 days into an ~68 day
gestation. Two maternal groups were scanned: a uterine artery
ablation group (N = 7, 24 pups) and a Sham Control group (N = 3,
13 pups). T1- and T2-weighted images were acquired with voxel
dimensions = 0.875x0.875x0.9mm3 for both acquisitions. IDEAL
water-fat images were also collected for each guinea pig with
voxel dimensions = 0.933x0.933x0.9 mm3. The T1- and T2weighted images (Figure 1a,b) were used to segment fetal liver,
brain, and total fetal volumes. IDEAL fat-only images (Figure 1c)
were used to segment total and visceral fetal adipose volumes.
Proton density fat fraction maps (Figure 1d) were used to obtain
liver fat fractions. Results: To represent 25% of the study
population, IUGR was defined as having a brain to liver volume
ratio above 0.80. Thus, the study population consisted of 8 IUGR
and 28 normal pups. Expressed as a percent of fetal volume, IUGR
fetuses had significantly smaller livers (5.3±0.8% vs 6.3±1.1%,
p=0.03) but larger brains (4.7±0.8% vs 3.6±0.5%, p<0.001) than the
normal group. IUGR pups had less total adipose tissue as a percent
of fetal volume than normals (9.0±3.9% vs 13.6±4.0%, p=0.04), but
no difference was seen in the proportion of adipose tissue
deposited in visceral depots (p=0.99). Furthermore, liver fat
fraction was not significantly different between groups (22±9% vs
23±5%, p=0.66). Conclusion: We have demonstrated the use of
MRI for detecting developmental differences in IUGR fetuses in
guinea pigs in utero. Future studies relating the differences seen in
utero to those seen after birth, as well as translation to human
imaging, are possible. Acknowledgements: GE Healthcare,
NSERC, CIHR, ORF and the Canada Research Chairs Program.
Contact Information: Kevin Sinclair [email protected]
[362|
THE ASSOCIATION BETWEEN MATERNAL ANTIOXIDANT LEVELS IN
MID-PREGNANCY AND PREECLAMPSIA. Jacqueline M. Cohen1,
Michael S. Kramer1, Robert W. Platt1, Olga Basso1, Susan R. Kahn1
1McGill University, Department of Epidemiology, Biostatistics and
Occupational Health
Introduction: Endothelial dysfunction is a feature of the
pathophysiology of preeclampsia hypothesized to be due to
oxidative stress. Antioxidant molecules including vitamins A and E
defend against the damaging effects of reactive oxygen species.
Most studies to date have measured antioxidant vitamin levels
after the clinical manifestation of the syndrome. We hypothesized
that maternal antioxidant levels would be lower in mid-pregnancy
among women eventually developed preeclampsia. Objective: To
assess whether antioxidant levels in mid-pregnancy are associated
with risk of preeclampsia. Methods: We conducted a case-control
study, nested within a cohort of pregnant women in Montreal.
Blood samples were obtained at 24-26 weeks and assayed for nonenzymatic antioxidant levels among cases of preeclampsia (n=111)
and unaffected controls (n=441). Women who developed
gestational hypertension alone were excluded. We used logistic
regression with the z-score of each antioxidant as the main
predictor variable for preeclampsia risk. We also stratified cases of
early-onset (<34 weeks) and late-onset preeclampsia and carried
out multinomial logistic regression. We summed levels of
correlated biomarkers (r-squared>0.3) and log-transformed
positively skewed distributions. We adjusted for body mass index,
primiparity, pre-existing diabetes, chronic hypertension, smoking,
and proxies for ethnicity and socioeconomic status. Results:
Lutein was significantly negatively associated with preeclampsia
risk; OR=0.6 (95% CI 0.5-0.8) per SD. We found no significant
associations for α-tocopherol, α-tocopherol/cholesterol, γtocopherol, retinol, lycopene, or carotenoids (sum of α-carotene,
β-carotene, anhydrolutein, α-cryptoxanthin, and β-cryptoxanthin)
in adjusted analyses. In multinomial logistic models, the relative
risk ratios (RRR) for early-onset preeclampsia were further from
the null than for late-onset preeclampsia in all cases except
lycopene. Only lutein was significantly associated with both early
and late-onset subtypes. Retinol and α-tocopherol/cholesterol and
were significantly associated with early- but not late-onset
preeclampsia. Conclusion: Most of the antioxidants were more
strongly associated with early-onset preeclampsia, suggesting that
oxidative stress may play a greater role in the pathophysiology of
early-onset preeclampsia. Alternatively, reverse causality may
explain this pattern. However, lutein was associated with both
early and late-onset subtypes and therefore may be a promising
nutrient to consider in future prevention trials, if future
prospective studies corroborate this finding. Acknowledgements:
CNPRM 2015
63
This study was funded by the March of Dimes Foundation and the
Canadian Institutes of Health Research. Contact Information:
[email protected]
[376]
AN INTEGRATED TRANSCRIPTIONAL AND CLINICAL ANALYSIS
REVEALS MULTIPLE MOLECULAR SUBTYPES OF PREGNANCY
PATHOLOGIES. Brian Cox1, Katherine Leavey2, Shannon
Bainbridge3
1Univeristy of Toronto, Physiology, 2University of Toronto,
Physiology, 3University of Ottawa
Introduction: Despite the high prevalence of diseases of
pregnancy, few diagnostics are available beyond the detection of
overt symptoms of disease, such as hypertension, reduced fetal
growth or preterm labor. Worse, no cures exist for the more
severe pathologies beyond premature delivery to reduce maternal
and infant morbidity and morality. While the placenta is often
considered the epicentre of many pregnancy pathologies, the
literature is fraught with contradiction and inconsistencies, and we
lack a molecular understanding of their etiologies. Objective: To
address the molecular complexity of placenta-related pathologies
of pregnancy, we hypothesize that they are multifactorial and
involve an unknown number of different molecular subclasses. We
propose that unsupervised analysis of integrated genomic and
clinical data will lead to the identification of the molecular origins
of these pathologies. Methods: gene expression data was
collected for 330 placenta samples from a broad range of
pathologies, representing preterm delivery, preeclampsia (PE) and
intrauterine growth restriction (IUGR). Of these, 157 samples were
drawn from the RCWIH BioBank and were annotated with over
200 clinical attributes from associated clinical records. The data set
was then subjected to unsupervised multivariate model-based
clustering, gene-set enrichment analysis, and correlative analysis
between cluster membership and the clinical data. Sixteen
samples were analyzed by array Comparative Genomic
Hybridization. Results: Clustering revealed five distinct molecular
subclasses of placental gene expression defining a landscape of
adverse and normal pregnancy outcomes. Preeclampsia fell into
four clusters, including a “canonical” cluster with elevated levels of
known PE markers and clinical presentation of higher body weight,
smaller placental weight, and early delivery. Several novel PE
clusters were also observed including 1) a viral or immunological
reaction pathology associated with IUGR (r=0.78, p<0.005); 2) a
cluster of chromosomal abnormalities supported by aCGH analysis;
and 3) a possible maternal origin of the pathology associated with
normal birth weight and term deliveries. Additionally, two preterm
labour clusters were observed, one of which was associated with
chorioamnionitis (12/15 cases, p<0.001) and delivery before the
30th week of gestation. Conclusion: We have identified that
significant molecular heterogeneity exists for common diseases of
pregnancy. Our results inform on new diagnostic candidates and
molecular pathways involved in these pathologies.
Acknowledgements: Funding provided by CIHR. Contact
information: Brian Cox [email protected]
64
[447]
A NOVEL MECHANISM FOR VASCULAR TONE REGULATION IN
ARTERIES BY SPHINGOSINE 1-PHOSPHATE THROUGH
ENDOTHELIAL BARRIER CONTROL AND NITRIC OXIDE
PRODUCTION. Daniel Kerage1, Megan Brown2, Randi B. Gombos3,
Denise G. Hemmings1
1University of Alberta/Obstetrics and Gynecology, Medical
Microbiology and Immunology, 2University of Alberta/Obstetrics
and Gynecology, 3University of Alberta/Obstetrics and Gynecology,
Physiology.
Introduction: Increased endothelial permeability is associated with
vascular complications but the mechanisms are unclear. While
leakage through the endothelium of veins into surrounding tissues
leading to edema is a well-known complication of permeability,
little is known about the impact of increased endothelial
permeability in resistance arteries. Sphingosine 1-phosphate (S1P)
is a bioactive lipid that both disrupts and enhances the endothelial
barrier through a balance of interactions with three receptors on
the endothelium, S1P1, S1P2 and S1P3, making it an ideal
regulator of endothelial permeability. Many factors such as high
S1P concentrations, thrombin, tumor necrosis factor-alpha,
vascular endothelial growth factor and infections increase
endothelial permeability, but the impact of these factors along
with vasoconstrictors on vascular tone in intact arteries is not
known. Objective: We hypothesized that increasing endothelial
permeability in resistance arteries would allow circulating
vasoconstrictors access to vascular smooth muscle cells leading to
increased vascular tone. Conversely, increasing endothelial barrier
function would prevent this access and S1P would be a major
regulator of this process through S1P1 and S1P3 receptors.
Methods: Endothelial permeability and vascular tone were
simultaneously measured in resistance arteries from control and
S1P3 knockout mice, mounted on a pressure myograph, using
novel methodology. S1P, thrombin, lipopolysaccharide (LPS) or
cytomegalovirus glycoprotein B (gB) with or without a
vasoconstrictor (U46619) were co-infused with a permeability
tracer inside pressurized resistance arteries. Inhibitors were
VPC23019 (S1P1/3), SQ29548 (thromboxane receptor) and LNAME (NO synthase). S1P1 was activated with the S1P1 agonist,
SEW2871. Results: Although intraluminal infusion of U46619
alone had no effect on vascular tone in resistance arteries, coinfusion with S1P (1µM) led to S1P3-dependent leakage of U46619
that induced vasoconstriction. S1P alone stimulated NO
production that reduced endothelial permeability and induced
vasodilation that modulated overall vascular tone. Co-infusion of
S1P (10 µM), thrombin, LPS or gB with U46619 also increased
vascular tone. The thrombin effects were blocked by co-infusion of
SEW2871. Conclusion: This study establishes a new paradigm for
control of vascular function in resistance arteries by S1P-regulated
endothelial permeability. Pathological increases in vascular tone
may be improved by targeting S1P receptors to reduce endothelial
permeability. These novel results inform new therapeutic solutions
for vascular-related complications including preeclampsia and
intrauterine growth restriction. Acknowledgements: Supported
by CIHR, NSERC and WCHRI. Contact Information: Dr. Denise G.
Hemmings [email protected]
CNPRM 2015
POSTER SESSIONS ABSTRACTS
1Queen's
TUESDAY EVENING, FEBRUARY 24TH
Developmental/Transgenerational Origins of
Health and Diseases
[244]
EPIGENETIC CHANGES ESTABLISHED IN UTERO THAT CONTRIBUTE
TO AN ALTERED ADULT METABOLISM.
University of Western Ontario1
1Children's Health Research Institute
Introduction: Intrauterine Growth Restriction (IUGR) is a
pregnancy condition where the fetus fails to grow to the full
potential and is associated with an increased risk for metabolic
disorders in adulthood. Our lab has established a murine model of
IUGR using a 30% maternal total-nutrient reduction (MNR)
resulting in offspring that acquired glucose intolerance at six
months but have no impairment in insulin secretion, suggesting
that peripheral tissues may be desensitized to circulating insulin.
Objective: The liver is a peripheral tissue that responds to insulin
and plays a key role in regulating metabolism. We hypothesized
that epigenetic modifications were established in the liver in
response to intrauterine nutrient-restriction that result in
persistent gene changes, altering the function and predisposing
the mice to glucose intolerance. Methods: Pregnant females
were randomly assigned to an ad libitum fed or the nutrientrestricted group at E6.5. At E18.5 ten litters were euthanized to
obtain pup weights and embryonic tissue. Remaining litters were
carried to term. At one month, liver RNA was sequenced from
random pups (control N=3, MNR N=6). At six months, IP-GTT was
preformed. Serum peptides ghrelin, leptin, GLP-1, GIP, insulin,
glucagon, leptin, PAI-1 and resistin, along with total cholesterol
were also measured at six months. Based on IP-GTT, six-month
liver RNA from intolerant MNR (N=4), tolerant MNR (N=4) and
controls (N=4) were sequenced. Differential expression and
sample clustering based on gene transcription was detected with
DESeq2 and Aldex2 (FDR0.1). Results: The six-month old MNR
offspring had significantly higher area under the curve (1360 +/78.22) than controls (957.1 +/- 96.87, p-value = 0.0033) during IPGTT, suggesting a mild glucose intolerance. However, individual IPGTT results revealed a spectrum of responses to the glucose bolus.
Overall six-month liver transcriptome profiles were not dependent
on maternal nutrition or IP-GTT results. Relative to controls, 69
transcripts with +/- 2-fold change were differentially expressed in
tolerant, intolerant or all MNR offspring. These transcripts were
involved in lipid and glucose metabolism, circadian rhythm, injury
response and immune function, but none of the candidate
transcripts were differentially expressed at one month.
Conclusion: The predisposition to acquire glucose intolerance in
the nutrient-restricted offspring was not due to persistent gene
expression changes in the liver. Future studies into other
peripheral organs such as the fat and skeletal muscle may provide
the link between nutrient-restriction in utero and glucose
tolerance in adulthood. Acknowledgements: I would like to thank
Dr. Victor Han and other Han lab members. Contact Information:
Bethany Radford (Biochemistry, University of Western Ontario)
[email protected]
[310]
MATERNAL HYPERTENSION PROGRAMS INCREASED STROKE
SUSCEPTIBILITY IN ADULT OFFSPRING. Nicole M. Ventura1, Albert
Y. Jin2, Nichole T. Peterson3, M. Yat Tse1, R. David Andrew1, Jeffrey
D. Mewburn4, Stephen C. Pang1
University/Department of Biomedical and Molecular
Sciences, 2Queen's University/ Kingston General
Hospital/Department of Biomedical and Molecular Sciences,
Department of Medicine (Neurology), 3Queen's University/
Kingston General Hospital/Department of Medicine (Neurology),
4Queen's University/Cancer Research Institute
Introduction: Adverse maternal influences during critical periods
of embryonic development have shown to have implications on
disease risk later in the offspring’s adult life. Due to the
developmental plasticity of the embryo, changes to the
intrauterine environment may stimulate fetal adaptations
resulting in permanent alterations in fetal physiology. Objective:
Our objective was to determine whether maternal hypertension
programs offspring susceptibility to tissue damage following
stroke in adulthood using a mouse model of chronic hypertension;
the atrial natriuretic gene-disrupted (ANP-/-) mouse. Methods:
Genetically identical heterozygous (ANP+/-) offspring were
generated by two means; (1) ANP wild-type (ANP+/+) females
were mated with ANP-/- males to produce offspring from
normotensive mothers (ANP+/-WT) (n=12), and (2) ANP-/- females
were mated with ANP+/+ males to produce offspring from
hypertensive mothers (ANP+/-KO) (n=12). Transient cerebral
ischemia was induced in male ANP+/-WT and ANP+/-KO offspring
between 13-15 weeks of age by temporary left middle cerebral
artery occlusion (MCAO). Sham operations were used as controls.
Following 24hr reperfusion, organ wet-weights were recorded and
infarct volumes measured by triphenol- tetrazolium chloride (TTC)
methods. Expression of the nitric oxide synthase (NOS) and
endothelin (ET) vasoactive systems was analyzed using
quantitative real-time PCR (qPCR) to assess differences in
cerebrovascular response between groups. In addition, the mRNA
expression of Na+/K+ ATPase channel isoforms ATP1a1, ATP1a3
and ATP1b1 was assessed. Confocal microscopy was conducted to
measure microvascular structure between heterozygote groups.
Results: Organ wet-weights did not differ between groups.
Significantly larger infarct volumes were observed in ANP+/-KO
mice (P=0.0034), suggesting increased susceptibility to stroke
tissue injury. Cerebral mRNA expression of Nos3 and Et-1 target
genes significantly increased in the ANP+/-KO-MCAO group as
compared to their sham controls (P<0.05) along with a trend
towards significance when compared to ANP+/-WT- MCAO mice.
No significant changes were observed in the Na+/K+ ATPase
channel isoforms, suggesting altered cerebrovascular adaptation
in ANP+/-KO mice without neuronal influences. Additionally, no
differences were observed in cerebral microvascular structure
following vessel volume analyses. Conclusion: Our data suggests
that maternal hypertension during pregnancy programs adult
offspring to be more vulnerable to cerebral tissue damage
following stroke by demonstrating increased infarct volume and
mRNA expression in target genes linked to increased stroke risk in
ANP+/-KO mice. Acknowledgements: Funding Source: Canadian
Foundation for Innovation (CFI). Contact Information: Nicole M
Ventura [email protected]
[316]
ALTERED MATERNAL VASCULAR FUNCTION IN A RAT MODEL OF
FETAL GROWTH RESTRICTION. Mais Aljunaidy1, Jude Morton2,
Sandra T. Davidge1
1Department of Obstetrics/Gynaecology, Department of
Physiology, Women and Children’s Health Research Institute;
University of Alberta, 2Department of Obstetrics/Gynaecology,
Women and Children’s Health Research Institute; University of
Alberta
CNPRM 2015
65
Introduction: Complications of pregnancy, such as preeclampsia
and intrauterine growth restriction, are a leading cause of both
maternal and fetal, morbidity and mortality and, further, can
affect the health of the offspring well into adult life. A recent study
has shown that a low oxygen environment during pregnancy leads
to signs of preeclampsia and impaired adaptations to pregnancy.
However, the impact on uterine artery function/blood flow, and
ultimately fetal outcomes, in this model has not been explored.
We assessed pregnancy outcomes in this model in order to obtain
a model in which to test potential treatment regimes. Objective:
To assess vascular function and fetal growth following maternal
exposure to hypoxia. Methods: Sprague Dawley rats were housed
either in normal atmospheric conditions or exposed to hypoxia
(10.5%) during pregnancy (gestational day (GD) 6-20; term=22
days). Uterine vascular function was assessed using both in vivo
(tail cuff plethysmography and ultrasound biomicroscopy at GD
20) and ex vivo (wire myography on uterine and mesenteric
arteries at GD 21) techniques. After euthanasia on GD 21, fetal and
placental biometrics were measured. Results: Maternal systolic,
diastolic and mean blood pressures were unaltered on GD 20.
Maximum velocity of uterine artery blood flow (normoxia:
828.39±79.20 mm/s vs. hypoxia: 513.84±53.44 mm/s, P<0.01) and
the uterine artery resistance index (normoxia: 0.63±0.04 vs.
hypoxia: 0.52±0.01, P<0.01) were both decreased in the dams
exposed to hypoxia. However, maximum velocity of the umbilical
artery blood flow was increased (normoxia: 189.31±15.12 mm/s
vs. hypoxia: 233.13±10.56 mm/s, P<0.05). Moreover, in the
hypoxic group, fetal body weight (normoxia: 5.50±0.15 g vs.
hypoxia: 4.60±0.19 g, P<0.01), crown-rump length (normoxia:
4.50±0.09 cm vs. hypoxia: 4.10±0.08 cm, P<0.01), abdominal girth
(normoxia: 4.60±0.15 cm vs. hypoxia: 4.00±0.09 cm, P<0.01) and
litter size (normoxia: 15.4±0.5 vs. hypoxia: 13.0±1.7, P<0.01) were
all reduced. There were no differences in uterine artery responses
to the vasoconstrictor phenylephrine or vasodilator sodium
nitroprusside, however, vascular sensitivity to the endotheliumdependent vasodilator methacholine (MCh) was decreased (pEC50
normoxia: 6.43±0.30 vs. hypoxia: 5.57±0.20, P<0.01). Conclusion:
Dams exposed to hypoxia demonstrated a maternal vascular
phenotype characterized by altered maternal/fetal blood flow and
intrauterine growth restricted offspring. Our future studies will
address possible intervention strategies. Acknowledgements: U
of A Recruitment and FoMD 75th Anniversary Awards, CIHR and
WCHRI. Contact Information: Mais Aljunaidy
[email protected]
[317]
THE LONG-TERM IMPACT OF NEONATAL HYPEROXIA EXPOSURE
ON RENAL MORPHOLOGY AND FUNCTION IN ADULT RATS.
Megan R. Sutherland1, Marie-Amélie Lukaszewski1, Chanel
Béland1, Anik Cloutier1, Mariane Bertagnolli1, Anne Monique Nuyt1
1CHU Sainte-Justine Research Center and the University of
Montreal
Introduction: Preterm neonates are exposed to high oxygen levels
relative to the intrauterine environment, at a time when
nephrogenesis (the development of nephrons in the kidney) is still
ongoing. We have previously shown that hyperoxic gas exposure
impairs renal development in neonatal rats and results in a
reduced nephron number and high blood pressure in adulthood.
Objective: The aim of this study was to determine the long-term
effects of neonatal hyperoxia exposure on renal function and
morphology. Methods: Hyperoxia-exposed Sprague-Dawley pups
were raised in 80% oxygen from P3 - P10 (H; n=8 litters). To
prevent maternal oxygen toxicity, H dams were interchanged
every 12 hours with a dam with pups raised in room air (NH; n=8
litters). Control litters were kept in room air (Ctrl; n=8 litters). At 1,
5, and 11 mo (1 male and 1 female /litter/age), animals were
66
placed in metabolic cages with urine collected for 16h overnight;
plasma and kidneys were collected the following day. Plasma and
urine samples were assessed for creatinine, sodium, and protein
levels. Histologically stained kidney sections from 11 mo animals
were systematically sampled, and renal corpuscle size,
glomerulosclerosis, fibrosis, and glomerular crescents (Figure 1A)
were assessed. Results: There was no difference in body or
kidney weights between groups at any age. There was no
difference in creatinine clearance (ClCr) between groups at 1mo
and 11mo; at 5mo, however, ClCr was significantly reduced
following hyperoxia exposure. There was also a trend at 5mo for
increased fractional sodium excretion. Urine albumin/Cr and total
protein/Cr levels increased with age, but there was no difference
between groups. The percentage of crescentic glomeruli was
significantly increased following neonatal hyperoxia exposure in
11mo males, but not females (Figure 1B). Renal corpuscle size,
glomerulosclerosis index, and renal fibrosis were not affected.
Conclusion: In younger and older rats (likely with lower renal
functional demand), kidney function was not significantly affected
by neonatal hyperoxia exposure. There was, however, an adverse
impact on creatinine clearance at 5 months of age. Additionally, by
11 months of age hyperoxia exposure resulted in a high
percentage of crescentic glomeruli in male kidneys, indicative of
glomerular injury. Overall, these findings suggest that individuals
exposed to high oxygen levels during development may have a
reduced renal functional capacity and an increased susceptibility
to renal disease in adulthood. Acknowledgements: This research
was supported by CIHR funding. Contact Information:
[email protected]
[347]
THE ASSOCIATION BETWEEN CESAREAN SECTION AND
CHILDHOOD OBESITY: A SYSTEMATIC REVIEW AND METAANALYSIS. Stefan Kuhle1, Olivia S. Tong1, Christy G. Woolcott1
1Perinatal Epidemiology Research Unit, Dalhousie University
Introduction: Birth by cesarean section has been recently
implicated in the etiology of childhood obesity but studies
examining the association have varied with regard to their
settings, designs, and adjustment for potential confounders.
Objective: The objective of the current study was to summarize
the available evidence and to explore study characteristics as
sources of heterogeneity in results of the association between
cesarean section and childhood obesity through a systematic
review and meta-analysis. Methods: The generic inverse variance
method was used to determine the relative effects and their
standard errors from the published findings. Random effects
meta-analysis was used to calculate pooled risk ratios (RR).
Subgroup analyses were conducted for study design (cohort vs.
case-control or cross-sectional), adjustment for maternal prepregnancy BMI (yes vs. no), age at BMI assessment (<6 years vs. ≥6
years), country income (high income countries vs. middle income
countries), main exposure of interest (cesarean section vs. early
life factors in general), and cesarean section rate (< 30% vs. ≥30%).
Funnel plot and Egger\'s test were used to assess publication bias.
Results: The literature search identified 28 studies. Nineteen
studies examined obesity as the primary outcome, while nine
studies examined overweight, either on its own or combined with
obesity as the primary outcome. Cesarean section had a RR of 1.34
CNPRM 2015
(95% confidence interval [CI] 1.18; 1.51) for obesity in the child
compared to vaginal birth. The I2 statistic (45%) indicated
moderate heterogeneity. The pooled RR for studies that adjusted
for maternal pre-pregnancy weight was lower than the pooled RR
for studies that did not adjust for maternal pre-pregnancy weight
(RR 1.29 vs. 1.55) Studies that examined multiple early life factors
and childhood obesity reported lower effect estimates than
studies that specifically examined the association between
cesarean section and obesity (RR 1.27 vs. 1.39). There was no
difference in pooled effects by age at BMI assessment, study
design, and country income. The pooled RR from studies for the
secondary outcomes outcome overweight and obesity combined
(n=13), overweight (excl. obesity) (n=6) were 1.16 (95% CI 1.051.27) and 1.16 (95% CI 1.06-1.27), respectively, for cesarean
section compared to vaginal birth. Conclusion: Children born by
cesarean section have a 34% higher risk of developing obesity in
childhood. Findings are limited by a moderate heterogeneity
between studies and the potential for residual confounding and
publication bias. Maternal pre-pregnancy weight is a key
confounder in the association between cesarean section and
offspring obesity. Contact Information: [email protected]
[394]
DNA METHYLATION MEDIATES THE IMPACT OF EXPOSURE TO
PRENATAL MATERNAL STRESS FROM THE QUEBEC ICE STORM
DISASTER ON BMI AND CENTRAL ADIPOSITY IN CHILDREN AT AGE
13½ YEARS. Lei Cao-Lei1, Kelsey Dancause2, Guillaume Elgbeili3,
Renaud Massart4, Moshe Szyf4, David P. Laplante3, Suzanne King1
1McGill University, Douglas Institute, 2UQAM, Kinanthroplogy,
3Douglas Mental Health University Institute, 4McGill University,
Pharmacology
Introduction: Animal research finds associations between prenatal
maternal stress (PNMS) and obesity or metabolic dysfunction in
the offspring. The study of PNMS in humans is compromised by
lack of randomization to stress conditions. Disasters provide
natural experiments to study PNMS. Project Ice Storm has studied
effects of the severity of maternal exposure and maternal distress
from a natural disaster on a variety of outcomes in the children.
Objective degree of maternal exposure predicts children’s body
mass index (BMI), obesity, and insulin secretion. Epigenetic
modification of gene function is considered one possible
mechanism by which PNMS results in poor outcomes in offspring.
Although effects of PNMS on DNA methylation have been shown
in animal studies, the ability of this epigenetic mechanism to
mediate effects of PNMS on adiposity in human children has not
been shown. Objective: Our goal was to determine the role of
maternal objective exposure and subjective distress on child BMI
and central adiposity at 13½ years, and to test the hypothesis that
DNA methylation mediates the effect of PNMS on growth.
Methods: Mothers were pregnant during the January 1998
Quebec ice storm or became pregnant within 3 months of the
storm. We assessed their objective exposure to the storm (threat,
loss, scope and change) and subjective distress (PTSD-like
symptoms) five months later in June 1998. Six months after their
due dates, we obtained information on other pregnancy life
events. At age 13½ their children were weighed and measured (n =
66); a subsample provided blood samples for epigenetics (n = 31).
Results: Objective PNMS correlated with central adiposity (Waistto-Height Ratio; r = .326, p = .012) and body mass index (BMI; r =
.241, p = .05); Subjective distress correlated with central adiposity
(r = .307, p = .018) but not with BMI. Other pregnancy life events
also predicted outcomes. Objective and subjective PNMS and
other pregnancy life events explained 21% of variance in central
adiposity, and 12% in BMI. Bootstrapping analyses showed that
the methylation level of genes from established type 1 and 2
diabetes mellitus pathways showed significant mediation of the
effect of objective PNMS on central adiposity and BMI,
respectively..Conclusion: Although subjective distress from the ice
storm predicted child adiposity in adolescence, objective prenatal
maternal stress predicts both BMI and central adiposity in
adolescence and seems to be mediated by DNA methylation of
genes associated with diabetes mellitus. Acknowledgements:
Project Ice Storm has been funded by the Canadian Institutes of
Health Research since 2003. We wish to acknowledge the families
who have persisted in the study. Contact Information: Suzanne
King [email protected]
[401]
HEPATIC MICROVESICULAR STEATOSIS IN CONJUNCTION WITH
SPECIFIC ALTERATIONS IN FATTY ACID AND AMINO ACID
METABOLISM IN YOUNG ADULTHOOD IS INDUCED BY A
CNPRM 2015
67
COMBINATION OF ADVERSE IN UTERO AND POSTNATAL
ENVIRONMENTS
Ousseynou Sarr1, Kristyn Dunlop2, Lin Zhao1, Ian Welch3, Timothy
RH Regnault4
1Department of Obstetrics and Gynecology, Children’s Health
Research Institute, Lawson Health Research Institute, Western
University, London, ON, Canada, 2Department of Physiology and
Pharmacology, Children’s Health Research Institute, Lawson
Health Research Institute, Western University, London, ON,
Canada, 3Animal Care and Veterinary Services, Western University,
London, ON, Canada, 4Departments of Obstetrics & Gynecology
and Physiology and Pharmacology Children’s Health Research
Institute, Lawson Health Research Institute, Western University,
London, ON, Canada.
Introduction: Epidemiologic and experimental studies have
provided evidence linking an adverse intrauterine environment
such as placental insufficiency with later development of adult
hepatic triglyceride accumulation (steatosis), the hallmark of NonAlcoholic Fatty Liver Disease (NAFLD). The increasing intake of
postnatal energy dense diet, commonly referred to as the Western
Diet (WD) is also thought to independently contribute to postnatal
liver steatosis development. However, the interaction between
adverse intrauterine environments and other steatogenic
contributors as postnatal WD, remains ill-defined. Objective: To
investigate whether an adverse in utero environment, resulting in
low birth weight (LBW), and postnatal WD feeding interact in
hepatic steatosis pathogenesis in young males, with particular
attention focused upon differential alterations in lipid and amino
acid metabolism. Methods: LBW guinea pigs, generated via
uterine artery ablation, and normal birth weight (NBW) controls
were fed either a WD or control diet (CD) after weaning. At 150
days of age, livers were harvested for hematoxylin and eosin
staining, qPCR, Western blotting, gas chromatography and mass
spectrometry. Results: In LBW/CD animals, steatosis was absent.
NBW/WD animals, however, displayed a macrovesicular steatosis,
the most common form of intrahepatic triglycerides accumulation
whereas in LBW/WD animals, microvesicular steatosis
predominated. A combination of LBW and WD induced significant
reductions in hepatic carnitine palmitoyltransferase I (CPT1) and
uncoupling protein 2 (UCP2) mRNA, amino acids (Asp, Phe, Tyr and
Trp) and long-chain acylcarnitines (C16, C18 and C18:1) compared
to NBW/WD. Further, independent of birth weight, WD resulted in
increased hepatic triglycerides, fatty acid translocase (CD36)
mRNA, expression of lipogenic genes and proteins (FAS, ACC, and
HK2), and metabolite-based lipogenic parameters (C16:1/C16:0,
C18:1/C18:0 and C16:0/C18:2n-6). Hepatic medium chain
acylcarnitine C12, long-chain acylcarnitines (C14, C14:1, C14-OH,
C16:1, C16-OH, C18-OH, C18:1-OH and C18:3) and amino acid
concentrations (Arg, Cys, Thr and Leu) were increased in WD
animals. Conclusion: These data highlight that WD and LBW/WD
induce a different hepatic steatosis pattern accompanied with
environment specific lipid and amino acid metabolism alterations.
The specific changes in mitochondrial genes, as well as markers of
altered lipid and amino acid metabolism and the consequent
microvesicular steatosis imply a less favorable liver health
prognosis for adversely in utero grown offspring fed a WD
postnatally. Acknowledgements: The authors thank Brad
Matushewski for his assistance with animal surgeries. Contact
Information: Ousseynou Sarr [email protected]
1Department of Psychiatry, McGill University and Psychosocial
Research Division, Douglas Hospital Research Centre,
2Psychosocial Research Division, Douglas Hospital Research
Centre, 3Department of Pharmacology and Therapeutics, McGill
University, 4Department of Pharmacology and Therapeutics and
Sackler Program for Epigenetics and Developmental
Psychobiology, McGill University
Introduction: Prenatal maternal stress (PNMS) can impact a variety
of outcomes in the offspring throughout childhood and persisting
into adulthood as shown in human and animal studies. Many of
the effects of PNMS on offspring outcomes likely reflect the
effects of epigenetic changes, such as DNA methylation, to the
fetal genome. However, no animal or human research can
determine the extent to which the effects of PNMS on DNA
methylation in human offspring is the result of the objective
severity of the stressor to the pregnant mother, or her negative
appraisal of the stressor, or her resulting degree of negative stress.
Objective: The main goal of this study was to determine the extent
to which genome-wide DNA methylation levels collected from a
cohort of adolescents in 2011 could be related to the cognitive
appraisals their mothers had made in 1998 about the Québec ice
storm which they had experienced during their pregnancies.
Methods: We examined the genome-wide DNA methylation
profile in T cells from 34 adolescents whose mothers had rated the
ice storm’s consequences as positive or negative (i.e., cognitive
appraisal). Results: The methylation levels of 2872 CGs differed
significantly between adolescents in the Positive and Negative
maternal cognitive appraisal groups. These CGs are affiliated with
1,564 different genes, and with 409 different biological pathways,
which are prominently featured in immune function. Importantly,
there was a significant overlap in the differentially methylated CGs
or genes and biological pathways that are associated with
cognitive appraisal and those associated with objective PNMS as
we reported previously. Conclusion: Our study suggests that
pregnant women’s cognitive appraisals of an independent stressor
may have widespread effects on DNA methylation across the
entire genome of their unborn children, detectable during
adolescence. Therefore, cognitive appraisals could be an
important predictor variable to explore in PNMS research.
Acknowledgements: We are grateful to families for their
continued participation in Project Ice Storm. This research was
supported by a grant from the Canadian Institute of Health
Research (CIHR) to Suzanne King. Contact Information:
[email protected]
[404]
PREGNANT WOMEN’S COGNITIVE APPRAISAL FROM A NATURAL
DISASTER AFFECTS DNA METHYLATION IN THEIR CHILDREN 13
YEARS LATER: PROJECT ICE STORM. Lei Cao-Lei1, Guillaume
Elgbeili2, Renaud Massart3, David P. Laplante2, Moshe Szyf4,
Suzanne King1
68
CNPRM 2015
Shannyn Macdonald-Goodfellow Tiziana Cotechini CIHR funding.
Contact Information: Maggie Chasmar [email protected]
Perinatal Brain Injury
[405]
ABERRANT MATERNAL INFLAMMATION CAN LEAD TO
GESTATIONAL DIABETES AND INSULIN RESISTANCE DURING A
PREECLAMPSIA-LIKE PREGNANCY. Maggie Chasmar1, Xiaoxuan
Zhao1
1Queen's University/Biomedical and Molecular Sciences
Introduction: Gestational diabetes (GD) is a state of carbohydrate
intolerance that first occurs in pregnancy. In response to
hyperglycemia, pancreatic beta cells increase insulin production
resulting in a state of hyperinsulinemia. If the beta cells cannot
compensate, this leads to insulin resistance and impaired glucose
tolerance. The etiology of GD is not completely understood, but
many cohort studies show that there may be a relationship
between inflammation and GD, as well as between GD and
preeclampsia. Objective: We aim to better understand how
aberrant maternal inflammation is linked to GD and insulin
resistance and to assess whether the use of therapeutics to target
inflammation can prevent those conditions. Methods: Bacterial
lipopolysaccharide (LPS) or saline was administered to dams on
gestational days 13.5-16.5, and to non-pregnant animals during
diestrous. The non-fasting blood glucose level was taken prior to
each administration, and fasting glucose and insulin levels were
measured at euthanasia (GD17.5). Insulin sensitivity and resistance
indexes were calculated using these fasting values.
Immunohistochemistry and immunofluoresence was used to
analyze morphological changes in the pancreatic islet cells.
Results: The results show that in LPS-treated dams, glucose levels
are significantly elevated; there is significantly greater islet cell
expansion and beta cell proliferation, but no significant difference
in beta-cell apoptosis. The changes were not significantly different
between LPS- and saline-treated non-pregnant dams, indicating a
pregnancy-specific condition. Conclusion: These findings
demonstrate that there might be a link between inflammation,
gestational diabetes and insulin resistance. In a state of
unimpaired glucose tolerance, islet cell expansion and beta cell
proliferation should lead to greater insulin production and a
subsequent decrease in blood glucose levels. However, this
decrease in blood glucose was not observed in animals treated
with LPS. Thus, the inflammatory state of the mother could be
influencing the action of insulin to decrease blood glucose because
glucose is not being readily cleared from the blood. Future
research is being done to see whether anti-inflammatory
therapeutics can be used to prevent the morphological changes in
the pancreas and improve glucose tolerance. Also, we will assess
the mechanism by which insulin resistance occurs in rats, by
studying the insulin-signaling pathway. This will provide a more
concrete link between inflammation, insulin resistance and GD,
and the increased risk of GD during complicated pregnancies.
Acknowledgements: Dr. Charles Graham - Graduate Supervisor
[252]
ROLE OF VAGUS NERVE IN FETAL GLUCOSENSING AND
NEUROINFLAMMATION. Mingju Cao1, Shikha Kuthiala1, Tina
Shafiee1, Hai Lun Liu1, Patrick Burns2, André Desrochers2, Gilles
Fecteau2, Martin G. Frasch3
1OBGYN / Neurosci, U de Montréal, Montréal, 2Clin Sci, U de
Montréal, St-Hyacinthe, 3OBGYN / Neurosci, U de Montréal,
Montréal, CRRA U de Montréal, St-Hyacinthe, QC
Introduction: Glucosensors are distributed throughout the body
and relay information about circulating glucose to the brain via
vagus nerve. However, little is known about the physiological role
of vagus nerve in glucosensing. Hyperglycemia post stroke
worsens neurological outcome. We hypothesized that vagotomy
(Vx) will result in hyperglycemia and this will be correlated to a
higher degree of neuroinflammation. Objective: Determine
whether and how vagus nerve regulates fetal glucosensing and
neuroinflammation. Methods: 38 near-term fetal sheep were
surgically prepared with vascular catheters and with or without
bilateral Vx and vagus nerve stimulation (VNS) electrodes. After 72
h of post-operative recovery, animals were divided into 4
experimental groups: Control group (n=11, sham Vx); LPS group
(n=13, sham Vx, received 400-800ng/ml of lipopolysaccharide
(LPS) daily for 2 days to induce inflammation); Vx+LPS group
(n=11, Vx and received LPS); Vx+VNS+LPS group (n=3, Vx and
received efferent VNS plus LPS). Fetal arterial blood was sampled
during surgery before and after Vx, on each post-operative day, on
experimental days at baseline and seven selected time points (354h) to profile inflammation (ELISA, IL-6, pg/ml), insulin (ELISA,
ng/ml) and glucose levels (mg/dL). Necropsy was performed 54h
post LPS, and neuroinflammation was quantified as Iba1+ brain
microglia immunofluorescence. Results are reported as
mean±SEM for P<0.05. Results: Surgery, Vx and post-operative
period had no effects on glucose averaging 17±5. Overall, glucose
levels in Vx+LPS were higher vs. Control and LPS groups at all time
points and VNS normalized them; LPS alone had no effects on
glucose and insulin levels. At baseline, Vx+LPS glucose levels were
21±5 vs. 16±3 in Control and LPS groups combined; insulin values
did not differ either. At 3h post LPS, Vx+LPS glucose was 20±4 vs.
15±3, insulin levels increased at 0.6±0.4 vs. 0.2±0.1, while IL-6
peaked 481±310 vs. 1±1 at baseline; at 48h post LPS, Vx+LPS
glucose was 22±6 vs. 17±3, while insulin values returned to
baseline. In the Vx+LPS, but not Control or LPS groups, higher
glucose levels at 3h correlated to higher Iba1 immunofluorscence
in brain (thalamus: r=0.96; dentate gyrus: r=0.95; grey matter:
r=0.94 (p=0.07). Conclusion: Complete withdrawal of vagal
innervation results in a 72 hours delayed onset of sustained
hyperglycemia for at least 54h. Under moderate fetal
inflammation conditions, this is related to a transient
hyperinsulinemia and higher levels of brain inflammation. This
suggests an important role of vagus nerve in both glucosensing
and neuroinflammation and warrants further investigation to help
prevent perinatal brain injury. Acknowledgements: CIHR, FRSQ,
MTPRF. Contact Information: Mingju Cao [email protected]
[265]
BILATERAL VAGAL NERVE STIMULATION REDUCES
LIPOPOLYSACCHARIDE-INDUCED INFLAMMATION IN FETAL
SHEEP. Hai Lun Liu1, Luca Garzoni2, Mingju Cao3, Lucien Daniel
Durosier3, Patrick Burns 4, P-Y Mulon4, Gilles Fecteau4, André
Desrochers4, Natalie Patey5, Christophe Faure2, Martin G. Frasch6
CNPRM 2015
69
1OBGYN/Neurosci,
UdeM, Montréal, QC, McGill University,
UdeM, Montréal, 3OBGYN/Neurosci, UdeM, Montréal,
4Clinical Sciences, UdeM, St-Hyacinthe, 5Pathology, UdeM,
Montreal, 6OBGYN/Neurosci, UdeM, Montréal, CRRA, UdeM, StHyacinthe, QC.
Introduction: Necrotizing enterocolitis (NEC) of the neonate is an
acute inflammatory intestinal disease that can cause necrosis,
systemic sepsis and multiorgan failure. It is characterized by high
prevalence, morbidity and mortality accounting for up to 8% of all
admissions to the neonatal intensive care unit. Chorioamnionitis
(CA) is a risk factor for NEC. Higher levels of vagal activity are
associated with decrease of systemic pro-inflammatory cytokine
levels and macrophage activation, mediated via the vagus nerve.
Little is known about the behaviour of this neuroimmunological
network in the fetus. We have shown in near-term fetal sheep that
- counterintuitively - vagatomy (Vx) results in a reduced ileum
inflammation following low-dose lipopolysaccharide (LPS)
exposure. We hypothesized that bilateral vagal nerve stimulation
(VNS) will suppress LPS-induced systemic and ileum inflammation.
Objective: To characterize the effects of VNS on the LPS-induced
systemic and gut inflammation. Methods: Fetal sheep were
prepared with vascular catheters with or without bilateral cervical
Vx and VNS electrodes, allowed 3 days of post-operative recovery
followed by i.v. LPS after baseline and at 24h or NaCl (Control). LPS
animals were divided into LPS, Vx+LPS and Vx+VNS+LPS groups.
VNS followed doi:10.1038/35013070. Blood was sampled at
selected time points. 54h post first LPS dose, necropsy was
performed. IL-6 plasma levels (ELISA) and the Iba1+
immunofluorescence in terminal ileum quantified the degree of
systemic inflammation and ileal macrophage activation,
respectively. Results: IL-6 values were higher at 3h in LPS vs.
control, but not vs. Vx+LPS and Vx+VNS+LPS groups (Fig. 1). From
24h onward (i.e., after the second LPS dose), IL-6 in the
Vx+VNS+LPS was undetectable. In parallel, Iba1+ cell intensity in
ileum was lower in Vx+VNS+LPS vs. LPS group, but not different
from controls (Fig. 2). Conclusion: VNS reduced the levels of
systemic and ileum inflammation to control values. Therapeutic
potential of VNS for early postnatal treatment of babies at risk of
sepsis with ensuing organ injury should be considered.
Acknowledgements: Funded by CIHR, FRQS, Molly Towell
Perinatal Research Foundation, QTNPR. Contact Information: Hai
Lun Liu [email protected]
2Pediatrics,
70
[281]
CHARACTERIZATION OF FETAL BRAIN MICROGLIAL
TRANSCRIPTOME PHENOTYPE IN A DOUBLE-HIT
NEUROINFLAMMATION PARADIGM. M Cortes1, M Cao2, C S
Moore3, S Y Leong3, L D Durosier2, P Burns4, G Fecteau4, A
Desrochers4, J P Antel5, M G Frasch2
1Animal Reproduction Research Centre (CRRA), Faculty of
Veterinary Medicine, Université de Montréal, 2Dept. of Obstetrics
and Gynaecology and Dept. of Neurosciences, CHU Ste-Justine
Research Centre, Faculty of Medicine, 3Montréal Neurological
Institute, McGill University, 4Dept. of Clinical Sciences, Faculty of
Veterinary Medicine, Université de Montréal, 5Neuroimmunology
Unit, Montréal Neurological Institute, McGill University
Introduction: Fetal neuroinflammation (FN) in preterm neonates
may result in life-long postnatal neurological disabilities. While reexposure to an inflammatory stimulus has been discussed as a
trigger for postnatal neuroinflammation, its mechanisms remain
poorly understood. We developed an in vivo - in vitro animal
model to study the mechanisms of the developmental
programming of lipopolysaccharide (LPS) induced FN with focus on
microglia phenotype. Near-term fetal sheep were exposed in vivo
to low dose LPS (second hit control, SHC) to mimic subclinical FN;
naive microglia were exposed in vivo to NaCl (naive control, NC)
and later on to LPS in vitro (naive LPS, NL). SHC were then exposed
to LPS in vitro (second hit LPS, SHL). We reported that in such
paradigm LPS second hit results in amplification of microglial
cytokine (IL-1B) production in vitro (Cao et al., IJDN, in press).
Objective: Through an in vivo - in vitro animal model, we aimed to
establish the transcriptome profile of microglial cells during LPSinduced fetal neuroinflammation. Methods: To deeper explore
the microglial phenotype we sequenced the whole microglial
transcriptome at high throughput. Firstly, we identified
differentially expressed genes in NL microglia. Secondly, we
compared naive controls to SH control. Third, we evaluated the
difference in response between NL and SHL microglia (Figure 1).
Results: Up regulation of inflammatory pathways NFKB, PIK3-Akt
and JAK-Stat in NL microglia was accompanied by a down
regulation of metabolic pathways. As shown in figure 2, FBP was
up regulated in SH microglia and was unique to these samples
(log2 = 4.057 and padj = 9.40 x 10^-2) confirming recent
observations in neonatal murine microglia that FBP may regulate
AP-1 and Nitrogen Oxide (NO) transcript amounts through the
JNK/p38 pathway (Kim et al, 2010, doi:10.1016/j.lfs.2011.12.011).
HMOX1 was down regulated in all 3 comparisons and was the only
significantly down regulated gene in SH microglia (log2 = -4.303,
padj = 8.13 x 10^-2). This supports the potential role of HMOX1 in
CNPRM 2015
neuroinflammatory response and as a determinant of «doublehit» microglial phenotype (Hua et al., 2014,
doi:10.1155/2014/718769). Conclusion: Transcriptome analysis
of microglia during neuroinflammation revealed that proinflammatory microglial phenotype acquired during in vivo
exposure to LPS is sustained and amplified in vitro, with HMOX1
and FBP genes playing a pivotal role during secondary exposure to
neuroinflammation in the developing brain. Acknowledgements:
This project was funded by the CIHR, FRQS, MTPRF and QTNPR.
Contact Information: M Cortes [email protected]
[336]
MATERNAL NUTRIENT RESTRICTION (MNR) IN PREGNANT
GUINEA PIGS IMPACTS FETAL GROWTH AND BRAIN
DEVELOPMENT. Andrew Ghaly1, Alexander Elias1, Alex Xu1, Karen
Nygard2, Brad Matushewski3, Robert Hammond4, Bryan S.
Richardson5
1University of Western Ontario/Physiology and Pharmacology ,
2University of Western Ontario/Science, 3University of Western
Ontario/Obstetrics and Gynaecology, 4University of Western
Ontario/Pathology, 5University of Western Ontario/Physiology and
Pharmacology/Obstetrics and Gynaecology/Children's Health
Research Institute
Introduction: Fetal Growth Restriction (FGR) offspring are at
increased risk for later adverse neurologic outcomes including
cognitive impairment, attention deficit disorders, schizophrenia,
and autism with risk proportional to the degree of FGR. MNR in
guinea pigs results in placental structural abnormalities that
reduce nutrient transport, decreasing birth weights by ~30%.
However, whether brain weights are similarly reduced, or
preserved by “brain sparing” mechanisms, and whether energy
levels are depleted leading to membrane failure and overt injury,
remain unknown. Objective: Our objective was to determine the
extent to which MNR in guinea pigs as a causative factor for FGR
impacts brain growth, the degree of “brain sparing”, and measures
of overt injury by quantifying brain weight, brain to liver weight
ratios, cellular necrosis and apoptosis. Methods: Guinea pig sows
were fed ad libitum (Control) or 70% of the control diet prepregnancy switching to 90% at mid-pregnancy (MNR). Animals
were necropsied near-term for fetal growth measures, and fetal
brains were immersion-fixed for later assessment of necrotic cell
injury using standard H&E criteria and apoptotic cell injury using
the TUNEL assay method. Significance was assumed for p<0.05.
Results: Nine control (31 fetuses) and twelve MNR (42 fetuses)
sows were necropsied with MNR fetal weights decreased 28%.
Select AGA-control (n=18) and FGR-MNR (n=18) fetuses
underwent full necropsy with FGR-MNR weights decreased 37%,
brain weights decreased 12% and brain to liver weight ratios
increased 48%. Overall, low levels of necrotic cells were observed,
with no significant differences between groups. While low levels of
CNPRM 2015
71
apoptotic cells were also observed, averaging 0.75/HPF and
1.18/HPF (63x) for AGA-control and FGR-MNR animals,
respectively, FGR-MNR levels of apoptosis were higher in the
periventricular white matter (2x), the hippocampus CA1 (3x), CA4
(1.7x) and dentate gyrus (3x). Conclusion: MNR in guinea pigs
results in FGR with small livers relative to brain weights; likely
indicating blood flow redistribution characteristic of asymmetrical
FGR. These fetuses have reduced brain weights, but with
substantial “brain sparing”, and with no increased necrotic cell
injury indicating that the threshold for membrane failure with
energy depletion has likely not been reached. However, apoptotic
indices were increased primarily in hippocampal regions that may
involve alterations in the balance of pro- and anti-apoptotic
factors and underlie risk for increased neurologic impairment seen
in FGR offspring. Acknowledgements: We acknowledge funding
from the Children's Health Research Institute and the Department
of Obstetrics and Gynecology at Western University. Contact
Information: [email protected]
[360]
THE UNIVERSAL DATA FORM PROJECT FOR FETAL ALCOHOL
SPECTRUM DISORDER (FASD). Jocelynn L. Cook1, Courtney R.
Green2, Sterling K. Clarren2, Christine Werk3
1Society of Obstetricians and Gynaecologists of Canada; Canada
Fetal Alcohol Spectrum Disorder Research Network, 2Canada Fetal
Alcohol Spectrum Disorder Research Network, 3Alberta Centre for
Child, Family & Community Research
Introduction: Fetal Alcohol Spectrum Disorder (FASD) is an
umbrella term used to describe the range of impairments that
result from prenatal alcohol exposure; however, the extent of
functional deficits varies. To date, there has been no systematic
evaluation of the frequency with which functional deficits or
clusters of functional deficits occur, or of the recommendations
for interventions made most frequently. Objective: The goal of
this study was to develop a database that would enable the
standardized collection of FASD diagnostic data across Canada, to
analyze and document the common problems and recommended
interventions. Methods: Separate adult and child forms were
developed using a set of common criteria that captured the
patient’s 4-digit diagnostic code; brain domain assessment results;
functional profile and, management referrals/recommendations.
Data was collected from 25 participating FASD diagnostic teams
across Canada. Data analysis was outsourced to The Child and
Youth Data Laboratory at the Alberta Centre for Child, Family &
Community Research. Results: A total of 218 children and 71
adults with an FASD diagnosis were included in the analysis. The
top three functional deficits for brain domains for children were
attention deficit/hyperactivity (63%); adaptive behaviour/social
skills/social communication (61%) and executive function and
abstract reasoning (61%); and for adults were adaptive
behaviour/social skills/social communication (62%); memory (55%)
and cognition (49%). The top management
referrals/recommendations for children were educational
supports; educational modifications; and speech-language
therapy; and for adults were daily income support; recreational
services and FASD advocacy. Conclusion: Multisite data collection
is feasible, but challenging. The results reflect the clinically severe,
diverse neurodevelopmental dysfunction associated with an FASD
diagnosis, without any specific single pattern(s) of dysfunction.
These data confirm that patient management requires not only
services across systems, but also follow-up support to translate
recommendations into functional interventions. These data reflect
the pan-Canadian FASD diagnostic clinical experience and can be
used to inform best practices and policies. Acknowledgements:
We wish to thank the Public Health Agency of Canada for
72
providing financial support for this project. Contact Information:
Jocelynn Cook [email protected]
Family Centered Care – Developmental
Outcomes and Interventions
[290]
THE ROLE OF OXYTOCIN IN THE INTERACTIVE BEHAVIOR OF
MOTHERS WITH AND WITHOUT MENTAL HEALTH PROBLEMS.
Simcha Samuel1, Barbara Hayton2, Ian Gold3, Nancy Feeley4, Sue
Carter5, Phyllis Zelkowitz6
1Department of Psychology, McGill University, Montreal, Canada,
2Department of Psychiatry, Jewish General Hospital, Montreal,
Canada, 3Department of Philosophy, McGill University, Montreal,
Canada, 4Centre for Nursing Research, Jewish General Hospital,
Montreal, Canada; Lady Davis Institute, Jewish General Hospital,
Montreal, Canada; Ingram School of Nursing, McGill University,
5Kinsey Institute, Indiana University, Bloomington, USA,
6Department of Psychiatry, Jewish General Hospital, Montreal,
Canada; Department of Psychiatry, McGill University, Montreal,
Canada; Lady Davis Institute, Jewish General Hospital, Montreal,
Canada
Introduction: A growing body of literature has linked peripheral
oxytocin (OT) levels to more optimal maternal interactive
behaviors(Feldman et al., 2010; Feldman et al., 2012; Feldman et
al., 2011). Recently, researchers have noted the inconsistent
effects of OT on prosocial behavior and social cognition in humans
(Bartz, Zaki, et al., 2011). Others have highlighted the moderating
role of individual differences, such as longstanding interpersonal
insecurities (Bartz, Simeon, et al., 2011). Human studies of OT and
mother-child interactions tend to focus on healthy mothers,
excluding those with psychiatric diagnoses. Objective: The
present study compared the link between OT and interactive
behavior in mothers with and without mental health problems and
their 2-month-old infants. Methods: In an extreme-case design,
we recruited a community sample of 124 women with low
depressive symptoms (scores below 8 on the Edinburgh Postnatal
Depression Scale; Cox et al., 1987), and a clinical sample of 74
women who sought help for mental health problems during
pregnancy or postpartum at a perinatal mental health service. The
groups did not significantly differ in parity, age, marital status, or
education. Blood was drawn to assess levels of plasma OT using an
enzyme-linked immunosorbent assay. Mother-infant free-play
sessions were coded using the Global Rating Scales (GRS; FioriCowley et al., 2000), which includes 4 maternal subscales
(sensitivity, non-intrusive, non-remote, non-depressive), 3 child
subscales (positive engagement, lively, non-distressed), and 1
dyadic subscale (interaction). Scores range from 1 (non-optimal) to
5 (optimal). Results: Compared to the community sample, the
clinical sample scored lower on several subscales of the GRS:
maternal sensitivity, maternal non-depressive, and interaction. In
the community sample, log OT levels were positively correlated
with maternal non-intrusive scores; higher OT levels appeared to
be protective against intrusive behavior and speech in mothers
with relatively low levels of distress. Conversely, in the clinical
sample, log OT levels were positively correlated with maternal
non-depressive scores; higher OT levels appeared to be protective
against sad, low energy, self-absorbed, and tense interactive
behaviors in mothers with relatively high levels of distress.
Conclusion: These results suggest that OT is related to a distinct
set of interactive behaviors in clinical versus community sample
mothers. This study extends the literature highlighting the
differential effects of OT, and cautioning against more global
statements about the correlates of OT in humans (Bartz, Zaki, et
al., 2011). Acknowledgements: CIHR # GTA-91755. Research
CNPRM 2015
Scholar Award from the FRQ-S. Contact Information:
[email protected]
[291]
RELIABILITY AND VALIDITY OF THREE SHORTENED VERSIONS OF
THE STATE ANXIETY INVENTORY SCALE DURING THE PERINATAL
PERIOD. Hamideh Bayrampour1, Sheila McDonald1, Tak Fung1,
Suzanne Tough1
1University of Calgary
Introduction: The early detection of anxiety can provide key
opportunities for interventions to improve pregnancy outcomes,
postpartum mental health, and early childhood development. Yet
the screening for anxiety in obstetric settings has been challenging
due to time and knowledge constraints. Three different six-item
forms of the State-Trait Anxiety Inventory (STAI) have been
constructed. Objective: The purpose of this study was to evaluate
and compare the psychometric properties of these three short
versions in the perinatal period. Methods: Data are drawn from
the All Our Babies study, a longitudinal pregnancy cohort in
Alberta, Canada. Internal consistency for the full version and the
three shortened versions was assessed using Cronbach’s alpha
coefficient for each data collection point. The item statistics, interitem correlations, and item-total statistics were also calculated.
The validity of the three shortened versions was assessed with
confirmatory factor analysis using the maximum likelihood
estimation technique to estimate and compare indicators of fit for
the three shortened forms of the STAI-S during pregnancy and at 4
and 12 months postpartum. Results: All shortened forms
demonstrated high internal consistency and reliability, with alphas
ranging from .81 to .85. All fit indices were greater than .93,
implying a good fit between each model and our data. In the
model comparisons, during pregnancy and at 4 months
postpartum, all fit index values were consistently higher for the
Marteau and Bekker scale than for the other two versions. In
contrast, at 12 months postpartum, the Chlan et al. version
demonstrated the best fit of the three versions. Conclusion: The
shortened versions appear to have acceptable psychometric
properties. Brief scales have the potential to provide an
economical means of assessing perinatal anxiety and can be
considered as equivalent alternatives to the full-scale version.
Acknowledgements: The authors acknowledge the Alberta
Children’s Hospital Foundation and the contribution and support
of AOB team members and our participants.All Our Babies funded
by Alberta Innovates Health Solutions Interdisciplinary Team Grant
#200700595. Dr. Bayrampour was supported by a Postgraduate
Trainee Award from the Alberta Innovates Health Solutions during
this research project. Dr. Tough is an Alberta Innovates Health
Solutions Health Scholar. Contact Information: Hamideh
Bayrampour [email protected]
[292]
Risk factors of antenatal anxiety: A systematic review. Hamideh
Bayrampour1, Angela Vinturache1, Charleen Salmon1, Suzanne
Tough1
1University of Calgary
Introduction: Anxiety is a common mental health problem during
pregnancy and is associated with several adverse maternal and
child outcomes with long term consequences. Therefore, early
detection and management of anxiety is an important public
health concern. Knowledge of risk factors of antenatal anxiety can
inform the development of screening strategies and interventions.
Objective: The purpose of this systematic review was to identify
and summarize individual and contextual factors contributing to
anxiety symptoms among pregnant women. Methods: To identify
relevant studies, the following databases were searched:
MEDLINE, PsycINFO, EBSCO's SocINDEX, Psychological and
Behavioral Sciences Collection, Cumulative Index to Nursing and
Allied Health Literature (CINAHL), SCOPUS, and EMBASE.
Additionally, a hand searching of the reference lists of retrieved
articles and specific searches of content experts were conducted
to identify additional studies. Cohort, case-control, or crosssectional studies using prospective or retrospective measures of
anxiety during pregnancy and that have been published in English
were included. The two authors independently assessed the
methodological quality of each included study using a modified
version of the Scottish Intercollegiate Guidelines Network (SIGN).
Results: Full texts of 279 articles were retrieved and reviewed.
Inconsistencies in defining and measuring anxiety were identified.
The most commonly used assessment tools were Spielberger State
Trait Anxiety Index and Hospital Anxiety and Depression Scale.
Various factors were significantly associated with the antenatal
anxiety. The factors most consistently reported to be linked to
antenatal anxiety were previous prental loss, inadequate social
support and pregnancy/medical complications. Conclusion:
Multiple, diverse demographic, medical, and psychosocial risk
factors contribute to elevated anxiety among pregnant women.
Implications of these findings for practice and directions for future
research were discussed. Acknowledgements: This review was
supported by a small grant from the Alberta Centre for Child,
Family and Community Research. Dr. Bayrampour was supported
by a Postgraduate Trainee Award from the Alberta Innovates
Health Solutions during this research project. Dr. Tough was
supported by a Salary Award from the Alberta Innovates Health
Solutions during this research project. Contact Information:
Hamideh Bayrampour [email protected]
[308]
HOW OFTEN DO WE USE BREASTFEEDING, SKIN-TO-SKIN CARE
AND SUCROSE TO REDUCE NEONATAL PROCEDURAL PAIN?
Ashley Desrosiers1, Denise Harrison1, Mariana Bueno2, Kowsar
Abdulla3, Marsha Campbell-Yeo4, Sandra Dunn5, JoAnn Harrold6,
Stuart Nicholls7, Jessica Reszel6, Janet Squires8, Bonnie Stevens9,
Jodi Wilding6
1Faculty of Health Sciences, University of Ottawa / Children's
Hospital of Eastern Ontario Research Institute, 2Department of
Maternal and Psychiatric Nursing, University of São Paulo ,
3Children's Hospital of Eastern Ontario, 4Faculty of Health
Professions and Departments of Pediatrics, Psychology and
Neuroscience, Dalhousie University, 5Better Outcomes Registry
and Network (BORN) Ontario, 6Children's Hospital of Eastern
Ontario Research Institute, 7Faculty of Medicine, University of
Ottawa, 8Faculty of Health Sciences, University of Ottawa / Ottawa
Hospital Research Institute, 9The Hospital for Sick Children
(SickKids)
Introduction: Healthy newborns experience at least one painful
procedure and sick infants undergo more painful procedures
during their hospitalization. Evidence shows breastfeeding (BF),
skin-to-skin care (SSC), and sucrose reduces pain in infants.
Despite this, the extent to which these strategies are used is not
clear. Objective: The objectives of this study were to: i)
determine current neonatal pain management practices in Ontario
and ii) ascertain barriers that limit use of BF, SSC and sucrose for
neonatal pain management. Methods: An electronic survey was
distributed to nurse managers and educators working in neonatal
and maternal/newborn units (n=91) entering data into the Better
Outcomes Registry & Network (BORN) Information System. The
survey consisted of four questions regarding current use of BF,
SSC, and sucrose during heel lance and venipuncture using a fourpoint scale (always, often, occasionally, never) and six optional
open-ended questions regarding barriers to using pain
management strategies. Responses to quantitative survey
questions were summarized using descriptive statistics and
qualitative survey responses were analyzed by content analysis.
CNPRM 2015
73
Results: Forty-two surveys were completed between July and
September 2013 (response rate=46%). Twenty-three (55%)
respondents answered that BF was occasionally used during heel
lance, however, 32 (76%) reported never using BF during
venipuncture. Eighteen (43%) participants reported occasionally
using SSC during heel lance and 32 (76%) reported never using SSC
during venipuncture. Half the units reported never using sucrose
during heel lance or venipuncture. Thirty-five of the 42
respondents answered the qualitative survey questions regarding
barriers to using the three pain management strategies in their
units. The most common barrier categories included: health care
professional factors such as comfort and skill level, baby factors
such as health status and feeding patterns, parent factors such as
preferences and culture, and organizational factors such as unit
environment and policies. Conclusion: There is suboptimal use of
BF, SSC, and sucrose during blood draws in neonates, despite
research evidence of their effectiveness. Respondents identified
barriers which limit the use of the three pain management
strategies in clinical practice. The results of this study have
informed the planning of a full scale trial to test a parent-targeted
knowledge translation intervention. The intervention is a video
aimed at parents of neonates and shows the effectiveness of BF,
SSC and sucrose during heel lance and venipuncture. This video
has the potential to increase use of the three effective pain
management strategies in neonatal and maternal newborn units.
Contact Information: Ashley Desrosiers [email protected]
[352]
USING COGNITIVE INTERVIEWING TO DEVELOP AN ONLINE
SURVEY OF PARENT PERSPECTIVES ON DATA SHARING . Zain S.
Velji1, Kiran P. Manhas2, Stacey Page 2, Shawn X. Dodd2, Xinjie Cui3,
Nicole Letourneau4, Suzanne Tough5
1University of Calgary, Faculty of Kinesiology , 2University of
Calgary, Department of Community Health Sciences , 3University
of Calgary, Alberta Centre for Child, Family, and Community
Research , 4University of Calgary, Faculty of Nursing , 5University of
Calgary, Department of Community Health Science
Introduction: Surveys are a valuable data collection method, but
their validity decreases if participants misinterpret or cannot
respond to questions. [1] Cognitive interviewing (CI) is a
qualitative method to identify survey problems. [2] This method
can advance survey validity and reliability by incorporating
participant perspectives during questionnaire development.
Higher response rates can be expected when using this technique.
[3] Despite its utility, CI is little used in perinatal epidemiology.
This project discusses the use and implications of CI to promote
the validity of an online survey of a complex and uncommon topic
in the parenting population: secondary data use and research data
repositories.. Objective: To determine how CI assists in modifying
and restructuring surveys to facilitate comprehension of unfamiliar
topics in perinatal populations. Methods: Participants were
recruited using a participant list from two Alberta birth cohorts.
Participants were called randomly and asked to participate in a
one-hour interview. Nine individual interviews were completed
where participants completed a draft, online questionnaire.
Probing questions were used to gauge understanding, survey
perceptions, and question appropriateness. Interviews were
audio-recorded and detailed notes were taken to capture
feedback. The interviewer debriefed after every 2-3 interviews
with two team members, which led to iterative probe
modification, interview focus redirection and development of
alternative questions and information. A matrix was developed to
compare and contrast data collected. This information and
interviewer experience were used to modify the survey. Results:
The CI yielded three major insights for survey improvement. First,
the interviewer witnessed varied participant experiences with the
74
survey: some participants enjoyed the process, while others
struggled to point of frustration. Reframing the language and
adding polar questions aimed to promote comprehension. Second,
the topic’s complexity revealed the utility of “educational”
questions, which may not provide new information, but would
allow participants to think through issues. Third, “educational”
questions and sufficiency of background information must be
tempered to avoid the survey length being overly-burdensome to
participants. The modified survey was distributed to a larger
population of parents from both cohort studies in August 2014.
Conclusion: CI can increase comprehension by witnessing
participant survey experiences and responses to probing
questions. This can increase the accuracy of data collection from
parents on a complex, uncommon topic. Acknowledgements:
Markin USRP Award
Contact Information: [email protected]/
[email protected]
[369]
THE 5-HTTLPR POLYMORPHISM OF THE SEROTONIN
TRANSPORTER GENE MODERATES THE RELATIONSHIP BETWEEN
PRENATAL MATERNAL STRESS AND AUTISM SPECTRUM
DISORDER SYMPTOMS: THE QUEENSLAND FLOOD STUDY. David
P. Laplante1, Maya Mouallem1, Guillaume Elgbeili1, Lei Cao-Lei2,
Vanessa Cobham3, Alain Brunet2, Sue Kildea3, Suzanne King2
1Douglas Institute Research Centre, 2McGill University and Douglas
Institute Research Centre, 3University of Queensland and Mater
Research Institute
Introduction: Autism Spectrum Disorder (ASD) is a
neurodevelopmental disorder with a strong genetic component
affecting 1% of children, mainly males. A recent study showed that
children carrying the La/La alleles on the 5-HTTLPR polymorphism
of the serotonin transporter risk were rated by their mothers as
having more severe ASD symptoms compared to children carrying
the S or Lg allele. We have shown that high levels of disasterrelated (1998 Quebec Ice Storm) prenatal maternal stress (PNMS)
were related to ASD symptoms in 6½ year-old children. However,
no study to date has determined whether the La/La genotype
moderates the relationship between PNMS and ASD symptoms in
young children. Objective: To determine whether the 5-HTTLPR
polymorphism moderates the relationship between in utero
exposure to high levels of PNMS and ASD symptoms in 30 monthold children. Methods: The mothers’ levels of objective and
subjective PNMS, cognitive appraisal, and peritraumatic distress
and dissociation were assessed at recruitment shortly after the
2011 Queensland Flood. The children’s ASD symptoms were
assessed by the mothers using the Autism Spectrum Rating Scales.
ASD data were available for 134 (72 boys) 30 month-old children.
Genetic data were available for 74 (40 boys) children. Additional
data concerning the mothers’ positive mental health, anxiety,
depression, and stress, and level of empathy were also collected.
Results: In boys, high maternal empathy and positively mental
health were associated with low ASD symptoms, explaining 12.0%
and 7.4% of the variance. High levels of subjective PNMS were
associated with more ASD symptoms, explaining 6.7% of the
variance. In girls, high maternal empathy was associated with low
ASD symptoms, explaining 27.1% of the variance. In children for
whom genetic data were available, low maternal positive mental
health and the La/La genotype were associated with more ASD
symptoms in boys, explaining 18.4% and 12.6% of the variance. A
cognitive appraisal × genotype interaction explained 9.0% of the
variance. Negative or neutral cognitive appraisal was related to
more ASD symptoms, but only in La/La allele carriers. In girls, high
maternal empathy and low current anxiety were associated with
fewer ASD symptoms, explaining 32.9% and 9.8% of the variance.
A peritraumatic dissociation × genotype interaction explained
CNPRM 2015
7.8% of the variance. High maternal peritraumatic dissociation was
related to more ASD symptoms, but only in La/La allele carriers.
Conclusion: This is the first study to determine that the 5-HTTLPR
polymorphism of the serotonin transporter gene moderates the
relationship between PNMS and ASD symptoms in young children.
Acknowledgements: Canadian Institutes of Health Research.
Contact Information: [email protected]
[383]
IMMIGRANT WOMEN’S EXPERIENCE OF POSTPARTUM
DEPRESSION IN CANADA: A NARRATIVE SYNTHESIS SYSTEMATIC
REVIEW. Dr Gina Marie Higginbottom1, Dr Myfanwy Morgan 2, Dr
Joyce O’Mahony 3, Yvonne Chiu 4, Kate Zhang5, Marilyn Young 6,
Joan Forgeron 6
1University of Alberta, Faculty of Nursing, 2King’s College, London,
3Mount Royal University, 4Multicultural Health Brokers Cooperative, 5Public Health Agency of Canada, 6Alberta Health
Services
Introduction: Understanding the ethnocultural orientation of
immigrant women in maternity is critical for their successful
integration and for social cohesion. A key aspect is the need for
timely identification and treatment of postpartum depression,
which has high prevalence in this vulnerable population and far
reaching implications. Objective: Funded by CIHR and partnering
with key stakeholders to ensure topic relevancy, we conducted a
narrative synthesis systematic review of quantitative and
qualitative primary research (Popay et al, 2006) to answer the
research question: What are the ethnoculturally defined patterns
of help-seeking behaviours and decision-making and other
predictive factors for therapeutic mental health care access and
outcomes in respect of postpartum depression for immigrant
women in Canada? Methods: Guidelines for systematic and grey
literature review were followed to identify and select literature.
Methodological quality was appraised using tools developed by
the Centre for Evidence Based Management. The narrative
synthesis methodology relied primarily on text to summarize and
explain findings, using four elements: a) developing a theory of
why and for whom, b) developing a preliminary synthesis, c)
exploring relationships in the data, and d) assessing the robustness
of the synthesis. ATLAS.ti software was used to synthesize
findings. Results: Our review has revealed precursors to
differences in health care access and utilization by immigrant
women with depressive symptomatology and these differences
are factors recognized to be critical determinants of effectiveness
of services and patient/client outcomes. Application of this
knowledge during the creation and enhancement of mental health
care programs will help provide culturally acceptable and
appropriate care. Conclusion: Findings will have direct relevance
in guiding provision of health care services, identify themes for
wider application for service delivery and public health initiatives
in relation to immigrant populations. Acknowledgements: CIHR
Funding. Contact Information: Dr Gina Higginbottom
[email protected]
Canadian Maternal Fetal Medicine Society
[229]
DELIVERY RECOMMENDATIONS FOR PREGNANT WOMEN WITH
RISK FACTORS FOR RHEGMATOGENOUS RETINAL DETACHMENT:
CURRENT PRACTICE AMONG CANADIAN OBSTETRICIANS AND
OPHTHALMOLOGISTS. Hannah Chiu1, Donna Steele2, Chryssa
McAlister1, Wai-Ching Lam1
1University of Toronto, Department of ophthalmology, 2University
of Toronto, Department of obstetrics and gynaecology
Introduction: Background: High-risk pathologies for
rhegmatogenous retinal detachment (RRD) in otherwise healthy
pregnant women are not contraindications for spontaneous
vaginal delivery. However, 74% of European obstetriciangynecologist (OBGYN) respondents in 2008 recommended
operative delivery for women at risk of RRD. This discrepancy is
likely due to an older study suggesting a causal relationship
between valsalva-like manoeuvres and RRD. Objective: The
purpose of this study is to determine current delivery
recommendations for healthy pregnant women with high-risk
pathologies for RRD amongst Canadian ophthalmologists and
OBGYNs. Methods: Anonymous prospective cross-sectional
survey sent via electronic link in 2013. Chi-square test of
proportions was used to compare delivery recommendations
between the two specialties. Multinomial logistic regression was
used to identify predictors for recommendations. Results: 356
participants responded including 92 ophthalmologists and 27
trainees, 185 OBGYN and 52 trainees. For healthy pregnant
women with previously treated retinal hole/tear or treated RRD,
significantly more OBGYNs recommended cesarean section and
significantly more ophthalmologists recommended spontaneous
vaginal delivery. Length of practice and type of practice setting
were significant predictors amongst obstetricians in their delivery
recommendations. Conclusion: This study is the first to include
obstetricians, ophthalmologists and their trainees in a survey of
the recommended mode of delivery for pregnant women with risk
factors of RRD. Our results suggest that obstetricians concerned
about potential RRD in pregnant patients may be unnecessarily
recommending operative management. Educational sessions on
the risk of RRD with spontaneous vaginal delivery may reconcile
the current differences in recommendations between
ophthalmologists and obstetricians. Contact Information:
[email protected]
[232]
CASE SERIES OF MULTIPLE REPEAT CESAREAN SECTIONS:
OPERATIVE MATERNAL AND NEONATAL OUTCOME. Abdullah
ALNOMAN, MD1, Darine EL-CHAAR MD, FRCSC2, Ziad El-Khatib,
MSc, PhD, MBAc3, Ahmad ALMRSTANI, MBBS, ABOBGN, SBOBGN4,
Mark WALKER, MSc, MD, FRCSC5
1Research Fellow, Ottawa Hospital Research Institute, The Ottawa
Hospital, University of Ottawa, Ottawa, Canada. Teaching
Assistant, Obstetrics and Gynecology, Faculty of Medicine, King
Abdulaziz University Hospital, Jeddah, Saudi Arabia., 2Assistant
Professor, Department of Obstetrics and Gynecology, The Ottawa
Hospital, University of Ottawa, Ottawa ON, 3Assistant Professor,
Department of Epidemiology and Community Medicine, University
of Ottawa, 4Assistant Professor, Department of Obsteterics and
Gynecology, Faculty of Medicine, King Abdulaziz University
Hospital, Jeddah, Saudi Arabia, 5Professor and Chair of the
Department of Obstetrics and Gynecology, University of Ottawa,
Ottawa ON
Introduction: Caesarian section is the most common procedure in
obstetrics, there are known morbidities associated with increasing
number of caesarean sections. Objective: To review the maternal
and neonatal morbidity and mortality associated with six or more
caesarean sections (CS). Methods: A retrospective chart review
of five patients having more than six CS deliveries, from 2000 to
2010, was performed at King Abdulaziz University Hospital (KAUH)
in Jeddah. A medical chart review tool was developed for data
collection. This tool included six sections: 1) Demographic data 2)
Maternal medical conditions 3) History of obstetrical problems in
current pregnancy 4) Intra-operative complication 5) Postoperative maternal complications 6) Post-operative neonatal
complications. Results: In the current series, there were no fetal
or maternal mortalities. Deliveries occurred in the range of 31-38
weeks. Four of the five cases required emergency caesarian
CNPRM 2015
75
section. There were two cases in the series with a placenta previa.
There was a single case of uterine dehiscence. Only one case
required a blood transfusion and was complicated with a placenta
accreta, bladder injury, urinary tract infection and prolonged
maternal hospital stay with NICU admission. All cases had
moderate to severe adhesion intraoperatively. Operative time was
long in all cases with a range 55-106 minutes. One of the five cases
had postoperative wound infection. Conclusion: It is necessary
for physician and patients to be aware of the maternal morbidity
associated with multiple CS. The long-term complications
associated with CS should be discussed with patients in the first
and subsequent pregnancies. This series highlighted that although
multiple casesarian sections, there are less complications than
expected despite limited sample size. Acknowledgements: We
would like to thank Dr.Suhaib Khayat, Dr.Safwan Altayeb and
Dr.Hisham Basamh for their contribution in the data collection.
Contact Information: [email protected]
[239]
MATERNAL PHYSICAL ACTIVITY DURING PREGNANCY: IMPACT
ON INFANT’S BIRTH WEIGHT AND BODY COMPOSITION. Michèle
Bisson1, Odette St-Onge2, Jean-François Bilodeau3, Isabelle Marc1
1Laval University/Pediatrics, 2Laval University/Radiology, 3Laval
University/Obstetrics and Gynecology
Introduction: Maternal physical activity during pregnancy may
have an impact on infant’s birth weight and body composition,
potentially influencing child’s long term metabolic health.
Objective: To evaluate in a longitudinal study the effect of physical
activity during pregnancy on infant’s birth weight, lean and fat
percentages and bone mineral content and density (BMC, BMD).
Methods: Self-reported physical activity (Pregnancy Physical
Activity Questionnaire) and 7-days of accelerometry were
collected at 17 and 36 wks of gestation. Birth weight was collected
from medical charts and infant body composition was evaluated
by DXA within Day 10 of life. Multiple regression models adjusted
for infant sex, parity, maternal pre-pregnancy BMI and gestational
age at delivery were created to evaluate the association between
birth weight and maternal 1°self-reported sports and exercise, 2°
number of counts/day (reflecting total activity), 3° time spent at
moderate and vigorous activity, and 4° vigorous activity (yes/no).
To explore physical activity predictors of infant body composition,
multiple regression models adjusted for the previously cited
confounders were created, further using a stepwise approach with
separated physical activity variables. Results: 55 low-risk
pregnant women (pre-pregnancy BMI=24.3±5.6 kg/m2; 69%
nulliparous) and their infant (birth weight=3449±384 g; gestational
age =39.8 ± 1.0 wks; 44% boys) were included. Based on
Matthew’s cut point, 53% of women did vigorous activity in early
pregnancy, which was associated with a significant reduction in
birth weight (adjusted mean difference= -230.8±89.7 g, p=0.013).
Levels of self-reported sports and exercise in late pregnancy were
independently associated with a lower birth weight, after
adjustment for confounders and sports and exercise in early
pregnancy (= -11.3±4.9 g per MET*h/wk, p=0.025). Infant fat and
lean mass percentages were both predicted by total number of
counts in early pregnancy (adjfat%= -0.97±0.48 % per 100,000
counts/day, p=0.047; adjfat%=.0±0.5 % per 100,000 counts/day,
76
p=0.043). Infant BMC and BMD were both predicted by selfreported sports and exercise in late pregnancy (adjBMC= = -0.2±0.1
g per MET*h/wk, p=0.033; adjBMD = -0.0004±0.0002 g/cm3 per
MET*h/wk, p=0.047). Conclusion: Maternal vigorous physical
activity, as well as sports and exercise, is associated with a
significant reduction in birth weight. Higher levels of total activity
also seem to modulate infant’s lean/fat ratio.
Acknowledgements: This study was funded by the Fondation des
Étoiles. M.B. is a doctoral scholarship holder from the Canadian
Institutes of Health Research. I.M. holds a Fond de Recherche du
Québec-Santé clinician scientist award. Contact Information:
[email protected]
[248]
THE EFFECT OF BACK PAIN AND URINARY INCONTINENCE ON
DAILY TASKS OF MOTHERS AT 12 MONTHS POSTPARTUM.
Co Authors: C. Mannion and A. Vinturache1, Shelia W. McDonald,
2, Suzanne C Tough2
1Faculty of Nursing, University of Calgary, Calgary, AB,
2Department of Community Health Sciences, Faculty of Medicine,
University of Calgary, Calgary, Alberta
Introduction: The prevalence of back pain(BP)and urinary
incontinence(UI)associated with pregnancy and childbirth varies
from 45-53% and 6-34% respectively.Both conditions can impair
performance of daily tasks and the quality of life for new mothers
but the area is understudied. Objective: To assess the impact of
BP and/or UI on healthy childbearing women and impairment of
daily tasks at 12 months postpartum. Methods: This secondary
analysis is from the All Our Babies study. Maternal self-reported
questionnaires on demographics, lifestyle, BP, UI and impairment
of daily tasks was collected at 25,34,36 weeks gestation and at 4
and 12 months postpartum. Associations between covariates,UI,
BP,and the ability to perform daily tasks was tested with Chisquare. Other associations were modelled using logistic and
multinomial regression. Results: At 12 months postpartum
1212(77%) experienced BP,773(49%)UI,and 620(40%)both BP and
UI. Women with a pre-pregnancy BMI (wt kg/ht m2)> 30.0 were
more likely to report BP. Caucasian women with high household
income most often reported UI symptoms. Labour induction was
associated with BP,and vaginal delivery with UI compared to
women with a C-section. Non-Caucasian ethnicity and lower
household income was associated with increased severity of BP.
Moderate impairment of daily tasks due to BP, was reported by
199(24%)and 90(11%)severely affected.Functional impairment due
to UI was reported by 267 women,52(19%)stated that UI
moderately to severely impaired their ability to perform daily
tasks. Multiparas were 2.7 times more likely to report severe
impairment due to BP than primiparas. Women with vaginal
deliveries were at more risk of moderate/severe impairment of
daily tasks due to UI compared to those women with C-section.
Conclusion: BP and UI are common 12 months postpartum.
Maternal performance of daily tasks and women’s health and
quality of life are more often impaired due to BP than UI.Careful
assessment of the presence and severity of the physical and
functional health status of women in the year after childbirth may
improve the quality of life for these women and inform patientcentered postpartum care. Demographic and obstetrical factors
such as age, parity, BMI and mode of delivery should be
considered in the evaluation of women to identify those at risk
and suggest preventative measures. Counseling pregnant women
about potential UI and recurrent BP during pregnancy and birth
and treatment options postpartum may contribute to improved
quality of life for new mothers and their families. Our study brings
new evidence of the risk factors that predict severity and impact of
these conditions on women functioning at 12 months postpartum.
Acknowledgements: Muci Wu for data assistance. Contact
CNPRM 2015
Information: Cynthia Mannion RN, Angela Vinturache MD
[email protected]
Institutes of Health Research (CIHR). Contact Information:
[email protected]
[253]
OVARIAN STIMULATION USE, INCLUDING CLOMIPHENE CITRATE,
AND INTRAUTERINE INSEMINATION USE AND THE RISK OF
MULTIPLICITY AND MAJOR CONGENITAL MALFORMATIONS: A
META-ANALYSIS. Chaabane Sonia1, Blais Lucie2, Fraser William3,
Bissonnette François4, Monnier Patricia5, Trasler Jacquetta 6,
Bérard Anick7
1Research Center, CHU Ste-Justine, Montreal, Qc, Faculty of
pharmacy, University of Montreal, 2Faculty of pharmacy,
University of Montreal, Research Center, Sacré-Coeur Hospital,
Montreal, 3Department of obstetrics and gynecology, CHU SteJustine, Montreal, Faculty of Medicine, University of Montreal, 4
Faculty of Medicine, University of Montreal. OVO Fertility Clinic,
CHUM, Montreal, 5MUHC University Reproductive Center,
Department of obstetrics and gynecology, Royal Victoria Hospital,
Montreal, Faculty of Medicine, McGill University, Montreal,
6Faculty of Medicine, McGill University, Montreal. Montreal
Children's Hospital Research Institute , Montreal, 7Research
Center, CHU Ste-Justine, Montreal, Faculty of pharmacy, University
of Montreal.
Introduction: The relationship between medically assisted
reproduction (MAR) use and the risk of major congenital
malformations (MCM) is controversial. Multiple pregnancies is a
recognized adverse effect of MAR; nevertheless, there is no
consensus on the incremental risk. Objective: Our meta-analysis
summarizes the literature on fertility treatments and risks for the
newborn, explains discrepancies between studies, and identifies
the gaps in knowledge for future research. Methods: We carried
out a systematic review to identify published papers between
1966 and 2012 in Medline, Embase and Cochrane Central Register
of Controlled Trials. We included observational studies and
randomized clinical trials related to the risk of multiple
pregnancies or MCM conceived following ovarian stimulation (OS)
alone, intrauterine insemination (IUI) and in-vitro fertilization (IVF)
with related procedures compared to spontaneously conceived
infants or infants conceived using other MAR. Results: We
identified 238 eligible studies. Among them, 186 reported data on
IVF, 37 reported data on OS used alone and 21 on IUI use.
Compared to natural conception, OS used alone was associated
with a greatly increased risk of multiple pregnancies (RR 11.68,
95% CI 7.00-19.47), major congenital anomalies of nervous system
(RR 1.79, 95% CI 1.12 -2.87) and major musculoskeletal
malformations (RR 1.49, 95% CI 1.01- 2.20). The risk of multiple
pregnancies further decrease and the risk of major
musculoskeletal malformations increase when data were
restricted to clomiphene citrate (the first line OS). Compared to
natural conception, the use of IUI was associated with greatly
increased risk of multiple pregnancies(RR 9.23, 95% CI 7.02-12.14)
and major musculoskeletal malformations (RR 1.66, 95% CI 1.262.18). Conclusion: A limited number of observational studies
focused on the risk of multiple pregnancies and MCM following OS
alone and IUI compared the data on IVF use. Results suggest that
overall OS used with or without IUI increases the risk of multiple
pregnancies and some types of MCM. Acknowledgements: A.B. is
on the endowment research chair on Medications, Pregnancy, and
Lactation at the Faculty of Pharmacy of the University of Montreal;
J.T. is a James McGill Professor of McGill University, and a member
of the Research Institute of the McGill University Health Centre;
W.F. is the principal investigator of the Canada Research Chair on
perinatal epidemiology at the University of Montreal. We thank
CIHR-Quebec Training Network in Perinatal Research (QTNPR) for
the training scholarship. This study was supported by the Drug
Safety and Effectiveness Network (DSEN) and the Canadian
[257]
EXPOSURE TO ORGANOPHOSPHORUS AND ORGANOCHLORINE
PESTICIDES, PERFLUORINATED COMPOUNDS, AND
POLYCHLORINATED BIPHENYLS IN PREGNANCY AND THE
ASSOCIATION WITH IMPAIRED GLUCOSE TOLERANCE AND
GESTATIONAL DIABETES MELLITUS: THE MIREC STUDY. Gabriel D.
Shapiro1, Linda Dodds2, Tye E. Arbuckle3, Jillian Ashley-Martin2,
Adrienne S. Ettinger4, Mandy Fisher3, Shayne Taback5, Maryse F.
Bouchard1, Patricia Monnier6, Renée Dallaire7, Anne-Sophie
Morisset1, William Fraser8
1Université de Montréal, 2Dalhousie University, 3Health Canada,
4Yale University, 5University of Manitoba, 6McGill University,
7Université Laval, 8Université de Sherbrooke
Introduction: Studies report increases in rates of gestational
diabetes mellitus (GDM) over recent decades. Environmental
chemicals may increase the risk of diabetes through impacts on
glucose metabolism, mitochondrial dysfunction, and endocrinedisrupting mechanisms including effects on pancreatic beta-cell
function and adiponectin release. Objective: To determine the
associations between pesticides, perfluorinated compounds (PFCs)
and polychlorinated biphenyls (PCBs) measured in early pregnancy
and impaired glucose tolerance (IGT) and GDM in a Canadian birth
cohort. Methods: Women enrolled in the Maternal-Infant
Research on Environmental Chemicals (MIREC) Study were
included if they had a singleton delivery and did not have preexisting diabetes. Exposure variables included three
organophosphorus pesticide metabolites detected in firsttrimester urine samples, as well as three organochlorine
pesticides, three PFCs, and four PCBs in first-trimester blood
samples. IGT and GDM were assessed by chart review in
accordance with guidelines from the Canadian Diabetes
Association and the National Diabetes Data Group. Logistic
regression, adjusted for maternal age, race, education and prepregnancy BMI, was used to calculate odds ratios (ORs) and 95% CI
for the association between quartiles of environmental chemicals
and both IGT and GDM. Analyses for organochlorine pesticides
and PCBs were additionally adjusted for total blood lipids, and
analyses for organophosphorus pesticide metabolites were
adjusted fo r urinary specific gravity. Results: Of 2001 women
recruited into the MIREC cohort, 1274 met the inclusion criteria
and had outcome and biomonitoring data available. Significantly
smaller odds of GDM were observed in the third and fourth
quartiles of dimethylphosphate (DMP) and in the fourth quartile of
dimethylthiophosphate (DMTP) in adjusted analyses (DMP Q3:
OR=0.2, 95% CI=0.1-0.7; DMP Q4: OR=0.3, 95% CI=0.1-0.8; DMTP
Q4: OR=0.3, 95% CI=0.1-0.9). Significantly elevated odds of IGT
were observed in the second quartile of perfluorohexane
sulfonate (PFHxS) (OR=3.5, 95% CI=1.4-8.9). No statistically
significant associations were observed between PCBs or
organochlorine pesticides and IGT or GDM. Conclusion: We did
not find consistent evidence for any positive associations between
the chemicals we examined and GDM or IGT. We cannot rule out
the influence of residual confounding due to unmeasured
protective factors associated with pesticide levels, such as
consumption of contaminated produce, on the observed inverse
associations between maternal organophosphorus pesticide
metabolites and GDM. These findings require further
investigation. Acknowledgements: This study was funded by the
Canadian Diabetes Association, CIHR, and Health Canada. Contact
Information: [email protected]
[266]
TRENDS IN OPTIMAL, SUBOPTIMAL, AND QUESTIONABLY
APPROPRIATE RECEIPT OF ANTENATAL CORTICOSTEROID
CNPRM 2015
77
PROPHYLAXIS. Neda Razaz1, Amanda Skoll2, John Fahey 3, Victoria
Allen 4, KS Joseph5
1School of Population and Public Health, University of British
Columbia, 2Department of Obstetrics and Gynaecology, University
of British Columbia and the Children’s and Women’s Hospital and
BC Women’s Hospital and Health Centre, 3Reproductive Care
Program of Nova Scotia, 4Department of Obstetrics and
Gynaecology, Dalhousie University , 5School of Population and
Public Health and Department of Obstetrics and Gynaecology,
University of British Columbia.
Introduction: Antenatal corticosteroid (ACS) prophylaxis for
women at risk of preterm delivery reduces infant morbidity and
mortality but unnecessary use may have adverse consequences.
Objective: We conducted a population-based study to determine
rates of optimal, suboptimal and questionably appropriate ACS
use. Methods: All live births in Nova Scotia, Canada from 1988 to
2012 were identified from the Nova Scotia Atlee Perinatal
Database. The frequency of ACS administration was quantified
within strata of gestational age and by maternal and obstetric
factors. Temporal trends in optimal (proportion of live births at 2434 weeks receiving ACS between 24 hours and 7 days before
delivery), suboptimal (proportion of live births at 24-34 weeks
receiving ACS 7 days before delivery) and questionably
appropriate ACS administration (proportion of live births ≥35
weeks receiving ACS) were quantified using odds ratios (OR) and
95% confidence intervals (CI). Results: Among 246,459 live births
between 1988 and 2012, 2.5% received any ACS. The rate of ACS
administration at 28-32 weeks gestation increased from 39.5% in
1988-1992 to 79.3% in 2008-2012 (OR 5.8, 95% CI 4.3-7.9), while
use at 33-34 weeks increased from 14.3% to 49.7% (OR 5.6, 95% CI
4.3-7.4). Optimal ACS use increased from 10% in 1988 to 23% in
2012 (OR 2.7, 95% CI 1.6-4.5), suboptimal administration increased
from 7% to 34% (OR 6.7, 95%CI 3.9-11.6) and questionably
appropriate use increased from 0.23% in 1988 to 1.7% in 2012 (OR
7.5, 95% CI 4.9-11.3). Of the women who received ACS in 2012,
52% delivered at ≥35 weeks (see Figure 1). Conclusion: Temporal
increases in optimal ACS use have been matched by similar
increases in suboptimal and questionably appropriate ACS use;
more than half the infants who received ACS were born at ≥35
weeks and thus unnecessarily exposed to corticosteroids in utero.
This highlights the need for more accurate methods for
determining impending preterm delivery. Acknowledgements:
This study was supported by a grant from the Canadian Institute of
Health Research (APR-126338). Contact Information:
[email protected]
[268]
IL-1 AND PGF2Α STIMULATE IL-1 RECEPTOR (R)1 AND 2 AND
ACCESSORY PROTEINS (ACP) AS WELL AS IL-6R IN HUMAN
MYOMETRIAL SMOOTH MUSCLE CELLS (HMSMC). Barbara
Verstraeten1,4, Kelycia Leimert1, Xin Fang2 and David M Olson1,2,3.
1Dept Physiology, 2Dept Ob/Gyn, 3Dept Pediatrics, University of
Alberta, Edmonton, Canada; 4Dept Ob/Gyn, Faculty of Medicine &
Health Sciences, Ghent University, Ghent, Belgium.
Introduction: Every delivery is an inflammatory process which
involves the transformation of the non-contractile uterus of
pregnancy to the active uterus of labour, able to expel the fetus.
Prostaglandin (PG)F2α, Interleukin (IL)-1β and IL-6 are known
mediators of this inflammatory response. The IL-1β receptors, IL1R1 and IL-1R2, form a complex with IL-1RAcP for signalling.
Previously, IL-1RAcPb mRNA expression had only been described
in the central nervous system. However, we recently found an
increase in expression of IL-1R1, IL-1R2, IL-1RAcP and IL-1RAcPb in
the rat uterus in late gestation. IL-6 has a key role in the onset of
parturition. The IL-6R binds IL-6, and complexes with glycoprotein
(gp)130 for signal transduction, with gp130 being the common
78
signalling component of the cytokine receptor within the IL-6
family. Recently, we showed that PGF2α stimulation induces
production of IL-6 by HMSMC. Objective: In this study, we
hypothesize that HMSMC express the four IL-1R genes and that
they are regulated by PGF2α and IL-1β. We also investigate
whether IL-1β, with or without PGF2α treatment, stimulates the IL6R and gp130. Methods: HMSMC were retrieved from women
not in labor at term, following caesarean section (n=5-9). The cells
were pre-treated with 5 ng/ml IL-1β for 24h, followed by PGF2α
(10-7 and 10-5 M) for 6h, or treated only with PGF2α. mRNA
abundance of IL-1R1, IL-1R2, IL-1RAcP, IL-1RAcPb, IL-6R, gp130 and
GAPDH as housekeeping gene was evaluated by RT-PCR. ANOVA
with Tukey HSD post-hoc tests or t-tests were performed for
statistical evaluation after log10 transformation. Results: Both IL1R1 and IL-1R2 expression increased in a dose-response manner to
PGF2α (p<0.001 and p<0.05). IL-1AcP displayed a similar trend (NS),
while IL-1RAcPb demonstrated an inverse relationship, with PGF2α
stimulating expression at lower doses (p<0.05). IL-1β stimulated a
significant increase in expression of these 4 genes (p<0.001).
Addition of PGF2α after IL-1 _pre-treatment did not induce a
further rise in expression. IL-6R expression was increased by IL-1β,
with an additive effect of PGF2α (p<0.001). There was no effect on
gp130 expression. Conclusions: The expression of IL-1R1, IL-1R2,
IL-1RAcP, IL-1RAcPb mRNA is regulated by PGF2α and IL-1β in
HMSMC. PGF2α has an additive effect on IL-6R expression after IL1β treatment. IL-1β stimulates its own receptors and accessory
proteins, as well as IL-6R. Furthermore, these are the first data
showing presence of IL-1RAcPb outside the human brain.
Together, these observations add a level of complexity to the
feed-forward aspect of uterine transformation for labour.
Acknowledgements: PhD Fellowship, Research Fund Flanders,
CIHR, March of Dimes. Contact information : Barbara Verstraeten
[email protected]
[273]
AN IN VITRO MODEL FOR STUDYING THE REGULATION OF
UTERINE CHEMOTACTIC FACTOR. Nanlin Yin1, Jun Takeda2, Xin
Fang3, Hongbo Qi4, David M Olson5
1University of Alberta, Dept Ob/Gyn, Physiology & Pediatrics;
Chongqing Medical University, Dept Ob/Gyn, 2University of
Alberta, Dept Ob/Gyn, Physiology & Pediatrics;Juntendo U Faculty
of Medicine, Dept Ob/Gyn , 3University of Alberta, Dept Ob/Gyn, 4
Chongqing Medical University, Dept Ob/Gyn, 5University of
Alberta, Dept Ob/Gyn, Physiology & Pediatrics
Introduction: Each delivery whether at term or preterm is
preceded by an invasion of circulating leukoctyes into the uterine
myometrium and decidua. They are attracted by a chemotactic
factor that we have identified in the fetal membranes (amnion,
chorion) and decidua. However, the regulation of expression for
this factor is unknown. Therefore we have developed an in vitro
human tissue culture model to study the regulation of its
experssion. Objective: Our aim is to describe the model and
characteristics of the chemotactic factor. Methods: Tissue
cultures: Fetal membranes with attached decidua vera from term,
not in labour placentas delivered by elective cesarean section at
the Royal Alexandra Hospital were used. The protocol was
approved by the AHS/UA REB and consent granted in each case.
Intact tissues were cut into 12mm pieces (100mg) by a punch.
Following washing, the pieces were placed into the wells of 6 well
culture plates (6.9 cm2) and incubated for 24h at 37°C in HEPESbuffered Dulbecco’s Minimum Essential Medium: Nutrient Mixture
F-12 (DMEM/F12) maintained at pH 7.4. Following 48h the media
were discarded and new DMEM/F12 containing either agonists or
vehicle was added for 24-96h. The medium was collected and
stored at -80°C for subsequent leukocyte migration activity (LMA).
LMA: Peripheral blood (5mL) was obtained from women
CNPRM 2015
immediately following term spontaneous vaginal delivery. The
leukocytes were separated by HetasepTM and gentle
centrifugation. Leukocytes (105) were inserted into the upper
compartment of a modified Boyden Champber and approximately
25µL (125µg protein) of medium containing chemoattractant was
placed into the lower compartment. The two compartments were
separated by a filter containing 3 µm pores. The chambers were
incubated for 90 min at 37°C. At the end of this time, the number
of cells that migrated to the lower chamber were quantified by
FACS analysis. Results: Tissue DNA and RNA remained steady
over 96h suggesting the minced tissues remained viable. There
was a time-dependent increase in the release of chemoattractant
activity into the media from 24h to 96h when it reached a plateau.
Upwards of 45,000 cells migrated when chemoattractant was
present. Blanks were negligible. Conclusion: We have successfully
developed a new model for studying the regulation of the uterine
cheomoattractant. Future studies will assess the responsiveness of
human fetal membrane in this model system to a number of
inflammatory and non-inflammatory agonists that mediate the
processes of parturition and preterm birth. Acknowledgements:
Chongqing Medical University, GAPPS, CIHR, and WCHRI. Contact
Information: Nanlin Yin [email protected]
[274]
TRAIL OF LABOR AFTER CESAREAN IN TWIN GESTATIONS: DOES IT
INCREASE MATERNAL OR NEONATAL COMPLICATIONS? Okby
Rania1, Diamant Hagit 1, Imterat Majdi1, Sergienko Ruslan2, Sheiner
Eyal3
1Department of Obstetrics and Gynecology, Faculty of Health
Sciences, Soroka University Medical Center, Ben-Gurion University
of the Negev, Beer-Sheva, Israel., 2Ben-Gurion University of the
Negev, Epidemiology and Health Services Evaluation, Beer-Sheva,
Israel, 3 Department of Obstetrics and Gynecology, Faculty of
Health Sciences, Soroka University Medical Center, Ben-Gurion
University of the Negev, Beer-Sheva, Israel.
Introduction: The optimal mode of delivery for twin pregnancies is
not yet established. A marked increase in the overall cesarean
delivery (CD) rate of twin pregnancies has recently been observed
all over the world. one of the indication for CD is previous CD.
Objective: To investigate the rate, success and pregnancy
outcome following a trail of labor after cesarean (TOLAC) in twin
gestations. Methods: A retrospective study including all twin
pregnancies with a single prior cesarean delivery between the
years 2006 to 2011 was performed. Women with medical
indications for cesarean delivery (CD) were excluded. Maternal
and neonatal outcomes were compared between women who
delivered by CD to those who underwent TOLAC. Stratified
analysis using a multiple logistic regression model was performed
to control for confounders. Results: During the years 2006-2011,
110 women met the inclusion criteria. Of these, 20% (n=22)
underwent a TOLAC. The success rate of vaginal birth after
cesarean was 77.2% (n=17). No cases of uterine rupture or
dehiscence were noted. No significant difference was documented
in neonatal outcome (including pH and Apgar scores) between the
TOLAC and the CD group. . Fertility treatment was noted as a risk
factor for repeated CD (35.2 vs. 4.5%, OR=8.6, 95% CI 1.21-61.3,
P=0.005). Using a multivariable analysis, with repeated CD as the
outcome variable, controlling for confounders such as maternal
age, and gestational age, fertility treatment was an independent
risk factor for repeated CD (adjusted OR=5.2, 95% CI 0.01-0.70;
P=0.02). Conclusion: A TOLAC in twin gestation seems to be a
safe option for the mother and newborn. Fertility treatment is an
independent risk factor for repeated CD in twins. Contact
Information: Rania Okby [email protected]
[275]
ANEMIA IN TWIN PREGNANCIES: DOES IT DIFFER FROM
SINGLETONS? Okby Rania1, Kosto Amit1, Shoham-Vardi Ilana 2,
Sergienko Ruslan2, Sheiner Eyal 1
1Department of Obstetrics and Gynecology, Faculty of Health
Sciences, Soroka University Medical Center, Ben-Gurion University
of the Negev, Beer-Sheva, Israel., 2Ben-Gurion University of the
Negev, Public Health, Beer-Sheva, Israel
Introduction: In singletons, maternal anemia has been found to be
associated with increased risk for preterm birth and small for
gestational age newborns. Objective: To investigate the effect of
second trimester anemia on maternal and perinatal outcomes in
twin pregnancies compare to those with normal hemoglobin
levels. Methods: A retrospective population-based study was
conducted, comparing maternal and neonatal outcome in women
carrying twins with second trimester anemia (defined by
hemoglobin < 10 gr/dl) to those with hemoglobin> or equal 10
gr/dl . Deliveries occurred in a tertiary medical center during the
year 2013. Results: During the study period, there were 307 twin
deliveries. Hemoglobin levels were available for 247 (80.4%) twins;
66 (26.7%) of these had anemia (or equal 10 gr/dl. No significant
difference were noted between the groups regarding other
obstetrical outcomes. Likewise, perinatal outcome was
comparable between the groups (Table). Conclusion: Second
trimester anemia increases the risk for blood transfusion for
women carrying twins. However, in our population, maternal
anemia in twins does not increase the risk for adverse perinatal
outcome. Contact Information: Rania Okby [email protected]
[276]
SHORT INTERPREGNANCY INTERVAL IN TWIN GESTATION: IS IT
ASSOCIATED WITH ADVERSE PERINATAL OUTCOME? Okby
Rania1, Mashiach Friedler jordana1, Shoham-Vardi Ilana PhD2,
Sergienko Ruslan2, Sheiner Eyal MD PhD1.
1 Department of Obstetrics and Gynecology, Faculty of Health
Sciences, Soroka University Medical Center, Ben-Gurion University
of the Negev, Beer-Sheva, Israel. 2 Ben-Gurion University of the
Negev, Public Health, Beer-Sheva, Israel
OBJECTIVE: To estimate whether a short interpregnancy interval
(IPI) is independently associated with an increased risk of adverse
obstetrical and perinatal outcomes in twin pregnancies.
METHODS: A retrospective population-based study was
conducted comparing maternal and neonatal outcome in women
carrying spontaneously conceived twins with short IPI (i.e. less
than 18 months) to those with longer IPI. Deliveries occurred in a
tertiary medical center between the years 1988 and 2010.
RESULTS: During the study period, there were 4428 twin
deliveries. After excluding primiparas and pregnancies conceived
after fertility treatments, 862 twin pregnancies were included in
the study. Of these, 412 (47.8%) had a short IPI (equal or less than
18 months). Mothers with short IPI were younger (28.8±-5.4 SD
vs. 31.8±4.8 SD years, P< 0.01) and were more likely to lack
prenatal care (9.2% vs. 4.9%, OR=1.45, 95% CI 1.03-2.04, P=0.01)
as compare to those with longer IPI. There were no significant
CNPRM 2015
79
differences among the two groups regarding the rate of preterm
birth, low birth weight, perinatal mortality, cesarean deliveries or
maternal complications (Table). CONCLUSION: Unlike a negative
effect of short IPI in singletons, short IPI in twin pregnancy, in our
population, was not associated with adverse maternal or perinatal
outcomes. Contact information: Rania Okby [email protected]
[277]
FERTILITY TREATMENTS AND PREVIOUS CESAREAN DELIVERY AS
RISK FACTORS FOR MATERNAL REQUEST OF CESAREAN DELIVERY
IN TWIN GESTATIONS. Rania Okby1, Yura Druyan1, Molly
Sonenklar1, Barak Aricha-Tamir1, Sheiner Eyal1
1Department of Obstetrics and Gynecology, Faculty of Health
Sciences, Soroka University Medical Center, Ben-Gurion University
of the Negev, Beer-Sheva, Israel.
Introduction: A marked increase in the overall cesarean delivery
(CD) rate of twin pregnancies has recently been observed.
Objective: We sought to examine the obstetrical characteristics of
those who choose un-indicated CD and to investigate trends in the
rate of CD for maternal request over a five years period. Methods:
A cross sectional study compared the rate and obstetrical
characteristics of patients who choose un-indicated CD during the
years 2006 and 2011 compared to those who deliver vaginally.
Results: Out of 525 twins that were included at the study, 61.7%
(n=324) were delivered by CD. Of these, 28.7% (n=93) were unindicated. Fertility treatments and previous CD were significant
risk factors for un-indicated elective CD (51.6% vs. 27.4%, OR=2.8,
95% CI 1.69-4.72, <0.001, and 26.9% vs. 3.5%, OR=10.18, 95% CI
4.21-24.62, P<0.001; respectively). No significant differences were
noted between the two groups regarding other characteristics
such as maternal age, parity, chorionicity or the rate of non-vertex
presentation of the second twin (Table). In addition, there was a
significant decrease in the rate of un-indicated CD between the
years 2006 and 2011 (63.8% vs 23.8%, OR=0.58, 95% CI 0.35-0.94,
P=0.02). Conclusion: Fertility treatments and previous CD are risk
factors for un-indicated CD. Interestingly, there was a decrease in
the rate of CD for maternal request over a the five years period.
Contact Information: Rania Okby [email protected]
[280]
Sampling frequency of fetal heart rate impacts the ability to
predict pH and BE at birth: retrospective cohort study. Xuan Li1,
80
Yawen Xu1, Christophe Herry2, Daniel Durosier3, Daniela Casati4,
Tamara Stampalija5, Andrew JE Seely2, Francois Audibert3, Zarko
Alfirevic6, Enrico Ferrazzi4, Xiaogang Wang1, Martin G Frasch7
1Department of Mathematics and Statistics, York University,
2Dynamical Analysis Laboratory, Ottawa Hospital Research
Institute, University of Ottawa, 3Department of Obstetrics and
Gynecology, University of Montreal, 4Department of Obstetrics
and Gynecology, University of Milan, 5Unit of Prenatal Diagnosis,
Institute for Maternal and Child Health, 6Department of Women’s
and Children’s Health, University of Liverpool, 7Department of
Obstetrics and Gynecology and Neurosciences, University of
Montreal
Introduction: FHR sampling rate used on the bedside is less than 4
Hz and insufficient to detect incipient fetal acidemia. In fetal sheep
model of human labour we showed that FHR sampling rates near
1000 Hz are needed. Trans-abdominal fetal ECG (t-a fECG)
sampling FHR at 900 Hz combined with a complex signals
bioinformatics approach showed promise in a human cohort. Here
we validate this finding in a retrospective human cohort study by
comparing the performance of the same bioinformatics approach
to predict pH and BE at birth in two cohorts with FHR sampled
either at 4 Hz and one cohort sampled at 900 Hz. Objective: Our
aim is to compare the predictive power of the two data sets using
different FHR sampling rate (4 Hz VS 1000 Hz) effectively.
Methods: The open access intrapartum CTG data base with n=552
subjects and a cohort of prospectively recruited n=11 labouring
women were used as 4 Hz FHR recording data sets. The t-a fECG
cohort of n=60 subjects was used as 900 Hz FHR data set. We have
determined the goodness of fit (R2) and root mean square error
(RMSE) as the performance indicators of the model on each
cohort. Results: The clinical characteristics of both cohorts were
similar (gestational age 280±8 days; gender 50% male; birth body
weight 3.5±0.5 kg; pH and BE at birth 7.24±0.1 and -6.3±3.7
mmol/L, respectively; 1' and 5' Apgar scores at birth 8.7±1.4 and
9.4±0.7, respectively). The 4 Hz FHR cohort rendered - for pH and
BE - R2=0.26 and 0.2 and RMSE=0.087 and 3.44, respectively. The
900 Hz FHR cohort rendered - for pH and BE - R2=0.9 and 0.77 and
RMSE=0.03 and 1.70, respectively; i.e., lower FHR sampling rate
increased the predicted error range 3-4fold. Conclusion:
Intrapartum fetal monitoring fails to accurately detect fetal
asphyxia, with the incidence of cerebral palsy virtually unchanged
or increased in preterm births. We show that increasing FHR
sampling rate to 900 Hz improves prediction of fetal pH and BE at
birth. This should improve early identification of babies at risk of
brain injury. Acknowledgements: This project is funded by CIHR,
FRQS, NeuroDevNet/MITACS and QTNPR. Contact Information:
Martin G. Frasch [email protected]
[289]
PREECLAMPSIA ACTS DIFFERENTLY IN SPONTANEOUS VS. INVITRO FERTILIZATION TWINS. Rania Okby1, Sergienko Ruslan2,
Eyal Sheiner1
1Department of Obstetrics and Gynecology, Faculty of Health
Sciences, Soroka University Medical Center, Ben-Gurion University
of the Negev, Beer-Sheva, Israel., 2Ben-Gurion University of the
Negev, Epidemiology and Health Services Evaluation, Beer-Sheva,
Israel
Introduction: The incidence of twin pregnancy has risen in the last
decades. Preeclampsia-toxemia (PET) is a major maternal
complication associated with multiple pregnancies. Objective: To
investigate risk factors and pregnancy outcome of spontaneous vs.
in-vitro fertilization (IVF) twins complicated with preeclampsiatoxemia (PET). Methods: A retrospective population-based study
was conducted comparing maternal and neonatal outcome in IVF
vs. spontaneously conceived twins. Deliveries occurred in a
tertiary medical center between the years 1988 and 2010. Women
CNPRM 2015
with chronic hypertension were excluded from the study.
Results: The study population included 4428 twin pregnancies, of
these 314 (7.1%) had preeclampsia. 64 (20.3%) were IVF twins and
250 (79.7%) were spontaneous twins. The mothers of IVF-twins
were older (31.55y vs 29.25 y, P=0.006). The rate of nulliparous
was higher in IVF-twins (82.8% vs 34%, OR=9.3, 95%CI 4.64-18.83;
P<0.001). GDM was more frequent in IVF twins. The rate of
cesarean delivery was higher among IVF twins (83.6% vs 62.2%,
OR=3.1, 95%CI 1.87-5.11; P<0.001). The mean gestational age at
delivery and the mean birth weight were significantly lower in IVFtwins (34.9 w vs 35.7w, P=0.01, 2124gr vs 2263gr P=0.008,
respectively). Conclusion: IVF twins with PET are significantly
associated with advanced maternal age, nulliparity and GDM. IVF
twins with PET are at an increased risk for cesarean delivery,
preterm delivery and low birth weight. However, there was no
difference in the perinatal mortality or 5 minutes apgar scores <7
among the two groups. Contact Information: Rania Okby
[email protected]
[296]
EXPLORING THE POTENTIAL OF LOW DOSE CARBON MONOXIDE
INHALATION FOR USE AS A GASEOUS THERAPEUTIC FOR
PREECLAMPSIA: A PILOT STUDY IN HEALTHY VOLUNTEERS.
Karalyn E McRae1, Richard Casselman1, Graeme N Smith2
1Department of Biomedical and Molecular Sciences, Queen's
University, Kingston, 2Obstetrics and Gynaecology, Kingston
General Hospital / Department of Biomedical and Molecular
Sciences, Queen's University, Kingston
Introduction: The heme oxygenase(HO)/carbon monoxide(CO)
system has been suggested in both in vivo and in vitro studies to
be involved in the pathophysiology of preeclampsia. Exogenous CO
may be a potential non-invasive therapeutic treatment method.
Data from our group has demonstrated that chronic exposure to
250ppm CO was effective in the prevention of hypertension and
proteinuria in a sFlt1-induced mouse model of preeclampsia.
Objective: This study aims to determine the effects of acute
intermittent low doses of CO on blood carboxyhemoglobin
(%COHb) and end-tidal breath carbon monoxide (EtCO) levels in
healthy female volunteers. Methods: Healthy female volunteers
(n=4) were exposed to 250ppm CO for 45 minutes; an initial dose
of 15 minutes followed by six hourly doses of 5 minutes. %COHb
and hemoglobin (Hb) were measured by head space gas
chromatography and Hemocue respectively every hour following
CO dosing. End-tidal breath CO was measured using a piCO
Smokerlyzer non-invasive breath test both before and just
following CO dosing. Data are presented as mean±SEM. Analysis
was performed by repeated measures one-way ANOVA with posthoc Dunn\'s test with significance of p<0.05. Results: Blood
%COHb increased from 0.83%±0.08% at baseline to 2.97%±0.24%.
Increases in blood %COHb differed significantly from baseline at
the 5th,6th and 7th dose (p<0.05). End-tidal breath CO levels
increased from 1.83±0.31 ppm at baseline to12.00±0.62 ppm,
12.58±0.65 ppm and 13.33±0.75 ppm after the 5th, 6th and 7th
doses respectively. Both blood %COHb and EtCO normalized to
baseline values (p>0.05) 24 hours following initial CO dose.
Conclusion: This preliminary data demonstrates that intermittent
dosing of inhaled 250ppm CO is effective in raising blood %COHb
and breath EtCO levels in healthy female volunteers. Translation of
CO dosing protocols from animal models to healthy volunteers is
the first step towards exploring the potential of CO as a gaseous
therapeutic for conditions such as preeclampsia.
Acknowledgements: This study was granted approval by the
Queen's University Health Science Research Ethics Board and all
participants provided written informed consent. Contact
Information: Karalyn E McRae [email protected]
[298]
IS THE RISK OF OBSTETRIC ANAL SPHINCTER INJURIES INCREASED
IN VAGINAL TWIN DELIVERIES?. Hadar Rosen1, Nir Melamed1,
Rania Okby1, Jon Barrett1
1Maternal-Fetal Medicine Division, Department of Obstetrics and
Gynaecology, Sunnybrook Health Sciences Centre, University of
Toronto
Introduction: Obstetric anal sphincter injuries (OASIS) are
associated with significant maternal short and long term morbidity
. Vaginal twins deliveries are characterized by a higher rate of
intrapartum interventions such instrumental deliveries and
intrauterine maneuvers that serve as known OASIS risk factors.
Objective: Our aim was to determine whether the unique
characteristics of vaginal twin deliveries are associated with an
increase in the rate of obstetric anal sphincter injuries (OASIS).
Methods: This was a retrospective study of all women with twin
pregnancies who underwent a trial of vaginal delivery in a single
tertiary medical centre between January 2000 and September
2014. The characteristics and rate of OASIS was compared to a
control group of all women with singleton pregnancies who
underwent a vaginal delivery during the same time period.
Multivariable analysis was used to determine whether twin
gestation is associated with OASIS while adjusting for potential
confounders. Results: Overall 717 women with twin gestations
were eligible for the study and their outcome was compared with
33,886 women with singleton deliveries. Compared with controls,
twin pregnancies were characterized by a higher rate of nulliparity
(54.8% vs. 49.5%, p=0.005), lower gestational age at delivery
(34.6±3.3 vs. 38.8±2.3, p<0.001), a higher rate of labor induction
(42.7% vs. 29.1%, p<0.001) and instrumental deliveries (27.5% vs.
16.7%, p<0.001), and a lower birth weight. Total breech extraction
for the second twin was performed in 29.0% (208/717) of twin
deliveries. The overall rate of OASIS was significantly lower in the
twins group (2.8% vs. 4.4%, p=0.03, OR=0.6, 95%-CI 0.4-0.9). This
was due to a lower rate of 3rd degree perineal tears (2.2% vs.
4.0%, p=0.02), while there was no difference between the twin
and singleton groups in the rate of 4th degree perineal tears (0.6%
vs. 0.4%, p=0.5). On multivariable analysis, OASIS was associated
with nulliparity (OR=3.9, 95%-CI 3.4-4.5), forceps delivery (OR=6.8,
95%-CI 5.8-7.8), vacuum extraction (OR=2.9, 95%-CI 2.5-3.3), lower
gestational age at delivery (OR=0.2, 95%-CI 0.1-0.3), episiotomy
(OR=0.8, 95%-CI 0.7-0.9) and birth weight over 3500g (OR=1.8,
95%-CI 1.6-2.0). However, the association between twins (vs.
singletons) gestation and OASIS was lost after adjustment of
gestational age at delivery (OR=0.7, 95%-CI 0.4-1.2). Conclusion:
Despite a higher rate of instrumental deliveries and intrauterine
maneuvers, the rate of OASIS is lower in twins vs. singleton
pregnancies, mainly due to a lower gestational age at delivery.
Acknowledgements: Dr. Jon Barrett Head, Maternal-Fetal
Medicine Division, Department of Obstetrics and Gynaecology,
Sunnybrook Health Sciences Centre. Contact information: Hadar
Rosen [email protected]
[302]
MATERNAL OBESITY CLASS AS A PREDICTOR OF INDUCTION
FAILURE. Stefania Ronzoni1, Hadar Rosen2, Nir Melamed2, Shay
Porat3, Cynthia Maxwell1, Dan Farine1
1OB/GYN, Mount Sinai Hospital University of Toronto, 2MaternalFetal Medicine Division, Department of Obstetrics and
Gynaecology, Sunnybrook Health Sciences Centre, University of
Toronto, 3OB/GYN, Haddasa Har Hatzofim Hebrew University,
Jerusalem, Israel, Israel.
Introduction: Previous studies have not evaluated how the degree
of BMI may affect the increasing failure rate of induction of labour
determined by a CS. The aim of our study is to analyze whether
maternal BMI represents an independent predictor of induction of
CNPRM 2015
81
labour failure in order to provide useful information and direct the
counselling of obese gravid women. Objective: To assess the
impact of both obesity classes (BMI) and gestational weight gain
(GWG) on induction of labor (IOL) failure defined as cesarean
delivery (CD) rates. Methods: Included were 7543 singleton term
pregnant women undergoing IOL at MSH (cervical dilation at
admission, CDA 3cm), divided into 4 groups according to their
WHO BMI class(kg/m2): Underweight (UW) (<18.5) n=325; Normal
weight (NW) (18.5-24.9) n=4633; Overweight (OW) (25-29.9)
n=1610; Obese (O) (30) n=975. GWG was considered in low,
within and above according to IOM recommendations (IOMr). We
compared CD rates among the different classes. Maternal
demographic characteristics included maternal age, parity,
macrosomia, gestational age (GA), CDA and IOL indications were
considered. Results: A significant higher rate of nulliparae (57,2%
vs 61,9%; p>0.05), macrosomia (15,0% vs 11.1%; p<0.0001), and
early induction (GA days 277,6±9,2 vs 280,5± 8,8; p<0.0001) due to
maternal indications (39,1% vs 21.1%; p<0.001) and with a lower
CDA (< 1 cm 66.4% vs 61.4%; p<0.005) were observed in O
compared with NW. In O, despite a significant lower GWG (g 14
±7,5 vs 16,5 ± 5,6; <0.001), a significant higher rate of above the
IOMr was present compared with NW (82.8% vs 43,9%; p<0.0001).
The overall CD rate was 27.4%. Compared to NW, OW and O
women present a significant higher rate of CD (OW 31.1% and O
36.9% vs 24.7% p<0.001). In a multivariate regression analysis BMI
adjusted for maternal age and parity, CDA, GA, GWG and
macrosomia, is resulted an independent factor affecting the failure
of induction (vs NW, OW OR 1.4 [CI 1.2-1.7] p<0.001; O OR 2.3 [CI
1.9-2.7] p<0.001). Table 1 presents the prediction rate of failure of
induction (CD) according to BMI class, parity and CDA..Conclusion:
Obesity represents an important and independent factor
associated with the risk of IOL failure. BMI represents a key factor
to take into account in IOL counselling. Acknowledgements: We
thank Dr. Cynthia Maxwell Dr. Dan Farine. Contact Information:
Hadar Rosen [email protected]
[319]
PREDICTION OF FETAL CARDIOVASCULAR DECOMPENSATION
DURING LABOUR FROM HEART RATE VARIABILITY: VALIDATION
IN FETAL SHEEP MODEL. Nathan Gold1 , Xiaogang Wang1 ,
Christophe Herry 3, Martin G. Frasch 2
1Dept. of Mathematics and Statistics, York University, 2Dept. of
OBGYN and Dept. of Neurosciences, University of Montreal,
3OHRI, University of Ottawa
Introduction: Repetitive umbilical cord occlusions (UCO) with
worsening acidemia induce fetal adaptive brain shut-down visible
in electroencephalogram accompanied by cardiovascular
decompensation evidenced by hypotensive blood pressure (BP)
episodes during fetal heart rate (FHR) decelerations. The onset of
this pattern is highly individual in time ranging from 10 min to 2
hours prior to reaching pH < 7.00. We hypothesized that fetuses
have individual cardiovascular phenotype with regard to responses
to rising acidemia with intermittent hypoxia, which would be
reflected in individual responses of FHR variability (fHRV) measure
root mean square of successive differences of R-R intervals
(RMSSD), a sensitive measure of vagal modulation of fHRV, which
82
is known to increase with worsening acidemia and can be
monitored at the bedside non-invasively. Objective: To develop
an online algorithm for the early detection of fetal acidemia during
labour by sensing the incipient cardiovascular decompensation
from fHRV signal. Methods: No mathematical tools existed to
address this challenge. We developed a novel statistical approach
to this problem and validated it in a data set of 27 physiological
recordings mimicking human labour by inducing intermittent UCO
of increasing frequency (Frasch et al, AJOG 2009) or severity
(Wang et al, PLoS One 2014) in near-term fetal sheep. The
algorithm uses continuous RMSSD to predict the temporal event
when consistent hypotensive BP pattern emerges in an individual
fetus. RMSSD was computed over 5 minute intervals for approx. 6
hours of each complete experiment and required 2.5 hours
training time during baseline and mild UCO periods. This is similar
to other machine learning methods. We then extracted change
point information from the fluctuations in RMSSD time series to
predict the individual hypotensive BP response. Results: Our
findings validated the hypothesis that the new algorithm can
identify individual time points when pathological hypotensive BP
responses to UCO commence during worsening acidemia. In the
26 out of 27 cases, the algorithm matched the expert prediction
(Wang et al, PLoS One 2014) detecting the hypotensive BP
response 17±36 min before its visible onset from RMSSD time
series. In one case, the algorithm failed due to multiple artefacts in
HRV signal. Conclusion: The novelty of the current work is that it
permits individualized statistical-level predictions about
pathological changes in BP that endanger fetal brain from RMSSD.
This method can be deployed online as part of the routine
intrapartum bedside FHR monitoring for earlier prediction of
incipient severe fetal acidemia. Acknowledgements: Funded by
CIHR, FRQS and Women’s Development Council, London Health
Sciences Centre, London, ON, Canada (MGF). Contact
Information:Nathan Gold [email protected]
[332]
SEASON AND LIFESTYLE FACTORS ARE DETERMINANTS OF
VITAMIN D STATUS IN PREGNANT WOMEN AND NEONATES.
Christy G. Woolcott1, Yves Giguère2, Hope A. Weiler3, Anne
Spencer1, Jean-Claude Forest2, B. Anthony Armson4, Linda Dodds1
1Dalhousie University, Obstetrics & Gynaecology and Pediatrics,
2Université Laval, CHU de Québec Research Centre & Molecular
Biology, 3McGill University, Dietetics and Human Nutrition,
4Dalhousie University, Obstetrics & Gynaecology
Introduction: Evidence suggests a beneficial effect of vitamin D on
perinatal health but low vitamin D status is prevalent in pregnant
women and neonates. Objective: The objective was to determine
the sociodemographic and lifestyle characteristics that are
associated with vitamin D status of mothers in midpregnancy and
neonates. Methods: Included were 1635 pregnant women from
Quebec City and Halifax, Canada, 2002-2010. Vitamin D status was
based on the concentration of 25-hydroxy-vitamin D [25(OH)D]
determined with a chemiluminescence immunoassay in maternal
sera collected at a median of 15 weeks’ gestation and in cord sera
at delivery. A questionnaire that included information on potential
determinants was completed in midpregnancy. Backward stepwise
logistic regression was used to identify independent predictors of
[25(OH)D] <50 nmol/L and odds ratios (OR) with 95% confidence
intervals (CI) were estimated. Backward stepwise linear regression
was used to identify independent predictors of [25(OH)D] on a
continuous scale and adjusted mean [25(OH)D] by category of the
predictors in the final model was estimated. Results: Of the
mothers, 732 (44.8%) had 25(OH)D concentrations below 50
nmol/L. Independent determinants of maternal [25(OH)D] <50
nmol/L included season, education, income, parity, pre-pregnancy
body mass index (BMI), physical activity, and dairy product
CNPRM 2015
consumption. Adjusted mean maternal 25(OH)D levels were
higher in summer than winter by 16.1 nmol/L (CI: 13.6, 18.7), in
the highest versus the lowest category of education by 6.1 nmol/L
(CI: 0.5, 11.8), in BMI <25 kg/m2 versus BMI ?35 kg/m2 by 8.2
nmol/L (CI: 4.0, 12.3), and in the highest versus the lowest physical
activity category by up to 9.5 nmol/L (CI: 2.9, 16.1). Supplement
use was not significantly associated with maternal 25(OH)D. Cord
[25(OH)D] <50 nmol/L, observed in 24.4% of neonates, had similar
determinants but with the inclusion of maternal age, supplement
use, and maternal [25(OH)D]. Conclusion: This study suggests
that vitamin D status of pregnant women and/or neonates can be
improved through supplementation, adequate dairy intake,
moving towards a healthy pre-pregnancy body weight, and
physical activity, but controlled studies are needed to determine
the effectiveness of interventions aimed at these factors.
Acknowledgements: Supported by the Canadian Institutes for
Health Research (Operating Grant 244113). Contact Information:
Christy Woolcott [email protected]
[337[
THE DEVELOPMENT OF AN OBSTETRICAL FEASIBILITY AND PILOT
STUDY DESIGN TOOL. Anne Berndl1, Lehana Thabane2, Sarah
McDonald3
1University of Toronto, Department of Obstetrics and Gynecology,
Division of Maternal Fetal Medicine, 2McMaster University,
Department of Clinical Epidemiology & Biostatistics, 3McMaster
University, Department of Obstetrics and Gynecology, Division of
Maternal Fetal Medicine, Department of Radiology and Clinical
Epidemiology & Biostatistics
Introduction: Feasibility and pilot studies are done prior to a larger
study with the intention of discovering if a study can be done,
however, there is little information available to help design
feasibility and pilot studies and none specific for the field of
obstetrics. A key aspect of feasibility and pilot studies is the choice
of appropriate outcomes. Obstetricians and obstetrical residents
undertaking clinical research may benefit from guidance in the
area of pilot and feasibility study design. Objective: To create an
Obstetrical Feasibility and Pilot Study Design Tool to facilitate the
process of selecting outcomes appropriate to a feasibility or pilot
study in the field of obstetrics. Methods: Literature surrounding
feasibility and pilot study design, as well as issues in conducting
obstetrical research was reviewed. Results: Potential outcomes
for pilot and feasibility studies were identified along with
obstetrical research issues such as difficulties in blinding obstetric
intervention, recruitment challenges due to women’s strong
opinions regarding their pregnancy management, consent during
labour, and acceptability of interventions to women, their families,
and the variety of care givers involved. Conclusion: Obstetrical
research design requires careful consideration of a number of
ethical and logistical topics as well as an understanding of the
multiple stake holders involved. An Obstetrical Feasibility and Pilot
Study Design tool has been created that integrates these issues
and may be of use to researchers. Contact Information:
[email protected]
risk of metabolic and cardiovascular disease. Adaptations to a
nutrient-rich environment during critical development stages in
utero leads to epigenetic alterations that may progress into
postnatal life. It has been hypothesized that as a consequence of
increased nutrient availability, fatty acid synthesis in the fetal liver
is increased, leading to increased fetal fat deposition. Magnetic
resonance imaging (MRI) is well suited to study fat deposition as it
is capable of completely separating water from fat during image
reconstruction. This enables fat-only and fat fraction images to be
obtained, allowing for the analysis of adipose tissue volumes as
well as organ fat content. Objective: To identify abnormalities in
fetal fat deposition in fetuses exposed to nutrient-rich
environments using water-fat MRI. Methods: Pregnant guinea
pigs were anaesthetized and scanned ~60 days into an ~68 day
gestation. Two maternal groups were scanned: a Western Diet
(WD) group (N = 7) with an increase in fat calories and simple
sugars, and a synthetic Control Diet (CD) group (N = 5). T1- and T2weighted images were acquired with voxel dimensions =
0.875x0.875x0.9mm3 for both acquisitions. IDEAL water-fat
images were also collected for each guinea pig with voxel
dimensions = 0.933x0.933x0.9 mm3. The T1- and T2-weighted
images were used to segment fetal liver, fetal brain, and total fetal
volumes. IDEAL fat-only images (Figure 1a) were used to segment
total adipose volumes and visceral adipose volumes. Liver fat
fractions were determined using proton density fat fraction maps
(Figure 1b). Results: In total, 16 WD pups and 14 CD pups were
scanned. Compared to the CD group, the WD pups were larger
(71±14 vs 59±19 cm3, p=0.06) and had larger livers (5.5±1.2 vs
4.0±0.9 cm3, p=0.001), although brain volumes were unchanged
(2.1±0.4 vs 1.9±0.4, p=0.36). WD pups had increased fat deposition
in the liver compared to controls (25±7% vs 14±9% fat fraction,
p=0.004), as well as increased adipose tissue volume normalized
by total volume (0.18±0.04 vs 0.12±0.05, p=0.009). While adipose
tissue volumes correlated well with liver fat fraction (Figure 2), the
ratio of visceral adipose tissue to total adipose tissue did not (data
not shown, R2 = 0.13). Conclusion: We have demonstrated the
capability of MRI to detect differences in fat deposition between
Western Diet pups and healthy controls. Future studies looking at
how altered fat deposition relates to epigenetic programming in
utero and translation to human imaging are possible.
Acknowledgements: NSERC, CIHR, ORF, and the Canada Research
Chairs Program. Contact Information: Kevin Sinclair
[email protected]
[348]
EXAMINING THE EFFECTS OF A WESTERN DIET ON FETAL GUINEA
PIGS USING MAGNETIC RESONANCE IMAGING. Kevin J Sinclair1,
Lanette J Friesen-Waldner1, Colin M McCurdy1, Curtis N Wiens2,
Trevor P Wade1, Barbra de Vrijer3, Timothy RH Regnault3, Charles
A McKenzie1
1Medical Biophysics, Western University, London, Ontario, Canada,
2Radiology, University of Wisconsin, Madison, Wisconsin, United
States, 3Obstetrics and Gynaecology, Western University, London,
Ontario, Canada
Introduction: Exposure to excess nutrients in utero as a
consequence of maternal obesity or high calorie diet increases the
CNPRM 2015
83
Figure 1: Coronal IDEAL water-fat separated images of a pregnant
guinea pig. a) Fat only image with fetuses contoured in yellow and
fetal livers in red, and c) Fat fraction map with fat fraction denoted
by colour bar.
births for infants in breech presentation at borderline viability.
Methods: Retrospective chart review of live breech births
between 23+0 and 25+6 weeks gestation at tertiary university
centre from 2003 to 2013 was conducted. Those delivered
vaginally were compared to those delivered by CS. Variables were
compared using either a t-test or a chi-squared test. Results were
considered significant if p<0.05. Results: 207 births were
included, 66 vaginal and 141 CS. There were no statistical
differences between the vaginal and CS delivery births in maternal
age, celestone and magnesium sulphate use prior to delivery, cord
gases, and length of stay in the NICU. The birth weights were
slightly but significantly higher in the CS group (615.97 g vs 674.85
g, p<0.001). The neonatal death rate (47 vs 33, p<0.001), was
significantly better in those born by CS. The APGAR scores at 5
minutes (3.86 vs 6.21, p<0.001), and 10 minutes (4.21 vs 6.99,
p<0.001), were similarly improved in those delivered by CS.
29.04% of uterine incisions were of the classical, high transverse or
inverted-T types. The estimated blood loss was significantly higher
in Caesarean sections (704 mL vs 352 mL, p<0.001), but there was
no difference in the rate of blood transfusion. Conclusion:
Vaginal deliveries were associated with higher rates of neonatal
mortality than CS in infants of borderline viability delivered
breech. A prospective study of planned method of delivery is
recommended to explore this finding further.
Acknowledgements: Sunnybrook Research Institute. Contact
Information: [email protected]
Medical Teaching and Neonatal Resuscitation
Research
[236]
Figure 2: Plot of adipose tissue volume as a ratio of total
volume against liver fat fraction. Error bars have been omitted
to reduce clutter. Correlation of data is given by the coefficient
of determination R2.
[459]
MODE OF DELIVERY OF INFANTS IN BREECH PRESENTATION AT
BORDERLINE VIABILITY. Kirsten M. Niles1, Jon Barrett2, Ori Nevo2,
Nir Melamed2, Howard Cohen2, Anne Berndl2, Dini Hui2, Noor
Ladhani2
1Obstetrics and Gynaecology, University of Toronto, Toronto,
2Obstetrics and Gynaecology, University of Toronto, Sunnybrook
Health Sciences Centre
Introduction: Breech presentation occurs at a high incidence in
preterm deliveries with 25-30% of pregnancies at 28 weeks are in
breech presentation compared to 4% at term. Current technology
has pushed the definition of early viability to as low as 22 weeks
with 8% survival in Canada and as high as 34% survival in Japan.
Survival drastically improves with each consecutive week of
development, but infants delivered at the cusp of viability
between 22+0 to 25+6 weeks are still at high risk of adverse
outcomes. There is currently no consensus on the ideal mode of
delivery for severe preterm breech infants as data is conflicted to
date. Additionally, Caesarean sections in severe preterm
gestations may also increase maternal morbidity. Objective:
Because of increasing survival at earlier gestational ages, the
optimal mode of delivery, especially in cases of breech
presentation is of increasing importance. The objective of this
study was to compare outcomes of vaginal and Caesarean (CS)
84
COMPARISON OF DIFFERENT SUSTAINED INFLATION AND CHEST
COMPRESSION RATIOS IN A PORCINE MODEL OF ASPHYXIA.
Elliott S Li1, Po-Yin Cheung2, Min Lu2, Tze-Fun Lee2, Megan
O’Reilly2, Georg M. Schmölzer2
1Faculty of Science, McGill University, Montreal, Quebec, Canada,
2Centre for the Studies of Asphyxia and Resuscitation, Neonatal
Research Unit, Royal Alexandra Hospital, Edmonton, Canada,
Department of Pediatrics, University of Alberta, Edmonton,
Canada
Introduction: Current resuscitation guidelines recommend a 3:1
Compression:Ventilation (C:V) ratio; however, the most effective
C:V ratio in newborns remains controversial. We recently
demonstrated that delivering chest compressions (CC) at a rate of
120/min superimposed with sustained inflations (SI) significantly
improved return of spontaneous circulation (ROSC), and reduced
mortality in asphyxiated newborn piglets when compared to
coordinated 3:1 compression:ventilation resuscitation. However,
the optimal rate of CC during SI has not been established.
Objective: To determine if different CC rates superimposed with SI
reduces time for ROSC in newborn piglets with asphyxia induced
bradycardia. Methods: Newborn piglets were exposed to 50minutes of normocapnic hypoxia followed by asphyxia; once
bradycardia was achieved, defined as a heart rate less than 25% of
baseline, piglets were randomized to receive either “SI+CC 90” or
“SI+CC 120”. Piglets randomized to “SI+CC 90” received
uninterrupted CC at a rate of 90/min superimposed by a SI of 30
sec. Piglets randomized to “SI+CC 120” received uninterrupted CC
at a rate of 120/min superimposed by a SI of 30 sec. The default
settings for airway pressures were a peak inflation pressure of 30
cm H2O, and a positive end expiratory pressure of 6 cm H2O. The
primary outcome was duration of CC to achieve ROSC. Results: A
total of 17 piglets (n=8 - SI+CC 90, n=9 - SI+CC 120) were
randomized to each group; the mean (SD) age was 3 (1) days vs. 3
CNPRM 2015
(1) days in the in the SI+CC 90 and SI+CC 120 group, (p=0.227)
respectively. Mean (SD) weight was 2037 (238)g vs. 1962 (118)g in
the SI+CC 90 and SI+CC 120 group, (p=0.919) respectively. Mean
(SD) arterial pH at bradycardia was 6.87 (0.09) vs. 6.87 (0.13) in
the SI+CC 90 and SI+CC 120 groups (p=0.957), respectively. Mean
(SD) blood lactate at bradycardia was 13.7 (1.7) mmol/L vs. 13.3
(1.3) mmol/L in the SI+CC 90 and SI+CC 120 group (p=0.594),
respectively. Survival was 7/8 piglets vs. 6/9 piglets for the SI+CC
90 and SI+CC 120 groups (p=0.312), respectively. Median (IQR)
ROSC was similar in the SI+CC 90 group with 34 (28-156) sec vs. 99
(31-300) sec and in the SI+CC 120 group (p=0.289). 3/8 in the
SI+CC 90 group and 5/8 in the SI+CC 120 group received oxygen
(p=0.317) and 3/8 in the SI+CC 90 group and 5/8 in the SI+CC 120
group received epinephrine (p=0.317). Conclusion: Performing
SI+CC 90 results in similar time for ROSC in newborn piglets when
compared to SI+CC 120. Acknowledgements: Heart and Stroke
Foundation Canada, Heart and Stroke Foundation Alberta,
Neonatal Resuscitation Program - Canadian Pediatric Society.
Contact Information: Georg Schmolzer
[email protected]
[297]
PLASTINATED PLACENTAS AS A TEACHING RESOURCE IN
OBSTETRICS AND GYNAECOLOGY EDUCATION. Karalyn E.
McRae1; Gregory A.L. Davies2,3; Ronald A. Easteal1; and Graeme N.
Smith1,3
1Department of Biomedical and Molecular Sciences, Queen’s
University, Kingston, ON, Canada 2Fetal Assessment Unit, Kingston
General Hospital, Kingston, ON, Canada 3 Department of Obstetrics
and Gynaecology, Kingston General Hospital, Kingston, ON,
Canada
Introduction: Knowledge of the gross anatomy of the placenta is
fundamental in order to identify potential clinical complications
during pregnancy. However, the placenta is difficult to study
without a three-dimensional appreciation of its structure.
Objective: The aim of this study was to develop a collection of
plastinated placenta specimens and accompanying clinical and
educational materials to provide learning resources for placental
pathologies and their associated pregnancy outcomes. These
plastinates and educational modules are used as teaching
resources for both undergraduate medical students and medical
residents and trainees in Obstetrics and Gynaecology. Methods:
Placentas were plastinated by standard S10 silicone plastination.
Clinical education materials included ultrasound images,
photographs and provided information on the potential pregnancy
outcomes associated with each placenta. Utility of the plastinates
was assessed using questionnaires completed by attendees at the
Annual International Human Placenta Workshop held at Queen’s
University, Kingston, ON. Attendees included graduate students,
post-doctoral fellows, medical residents, research investigators
and clinicians. Results: Data collected by questionnaire
demonstrated a positive response towards the use of plastinates
as a learning resource to supplement learning from fresh
placentas. All respondents also expressed the desire to have the
plastinated placentas available for future learning opportunities.
Conclusion: Plastinated placentas are a valuable addition as
teaching resources for many demographic groups with an interest
in placental anatomy and pathology. Medical trainees and
residents in obstetrics and gynaecology would benefit from the
availability of placental plastinates as educational tools.
Acknowledgements: This study was granted approval by the
Queen\'s University Health Science Research Ethics Board.
Contact Information: Karalyn McRae [email protected]
[328]
UTILITY OF A NOVEL METHOD FOR ASSESSING QUALITY OF CHEST
COMPRESSIONS IN A NEWBORN MANIKIN. Anne Lee Solevåg1,
Po-Yin Cheung1, Elliot Li2, Khalid Aziz1, Megan O'Reilly2, Bo Fu3, Bin
Zheng3, Georg Schmölzer2
1Department of Pediatrics, University of Alberta, 2Centre for the
Studies of Asphyxia and Resuscitation, Royal Alexandra Hospital,
3Department of Surgery, University of Alberta
Introduction: In order to optimize the quality of neonatal chest
compressions (CC), we need methods for measuring CC efficacy.
Objective: The aim was to investigate utility of a novel system to
measure applied pressure during five minutes of simulated
neonatal CC. In addition, we assessed the system utility to
calculate CC rate. Methods: We used the FingerTPS™ system
(PPS, Los Angeles, CA) for wireless tactile pressure measurement,
measuring pressure in lb. per square inch. A one-inch (2.5 cm)
sensor was placed on the chest of a ResusciBaby (Laerdal,
Stavanger, Norway). A convenience sample of 16 Neonatal
Resuscitation Program (NRP) providers performed CC on the
manikin using the two-thumb method and focusing their thumb
pressure at the sensor. Each participant performed CC at a rate of
90 per minute, pausing for a ventilation after every third CC, for 5
minutes. Changes in applied pressure during the 5 minutes of CC
were compared to changes in pressure as measured in mmHg by
an arterial pressure transducer attached to a 50 mL saline-filled
infusion bag placed within the chest of the manikin. This method
for assessing CC efficacy has previously been validated. Results:
Both the FingerTPS™ tracings and the tracings from the pressure
within the saline-filled bag, showed an early, relatively abrupt
decline in applied pressure, followed by a nadir for the remainder
of the study. The mean percentage of decline from baseline to
nadir was 19 and 17% as measured with the FingerTPS™ and the
saline-filled bag, respectively. This decline was measured at a
mean time of 65 and 69 sec for the FingerTPS™ and the saline bag,
respectively. Mean CC rate measured by the FingerTPS™ was 98
per minute. Conclusion: The FingerTPS™ gave us accurate and
objective information about relative changes in applied pressure,
and correlated with pressures generated in the manikin. . It also
gave plausible information about CC rate. It is a simple and noninvasive system, which can potentially improve CC in the clinical
situation by giving real-time feedback on applied pressure and CC
rate. Acknowledgements: We wish to thank the NRP providers
that took part in this study. Contact Information: Anne Lee
Solevåg [email protected]
[330]
SHORT-TERM EFFECTS OF 21% AND 100% OXYGEN IN
ASPHYXIATED NEWBORN PIGS DURING CHEST COMPRESSIONS: A
META-ANALYSIS. Anne Lee Soleåg1, Po-Yin Cheung1, Rikard
Linnér2, Doris Cunha-Goncalves 2, Valeria Perez de Sa 2, Britt
Nakstad3, Ola Didrik Saugstad4, Georg Schmölzet1
1Department of Pediatrics, University of Alberta, 2Department of
Clinical Sciences, Anesthesia and Intensive Care, Lund’s University,
Sweden, 3Department of Pediatric and Adolescent Medicine,
Akershus University Hospital, Lørenskog, Norway, 4Department of
Pediatric Research, Division of Women and Child Health, Oslo
University Hospital, University of Oslo, Norway
Introduction: Birth asphyxia potentially leads to cardiopulmonary
resuscitation (CPR) of newborn infants. Although birth asphyxia
causes oxygen deficiency, exposure of an asphyxic infant to
hyperoxia is detrimental. The current neonatal resuscitation
guidelines recommend an initial oxygen concentration of 21%
during respiratory support. However, when chest compressions
(CC) are required oxygen is increased to 100%. Currently, no
evidence from human infants is available about the effect of
various oxygen concentrations during neonatal CPR. Lower oxygen
concentrations can potentially reduce oxidative stress and organ
damage during hypoxia and reoxygenation. Objective: To
CNPRM 2015
85
examine the current available literature about the use of various
oxygen concentrations during neonatal animal CPR and the effect
on short-term outcomes. Methods: We performed a systematic
search of MEDLINE, EMBASE and CINAHL (1946-2014). The search
terms included “newborn/infant”, “chest compression”, and
“cardiopulmonary resuscitation”. A meta-analysis of the included
studies (n=2) was performed using RevMan 5.3. We used a
random effect model to calculate Mean Difference in time to
return of spontaneous circulation (ROSC), mortality and mean
arterial blood pressure (MAP) following CPR with either 21% or
100% oxygen. Results: Data from 68 pigs (12-36 hours of age; 1.42.7 kg) with asphyxia-induced cardiac arrest or profound
bradycardia were included. Time to ROSC [figure1] and mortality
(OR 0.44 (0.02,9.78)) were similar between groups. Mean
difference (95% CI) in MAP immediately after ROSC was 10.1 (0.8,
19.4) mmHg; lower in animals resuscitated with 100% oxygen
compared to 21% oxygen (p=0.03) [figure2]. Four hours after
ROSC, MAP was similar between groups. Conclusion: Current
available evidence suggests that ROSC and mortality are similar in
newborn piglets resuscitated with 21% or 100% oxygen. Clinical
trials are needed to examine this in newborn infants.
Acknowledgements: We wish to thank Ingrid Dannevig who
performed one of the studies included in the meta-analysis.
Contact Information: Anne Lee Solevåg
[email protected]
[349]
THE DEVELOPMENT OF A FOLEY CATHETER CERVICAL RIPENING
MODEL FOR RESIDENCY EDUCATION AND TRAINING. Amanda
Michael1
1University of Toronto, Sunnybrook Health Sciences
Introduction: The Foley catheter is an effective, economical, and
safe technique for cervical ripening utilized in contemporary
obstetrical practice. However, there are limited opportunities to
practice and master this procedure in residency training, prior to
use in patient care. Recent literature attributes lack of resident
experience with Foley usage as a barrier to participation in trials
using Foleys for cervical ripening. Objective: This study’s
objective is to develop an inexpensive, reusable model of an
unripe cervix through which a Foley can be passed. The goal of this
model is to realistically simulate Foley catheter cervical ripening
for residency skills training, enabling familiarity of this technique
prior to use on patients. Methods: A plastic bottle, condom,
modeling clay, and funnel were used to design a dynamic model of
a vagina, cervix, and uterus. These materials were manipulated to
represent different stages of cervical ripening, with variations in
cervical effacement, dilatation, and consistency. Results: The
models were inexpensive and simple to create, each costing less
than five Canadian dollars, and taking under ten minutes to
produce. The reusability of the prototypes was confirmed by
passing a Foley catheter through each model twenty times.
Conclusion: We present a prototype model that is inexpensive and
reproducible for teaching and practicing cervical ripening with a
Foley. Future steps include piloting these models among
experienced staff members to confirm model suitability for use in
residency training. Ultimately, we hope to incorporate these
models into academic teaching for Obstetrics and Gynecology
residents at the University of Toronto. Contact Information:
[email protected]
86
[353]
IMPACT OF HAVING A DEDICATED RESUSCITATION ROOM ON
STABILIZATION TIME AND QUALITY OF CARE. Dr. Shikha Gupta1,
Dr. Sandesh Shivananda1
1Department of Neonatalology, McMaster Children's Hospital
Introduction: Resuscitation rooms, which are separate areas from
delivery and operative areas, are environments that are specially
designed to provide adequate space for resuscitating and
stabilizing newborn infants. Although such rooms are being used
by many neonatal centres in different parts of the world, no study
to date has evaluated the impact of having such rooms on overall
resuscitation practices and quality of care. Objective: The
objective of our study was to assess the impact of having a
dedicated resuscitation room, called the infant stabilization room
(ISR), on time to full stabilization of an infant, as well as quality of
care. Methods: We conducted a prospective cohort quality
improvement study at a level three perinatal centre (McMaster
Children’s Hospital, Hamilton, Ontario). All infants less than or
equal to 33 weeks gestational age were included. The study was
conducted over a period of 3 years (February 2011 to June 2014),
and was divided into 4 phases – pre-implementation phase
(February 2011-January 2012), implementation phase (February
2012-July 2012), post-implementation phase (August 2012-July
2013) and sustainability phase (August 2013-June 2014). ISR was
successfully commissioned. Workflow, design, equipment, staffing
and roles of medical personnel were modified and tested using
simulation, in-servicing and multiple PDSA cycles. Patient health
records were reviewed for all the babies in the study and relevant
data was extracted. Outcomes of interest included time to
intubation, insertion of umbilical lines or peripheral IVs, initial
imaging, surfactant and full stabilization of the newborn infant,
and well as other quality of care parameters. Results: Total
number of preterm infants included in the study was 769. Phase
one had 233 infants, phase two had 102 infants, phase 3 had 244
infants, and phase 4 had 190 infants. Baseline characteristics such
as mean gestational age, mean birth weight and gender
distribution were similar across all the four phases of the study.
The number of resuscitations occurring in the ISR increased over
the course of the study. Quality of care provided also improved
over time. The ISR provided more space and avoided overcrowding. Resuscitation and stabilization were able to occur as a
continuum. One baby, one bed and one ventilator strategy for the
first 48 hours promoted minimal handling of the infants. Parents
experienced less chaos and anxiety, and were able to attend
resuscitations in the ISR. Post-stabilization, we were able to show
a stable infant to mother prior to heading to the neonatal
intensive care unit. Conclusion: Having a dedicated resuscitation
room improves teamwork and quality of care provided to newborn
infants. Contact Information: [email protected]
Chronic Lung Disease of Prematurity
[240]
INCIDENCE OF BRONCHOPULMONARY DYSPLASIA (BPD) IN
SYMPTOMATIC, UREAPLASMA POSITIVE AND MACROLIDE
TREATED PRETERM INFANTS: A MATCHED RETROSPECTIVE
COHORT STUDY. Aravanan Anbu Chakkarapani1, Sandesh
Shivananda1
1Division of Neonatology, Department of Paediatrics, McMaster
University
Introduction: Ureaplasma infection increases the risk of BPD in
preterm infants (relative risk of 2.3). Role of treating infants with
signs and symptoms of pneumonia and positive culture (selective
approach) on the incidence of BPD is unknown. Objective:
Compare the incidence of BPD in symptomatic, ureaplasma
CNPRM 2015
positive and treated preterm infants and in infants who were not
symptomatic, not tested and not treated. Methods: A
retrospective matched cohort study was conducted in infants
admitted to a level III Neonatal Intensive Care Unit (NICU)
between Jan 2007 to Dec 2012. Infants of < 29 weeks, with signs
and symptoms suggestive of ureaplasma pneumonia in first 4
weeks of life and positive endotracheal or nasopharyngeal culture
and who received macrolides were included in the study group.
Infants of < 29 weeks, who were not symptomatic, not tested and
not treated with macrolides were the controls. Controls were
matched to cases on two or more of the following attributes:
Gestational age + 1 week, Birth weight +100 grams, Gender, Year
of admission. Ratio for case and control was 1:2 . Results: There
were 31 and 62 infants in cases and control groups. The mean (SD)
gestational age and birth weight were 25 weeks and 750 grams
respectively. The baseline demographics data between cases and
controls were similar. Erythromycin was the most frequently used
(90%)in the study group (Table 1) . The incidence of BPD (O2 or
positive pressure at 36 week PCA) in cases and control groups
were 14/31(45%), 26/62 (42%) (p value = 0.52) respectively.
Similarly there was no sign difference in mortality and morbidity in
cases and controls groups. (Table 2). Sub group analysis of BPD
doest not show any sign of difference between cases and controls
(Table 3). The duration of ventilation days, CPAP days and caffeine
days were similar in both groups (Table 4). Conclusion: Treating
infants with signs and symptoms of pneumonia and positive
culture (selective approach) did not impact the incidence of BPD. A
prospective study evaluating the incidence of BPD following predefined criteria for early testing and treating ureaplasma infection
is warranted. Acknowledgements: Wendy Seidlitz in the data
Management team. Shari Gray, the pharmacist at McMaster
Children's Hospital pharmacy. Dr Lehana Thabane, the statistician
at McMaster University. Contact Information: Aravanan Anbu
Chakkarapani [email protected]
[242]
SURGICAL LIGATION OF DUCTUS ARTERIOSUS: EARLIER MAY NOT
BE BETTER? Dr Audrey Hebert1, Dr Sylvie Belanger1
1Laval University, Neonatology department, Centre Mere-Enfant
Soleil CHU de Quebec
Introduction: Optimal time for patent ductus arteriosus (PDA)
surgical ligation remains a subject of controversy in very-low-birthweight infants. Late surgical closure has been associated with
longer delay for full oral feeding and increase rate of necrotizing
enterocolitis. However, few studies have assessed the risk factors
for immediate post-operative complications like post-ligation
cardiac syndrome characterized by oxygenation failure and
hemodynamic instability, 8-12 hours after surgical intervention.
Objective: The primary objective of our study was to investigate
early post-operative outcomes in patients who underwent early
(14 days of life) versus late surgical (>14 days of life) PDA ligation.
Early post-operative outcomes were need for crystalloid boluses,
cardiotropic agents and iNO. Methods: We devised a
retrospective cohort study that included all infants born < 29
weeks gestational age that underwent PDA ligation between
March 2010 and July 2014 at the CHU de Québec neonatal
intensive care unit. Early ligation was defined as 14 days of life
and late ligation >14 days of life. Individual patient characteristics
and outcomes were assessed using medical charts. Results: A
total of 42 patients were included in the study, 21 had early
ligation and 21 late. Baseline characteristics such as weight and
gestational age between groups did not statistically differ nor did
the preoperative incidence of pulmonary hemorrhage or use of
vasopressors, however patients who had early ligation tended to
gave higher pre-operative FiO2 (p=0.76). After surgery, 43% of
patients in the early group required cardiotropic agents vs. 19%
the late group (p=0.09). We observed the same trend in the use of
post-operative iNO; 38% of patients in the early group vs. 24% in
the late group (p=0.31). Although not statistically significant
probably due to our small sample size, our results show a trend in
greater post-operative complications in the early surgical group.
Conclusion: Our study has demonstrated that early PDA surgical
ligation may increase the risk of hemodynamic and ventilatory
post-operative deterioration compared to late ligation. The ideal
timing of surgical ligation remains controversial, however our
results add to the argument that patients may benefit from
optimal medical stabilization before surgical ligation to maximize
their chances of better outcome in the immediate post-operative
period. Acknowledgements: Dr Sylvie Belanger David Simonyan.
Contact Information: [email protected]
[382]
REGULATION OF VASOCONSTRICTOR RECEPTOR COMPLEX
ACTIVITY BY PALMITOYLATION IN HYPOXIC PPHN. Anurag S
Sikarwar, Martha Hinton, Shyamala Dakshinamurti.
University of Manitoba, Winnipeg, Canada; Biology of Breathing,
Manitoba Institute of Child Health, Winnipeg, Canada.
Background: Persistent pulmonary hypertension of the newborn
(PPHN) is marked by increased pulmonary arterial responsiveness
to vasoconstrictors. Thromboxane (TP) and endothelin (ETA) are
powerful vasoconstrictor receptors implicated in hypoxic
pulmonary hypertension. We previously reported that pulmonary
arterial hypoxia increases palmitoylation of G-protein alpha q
(Gαq), resulting in (TP) hyperresponsiveness, increased coupling of
TP to Gαq, and enhanced TP-mediated Ca2+ release in pulmonary
artery myocytes. Palmitoylation is a dynamic, reversible posttranslational protein modification initiated by acyl transferase and
limited by acyl protein thioesterase 1 (APT1) enzymes. Regulation
of depalmitoylation in pulmonary vasoconstrictor signaling is not
studied. Objective: We examine palmitoylation state control of
TP and ETA signaling using depalmitoylation inhibitor palmostatin
B in pulmonary artery myocytes under normoxic and hypoxic
conditions. Design/Methods: Primary cultured myocytes from
3rd-6th generation newborn porcine pulmonary arteries were
synchronized in a contractile phenotype by serum deprivation,
then placed in hypoxic (10% O2) or normoxic (21% O2)
environment for 72h. Effect of palmostatin B (10μM, 1 hr) on TP
and ETA stimulated calcium mobilization was studied by Fura 2AM
in normoxic and hypoxic pulmonary artery myocytes; APT1
expression by Western blot; effects on TP-Gq and ETA-Gq coupling
by co-immunoprecipitation. Results: Protein palmitoylation
increased in hypoxia. The Ca2+ response to both TP and ETA
challenge was increased in hypoxic myocytes, alleviated by
inhibition of palmitoylation. Unexpectedly, inhibition of
depalmitoylation also attenuated the hypoxic increase in TP and
ETA-stimulated Ca2+ mobilization; palmostatin B right-shifted
(desensitized) the hypoxic dose-response relationship, while
having the opposite effect in normoxic myocytes. APT1 expression
was unchanged in normoxic and hypoxic myocytes. Conclusions:
In hypoxia, the myocyte constrictor response clearly increases
with Gαq palmitoylation state, as does Gαq membrane trafficking
and coupling. However a depalmitoylation inhibitor, increasing
global protein palmitoylation, decreases agonist-mediated Ca2+
responses in hypoxic cells. We speculate that APT1 activity is too
non-specific a target to manipulate palmitoylation state of TP and
ETA receptor complexes without triggering off-target effects that
alter Ca2+ mobilization by other means. Acknowledgements:
Funding from CIHR and HSFC. Contact information: Anurag Singh
Sikarwar [email protected]
CNPRM 2015
87
Perinatal Epidemiology and Randomized Trials
[234]
EPIDEMIOLOGY OF LOW AND HIGH BIRTH WEIGHT AMONG FIRST
NATIONS AND NON-FIRST NATIONS POPULATIONS OF ALBERTA
FROM 2000 TO 2009. Richard T Oster1, Ellen L Toth1
1University of Alberta / Department of Medicine
Introduction: High birth weight (HBW) is more common among
First Nations, yet birth weight epidemiology is poorly understood
in this population. Objective: We determined prevalence,
longitudinal changes, and associated risk factors for various birth
weight categories in Alberta over a 10 year period. Methods: We
performed a retrospective analysis of de-identified administrative
data (426,945 delivery records) for the years 2000-2009. Ageadjusted prevalence for HBW (=4000g), very HBW (=4500g), low
birth weight (LBW; =2500g), and very LBW (=1500g) were
calculated and compared by ethnicity, as were trends via Average
Annual Percent Change analyses. Risk factors were explored via
multivariable logistic regression analysis. Results: Compared to
non-First Nations, First Nations had significantly higher (p < 0.01)
overall age-adjusted prevalence for HBW (17.7% vs. 11.0%), very
HBW (4.2% vs. 1.6%), LBW (8.8% vs. 7.1%), and very LBW (2.6% vs.
1.6%). HBW prevalence decreased and other birth weight
categories remained stable over time in First Nations. For non-First
Nations, decreases in prevalence over time were observed for
both HBW and very HBW, however LBW prevalence increased.
Among First Nations women, potentially manageable risk factors
for LBW included pregestational renal disease, hypertension, and
maternal weight =45 kg, as well as poor weight gain, smoking,
illicit drug use, and alcohol consumption. Gestational diabetes and
pregestational maternal weight =91 kg were potentially
manageable risk factors for HBW among First Nations women.
Conclusion: LBW and HBW remain more common in Alberta First
Nations compared to non-First Nations; however prevalence is not
increasing. Contact Information: Richard Oster
[email protected]
[237]
HIGHER CESAREAN DELIVERY RATES ARE ASSOCIATED WITH
HIGHER INFANT MORTALITY RATES IN INDUSTRIALIZED
COUNTRIES. Shi Wu Wen1, Ri-hua Xie2, Laura Gaudet1, Daniel
Krewski2, Ian D Graham3, Mark C. Walker1
1University of Ottawa Faculty of Medicine Department of Ob/Gy,
2McLaughlin Centre for Population Health Risk Assessment,
Institute of Population Health, University of Ottawa, 3Clinical
Epidemiology Program, Ottawa Hospital Research Institute
Introduction: The most recently available data from the WHO
indicate that more than half of high-income countries have a
cesarean delivery rate in excess of 25%. When the cesarean
delivery rate exceeds a certain threshold, it may actually do more
harm than good overall. Cesarean delivery performed for
unjustifiable medical reasons may adversely affect the health and
wellbeing of infants because it may shorten gestational duration,
bypass the normal birth canal and normal labor processes which
offer benefits to newborns, and affect the initiation of breastfeeding and quality of breast milk. Objective: To assess the
association between cesarean delivery rates and infant mortality
rates in high-income industrialized countries. Methods: We
focused our study on members of the Organization for Economic
Co-operation and Development (OECD) that met United Nations’
definition of high income countries. We conducted a correlation
analysis of GDP per capita, Gini index, population density of
obstetrician-gynecologists, population density of midwives, and
preterm birth rate with country-specific cesarean delivery rate and
infant mortality rate. We then performed multiple linear
regression analysis to examine the association of cesarean delivery
88
rate with infant mortality, adjusting for confounding factors.
Results: We gathered data for 31 eligible countries for 2010 (or
the nearest year when 2010 data were not available). Countryspecific cesarean delivery rate and preterm rate were positively
correlated with infant mortality rate while GDP per capita was
negatively correlated with infant mortality rate. Gini index and
population density of obstetrician-gynecologists were positively
associated with cesarean delivery rate. The association between
cesarean delivery rate and infant mortality rate disappeared after
adjustment for confounding factors such as GDP per capita and
preterm birth but the positive association did not show any
attenuation after excluding data from the United States or from all
non-European countries. No association between cesarean
delivery rates and fetal death rates was observed, either with or
without excluding pregnancies < 28 weeks of gestation.
Conclusion: In high-income industrialized countries, cesarean
delivery rate is positively associated with infant mortality.
Acknowledgements: Dr. Wen is a recipient of Mid-Career Award
from CIHR’s Institute for Gender-Ontario Women’s Health Council.
Dr. Krewski is the Natural Sciences and Engineering Research
Council of Canada Chair in Risk Science at the University of
Ottawa. Dr. Mark Walker is supported by a University of Ottawa
Tier 1 Chair in Perinatal Epidemiology. Contact Information: Shi
Wu Wen [email protected]
[241]
PRENATAL PERFLUORINATED COMPOUND EXPOSURE AND
GESTATIONAL WEIGHT GAIN. Jillian Ashley-Martin1, Linda Dodds1,
Tye E Arbuckle2, Adrienne S Ettinger3, Gabriel D Shapiro4, Mandy
Fisher2, Shayne Taback5, Maryse Bouchard4, Patricia Monnier6,
Renee Dallaire7, Anne-Sophie Morisset4, William D Fraser4
1Dalhousie University, 2Health Canada, 3Yale University, 4University
of Montreal, 5University of Manitoba,, 6McGill University, 7Laval
University
Introduction: A majority of North American women exceed the
recommended amount of weight gain during pregnancy and face
an increased risk of adverse maternal and fetal sequelae. Though
environmental chemicals, such as perfluorinated compounds, have
been hypothesized to have obesogenic properties, the
epidemiologic evidence is limited. Perfluorinated compounds are
persistent, ubiquitous chemicals widely used in non-stick
cookware, furniture, and clothing. Objective: The objective was
to examine the association between prenatal exposure to
perfluorinated compounds and gestational weight gain (GWG).
Methods: This study utilized prenatal exposure and sociodemographic data collected in the Maternal-Infant Research on
Environmental Chemicals (MIREC) Study, a trans-Canada cohort
study of 2001 pregnant women recruited from 10 sites between
2008 and 2011. The analysis was restricted to term (37 weeks),
singleton births with no missing covariate or chemical data
(n=1578). Three perfluorinated compounds were measured in
maternal plasma during the first trimester. GWG was examined as
a continuous variable and according to the US Institute of
Medicine (IOM) gestational weight gain guidelines. Logistic
regression models, adjusted for maternal age, parity, smoking, and
pre-pregnancy BMI, were used to estimate the association
between perfluorinated compound exposure and excess GWG
according to the US IOM guidelines. The outcome group (n=835)
was women classified as having excess GWG according to the US
IOM guidelines whereas women classified as having either normal
or inadequate GWG were the referent group (n=743). The
relationships between log-transformed exposure variables and a
continuous measure of GWG were evaluated using restricted cubic
spline curves. Results: Elevated plasma concentrations (4th vs 1st
quartile) of perfluorooctanoic acid (PFOA), perfluorooctane
sulfonate (PFOS), and perfluorohexane sulfonate (PFHxS) were
CNPRM 2015
associated with an increased risk of excess GWG (PFOA: OR=1.4
95% CI:1.0-2.0; PFOS OR=1.4 95% CI:1.0-1.9, PFHxS OR= 1.2 95%
CI:0.9-1.6). In the spline curve analyses, PFOA was associated with
continuous GWG (p-value association = 0.03) in a non-linear
manner (p-value linearity=0.07); neither PFOS nor PFHxS were
significantly associated with continuous GWG. Conclusion: These
findings suggest a positive association between perfluorinated
compound exposure, particularly PFOA, and weight gain patterns
during pregnancy. Given the ubiquity of both PFOA exposure and
excess weight gain during pregnancy, further investigation into the
mechanisms underlying these relationships is warranted.
Acknowledgements: This study was funded by the Canadian
Diabetes Association, CIHR, and Health Canada. Contact
Information: [email protected]
[243]
IMPACT OF BIRTH ROUTE ON LATE ONSET SEPSIS (LOS)
INCIDENCE IN PRETERM NEONATES <33 WEEKS GA. Francois
Oliver1, Valerie Bertelle2, Prakesh S Shah3, Christine Drolet1, Bruno
Piedboeuf 1
1CHU de Québec/Departments of Paediatrics, 2CHU de
Sherbrooke/Departments of Paediatrics, 3Mount Sinai
Hospital/University of Toronto/Departments of Paediatrics
Introduction: Birth route (vaginal or caesarean) is influencing the
neonatal microbiome and therefore could affects susceptibility to
infection. Not many large studies have examined association
between route of birth and late onset sepsis (LOS) in preterm
neonates <33 weeks gestation. Objective: To examine differences
in risk of LOS in very preterm neonates (GA<33) between the birth
route groups, caesarean and vaginal delivery. The incidence rate of
Coagulase Negative Staphylococcal (CONS) sepsis was also
assessed. Methods: In this retrospective study, data from infants
with GA between 22 and 32 weeks admitted to participating NICUs
in the Canadian Neonatal Network during 2010 to 2013 were
reviewed. Infants with major congenital anomaly, death or sepsis
before 3 days of life were excluded. LOS was defined as positive
blood or cerebrospinal fluid culture after 2 days of age. Odds
ratios were calculated by a multiple logistic regression model
including factor influencing LOS. Results: Total of 15700 eligible
neonates were identified. The incidence of LOS was not different
in the caesarean group compared to the vaginal delivery group
(OR: 0.95; 95% CI 0.85-1.08). The incidence of CONS sepsis was
slightly higher in the caesarean group (9.19% vs 8.07%, p = 0.01)
but this difference was no longer significant after adjusted analysis
(OR: 1.10; 95% CI 0.96-1.26). However, a lower incidence of LOS
caused by bacteria other than CONS was documented in the
caesarean group (OR: 0.68; 95% CI 0.56-0.82). In the caesarean
group, 15.6% of infants were exposed to a rupture of membranes
exceeding 24 hours. This might have diminished the association
between LOS and delivery mode by influencing microbiome.
Necrotising enterocolitis rate did not differ between both groups
(4.87% vs 4.66%, p = 0.5509). Conclusion: In this study, we did
not find an association between route of birth and LOS incidence.
However, the lower incidence of LOS caused by bacteria other
than CONS suggest that birth route influence the infants’ bacterial
flora, which could subsequently influence bacterial etiology of
sepsis. It is also possible that other factors influence microbiome
after birth and may diminish the association between birth route
and LOS. Acknowledgements: Priscilla Chan, Canadian Neonatal
Network Coordinator, Mount Sinai Hospital Stéphane Turcotte,
M.Sc.Biostatistician, Plateforme de recherche clinique du CHU
Xiang Y. Ye, MSc.Statistician, Micare research centre, Mount Sinai
Hospital. Contact Information: [email protected]
[249]
GESTATIONAL DIABETES AND LARGE FOR-GESTATIONAL AGE
(LGA) INFANTS ARE COMMON IN A MULTIETHNIC POPULATION
OF LOW-INCOME PREGNANT WOMEN IN MONTREAL. Ménard,
Véronique1, Weiler, Hope1
1Université McGill/École de diététique et de nutrition humaine
Introduction: Pregnancy is a critical period where maternal
nutrition and lifestyle choices have major influences on maternal
and child health. Low income, prevalent in single parents who
tend to be women (19.7%) and recent immigrants (16.4%),
increases the risk of adverse pregnancy outcomes. These pregnant
women may not have resources to afford food, shelter and other
necessities and may experience health inequities that impact
pregnancy. Community-based interventions using the Higgins’
method aim to improve pregnancy outcomes in low-income
women through education and provision of food and
supplements, although its consequences on pregnancy outcomes
are not clear. Objective: The objective of this study is to describe
frequencies and temporal shifts of adverse pregnancy outcomes
between 2008 and 2013 in women attending the Montreal Diet
Dispensary. Methods: A retrospective chart review was
undertaken to establish the frequency of pregnancies complicated
by preeclampsia, gestational diabetes mellitus (GDM), maternal
anemia as well as low birth weight (LBW) and large-for-gestational
age (LGA) infants. Results: Between 2008 and 2013, 5689
pregnancies were reviewed. Pregnancy complications included
1272 (22%) women with maternal anemia, followed by 683 (12%)
and 424 (7%) with GDM and LGA infants, respectively (Figure 1)
but prematurity (n=231; 4%), LBW (n=175; 3%), high blood
pressure (n=155; 2.7%) and preeclampsia (n=6; 0.001%) were
below the general population frequency. Conclusion: These data
suggest that prevention of LBW and prematurity are well
supported by the Higgins method and outcomes such as GDM and
LGA infants need to be addressed in low-income pregnancies.
Acknowledgements: Jackie Demers from the Montreal Diet
Dispensary and Dr Jean-Marie Moutquin for their support in the
project. Contact Information:
[email protected]
[272]
WHAT DO WOMEN WITH POSTPARTUM DEPRESSION
SYMPTOMS AND THEIR PARTNER PERCEIVE TO BE THE CAUSE OF
THE SYMPTOMS? Nancy Feeley1, Catherine Habel2, Barbara
Hayton3, Phyllis Zelkowitz3, Linda Bell4
1McGill University & Jewish General Hospital, 2McGill University,
3Jewish General Hospital, 4Sherbrooke University
Introduction: Postpartum depression (PPD)is a mental health
disorder that affects more than 10% of women in the first year
following birth. Despite the efficacy of treatments available,
numerous studies find that women with depressive symptoms are
reluctant to seek help and decline referral for mental healthcare. A
major reason for poor uptake of care is a lack of fit between
woman’s perception of her needs and the care offered. How
women and their partners understand the symptoms may shape
help-seeking behavior and care preferences. However, there has
been little systematic study of women’s or their partner's
understanding of what caused the symptoms. Objective: This
qualitative descriptive study examined two questions: What are
men’s and women’s perceptions of the causes of women’s PPD
symptoms? What are the similarities and the differences between
men and women? Methods: Couples were included if: both
partners agreed to participate and be audio-taped during the
interview, the women had given birth in the 12 months that
preceded the interview, and the women obtained a score of 12 or
more on the Edinburgh Postnatal Depression Scale. Thirty women
and their partners were interviewed simultaneously and
separately at home. Nineteen couples had accepted a referral and
11 declined. Interviews were transcribed and subjected to
inductive analysis. Codes were condensed into categories of
CNPRM 2015
89
perceived causes. No new causes emerged after 24 couples had
been interviewed. Categories endorsed by each participant were
entered into data matrices and these were used to compare
women and men. Results: Participants described nine causes
underlying women's depressive symptoms: societal expectations
and pressure on women, physical health problems after childbirth,
transition to parenthood, lack of social support, personality and
past psychological history, child health and temperament
challenges, unmet health care needs, unmet expectations for
childbirth, and major life stress events (e.g., death of loved one).
With one exception, both men and women endorsed all causes.
Only men mentioned societal pressure on women. Participants
perceived symptoms as having multiple causes. Conclusion:
Women and partners tend to externalize symptoms. Women may
not see societal expectations as giving rise to symptoms because
they consider their symptoms through an individual rather than a
gender lens. Assessment of the perceptions of women and
partners may allow for care to be tailored to beliefs about the
cause, and care options more be more acceptable.
Acknowledgements: Nancy Feeley is supported by a Research
Scholar Award (FRQS). The study was funded in part by RRISIQ
(The Quebec Network on Nursing Intervention Research).
Contact Information: [email protected]
[279]
IMPACT OF BIAS IN RANDOMIZED CLINICAL TRIALS (RCTS) ON
THE EFFECT OF ANTIMALARIAL DRUGS PRESCRIBED DURING
PREGNANCY FOR PREVENTION OF MALARIA ON LOW BIRTH
WEIGHT (LBW). Flory Tsobo Muanda1 ; Anick Bérard1
1Faculty of Pharmacy, University of Montreal.
Introduction: Untreated Malaria can cause adverse outcome both
for mother and foetus. all strategies currenlty used to treat this
disease is hampered by an increase of resistance to antimalarial
drugs and insecticide. In contrast, the influence of study design
characteristics on the effect of antimalarial drug in malaria setting
has not been reported yet in literature. Objective: (1) to describe
biases that may arise from the main components of randomised
controlled trials (RCTs) conducted in malaria area during
pregnancy and whether the introduction of Consolidated
Standards of Reporting Trials (CONSORT) statement since 1996
may influence the quality of reports of trials; (2) to examine the
impact of bias on the treatment effect estimate of antimalarial
drugs used for prevention during pregnancy on low birth weight.
Methods: RCTs and risk of bias assessment of each study were
retrieved from a previous systematic review evaluating the effect
of antimalarial drugs used for prevention of malaria during
pregnancy on the risk of low birth weight (LBW). Proportion of
trials with low, high and unclear risk of bias was computed overall
and individually for each domain of bias using the Cochrane risk of
bias tool. To investigate the influence of the CONSORT statement,
the quality of reports of RCTs were compared between trials
published before and after the introduction of that statement. A
metaregression analysis were performed to examine whether a
difference exist between treatment effect estimates in subgroup
of trials having low risk of bias and high or unclear risk of bias
Results: A total of 23 RCTs were included in this study. Most trials
had overall high (78%) or unclear (13%) risk of bias. only 2 studies
out of 23 (9%) were classified as having a low risk of bias. The
introduction of the CONSORT statement was significantly
associated with an increase of proportion of trials having a low risk
of bias for sequence generation (0% vs 45%; p=0.04) and allocation
concealment (0%vs 50%; p=0.02). The effect of antimalarial drugs
used during pregnancy on the risk of LBW did not significantly
differ between trials having low risk of bias and trials having high
or unclear risk of bias for each domain assessed by the Cochrane
risk of bias tool. Conclusion: Most of trials during pregnancy in
90
malaria setting had a high or unclear risk of bias. The
implementation of CONSORT statement was associated with an
improvement of the quality of reporting of trials mainly for
sequence of generation and allocation concealment. There was no
large difference of treatment effect estimates between trials
having low risk of bias and trials having high risk or unclear risk of
bias. Acknowledgements: thanks to Mr Dupont. Contact
Information: [email protected]
[285]
HUMAN PAPILLOMAVIRUS (HPV) PERINATAL TRANSMISSION
AND RISK OF HPV PERSISTENCE AMONG CHILDREN: A COHORT
STUDY. Joseph Niyibizi1, Marie-Hélène Mayrand2, François
Coutlée3, Patricia Monnier4, William Fraser5, Ana-Maria Carceller6,
Diane Francoeur5, Isabelle Girard7, Marie-Josée Bédard8, Helen
Trottier1
1University of Montreal, Department of Social and Preventive
Medicine, Sainte-Justine Hospital, Research Center, Montreal;
2University of Montreal, Department of Social and Preventive
Medicine, CHUM (Centre Hospitalier de l’Université de Montréal)
Dept. of Obstetrics and Gynecology; 3CHUM (Centre Hospitalier de
l’Université de Montréal) Dept. of Microbiology, 4McGill
University, Royal Victoria Hospital; Dept. of Obstetrics and
Gynecology Montreal, 5Sainte-Justine Hospital, Dept. of Obstetrics
and Gynecology, Montreal, 6Sainte-Justine Hospital, Dept. of
CNPRM 2015
Pediatrics, Montreal, 7St-Mary’s Hospital Center, Dept. of
Obstetrics and Gynecology, Montreal., 8CHUM (Centre Hospitalier
de l’Université de Montréal) Dept. of Obstetrics and Gynecology.
Introduction: Background: The perinatal epidemiology of HPV and
its impact on newborns and children is not well understood
although it is recognised that subclinical and clinical infections
occur following perinatal transmission. Objective: Objective: To
measure the risk and determinants of HPV perinatal transmission;
the risk and determinants of HPV persistence among children; and
to describe the pregnancy outcomes related to placental HPV
infection. Methods: Methods: First trimester pregnant women
(ages 18-30 years) were recruited in a prospective cohort study in
Montreal, Canada. Self-collected cervicovaginal swabs were taken
at enrolment and in the 3rd trimester (if positive at enrolment)
and tested for 36 HPV genotypes by Linear Array. Placental
specimens were collected and children of positive mothers are
being followed until 2 years of age. At an interval of 3-6 months,
conjunctival, buccal, pharyngeal and genital samples are collected
form children. Patient charts are reviewed to document pap
testing results and pregnancy outcomes. Blood samples from
mothers (1st trimester) and children (at birth, 6, 12, 18, 24
months) are collected for seroreactivity to HPV types 6/11/16/18
capsids using HPV Virus-Like-Particle-Based Enzyme Immunoassay.
Results: Results: 167 pregnant women were enrolled, 44.9% were
HPV positive (1st trimester) and 79.7% were still infected in the
3rd trimester. Among mothers HPV positive at enrolment, 69.0%
harbored at least one High-Risk HPV and 51.0% had multiple
genotypes (range 2 to 11). Placenta samples were positive in
22.9% and 2.9% of women who were respectively positive and
negative at enrolment. The perinatal transmission rate was 11.2%
(all mucosal samples). More than 50% of perinatal infections
persist until 6th month. Follow-up visits are ongoing and final
results will be available in 2015. Conclusion: Preliminary
Conclusion: We found a significant prevalence of HPV in pregnant
women. HPV has been detected in the placenta and a nonnegligible number of newborns had HPV at different sites. This
study will further our understanding of the impact of HPV during
pregnancy and of the perinatal transmission at different body sites
in children born from HPV positive mothers. Acknowledgements:
The authors are grateful to the Study manager (Louise Laporte)
and to the Clinical Research Nurses (Lise-Angela Ouellet, Nathalie
Bureau, Maryse Thibeault) for their contribution to subject
enrollment and specimen collection. Author Contributions
Conceived and designed the study: HT, MHM, WF, PM, AMC, DF,
IG, MJB. Enrolled subject and provided clinical specimens : MHM,
WF, PM, AMC, DF, IG, MJB Performed the experiments: FC
Analyzed the data: HT, JN, MHM Wrote the paper: JN, HT.
Contact Information: [email protected]
[286]
ANTIDEPRESSANT USE, ESPECIALLY SSRIS USE, DURING
PREGNANCY AND THE RISK OF AUTISM SPECTRUM DISORDERS: A
META-ANALYSIS. Boukhris Takoua1, Sheehy Odile 2, Bérard Anick3
1Faculty of Pharmacy, University of Montreal, 2Research Center,
CHU Sainte-Justine, Montreal, 3Faculty of Pharmacy, University of
Montreal
Introduction: Antidepressants are widely used during pregnancy.
Several studies have suggested adverse outcomes linked to the
use of antidepressants during pregnancy such as congenital
malformations, prematurity, and low birth weight. However, there
is a knowledge gap regarding the potential association between
gestational exposure to antidepressants and the risk of autism
spectrum disorders (ASD). Objective: We sought to present a
review of the literature and a meta-analysis on the association
between gestational use of antidepressants and the risk of ASD.
Methods: We conducted a review of the literature search and
meta-analysis of epidemiological Studies. We searched in EMBASE
and MEDLINE from 2007 to the present (English language) for
studies assessing the association between antidepressants use
during pregnancy and the risk of autism spectrum disorder (ASD)
in children. Combined estimates were calculated using
DerSimonian and Laird random effects meta-analysis model;
heterogeneity was tested with I-squared statistic, and publication
bias with a funnel plot. Results: We identified seven published
studies that have explored the association between
antidepressants use during pregnancy and the risk of ASD (3 casecontrol, 3 cohort, and 1 nested case-control). Four studies found a
statistically significant increased risk of ASD associated with
antidepressants use during pregnancy. Three studies suggested
that gestational use of antidepressants was not significantly
associated with an increased risk of ASD. Three studies found a
statistically significant association between SSRI exposure during
pregnancy and the risk of ASD. Considering all published studies,
the combined estimate for antidepressants in general was 1.47
(95% CI: 1.17-1.85), and for SSRI specifically was 1.57 (95% CI:
1.15-2.13). Conclusion: This is the first review and meta-analysis
on the risk of ASD associated with the use of antidepressants
during pregnancy. This study suggests that exposure to
antidepressants during pregnancy, more specifically SSRI as a
class, appear to be associated with increased risk of ASD. More
research is needed to assess the risk stratifying on antidepressant
classes and types as well as dosages. Acknowledgements: The
authors are grateful to others members of the Research Chair on
Medications, Pregnancy and Lactation group; and would like to
thank funder: Quebec Training Network in Perinatal
Researchfunders(QTNPR). Contact Information:
[email protected]
[301]
DR. INTERNET:PATTERNS OF INTERNET USE BY OBSTETRICAL
PATIENTS IN THE DIGITAL AGE. Hadar Rosen1, Adriana
Dekirmendjian2, Mahshid Mohseni2, Dan Farine3
1Maternal-Fetal Medicine Division, Department of Obstetrics and
Gynaecology, Sunnybrook Health Sciences Centre, University of
Toronto, Ontario, Canada, 2OB/GYN, Mount Sinai Hospital
University of Toronto, Toronto, ON, Canada. , 3OB/GYN, Mount
Sinai Hospital University of Toronto, Toronto, ON, Canada.
Introduction: A common practice among digital age patients is
using internet based data to access information regarding their
personal health conditions. Some of the data available has not
been validated and patients are exposed to and influenced by
inaccuracies. Objective: Our aim was to explore obstetrical
patients internet use patterns for health care information access
and implications on patient-doctor relationship. Methods: 380
gravid patients completed a self-reported survey in our tertiary
centre Aug-Nov 2013 quantifying pregnancy related internet
usage, valued topics, visited sites and implication on care. Patients
categorized into 2 groups based on pregnancy complication
presence (complications=107, no complication =273). Results:
Internet Use: 91.3% reported conducting pregnancy-related
searches. 97.6% done from home. Avg time spent was 2.7hrs/wk.
(Range:0.5-15hrs/wk). Topics: Patients ranked importance of
various topics on a scale of 1-5. General pregnancy information
preferred with 59.5% ranking as 4/5 (mean 3.4), followed by
information about pregnancy complications which 51.3% judged
as 4/5 (mean 2.9).Life style in pregnancy third most valued topic
with 46.1% ranks 4/5 (mean 2.8) .Satisfaction: 63.2% scored
satisfaction with the information obtained online as 4/5 (mean
3.7).Impact of Web-based Information on Patient-Doctor
Relationship: 63% obtained more information online than through
their doctor. 36% report importance of information obtained
online as 4/5 (mean 2.3). 69% discussed information retrieved
CNPRM 2015
91
online with their physicians while only 37% of patients found
discussing internet obtained information with their doctor to be
4/5 (mean 2.3). 29 % used internet obtained information guiding
their health care decisions (mean 1.6). Over all patients with
pregnancy complications use internet to obtain information more
than those without complications (p=0.002), and are more likely to
use the information for self guided care (p=0.02). Conclusion:
Internet use to obtain pregnancy related information is a common
practice among gravid patients in the digital age, more so in high
risk patients This raises important issues such as need for peer
reviewed reliable sites for patient reference, the widespread use
of information for self directed care, and has an impact on doctorpatient trust. Acknowledgements: We thank Dr. Dan Farine,
MFM OB/GYN, Mount Sinai Hospital University of Toronto,
Toronto, ON, Canada. Contact Information: Hadar Rosen
[email protected]
[314]
USE OF MACROLIDES DURING PREGNANCY AND THE RISK OF
BIRTH DEFECTS: A POPULATION-BASED STUDY. Anick Bérard 1,
Noha Iessa 1, Odile Sheehy 2, Fabiano Santos 3, Hedvig Nordeng 4
1Research Center, CHU Ste-Justine, Montreal; Faculty of Pharmacy,
University of Montreal, 2Research Center, CHU Ste-Justine,
Montreal, 3Department of Oncology, McGill University, Montreal,
4PharmacoEpidemiolgy and Drug Safety Research Group, School of
Pharmacy, University of Oslo, Norway
Introduction: Macrolides are frequently prescribed during
pregnancy. They have previously been linked to the occurrence of
congenital heart defects and pyloric stenosis but findings are
inconsistent, particularly when stratification is done on specific
macrolides for congenital heart defects. Objective: To estimate
the risk of major congenital malformations after foetal exposure to
macrolides, with a focus on cardiac malformations and pyloric
stenosis. Methods: Population-based cohort study in Quebec,
during the years 1998-2008. Exposures were categorized into:
pregnancies with macrolide-exposure (azithromycin,
clarithromycin, erythromycin); penicillin-exposure; and unexposed
women. Two exposure windows were defined: maternal use of
macrolides or penicillin in the first trimester of pregnancy (major
congenital malformations) and the last 60 days before delivery
(pyloric stenosis). Cases of major congenital malformations were
identified in the first year of life, with a focus on cardiac
malformations, atrial/ ventricular septum defects and pyloric
stenosis. Generalised estimating equation (GEE) models were used
to obtain odds ratios (OR) and 95% confidence intervals (CI).
Analyses were adjusted for potential confounders. Results: There
were 135,859 and 146,033 pregnancies that met the inclusion
criteria for the first trimester and last 60 days of pregnancy time
windows respectively. During the first trimester of pregnancy, 914
women were exposed to azithromycin, 734 to erythromycin, 686
to clarithromycin, and 9,106 to penicillin. After adjustment for
potential confounders, the use of azithromycin (OR 1.19, 95% CI:
0.98, 1.44; 120 exposed cases) during early pregnancy was
associated with the risk of major congenital malformations, when
compared to no use of antibiotics. There were no statistically
significant associations between exposure to other macrolides or
penicillin in the first trimester and major congenital
malformations, or between exposure to all macrolides during the
last 60 days of pregnancy and pyloric stenosis (OR 2.13, 95% CI:
0.30, 15.22; 1 exposed case). Conclusion: In this study, first
trimester exposure to erythromycin was not associated with an
increased risk of cardiac malformations, and exposure to
macrolides during the last 60 days of pregnancy was not
associated with pyloric stenosis. However azithromycin use during
the first trimester was associated with an increased risk of major
congenital malformation (borderline significance), but no specific
92
patterns of malformation was observed. Acknowledgements:
This study was funded by Fonds de la Recherche en Santé du
Québec (FRSQ) and the Réseau Québécois de Recherche sur
l’Usage des Médicaments (RQRUM). Contact Information: Noha
Iessa [email protected]
[315]
DIFFERENCES IN THE USE OF OBSTETRICAL INTERVENTIONS AND
PROCEDURES BY FIRST NATIONS STATUS IN BRITISH COLUMBIA.
Corinne A. Riddell1, Jennifer A. Hutcheon2, Leanne S. Dahlgren2
1Department of Epidemiology, Biostatistics, and Occupational
Health, McGill University, 2Department of Obstetrics and
Gynecology, University of British Columbia, Vancouver, British
Columbia
Introduction: Perinatal mortality is higher in babies of Aboriginal
mothers than in the general Canadian obstetrical population. It is
unknown to what extent this increased risk may be related to
decreased provision or uptake of obstetrical services and
procedures in First Nations women. Objective: Objective 1: To
compare indicators of obstetrical care quality between First
Nations and non-First Nations women in British Columbia (BC).
Objective 2: To examine differences in the use of obstetrical
interventions during labour and delivery (such as labour induction,
augmentation, and cesarean delivery). Methods: We linked
obstetrical and neonatal medical records with the First Nations
status file for all nulliparous women delivering singletons births in
BC, 1999-2011. Logistic regression was used to model the
relationship between First Nations status and indicators of
obstetrical quality (such as GBS screening at term, use of early
ultrasound, labour induction in women with prolonged rupture of
membranes at term or postdates pregnancies, and timing of
planned cesarean delivery at term), controlling for distance to
hospital. In models of obstetrical interventions, we further
controlled for maternal age, body mass index, diabetes, and
hypertension. The adjusted average marginal risk differences (RD)
and 95% confidence intervals (CI) from the models were
calculated. Results: There were 220,350 singleton deliveries to
nulliparous women, of whom 9,152 had First Nations status. First
Nations women were less likely to have an early ultrasound, even
after adjusting for distance (62 vs 72%, RD=-10.2 [95% CI -11.3, 9.3]), while their propensity to receive GBS screening was clinically
similar before and after adjustment (54 vs 56%, RD=-1.7 [-2.9, 0.6]). First Nations women had lower rates of induction of labour
among term gestations with prolonged pre-labour rupture of
membranes (61 vs 67%, RD=-5.9 [-11.8, 0.0]) and at postdates
gestation (39 vs 50%, RD=-10.6 [-13.8, -7.5]). While First Nations
women had a lower overall risk of cesarean, adjustment for
maternal age removed this effect. However, a reduced use of
labour induction persisted even after adjustment for confounders
(21 vs 27%, RD -5.9 [-7.4, -4.5]). Conclusion: Some aspects of
antenatal care were found to be suboptimal for First Nations
women, with the most important differences being in the
likelihood of having an early ultrasound, and the reduced rates of
indicated induction of labour. Even after adjustment for distance
to hospital, disparities in these rates persist. Acknowledgements:
This study was funded by the Canadian Institutes of Health
Research (CIHR). CAR was supported by a CIHR doctoral research
award and a CIHR Interdisciplinary Capacity Enhanced Team Grant.
Contact Information: [email protected]
[325]
INTERLEUKIN-17A EXPRESSION IN ENDOMETRIOTIC TISSUE AND
PLASMA SAMPLES FROM WOMEN WITH ENDOMETRIOSIS.
SooHyun Ahn1, Andrew Edwards1, Diane S. Nakamura1, Bruce
Lessey2, Conrad Reifel1, Chandrakant Tayade1
1Queen's University, Department of Biomedical and Molecular
Sciences, 2Greenville Hospital System Greenville SC United States
CNPRM 2015
Introduction: Endometriosis is a common gynecologic disease
suffered by millions of women in reproductive age world wide. The
disease presents itself in multiple manifestations, including
peritoneal implants, ovarian cysts and deep infiltrating form, with
rare occurrences documented outside of the pelvic cavity.
Common symptoms of endometriosis include chronic pelvic pain
and subfertility. Despite experiencing the symptoms at a young
age, it is well established that many women have a delay in
diagnosis of endometriosis. The etiology of endometriosis still
remains elusive, and pathogenesis seems multifaceted. Most
importantly, laparoscopy surgery remains the gold-standard for
diagnosing endometriosis, making identification of biomarkers
pertinent. Cytokines present within the environment of
endometriosis are believed to contribute to the pathogenesis of
the disease by promoting inflammatory conditions surrounding
the implantation of endometriotic lesions. Interleukin-17A is a
member of proinflammatory cytokines implicated in the
pathogenesis of various chronic inflammatory diseases such as
rheumatoid arthritis and psoriasis. However, its role in the disease
progression of endometriosis is poorly understood. Objective:
The objective of this study was to elucidate the involvement of IL17A in the pathogenesis of endometriosis. Methods: To
investigate this, IL-17A concentration was measured in plasma,
endometrium and ectopic lesion samples from women with
endometriosis and in plasma and endometrium samples from
women without endometriosis. Immunostaining for IL-17A was
conducted on matched endometrium and ectopic lesion sections.
To elucidate biological function of IL-17A, WST-1 proliferation
assay, cell cycle analysis with Propidium Iodide (PI) , and
supernatant analysis were performed with endometrial epithelial
carcinoma cells (EECCs). Expression of IL-17A, IL-17RA, and IL-17RC
mRNA from EECCs and primary EECs was measured using
quantitative PCR. Flow cytometry was performed on EECCs to
detect IL-17RA expression on the cell surface. Results: Results
show presence of IL-17A in plasma samples and ectopic tissue
samples from women with endometriosis. Imunohistochemistry
confirmed the presence of IL-17A positive cells within both the
epithelium and stroma of eutopic and ectopic tissue sections. Even
though IL-17A has shown no proliferative or apoptotic effect on
EECCs, its stimulation on EECCs induced increased production of GCSF, VEGF, PDGF-AA, and SDF-1. Conclusion: Follow up
investigation is needed to deepen the understanding of the
relationship between the presence of IL-17A and the pathogenesis
of endometriosis. Acknowledgements: I thank Dr. Bruce Lessey
for the valuable human samples that contributed to this research.
Contact Information: SooHyun Ahn 7sha1[email protected]
[491]
SEVERE MATERNAL CARDIAC COMPLICATIONS IN PREGNANCY
AND POSTPARTUM: A NATIONAL POPULATION BASED STUDY.
Shiliang Liu, Jocelyn Rouleau, Juan Andres Leon, Joel G. Ray, and
the Canadian Perinatal Surveillance System (Public Health Agency
of Canada, Ottawa, Canada)
Objective To determine the incidence of maternal severe cardiac
complications (SCC) arising in pregnancy and soon after delivery,
and the associated risk of maternal mortality. Design Population
based cohort study. Setting All of Canada, excluding the province
of Quebec, 2003-2012. Population All hospital deliveries and
postpartum rehospitalisations in Canada. Methods We identified
pregnant and recently delivered women with a SCC, defined as (a)
heart failure or peripartum cardiomyopathy, (b) myocardial
infarction, and/or (c) cardiac arrest, identified using ICD-10 codes
O742, O754, O891, O903, I21-I22, I42, I43, I46 and I50. We
explored the temporal changes in the incidence rate of each type
of SCC, and all three together. Crude and adjusted period changes
were assessed using logistic models, adjusting for maternal age,
pre-existing medical conditions (the hypertensive disorder of
pregnancy and diabetes mellitus), and obstructed labour and
caesarean delivery. Results There were 4148 cases of SCC, of
which heart failure and peripartum cardiomyopathy accounted for
92% of all cases. The incidence rate of SCC varied between 10.7
and 13.2 per 10000 deliveries during 2002-2007, and then
increased from 11.8 in 2008 to 20.2 per 10000 in 2012. Comparing
the period of 2003-2007 to 2008-2012, the adjusted incidence rate
ratio was 1.21 (95% confidence interval [CI], 1.13 to 1.29%).
Maternal in-hospital mortality < 42 days of childbirth declined
significantly between these two time periods (adjusted RR 0.68,
95% CI 0.48 to 0.97), but late maternal in-hospital mortality (43364 days after childbirth) increased non-significantly (adjusted RR
1.80, 95% CI 0.83 to 3.91). Conclusions: There has been a recent
increase in the incidence of maternal SCC in pregnancy and
postpartum. Further investigation is required to explain why this is
so. Contact information: [email protected]
Preeclampsia and Placenta Development
[245]
MATERNAL AND CORD BLOOD MANGANESE LEVELS AND SMALL
FOR GESTATIONAL AGE INFANTS: THE MIREC BIRTH COHORT
STUDY. Linda Dodds1, Jillian Ashley-Martin1, Tye E. Arbuckle2,
Adrienne S. Ettinger3, Gabriel D. Shapiro4, Mandy Fisher2, Shayne
Taback5, Patricia Monnier6, Renee Dallaire7, Anne-Sophie
Morisset4, William D. Fraser8, Maryse F. Bouchard9
1Dalhousie University, Department of Obstetrics & Gynecology and
Pediatrics, 2Health Canada, 3Yale University, Department of
Epidemiology and Public Health, 4University of Montreal,
5University of Manitoba, Department of Pediatrics, 6McGill
University, Department of Obstetrics and Gynecology, 7Laval
University, 8Université de Sherbrooke, Department of Obstetrics
and Gynecology, 9Université de Montreal, CHU Sainte-Justine
Research Centre
Introduction: Manganese is an essential nutrient in humans and
has a role in several metabolic processes. However, in excess
amounts, manganese is also a potential toxicant. The few studies
that have been conducted in pregnant women suggest an inverted
U-shaped relationship between maternal blood manganese levels
and birth weight. Objective: To explore the potential relationship
between maternal and cord blood manganese concentrations with
birth weight and small for gestational age (SGA). Methods: This
analysis focused on women enrolled in the Maternal Infant
Research on Environmental Chemicals (MIREC) Study who
delivered singleton, term infants. Manganese was measured in
third trimester and cord whole blood. Manganese levels were
categorized based on values < 5th percentile, 5th to <25th
percentile, 25th to <75th percentile, 75th to < 95th percentile and
> 95th percentile. Birth weight was evaluated as a continuous
measure and SGA was defined as the bottom ten percentile for
gestational age and sex based on Canadian standards. Logistic
regression analyses were used to estimate adjusted odds ratios
(aORs) and 95% confidence intervals (CIs) for SGA. LOESS curves
were used to evaluate the relationship between manganese level
and birth weight. Results: There were 1521 and 1297 women
with third trimester and cord blood manganese measurements,
respectively, and information on outcomes and covariates. The
manganese levels observed in the MIREC cohort were consistent
with other studies (for both third trimester and cord blood) at the
bottom 5th percentile (0.7µg/dL and 1.8µg/dL for third trimester
and cord blood respectively), but were lower than other reported
studies at the 95th percentile (2.0 µg/dL and 5.4 µg/dL for third
trimester and cord blood respectively). Using third trimester
measures, the LOESS curve indicated lower birth weight with
CNPRM 2015
93
lower manganese levels, but there was no suggestion of lower
birth weight with higher levels of manganese. The aOR and 95% CI
for SGA for third trimester manganese levels in the bottom 5th
percentile was 1.5 (0.5-3.8) compared to manganese levels in the
25th to <75th percentile. The aOR and 95% CI for SGA for third
trimester manganese levels greater than the 95th percentile was
1.3 (0.5-3.4) compared to manganese levels in the 25th to <75th
percentile. Similar results were found for cord blood manganese
concentrations. Conclusion: We did not observe an inverted Ushaped relationship between manganese concentrations and birth
weight, as suggested in other studies. This may be explained by
lower manganese levels in the top percentiles seen in the MIREC
cohort compared to other studies. Acknowledgements: Funding
was provided by the Canadian Diabetes Association, CIHR, and
Health Canada. Contact Information: [email protected]
[263]
PRENATAL MATERNAL STRESS ALTERS PLACENTAL ENDOCRINE
FUNCTIONS: FETAL SEX IMPLICATIONS. Joey St-Pierre1, David P.
Laplante2, Guillaume Elgbeili2, Suzanne King3, Cathy Vaillancourt1
1INRS-Institut Armand Frappier and BioMed research Centre,
Laval, QC, 2Douglas Institute Research Center, Montréal, QC,
3Douglas Institute Research Center and McGill University,
Montréal, QC
Introduction: Prenatal Maternal stress (PNMS) is associated with
reduced type 2 11- hydroxysteroid deshydrogenase (11-HSD2)
and type 1 glucose transporter (GLUT1). Cortisol exerts its action
by binding to glucocorticoid receptor alpha (GR-) that acts as a
transcription factor. The enzyme 11-HSD2 protects the fetus
from adverse cortisol levels from the mother by converting cortisol
to inactive cortisone. Objective: This study aims to determine if
the placenta mediates the effects of disaster-related PNMS (i.e.,
2011 Queensland Flooding, Australia) on placental endocrine
function.We hypothesize that: (i) Increased PNMS will be
associated with lower placental 11-HSD2 gene expression which
will be moderated by fetal sex; and (ii) Increased PNMS will be
associated with a lower placental index which will be moderated
by placental 11-HSD2, GLUT-1 and/or GR- gene expression.
Methods: We assessed the women’s level of objective hardship
(i.e., events they experienced) and subjective distress (i.e., their
psychological reaction to the flooding) shortly after the flooding.
Placental villi (trophoblastic tissues) from 96 placentas were
processed and samples flash frozen immediately after delivery.
Gene expression was evaluated by RT-qPCR. Results: Results
indicate that a higher level of subjective PNMS is associated with
greater 11-HSD2 gene expression for male fetuses and lower
11-HSD2 gene expression for female fetuses (R2=0.074). Results
also indicate that high levels of objective PNMS coupled with high
levels of 11-HSD2 gene expression (R2=0.092), low levels of
GLUT-1 gene expression (R2=0,126), and/or low levels of GR-α
gene expression (R2=0.117) is associated with higher placental
index (fetal weight to placental weight). Conclusion: These
results suggest that disaster-related PNMS influences placental
gene expression in a sex dependent manner. Moreover, placental
gene expression moderates the relationship between PNMS and
placental index. Acknowledgements: This work was supported by
the CHIR (grant MOP-115067) as well as the Fonds de la Recherche
en Santé du Québec, Fondation Armand-Frappier and the Réseau
Québécois en Reproduction. Contact Information: [email protected]
[294]
MICRORNAS IN HUMAN PLACENTAE FROM INTRAUTERINE
GROWTH RESTRICTED PREGNANCIES . Zain Awamleh1, Victor
Han1
1University of Western Ontario/Department of Biochmistry
94
Introduction: The placenta is a regulator of the intrauterine milieu
and transporter of oxygen and nutrients from the mother to the
fetus. Placental insufficiency is one of the major contributors to
the etiology of intrauterine growth restriction (IUGR), the
pathophysiology of which is still unknown. IUGR is characterized
by the inability of the fetus to grow to its full potential, and the
birth weight of an IUGR fetus is less than the 10th percentile for
gestational age. Micro(mi)RNAs are believed to play a role in
placental growth and development by targeting critical genes
required for proper placental function. Objective: The objectives
of this study are first to identify and characterize differentially
expressed miRNAs in human late-onset intrauterine growth
restricted placenta. Second, to identify and characterize gene
targets that may directly impact placental growth and
development. Methods: A total of 11 human placenta samples,
six IUGR, and five control samples matched for gestational age
(weeks 38-40) were used in this study. MiRNAs have been isolated
from placental tissues and sequenced using the Illumina
Hiseq2500. DESeq2 was then used for differential expression
analysis. To predict targets of differentially expressed miRNAs with
greater than 2-fold change, DIANA microT-CDS and Target Scan
were used, along with WebGestalt for pathway enrichment. Realtime PCR will be used to confirm miRNAs of interest. Additionally,
Luciferase assays will be used to validate the miRNA-mRNA
interactions and western blots to assess any changes in
downstream proteins. Results: A total of 18 differentially
expressed miRNAs between control and IUGR placenta with
greater than 2-fold change have been identified. Some of these
miRNAs include hsa-mir-7-1-3p and hsa-mir-675-3p both of which
have been shown to target the IGF system. Other miRNAs target a
variety of genes that are in the mTOR signalling pathway and the
Wnt signalling pathway both of which are important for cell
growth and proliferation. Conclusion: IUGR is the inability of the
fetus to grow to its full genetic potential in utero, which could be
attributed to placental insufficiency. In this project the role of
miRNAs is being investigated in late-onset intrauterine growth
restriction, using human placental tissue from IUGR pregnancies
and gestational age matched controls. Differentially expressed
miRNAs and their gene target have been identified. Future work
will focus on confirmation and validation of results. This study
provides further insight into miRNAs as an epigenetic mechanism,
and will help delineate how changes in gene expression contribute
to placental growth and development. Acknowledgements: Han
Lab members Committee members Children's Health Research
Institute. Contact Information: Zain Awamleh [email protected]
[304]
TRANSIENT EPCAM+ TROPHOBLAST POPULATION IN EARLY
HUMAN PLACENTA VILLI DEVELOPMENT. Frances Wong1, Brian
Cox1
1University of Toronto, Department of Physiology
Introduction: The vascular exchange region of the human
placenta, called the villus, brings fetal and maternal blood systems
into close proximity to facilitate gas and nutrient exchange. The
vascular system develops within the villi starting at gestational
week 5 and vascular defects cause placental defects in up to 10%
of all pregnancies, predisposing the mother and her child to life
long chronic disease . We propose our lack of knowledge in human
villus development is preventing advances in technologies to
counter pregnancy complications. Objective: As most
developmental processes involve transitory progenitor and stem
cell populations that drive and organize developing cellular
networks, I hypothesize a cellular analysis of the human placenta
will identify populations of transitory cells that direct villus
development. Methods: Through a systems biology approach,
human placenta samples were dissociated into two fractions:
CNPRM 2015
trophoblast and stromal enriched fractions. The trophoblast
fraction was analyzed by a flow cytometry based screen of 370 CD
antigens to identify transitory populations of cells in replicate
samples from week 6 and 10, which span the critical period of
villus formation. The high throughput flow cytometry assay was
conducted on trophoblast fractions and target populations are
validated using targeted flow cytometry, histology, and genome
wide gene expression analysis, as outlined in Fig1. Results: Using
the most stringent filtering criteria, 4 increasing and 6 decreasing
developmentally regulated populations were confidently identified
in both replicates of the screen (Fig2). I have confirmed two
markers of transient, decreasing trophoblast cells are labeling
independent populations . Targeted flow cytometry analysis
confirmed distinct EpCAM+ and EpCAM- populations in week 5
placentas. A CDCP1 population was identified that does not coexpress EGFR or EPCAM. These populations have been isolated for
microarray analysis. Histological analysis revealed EpCAM labels
most cytotrophoblast prior to week 7 but by week 8, its expression
is restricted to the cytotrophoblast in the column at the leading
edge of villus tree development. Conclusion: This resource of CD
antigen expression in early human villi development will be a
valuable asset to studying placenta organogenesis. My work has
developed strong evidence to support the existence of transient
populations of cells in the human placenta. Microarray data will be
used to identify changes in gene expression that occur as
cytrotrophoblasts switch from EpCAM positive to negative and
how this drives villus tree development. Acknowledgements:
This project is funded by NSERC and the University of Toronto.
Contact Information: [email protected]
[309]
EFFECTS OF SELECTIVE SEROTONIN-REUPTAKE INHIBITORS ON
PROLIFERATION, SYNCYTIALIZATION AND HORMONAL
DIFFERENTIATION OF BEWO HUMAN CHORIOCARCINOMA CELLS.
Hélène Clabault1, Denis Flipo2, Thomas Sanderson1, Cathy
Vaillancourt1
1INRS-Institut Armand-Frappier and BioMed Research Centre,
Laval, QC, 2Université du Québec à Montréal
Introduction: Between 15% and 20% of women are depressed
during pregnancy. Selective serotonin-reuptake inhibitors (SSRIs)
are the most prescribed class of antidepressants for pregnant
women, although effects of SSRIs on placental function have never
been studied. A healthy pregnancy depends on the quality of
placental trophoblast development and function. In floating villi,
villous trophoblast cells (mononucleated) fuse and differentiate
into syncytiotrophoblast (syncytialization) which produce
hormones such as human chorionic gonadotrophin (hCG).
Objective: The aim of this study was to determine whether SSRIs
commonly used during pregnancy affect trophoblast fusion,
proliferation and/or hormonal differentiation in BeWo cells, a
model of the villous trophoblast. Methods: BeWo cells were
treated with increasing concentrations (0.03-10µM) of SSRIs
(fluoxetine, norfluoxetine and sertraline) in the presence or
absence of forskolin (20µM) (to induce syncytialization). Cell
proliferation was monitored in real-time using an xCELLigence©
system based on cell-impedance measurements. Morphological
differentiation (fusion) was determined by immunofluorescence
CNPRM 2015
95
with an antidesmoplakin antibody and counter-staining of nuclei
with propidium iodide. Secretion of hCG was measured by ELISA to
evaluated functional differentiation. Results: Fluoxetine
decreased BeWo cell proliferation, whereas norfluoxetine and
sertraline had no effect. None of the SSRIs affected basal or
forskolin-stimulated BeWo cell fusion at the concentration tested.
Norfluoxetine and sertraline, but not fluoxetine, had a small
inhibitory effect on the functional differentiation (hCG secretion)
of BeWo cells, which was not concentration dependent or
statistically significant. Conclusion: This study suggests that SSRIs
(fluoxetine, norfluoxetine and sertraline) do not alter villous
trophoblast viability or syncytialization (fusion and functional
differentiation) and thus placental development. Our observations
will be confirmed using primary cultures of villous trophoblast cells
and expanded to include additional SSRIs. Acknowledgements: I
acknowledge March of Dimes and the Office Franco-Québécois
pour la jeunesse. Contact Information:
[email protected]
[312]
ALTERED PLACENTAL PHOSPHOLIPASES A2 MRNA EXPRESSION IN
PREECLAMPSIA. Mélanie Brien1, Jessica Larose2, Jean-François
Bilodeau3
1CHU de Québec Research Center / Laval University / Faculty of
medicine, 2CHU de Québec Research Center, 3CHU de Québec
Research Center / Laval University / Obstetrics, gynecology and
reproduction
Introduction: More than 30 isoforms of phospholipases A2 (PLA2)
enzymes have been identified so far. These enzymes can be
further subdivided into 6 families comprising, amongst others, the
cytosolic (cPLA2), the secretory (sPLA2) and the Lipoproteinassociated (LP-PLA2) families. The PLA2 are known to be essential
to the formation of eicosanoids by freeing arachidonic acid from
cellular membrane phospholipids. Moreover, F2-isoprostanes
produced during oxidative stress by the peroxidation of the bound
arachidonic acid can also be released by PLA2. Free F2-isoprostanes
can act as a vasoconstrictor and a platelet activator. The
augmentation of vasoactive eicosanoids including F2-isoprostanes
has been associated with the pathophysiology of preeclampsia
(PE). Objective: To characterize the mRNA expression levels of
different phospholipases A2 in preeclampsia, according to the
mode of delivery and to the sampling sites from the placental
layers: amnion-chorion and villi. Methods: PLA2 expression was
measured in placentas of normotensive (n=9) and preeclamptic
(n=9) pregnancies using RT-qPCR. Specific primers were design for
the phospholipases A2. The two following reference genes, YWHAZ
and SDHA, were used as internal control in all PCR samples in
order to normalize the results. The GeNorm software was used to
calculate the reference genes stability measurements M. The
relative mRNA expression was expressed as the ratio of target
gene to M values. Results: The sPLA2 type II mRNA expression
following vaginal delivery is 2.5 fold higher in the villi of
preeclamptic placentas than the normotensive control group
(p=0.015), while no change was detected in the amniochorionic
membrane. The cPLA2 mRNA expression in the amniochorionic
layer is higher in PE than the control group (p=0.07) but, there was
no change observed for the mRNA expression in the villi. The LpPLA2 mRNA expression is higher in both layers in PE than the
control group (Amniochorionic: p=0.09, and villi: p=0.056).
Conclusion: Specifics phospholipases A2 can be upregulated in
placentas during preeclampsia. This augmentation could be link to
vasoactive eicosanoids generation and F2-isoprostanes.
Acknowledgements: This work was supported by a grant from the
Canadian Institutes of Health research (CIHR, grant# MOP-84219
to J.-F.B). Contact Information:
[email protected]
96
[313]
MATERNAL NICOTINE EXPOSURE LEADS TO IMPAIRED DISULFIDE
BOND FORMATION AND AUGMENTED ENDOPLASMIC
RETICULUM STRESS IN THE RAT PLACENTA
Michael K Wong1, Catherine J Nicholson2, Alison C Holloway2,
Daniel B Hardy3
1Western University, Physiology and Pharmacology, 2McMaster
University, Obstetrics and Gynaecology, 3Western University,
Obstetrics and Gynaecology
Introduction: Approximately 15% of women continue to smoke
during pregnancy due to the highly addictive nature of nicotine.
While nicotine replacement therapies are considered to be a safer
alternative, nicotine alone has been found to cause hypoxia and
compromised placental development. Although the underlying
mechanisms remain elusive, recent studies have identified that
augmented endoplasmic reticulum (ER) stress is linked to placental
insufficiency. Moreover, ER function depends on proper disulfide
bond formation – a partially oxygen-dependent process mediated
by protein disulfide isomerase (PDI) and ER oxidoreductases.
Objective: Given that: (1) nicotine induced hypoxia in the rat
placenta, and (2) hypoxia and placental insufficiency were
associated with poor disulfide bond formation and ER stress, the
objective was to determine whether maternal nicotine exposure in
vivo leads to augmented placental ER stress and impaired disulfide
bond formation in the rat placenta. Methods: Female rats
received daily subcutaneous injections of either saline (vehicle) or
nicotine bitartrate (1mg/kg) for 14 days prior to mating and during
pregnancy. This dose has previously resulted in maternal and
neonatal serum cotinine concentrations similar to either moderate
female smokers and/or low-dose nicotine replacement therapy
user. Placentas were harvested on embryonic day (e) 15 for
analysis. Protein and mRNA expression of markers involved in ER
stress (e.g., phosphorylated eIF2α, Grp78, Atf4, and CHOP),
disulfide bond formation (e.g., PDI, QSOX1, VKORC1), hypoxia
(Hif1α), and amino acid deprivation (GCN2) were quantified via
Western blot and/or Real-time PCR.Results: Maternal nicotine
exposure led to increased expression of phosphorylated eIF2α and
Grp78 (p<0.05) in the rat placenta, demonstrating the presence of
augmented ER stress. Nicotine exposure also led to increased
expression of Atf4 and CHOP (p<0.05), suggesting activation of ERstress apoptotic pathways. Decreased expression of PDI, VKORC1,
and QSOX1 (p<0.05) reveal an impaired disulfide bond formation
pathway, which may underlie nicotine-induced ER stress. Finally,
elevated expression of Hif1α and GCN2 (p<0.05) indicate hypoxia
and amino acid starvation in nicotine-exposed placentas,
respectively. Conclusion: This study has demonstrated that
nicotine can augment ER stress in the rat placenta potentially
through the impairment of key players in disulfide bond
formation. Furthermore, given that nicotine alone exerts severe
effects on placental function, and consequently, on fetal and
postnatal health, this study further implicates that caution is
required for women considering nicotine replacement therapy for
smoking cessation in pregnancy. Contact Information: Michael
Wong [email protected]
[321]
DIFFERENTIAL EXPRESSION OF CHEMOKINES AND RECRUITMENT
OF UTERINE LEUKOCYTES AT THE PORCINE MATERNAL-FETAL
INTERFACE. Mallikarjun Bidarimath1, Kasra Khalaj1, Jocelyn M.
Wessels2, Rami T Kridli3, Chandrakant Tayade1
1Department of Biomedical and Molecular Sciences, Queen’s
University, Kingston, Ontario, Canada, K7L 3N6, 2Department of
Obstetrics and Gynecology, McMaster University, Hamilton,
Ontario, Canada, L8S 4L8, 3Department of Biomedical Sciences,
Ontario Veterinary College, University of Guelph, Guelph, Ontario,
Canada, N1G 2W1
CNPRM 2015
Introduction: Spontaneous fetal loss leading to decrease in the
litter size in North American porcine species is a prime concern to
the pork industry. Approximately 25 - 40% of conceptuses are lost
during the peri-implantation and mid gestation periods. Previous
studies have indicated that reduced vasculature at the conceptus
attachment sites (CAS) is associated with the fetal loss. During
early pregnancy in many species including pigs, the endometrium
becomes enriched with immune cells. Although there is literature
evidence about recruitment of immune cells, very little
information is available on how these immune cells are recruited
and or their pregnancy specific functions. Traditionally known to
recruit immune cells to mediate inflammation, chemokines are
now known to exert a range of biological effects. We hypothesize
that leukocytes are recruited and positioned within the maternalfetal interface by specific chemokine signals. Objective: To
understand how immune cells are recruited and positioned within
the porcine maternal-fetal interface during early and midgestation. Methods: Endometrial and trophoblast samples were
collected from healthy and arresting CAS of specific pathogen free
Yorkshire sows at gestation day (gd) 20 and gd 50. The total RNA
isolated from these samples was reverse transcribed and resultant
cDNA was stored at -20oC. Specific cytokines and chemokines
(TNF, IFN-G, CXCL10, CXCL11, CXCR3, CXCR2, CXCL12, CXCR4, CCL5,
CCR5, CXCL9, CCL2, CCR2, DARC, CCRL1, CCR1, CCR3, CCR4, CCL1,
CCL17, CCL20, CCL21 and CCR10) involved in leukocyte
recruitment were quantified at mRNA level using custom designed
Q-PCR arrays. Localization of lymphocytes within endometrium
were studied using CD45+ immunohistochemistry. Results:
Compared to healthy CAS, chemokines such as CCL5/RANTES,
CCR5 were significantly up-regulated in endometrium associated
with arresting CAS (P<0.05) at gd 20. Significant differences exist in
endometrium for decoy receptor, DARC which was downregulated (-24.76 fold change; P<0.05). In trophoblasts isolated
from arresting CAS, no differences were evident for chemokines
compared to healthy CAS at gd 20. However, CCL1 was
significantly up-regulated in the trophoblasts isolated from
arresting compared healthy CAS (P<0.05) at gd 50. No changes in
the expression of chemokines were found in the lymphocytes
isolated from arresting compared to healthy CAS at gd 20 and gd
50 (P<0.05). Our preliminary results confirms the Immunolocalization of lymphocytes in the endometrium. Conclusion: Our
data suggest that specific chemokines are involved in recruitment
and localization of leukocytes to the endometrium during early
and mid-gestation in pigs. Acknowledgements: NSERC CRD,
Ontario Pork and OMAFRA, BIONICHE. Contact Information:
Mallikarjun Bidarimath [email protected]
[322]
VITAMIN D STATUS IS LOW IN MOTHERS WITH PREECLAMPSIA
AND THEIR INFANTS: A CASE CONTROL STUDY FROM SERBIA.
Marija Djekic-Ivankovic1, Hope Weiler2, Glenville Jones 3, Martin
Kaufmann3, Jovana Kaludjerovic4, Vesna Aleksic-Velickovic1, Ljuba
Mandic5, Maria Glibetic1
1Institute for Medical Research/University of Belgrade, 2School of
Dietetics and Human Nutrition/McGill University, 3Department of
Biomedical & Molecular Sciences/Queen's University,
4Department of Oral Medicine, Infection, and Immunity/Harvard
School of Dental Medicine, 5Faculty of Chemistry/University of
Belgrade/Department of Biochemistry
Introduction: Low 25-hydroxyvitamin D3 (25-OH-D3)
concentration in pregnancy increases the risk of preeclampsia (PE)
based on studies from countries with vitamin D fortification
programs. Response to vitamin D supplementation is complicated
by the presence of 3-epi-25-hydroxyvitamin D3 (3-epi-25-OH-D3)
representing up to 40% of total 25-OH-D3 in infants. Objective:
The aim of the study was to examine vitamin D intake and status
of women with and without PE and their infants in Serbia, a
country without mandatory vitamin D food fortification, and
describe the proportion of total 25-OH-D3 in the epimer form in
relation to maternal and neonatal outcomes. Methods: A casecontrol study (n=60) of pregnancies with (case) and without
(control) PE was conducted in Serbia in the winter. Blood samples
were obtained at delivery from mothers and the cord to enable
assessment of 25-OH-D3, 3-epi-25-OH-D3 and 24,25dihydroxyvitamin D3 (24,25-(OH)2D3) by LC-MS/MS. Group
differences were tested with ANOVA, Bonferroni post hoc test and
P<0.05. Results: Vitamin D intake from supplements was not
different between case and control mothers, however, women
with PE delivered infants at younger mean gestational age and had
lower plasma 25-OH-D3, 3-epi-25-OH-D3 and 24,25-(OH)2D3
(table). Case infants were of lower birth weight (Case: 2622 ± 796
vs Control: 3388 ± 381 g, p<0.001), not different in total plasma
25-OH-D3 (Case: 9.38 ± 1.05 vs Control: 11.17 ± 0.99 ng/ml,
p=1.000) but with higher proportion of 3-epi-25-OH-D3 (Case: 7.95
± 0.22 vs Control: 7.01 ± 0.21 % of total 25-OH-D3, p=0.013). A
high prevalence of vitamin D deficiency, defined by plasma 25-OHD3 < 12 ng/ml, was Conclusion: These data underscore the
importance of prenatal supplementation and food fortification
policy that should be addressed by Serbian public health.
Acknowledgements: This work was supported by the Ministry of
Education, Science and Technological Development of the
Republic of Serbia (grant number III 41030). Contact Information:
Marija Djekic-Ivankovic [email protected]
[339]
UTERINE NK CELL CONJUGATIONS IN EARLY MURINE
GESTATIONAL DECIDUA. Allison M Felker1, B Anne Croy2
1Department of Biomedical and Molecular Sciences, Queen's
University, 2Department of Biomedical and Molecular Sciences,
Queen's University
Introduction: Endometrial decidualization is accompanied by a
huge leukocyte influx to the decidua basalis that is dominated by
unique cytokine and angiokine producing uterine natural killer
(uNK) cells. Whole mount in situ immunohistochemistry (WM-IHC)
of viable early mouse (C57BL/6; B6) implantation sites (IS)
revealed conjugated CD45+ leukocyte pairs that did not involve
trophoblasts. Composition and importance of these conjugation
events is unknown. Objective: To determine the frequency, time
course of development, and composition of CD45+ leukocyte
conjugates during early pregnancy in B6 mice. Methods:
Syngeneic B6 pregnancies were studied at gestation day (gd)5.5,
6.5, 8.5, and 9.5 by WM-IHC and epifluorescence microscopy. IS
were collected after euthanasia, halved midsagittally and
incubated at 4°C in 200µL PBS-1% BSA-0.1% sodium azide (PBA)
with 10µg/mL IgG Fc receptor blocking antibody, anti-CD45,
Dolichos biflorus agglutinin (DBA) Lectin (an angiogenic uNK cell
subset marker), and one of the following directly conjugated
fluorescent antibodies: anti-CD4, CD8, CD11c, CD31, CD68, MHC II,
or Ly49C/I (marks a 2nd uNK cell subset). After 1 h, 1mL of PBA
was added, IS were placed on slides, coverslipped and viewed
using an AxioCam-equipped Zeiss M1 Imager. 200x magnified
images were analyzed to identify the number and composition of
CD45+ leukocyte conjugates. A minimum of 50 CD45+ dimers was
scored for each antibody combination (n=3
pregnancies/timepoint). Results: Leukocytes expressing CD31
doubled in frequency between gd5.5-6.5 (42.5%-76.6%) and
contributed to almost all conjugates as homodimers and
heterodimers. The frequency of CD45+ cells in conjugates
increased from gd5.5-8.5 (3.6%-19%) and declined at gd9.5 (9.8%).
Ly49C/I+ uNK cells, antigen presenting cells (APCs) and T cells were
identified as paired with DBA+ uNK cells. At gd6.5, the dominant
cells in conjugation with DBA+ uNK cells were Ly49C/I+ uNK cells
CNPRM 2015
97
(26.7%) and APCs (CD11c+: 14.4%; CD68+: 12.3%; MHCII+: 13.5%).
By gd8.5 the dominant partners with DBA+ uNK cells were
Ly49C/I+ uNK cells (24.9%) and T cells (CD8+: 34.4%; CD4+: 16.7%).
Conclusion: Leukocyte-leukocyte conjugations occur in early
decidua basalis and increase over the pre-placental interval of
pregnancy. Their numbers peak 4 days after implantation, a time
appropriate for initiation of adaptive immune responses. Cells
participating in conjugations are CD31+ and include homodimers
(potentially dividing) and heterodimers within and outside of the
uNK cell lineage. Whether these conjugations represent cell
triggering or killing interactions is under study. Contact
Information: Allison Felker [email protected]
Newborn Health
[255]
INDOMETHACIN DOSE-INTERRUPTION & MATERNAL
CHORIOAMNIONITIS AS RISK FACTORS FOR INDOMETHACIN
TREATMENT FAILURE IN PRETERM INFANTS WITH PDA. Souvik
MItra1, Muzafar Gani Abdul Wahab1
1Division of Neonatology, Department of Pediatrics, McMaster
University, Hamilton, ON
Introduction: Indomethacin has been used as the primary
pharmacotherapeutic agent for closure of PDA in preterm infants.
However, it is frequently observed that infants respond differently
to indomethacin treatment with some infants requiring multiple
courses of the drug and subsequently surgical ligation. Objective:
To identify perinatal and neonatal factors associated with failure
of a primary course of indomethacin for PDA in preterm infants.
Methods: We studied preterm infants who received intravenous
indomethacin for PDA treatment from 2010-2013. We identified
those who failed primary pharmacotherapy and required
subsequent courses or surgical ligation. Failure of primary course
of indomethacin was defined as infants requiring more than one
full course of indomethacin for closure of PDA or received one full
course of indomethacin followed by surgical ligation for closure of
PDA. A number of perinatal/neonatal variables in the infants with
and without primary indomethacin failure were compared initially
for univariate analysis. Following univariate analysis, those
variables which had significant difference between the two groups
were selected to carry out logistic regression analysis to find out
independent risk factors for indomethacin failure. Results: Out of
77 infants analyzed, 36 (46.7%) had primary indomethacin failure
and nine infants (11.7%) underwent surgical ligation. Univariate
analysis revealed that infants with primary indomethacin failure
were significantly more immature, of male sex, did not receive a
complete course of antenatal corticosteroids, indomethacin dose
interruption was documented during clinical care and their
mothers had clinical chorioamnionitis.(table 1). The multivariable
logistic regression analysis showed that dose interruption and
clinical chorioamnionitis were independent risk factors for
indomethacin failure (table 2). Conclusion: Indomethacin dose
interruption and clinical chorioamnionitis appear to be
independent risk factors for primary indomethacin failure in
preterm infants. This study generates an important and previously
unexplored hypothesis regarding the role of dosage interruption in
treatment failure. This could pave the way for future prospective
cohort studies to better analyze this interaction and also
prospective RCTs to potentially find a solution to this problem.
Acknowledgements: Wendy Seidlitz, Clinical Informatics Specialist,
McMaster Children\'s Hospital, Hamilton Health Sciences for initial
data compilation. Contact Information: Souvik Mitra
[email protected]
98
[256]
DO PRETERM INFANTS WITH PDA WHO FAIL INDOMETHACIN
TREATMENT HAVE LOWER PLATELET COUNTS? : A SYSTEMATIC
REVIEW AND META-ANALYSIS. Souvik MItra1, Bosco Paes2,
Anthony K C Chan2
1Division of Neonatology, Department of Pediatrics, McMaster
University, Hamilton, ON, 2Department of Pediatrics, McMaster
University, Hamilton, ON
Introduction: Indomethacin is one of the most commonly used
pharmacotherapeutic agents for closure of PDA in preterm infants.
Failure of a primary course of indomethacin to close the PDA is not
uncommon. Several observational studies have linked low platelet
counts to indomethacin failure. Recent animal studies have also
highlighted the potential role of platelets in PDA closure.
Objective: To conduct a systematic review and meta-analysis of
the association of platelet counts and indomethacin failure in
preterm infants with PDA. Methods: Data Sources: The authors
searched MEDLINE, Embase, CINAHL and PubMed, reviewed
reference lists of relevant articles, abstracts and conference
proceedings (Society for Pediatric Research, European Society for
Pediatric Research 1990-2014), sought results of unpublished
trials, and contacted the primary authors of relevant studies.
Study Selection: Studies were included if they reported the use of
indomethacin for PDA closure, compared a group which failed
indomethacin treatment versus a group which didn’t and reported
primary data that could be used to measure the association
between platelet counts and indomethacin failure. Data
Extraction: Two reviewers independently screened the search
results, applied inclusion criteria and assessed methodological
quality using the Newcastle-Ottawa Scale. One reviewer extracted
data and a second reviewer checked data extraction. Results were
expressed as mean difference in platelet counts and were
calculated using a fixed effects model. Results: We identified 716
potentially relevant studies from the electronic databases. Nine
studies reported platelet counts with indomethacin failure, but
five did not meet our a priori data abstraction criteria. Four studies
involving 669 preterm neonates with 139 cases of indomethacin
failure were included. Platelet counts were found to be
significantly lower in infants with failed indomethacin treatment
[Mean difference - 25.07x109/L; 95 % CI: -39.30x109 , -
CNPRM 2015
10.84x109/L; I squared=0]. Conclusion: Platelet counts appear to
be significantly lower in infants with indomethacin failure. Though
these preliminary findings align with the pathophysiological role of
platelets in PDA closure, more prospective cohort studies that
consistently report platelet counts in prostaglandin inhibitor
failure are needed so that a larger meta-analysis can be conducted
to establish or refute a significant association.
Acknowledgements: THIN (Thrombosis & Hemostasis in
Newborns) Research Group, McMaster Children's Hospital,
Hamilton Health Sciences. Contact Information: Souvik Mitra
[email protected]
[259]
DO THE PERCUTANEOUSLY INSERTED CENTRAL VENOUS
CATHETER RELATED COMPLICATIONS IN PRETERM INFANTS VARY
DEPENDING ON THE SITE OF INSERTION? Rani A Bashir MD,
MRCPCH1, Sakeer Vayalthrikkovil MD, MRCPCH1, Amuchou
Soraisham MD,DM,FRCPC2
1Section of Neonatology, Department of Pediatrics, University of
Calgary, Calgary AB, 2Section of Neonatology, Department of
Pediatrics, University of Calgary, Calgary, AB.
Introduction: Percutaneously inserted central venous catheters
(PICCs) are associated with a variety of complications including
catheter line associated blood stream infection (CLA-BSI),
occlusion, phlebitis and catheter fracture. However, there is
limited information comparing the PICC related complications
based on the site of insertion in preterm neonates. Objective: To
examine whether there is an association between PICC insertion
site and PICC related complications in preterm infants. Methods:
We performed a retrospective analysis of all PICCs placed in
preterm infants between January 2006 and December 2010. The
details of PICC insertion, maintenance and complications were
retrieved from the NICU database.PICC related complications were
analyzed based on the site of insertion using Chi-square or
independent-samples t test where appropriate. Results: A total
of 1106 PICC lines were inserted in 820 preterm infants. The
median gestational age was 29 weeks (IQR 26, 31) and median
birth weight was 1120 g (IQR 870, 1470). Of 1106 PICCs, 777(70%)
were inserted at upper extremities(UE) via cephalic and basilic
veins; and 329 (30%) were inserted in lower extremities(LE) via
saphenous veins. The median age at PICC insertion in UE was 6
days (IQR 3, 14) and LE was 9 days (IQR 4, 19). There was no
difference in duration of catheter between the sites (median 10
days). The PICC related complications are compared in [table 1].
Right UE PICCs had the maximum rate of infiltration (17.2%) but
least line occlusion (6.5%). Line occlusion was most frequent
among right LE PICC (16.7%). Left LE PICC had the lowest rate of
line infiltration (3.9%). There was no difference in CLABSI between
the two groups. Table 1: Comparison of central line associated
complications Upper extremity PICC Lower extremity PICC Odds
ratio, 95% CI N=777 N=329 Infiltration, n(%) 119 (15.3) 24 (7.2)
2.29 (1.45, 3.36) Occlusion, n(%) 67 (8.6) 49(14.8) 0.53 (0.36, 0.79)
Phlebitis, n(%) 29 (3.7) 12 (3.6) 1.02 (0.51, 2.03) Dislodgement,
n(%) 4 (0.51) 1 (0.3) 1.69 (0.18, 15.2) CLABSI, n(%) 43 (5.5) 18 (5.4)
1.01 (0.57, 3.55) Any complication ,n(%) 249 (32) 95 (29) 1.16
(0.87, 1.54). Conclusion: In preterm infants, PICC related
complications vary depending on the site of insertion. Line
infiltration was most common in right upper extremity PICC
whereas line occlusion was maximally seen in PICC inserted via
lower extremity. Acknowledgements: We acknowledge NICU
transport nurses. Contact Information:
[email protected]
[269]
CLINICIAN’S JUSTIFICATIONS TO TRANSFUSE RED BLOOD CELLS,
PLATELET CONCENTRATES AND PLASMA IN A NEONATAL
INTENSIVE CARE UNIT. Andréanne Villeneuve1, Anie Lapointe1,
Thierry Ducruet2, Jacques Lacroix2, Christian Lachance1
1University of Montréal, CHU Ste-Justine, Department of
Paediatric, division of Neonatology, 2University of Montréal, CHU
Ste-Justine, Department of Paediatric, division of paediatric
intensive care
Introduction: Blood component transfusions are frequent in the
neonatal intensive care unit (NICU) despite a paucity of evidence
of benefit in many clinical situations. Objective: To describe
clinician’s rationale behind their decision to transfuse red blood
cells (RBC), platelets concentrates or plasma. We expect to find a
significant variability in stated determinants of transfusion.
Methods: In this prospective cohort study, caregivers who ordered
a first RBC, platelets and/or plasma transfusions in all consecutive
neonates admitted into the NICU of Université de Montréal
affiliated Sainte-Justine Hospital (level 3B) from May 30th to
November 6th 2013 were included. One or more justifications
were collected for each transfusion, using a printed validated
questionnaire. Patient’s clinical information was extracted from
medical charts. Results: Among the 402 patients admitted to
NICU, 67 (16.7%) were transfused. Their mean (SD) birth weight
and gestational age (GA) were 1.79 (1.2) kg, and 31 (6) weeks;
34.3% of them were less than 28 weeks of GA at birth, and 20.9%
were born at term. At least one RBC, plasma and platelets
concentrates were given in 54 (13.4%), 25 (6.2%) and 37 (9.2%)
infants, respectively. Primary reasons for admission was
prematurity (70.2%), respiratory disease (77.6%) and suspected or
proven bacterial infection (29.9%) Caregiver’s response rate to
questionnaires was 98.5%. It is Residents or fellows have ordered
the transfusion in most instances (TABLE 1). The most frequent
justifications for RBC transfusion were: low hemoglobin level
(81.1% of RBC transfusions), underlying illness (62.3%) –mostly
prematurity and necrotizing enterocolitis (NEC) –, and to increase
oxygen delivery (52.8%). Mean (SD) hemoglobin concentration
before the first transfusion was 8.5 (1.3) (range 6.2-13.7) g/dl. A
low platelets count, the underlying disease – perinatal asphyxia,
NEC and septic shock were most frequent – and severity of illness
justified 86.5%, 78.4% and 37.8% of platelets transfusions,
respectively. Pre first transfusion mean (SD) platelets count was 59
(28) (range 12-137) x109/l. Plasma transfusion was mainly justified
by the underlying disease (80%) – mostly perinatal asphyxia, septic
shock and pulmonary hemorrhage –, prolonged INR (72%) (mean
(SD) 2.7 (0.6); range 2-3) and severity of illness (60%). Conclusion:
This single center study confirms the heterogeneity of blood
components transfusion stated practices. This lack of uniformity
might expose vulnerable neonates to unnecessary transfusions. It
underlines the need for consensus on their use in NICU patients.
Acknowledgements: Financial support: Fonds de la recherche en
santé du Québec, grant #24460. Contact Information:
[email protected]
[271]
RENAL HAEMODYNAMICS AND ACUTE KIDNEY INJURY (AKI)
DURING THERAPEUTIC HYPOTHERMIA (TH) AND RE-WARMING
(RW) IN NEONATES WITH HYPOXIC-ISCHAEMIC
ENCEPHALOPATHY (HIE). Miroslav Stavel1, Joseph Ting1, Kiran
More1, Pankaj Sakhuja1, Aideen Moore1, Patrick McNamara1
1NICU, Hospital for Sick Children, Toronto
Introduction: Birth asphyxia is associated with AKI; severity may
correspond with degree of hypoxia. Previous work by our group
CNPRM 2015
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demonstrated lower cardiac output in neonates undergoing TH.
The relevance of these changes to AKI remains unknown.
Objective: To describe longitudinal renal haemodynamic changes
during TH and RW and evaluate their relationship with cardiac
output in neonates with and without AKI. Methods: Prospective
observational study of 18 term and near-term infants with HIE
who received TH. Doppler ultrasound was used to assess left
ventricular output (LVO) and renal artery (RA) blood flow
parameters - systolic and end-diastolic velocity (Vs and Vd), and
resistive index (RI) during cooling [TH I (24h) and II (72h)] and post
re-warming [RW I (12h) and II (>24h)]. AKI was defined as
anuria/oliguria (<1 ml/kg/h) for ≥24h and a serum creatinine >100
mmol/l; or anuria/oliguria for >36h; or any serum creatinine >125
mmol/l; or rising serum creatinine postnatally. Results: There was
no difference in baseline demographics or severity of HIE between
neonates with (n=8) vs without (n=10) AKI. All 18 infants survived
till discharge. Neonates who developed AKI had higher RA RI 24h
after TH was initiated [Table 1]. There was a temporal increase in
LVO in both groups (p<0.01, 2-way ANOVA), without intergroup
difference. Neonates in the non-AKI group only showed an
increase in RI (p=0.01) and a trend towards increase in RA Vs over
time (p=0.05). Early changes in end-diastolic flow (EDF) were seen
in both groups, which normalized over time. Conclusion: Elevated
RA RI at 24 hours after introduction of TH is associated with and
predicts AKI. The fall in cardiac output and renal systolic flow after
TH is not associated with AKI. Contact Information:
[email protected]
[282]
ASSESSMENT OF WROP ALGORITHM AS SCREENING TOOL FOR
PRETERM INFANTS IN MANITOBA TO DETECT RETINOPATHY OF
PREMATURITY (ROP). Raiya Al Habsi, MD1 , 1, Nasser Al-Shafouri,
MD1, Ebtihal Ali, MD1, Abrar Hussain, MD1, and Ronald John
Baier1
1 University of Manitoba/ Neonatology
Introduction: The WinROP algorithm may reduce the need for
ophthalmologic examinations in premature infants who are at low
risk of developing severe vision threatening retinopathy of
prematurity (ROP). This algorithm classifies infant as high or low
100
risk according the weekly weight gain in infants less than 32 weeks
gestational age. Objective: This study was conducted to assess
the validity of WinROP algorithm to detect infants at high risk for
sight threatening ROP in our population of premature infants.
Methods: This study was a retrospective chart review of infants <
32 weeks born between 2008-2012. Online WinROP classification
was performed from birth to a corrected GA of 40 weeks or until
discharge, whichever came first. Weekly body weights and highest
stage ROP were entered into the WinROP algorithm.The program
will flag the infant who are at high risk of developing sight
threatening ROP. Results: In our preliminary results for 102
infants, 60 infants were classified as low risk. None of them
developed severe ROP or needed treatment. Forty-two (42)
patients were flagged by the algorithm as being high risk for ROP,
of those 5 developed advanced ROP which needed treatment.
Sensitivity and specificity were 100% and 62% respectively,
negative predictive value was 100% and positive predictive value
was 12%. Mean birth weight for infants enrolled in study was 1238
grams and mean gestational age was 28 weeks and 6 days. Mean
birth weight for those who developed ROP required was 824
grams and mean gestational age was 26 weeks and 0 days.
Conclusion: The WinROP algorithm correctly identified all infants
as high risk who subsequently developed advanced ROP and were
treated. None of the infants who were identified as low risk
developed severe ROP. The WinROP algorithm can be a valuable
screening tool for ROP screening as an adjuvant to reduce the
number of ROP screening. Acknowledgements: Dr Clark(
Ophthalmologist at Health Science Hospital, Winnipeg). Contact
Information: Raiya Al Habsi [email protected]
[306]
CONGENITAL METHAEMOGLOBINEMIA DUE TO HB F-M-FORT
RIPLEY IN A PRETERM NEWBORN. Satvinder Ghotra1, Chantale
Pambrun1, Conrad Fernandez1, Ashley Smith1, Sandhya Parkash1,
Rasoul Koupaei1, Krista Jangaard1
1IWK health centre, Pediatrics
Introduction: Methaemoglobinemia is a rare cause of cyanosis in
the newborn period. Congenital methaemoglobinemia, due to M
Hemoglobin or deficiency of an enzyme cytochrome b5 reductase,
are even more rare. Objective: We present a case of congenital
methaemoglobinemia in a preterm infant due to a gamma globin
gene mutation resulting in the M Hemoglobin called Hb F-M-Fort
Ripley. Methods: A preterm baby boy born at 29 weeks, 3 days of
gestation had persistent central cyanosis immediately after
delivery not attributable to a respiratory pathology. Cyanosis
persisted despite surfactant therapy, invasive ventilatory support
and 100% oxygen administration. Cardiac disease was ruled out on
echocardiography. The baby was screened for
methaemoglobinemia. Results: Serum methaemoglobin levels
were not significantly elevated, but co-oximetry reported unstable
measurement due to interfering substances. Cytochrome b5
reductase levels were normal. The newborn screening for
hemoglobinopathy did not detect any variant hemoglobin. Genetic
testing revealed the mutation associated with Hb F-M-Fort Ripley.
Maternal newborn records revealed a diagnosis of
methaemaglobinemia at term, which was self-resolving. The baby
required ventilatory support and oxygen therapy for respiratory
distress syndrome and bronchopulmonary dysplasia. Targeted
oxygen saturation monitoring parameters were defined to
maintain pAo2 between 40-60 mmHg. No specific therapy for
methaemoglobinemia was administered. The baby was discharged
home at a corrected gestational age of 38 weeks. His pulse
CNPRM 2015
oximetry saturations at discharge were 85-87%. He had no
apparent cyanosis and saturations of 92% at a corrected
gestational age of 42 weeks. Given that the variant hemoglobin is
caused by a mutation in the gamma gene, the symptoms are
transient and gradually improve as the HbF converts to HbA.
Conclusion: To our knowledge, this is the first report of congenital
methaemoglobinemia due to M hemoglobin in an extreme
preterm infant <30 weeks. Although rare, congenital
methemoglobinemia should be considered in the differential while
managing a preterm with central cyanosis. Laboratory
methaemoglobin levels may not be diagnostic and newborn
screening may not pick up abnormal variants of fetal hemoglobin.
Genetic testing may confirm the diagnosis. Target pulse oximetry
saturations established for preterm newborns may not be valid in
such cases. Oxygen therapy should be guided by pAo2. Contact
Information: Satvinder Ghotra [email protected]
Fusch [email protected]
[334]
POSTNATAL DILATATION OF UMBILICAL CORD VESSELS AND ITS
IMPACT ON WALL INTEGRITY: AN IN VITRO STUDY. Jenny Peng1,
Niels Rochow1, Jan Jansen2, Dragos Predscu1, Bryon DeFrance3,
Say-Young Lee1, Christoph Fusch1
1Pediatrics, McMaster University, Hamilton, Ontario, 2Pathology
and Molecular Medicine, McMaster University, Hamilton, Ontario,
3Obstetrics & Gynecology, McMaster University, Hamilton, Ontario
Introduction: In Neonatal Intensive Care Units, respiratory
insufficiency among low-birth weight infants has been a major
cause of mortality. For preterm infants, central umbilical
cannulation has been widely performed for administering
antibiotics, electrolytes, and nutrients. These umbilical vessels can
become a source of vascular access to connect the preterm infant
to an artificial placenta (AP) that provides sufficient gas exchange
to overcome respiratory distress. The concept of an AP requires
large bore access via umbilical vessels. In utero, umbilical artery
(UA) and vein (UV) have wide diameters (3-5 and 6-10mm,
respectively). After birth, these vessels constrict, and need to be
re-expanded to maintain high extracorporeal flow rate for
successful application of an AP. However, re-opening of the UA
and UV via catheterization may compromise vessel wall integrity.
Objective: To study the impact of expansion on the vascular
integrity of the UA and UV and identify a threshold diameter for
safe expansion. Methods: Umbilical cords were collected from
term pregnancies (N=12). Cannulation and dilatation were
performed in UA and UV from cord sections by inflating
percutaneous transluminal angioplasty (PTA) catheters (3-8 mm
for UA and 4-15mm for UV). Upon 30s dilatation, cord sections
were harvested. Paraffin-embedded transverse sections (4µm
thickness) were HE & Van Gieson stained. Areas of damage, shown
by splicing, were measured using ImageJ, and the ratio of splicing
area to vessel area was compared among dilatations. Results:
Umbilical vessel expansion led to parallel splicing, shown by areas
devoid of extracellular matrix (ECM) and nuclei, in the tunica
intima and media. Figure 1 demonstrates these parallel splicing
(indicated by black arrows) in dilated UA and UV in comparison to
control, non-dilated vessels. In all vessel expansions, no vertical
splicing was observed. Results suggest a threshold expansion of
UA 6mm and UV 7mm, as maximal vessel damage was observed
above this threshold (3.6±2.9% for UA 7mm and 5.2± 2.3% for UV
8mm expansions). Figure 2 shows the percentage of splicing area
per vessel for increasing expansion diameter in UA and UV.
Conclusion: Loss of vessel integrity may have led to fewer splicing
past expansions where maximum splicing was observed (UA 7mm
and UV 8mm). The thresholds that are suggested for safe
expansions (UA 6mm and UV 7mm) are similar to in utero
conditions. Results demonstrate proof of concept for attaining
large bore access for the AP. Contact Information: Christoph
[454]
THE USE OF C-REACTIVE PROTEIN FOR THE DIAGNOSIS OF LATE
ONSET SEPSIS IN VERY PRETERM INFANTS. Marc Beltempo1,
Isabelle Viel-Thériault2, Roseline Thibeault2, Bruno Piedboeuf2
1McGill University Health Center, Departement of Paediatrics,
2CHU de Québec, Departement of Paediatrics
Introduction: C-reactive protein (CRP) is a well-studied test for the
evaluation of early-onset sepsis in term infants. However, little is
know about the use of CRP in the evaluation of late-onset sepsis in
preterms. Objective: The objective of this study was to compare
the sensitivity and specificity of CRP with the complete blood
count (CBC) for evaluation of late-onset sepsis in very preterm
infants. Methods: We conducted a retrospective study on all very
preterm infants (born <1500g) admitted at the CHU de Québec
NICU from 2008 to 2013 who had an evaluation for suspected lateonset sepsis. CRP levels were measured at time of initial suspected
sepsis in patients (T0) and 16-24h (T24) after. The positive CRP cutoff value was ≥10 mg/L. A complete blood count (CBC) was drawn
T0 and T24. The CBC was considered positive if any of the
following anomalies were present: white blood count
<5,000/mm3, immature neutrophil to total neutrophil ratio >0.10
or platelet count <100,000/uL. The sensitivity and specificity for
predicting LOS were calculated for each test and for the
combination of both. McNemar’s test was used to compare the
sensitivity and specificity between tests. Results: A total of 428
preterm infants underwent testing for suspected late-onset sepsis,
130 (30%) had culture proven infections. The sensitivity and
specificity of CRP for culture proven infections at T0 were 43%
(95% CI 34-52) and 80% (95% CI 75-85). Sensitivity and specificity
of the CBC were 48% (95% CI 39-57) and 81% (95% CI 74-86). The
combined CRP-CBC showed the highest sensitivity at T0; 60% (95%
CI 51-69) (P<0.001) but a lower specificity 67% (95% CI 6172)(P<0.001) when compared to both individual tests. The CRP’s
sensitivity at T24 was 81% (95% CI 73-88), the CBC’s was 58% (95%
CI 49-66) and the combined CRP-CBC was 83% (95% CI 77-90). The
sensitivity of CRP was superior to the CBC (P<0.001) and was not
statistically different than the combined CRP-CBC (P=0.41). The
specificity of CRP at T24 80% (95% CI 75-85) was superior to the
combined test CRP-CBC 67% (95% CI 61-72) (P < 0.001).
Conclusion: Our study shows that the combination of CRP and CBC
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is superior to both individual tests at the time of initial evaluation
of late-onset sepsis in very preterm infants. We have also
demonstrated that CRP is more sensitive and specific 24H after
initial evaluation and could serve as a single test at that time
instead of a CBC. Acknowledgements: We would like to thank
Anne-Sophie Julien, biostatistician for statistical support. Contact
Information: [email protected]
102
CNPRM 2015
WEDNESDAY EVENING, FEBRUARY 25TH
Developmental/Transgenerational Origins of
Health and Diseases
[406]
REPEATED MATERNAL STRESS ACROSS GENERATIONS
PROGRAMS PHYSICAL AND MENTAL HEALTH DECLINE IN AGING
RATS. Mirela Ambeskovic1, Yaroslav Ilnytskyy2, Erin A.
Falkenberg1, Youli Yao2, Alena Babenko1, Igor Kovalchuk 2,
Gerlinde A.S. Metz1
1University of Lethbridge, Canadian Centre for Behavioural
Neuroscience, 2University of Lethbridge, Biological Science
Introduction: Prenatal stress was shown to affect brain
development, neuroendocrine stress response and susceptibility
to mental illness, such as depression, in adulthood. The impact of
prenatal stress may accumulate across generations and
compromise the chances of healthy aging. Objective: Here we
investigated: 1) the effect of aging on depression-like behaviours,
stress response and epigenetic regulation by microRNAs; (2)
whether multigenerational prenatal stress (MPS) accelerates signs
of aging in mental and physical wellbeing. Methods: Male F4
generation offspring were derived from a lineage in which their
ancestral mothers (F0-F3) were stressed during pregnancy. Nonstressed controls were also tested. The male offspring was tested
for depression-like behaviours at the age of 6 (young ), 12 (middle
aged) and 18 (aged) months using a forced swim task. Behavioural
outcomes were related to plasma corticosterone (CORT) levels,
and to microRNA expression in the prefrontal cortex (PFC), a brain
area centrally involved in clinical depression. Morbidity and
mortality were also recorded. Results: The findings showed that
aging increased the risk of depression-like behaviours, which was
further exacerbated by MPS. Along with the higher incidence of
depression, MPS also down-regulated cortical expression of miR124, a recognized biomarker and therapeutic target in depression.
Additionally, MPS disturbed the stress response and accelerated
age-associated decline in overall health and longevity.
Conclusion: These findings suggest that ancestral programming by
stress is a significant determinant of lifetime mental health
trajectories and risk of common age-related diseases through
altered epigenetic regulation. MicroRNAs may represent
predictive biomarkers of age-related diseases.
Acknowledgements: The authors would like to thank Sarah Lorenz
for excellent assistance with the experiment. The authors
acknowledge support by the Alberta Innovates-Health Solutions
Interdisciplinary Team Grant #200700595 “Preterm Birth and
Healthy Outcomes” (GM) , grants from Alberta Innovates-Health
Solutions (GM), the Natural Sciences and Engineering Research
Council of Canada (GM), the Canadian Institutes of Health
Research #102652 (GM), and the Parkland Research Institute
(MA). Contact Information: [email protected]
[423]
SEX DIFFERENCES IN THE FETAL PROGRAMMING OF
HYPERTENSION: ROLE OF ADRENAL PHENYLETHANOLAMINE NMETHYLTRANSFERASE GENE EXPRESSION. Sandhya Khurana1,
Julie Grandbois2, Phong Nguyen2, Heather Peltsch2, Stephanie
Mercier3, Krishnan Venkataraman 4, T.C.Tai5
1Medical Sciences Division, Northern Ontario School of Medicine ,
2Department of Biology, Laurentian University, 3School of Human
Kinetics, Laurentian University, 4Department of Gerontology,
Huntington University, 5Medical Sciences Division, Northern
Ontario School of Medicine
Introduction: Human health and disease are influenced by the
genetic make up of an individual, but also to a great degree by the
environment. The prenatal environment can be a significant
determinant of long-term health outcomes. An adverse fetal
milieu such as undernourishment or exposure to environmental
insults can have long-term developmental consequences
impacting adult health, a phenomenon known as fetal
programming. Epidemiological data suggests that conditions in
utero can be linked to diseases like hypertension, diabetes and
other pathophysiological conditions in adulthood. Fetal
programming of adult diseases can be mediated by
glucocorticoids; either endogenous (eg. maternal stress), or
exogenous (eg. synthetic glucocorticoid administered to aid in the
development of premature babies). Glucocorticoids regulate
catecholamine biosynthesis which are critical for blood pressure
homeostasis, with elevated levels leading to hypertension.
Objective: Our objective was to understand how stress
experienced during fetal life could be an antecedent for the
development of hypertension. Our focus is the regulation of
phenylethanolamine N-methyltransferase (PNMT), the terminal
enzyme in the catecholamine biosynthetic pathway. PNMT is
directly responsible for adrenaline synthesis, and has been linked
to hypertension. Methods: Pregnant Wistar-Kyoto dams, were
injected with 100g/kg/day of the synthetic glucocorticoid
dexamethasone (DEX) in the third trimester of pregnancy. Blood
pressure and weights of the offspring were measured from week
3-18, at which point the animals were sacrificed and tissues
collected. Total RNA and protein were extracted from the
adrenals, and the expression of PNMT and its regulatory
transcription factors analyzed by qPCR and Western. Plasma
adrenaline was quantified by ELISA. Results: Results reveal that in
utero exposure to DEX promotes the development of hypertension
in the offspring, with males showing a more pronounced increase
in blood pressure than females. Plasma adrenaline levels were
elevated in rats exposed to DEX. The mRNA transcripts for PNMT,
and its transcriptional regulators Egr-1, Sp1, GR and AP-2, were
elevated in these animals compared to saline controls, with
differences in both males and females. The results suggest that
prenatal glucocorticoid exposure increases adrenal PNMT gene
expression via altered transcriptional regulatory mechanisms.
Conclusion: The influence of prenatal gluococorticoid stress
addresses key questions in understanding the origins of
hypertension. The study emphasizes that the tightly regulated
catecholamine biosynthesis can be disarrayed by in utero insults,
resulting in elevated catecholamines and subsequent hypertension
in adulthood. Acknowledgements: CIHR. Contact Information:
[email protected]
[425]
ROLE OF THE RENIN-ANGIOTENSIN SYSTEM IN FETAL
PROGRAMMING OF HYPERTENSION. Chad Williamson1, Sandhya
Khurana2, Julie Grandbois1, Phong Nguyen1, Collin J. Byrne1, T.C.
Tai2
1Laurentian University/Department of Biology, 2Northern Ontario
School of Medicine/Medical Sciences Division
Introduction: The renal renin-angiotensin system (RAS) and
sodium transporters are important mechanisms involved in blood
pressure control and changes have been shown in both a genetic
model of hypertension (spontaneous hypertensive rat – SHR) and
in a glucocorticoid-induced, fetal programming model (FP) of
hypertension. In the SHR, renal expression of ACE2 is decreased
while ACE1, AT1R and (pro)renin receptor are increased. Also,
studies predict that the mas1 receptor, an AT1R antagonist,
increases when ACE2 is downregulated. Sexual differences also
exist for RAS components such as angiotensinogen (ANGT) and
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103
AT2R. However, inconsistencies in these expression patterns have
been shown in FP rats and the exact RAS mechanism for this
model is still unclear. Moreover, the NCC transporter is
upregulated in the SHR kidneys but this increase is unclear in the
FP model. Interestingly, renalase, a novel enzyme that degrades
catecholamines, is increased in the SHR kidney but whether it is
mirrored in glucocorticoid-based FP models is unclear. Objective:
The purpose of this study was to examine whether differences
exist between genetic (SHR) and FP models with regard to the
expression of RAS and NCC-related genes that contribute to
hypertension. Any potential sex differences in the FP model were
also examined as well. Methods: Pregnant Wistar-Kyoto rats
(WKY) were administered dexamethasone (100 ug/kg/day) during
the third trimester and tissues were collected for analysis at the
postnatal age of 19 weeks. Tissues were also collected from WKY
and SHR rats. Total RNA from kidney tissue was extracted from
coronal sections through the hilus and homogenized with TRI
reagent. Extracted RNA was reverse transcribed using M-MLV RT,
amplified with GoTaq Flexi DNA polymerase for the genes of
ANGT, renin, AT1Ra, AT1Rb, AT2R, ACE1, ACE2, Mas1 receptor,
(pro)renin receptor, NCC transporter and renalase. Band
intensities were quantified using densitometry and normalized to
the 28s gene. Results: Preliminary data show increases in the SHR
for the expression of AT1Ra (1.98-fold; p<0.001), AT1Rb (1.36-fold,
p<0.05), ANGT (1.26-fold; p<0.01) and the mas1 receptor (1.22fold; p<0.05) compared to WKY. ACE1 and renin were unchanged
in the SHR. FP rats show a decrease in ANGT in females compared
to male rats (3.88-fold; p<0.001). Conclusion: This study
highlights contrasting RAS-related mechanisms that might
contribute to the development of hypertension between the two
models. The genetic model shows upregulation of certain genes in
the RAS which are not observed in the FP model. Future studies
will focus on extending the characterization of differential
expression between the genetic and FP models of hypertension.
Acknowledgements: Funding provided by CIHR. Contact
Information: [email protected]
[433]
THE ROLE OF HISTONE DEACETYLASE (HDAC) AND DNA
METHYLTRANSFERASE (DNMT) IN THE FETAL PROGRAMMING OF
HYPERTENSION
Jeremy Lamothe1, Sandhya Khurana2, Chad Williamson3, Collin J.
Byrne3, Stephanie Mercier4, T.C. Tai2
1Department of Chemical Science, Laurentian Univeristy, 2Medical
Science Division, Northern Ontario School of Medicine,
3Department of Biology, Laurentian University, 4School of Human
kinetics, Laurentian University
Introduction: The causes of hypertension are complex and involve
both genetic and environmental factors. A sub-optimal
environment during fetal development has been linked to the
development of adult diseases including hypertension. Fetal
programming studies have shown that timed in-utero exposure to
higher levels of the synthetic glucocorticoid dexamethasone can
result in the development of hypertension in adult rats. Evidence
suggests that in-utero stress can alter patterns of gene expression,
possibly a result of alterations in the topology of the genome by
epigenetic markers such as DNA methyltransferases (DNMTs) and
histone deacetylases (HDACs). The mechanisms behind this type of
in-utero programming may provide a key link necessary for the
prevention and treatment of hypertension. Objective: The
objective of this study was to determine the effects of epigenetic
regulators in the fetal programming and the development of
hypertension. Specifically this research examined the effects of the
HDAC inhibitor valproic acid (VPA) and the DNMT inhibitor 5-aza2’-deoxycytidine (5aza2DC) on blood pressure (BP) and gene
expression in programmed rats. Methods: Pregnant WKY dams
104
were injected with dexamethasone (100?g/kg/day S.C.)
throughout the third trimester of pregnancy (GD14-21). Following
birth, a subset of the fetal programmed and control pups were
given either VPA (250mg/kg/day I.P.) or 5-aza-2’-deoxycytidine
(5aza2DC) (1mg/kg/day I.P.) starting at 12 weeks of age; the onset
of hypertension, until termination at 15 weeks. BP was measured
(Coda 6, Kent Scientific) from weeks 4 to 15. Adrenals and plasma
were collected for gene expression analysis and catecholamine
concentration determination respectively. Results: Preliminary
data from BP measurements suggest that both VPA and 5aza2DC
attenuate the development of hypertension and restore elevated
BP to control levels. VPA injections resulted in a decrease in
average mean arterial pressure (MAP) from 133 to 112mmHg in
females and 140 to 105mmHg in males, by the end of the 3-week
injection period. Similarly 5aza2DC treatment decreased the
average MAP from 131 to 117mmHg in females and 154 to
122mmHg in males, over the same time course. Conclusion: This
research provides intriguing evidence for the role of altered
epigenetic regulators in the pathogenesis of hypertension in a
fetal programming model. Both VPA and 5aza2DC administration
prevent hypertensive programming in programmed rats. This
study has uncovered an epigenetic mechanism between maternal
stress and the development of hypertension in the adult rat.
Future analysis will examine the effects of these epigenetic
inhibitors on gene expression associated with hypertension.
Acknowledgements: Funded by CIHR and NSERC. Contact
Information: [email protected]
[440]
TRANSIENT NEONATAL HIGH OXYGEN EXPOSURE ALTERS ENERGY
METABOLISM IN ADULT MALE RATS: FOCUS ON CIRCADIAN
RHYTHM. Lukaszewski Marie-Amélie1, Sutherland Megan1,
Bertagnolli Mariane1, Cloutier Anik1, Nuyt Anne Monique 1
1Research center, CHU Sainte-Justine
Introduction: Prematurity is a risk factor for insulin resistance and
other features of the metabolic syndrome (MS). Preterms face an
environment enriched in O2 compared to the intrauterine
environment, leading to oxidative stress (OS). Studies have shown
in adults that OS is a risk factor for pathologies linked to MS, but is
also associated with circadian rhythm (CR) perturbations.
Furthermore, CR dysfunction can also lead to metabolic alterations
and so, to the MS. However, whether neonatal OS can lead to MS
and altered CR in adults is unknown. Objective: To determine
whether transient neonatal high O2 exposure disrupts long-term
CR regulation of energy metabolism in adult rats. Methods:
Sprague-Dawley rat pups and their mothers were exposed to 80%
O2 (hyperoxia H) vs room air (control C) from day 3 to 10 of life
(P3-P10). Weight gain and food intake were monitored weekly. At
4 months, oral glucose tolerance tests (OGTT) were performed at
8h (sleep phase) and 20h (active phase), and both blood glucose
and insulin were assessed. Locomotion activity was recorded over
24h prior to sacrifice. The weight of metabolic tissues (liver and
adipose tissue) and lipid concentrations over 24h were also
analyzed. n=8 males per time point (6 time points - every 4h over
24h) per group. Results: H rats had an increased food intake per
gram of animal (P<0.05), leading to a greater body weight from 12
weeks of age (P<0.001). At 4 months, the weight of the liver,
epididymal and perirenal adipose tissues relative to femur length
were higher in the H group (17%, 17%, 30% increase respectively).
H rats showed greater locomotion between 12h and 18h (P<0.05),
but not during the rest of the day. There was no difference
between groups in glucose response or insulin concentration at
8h. However, at 20h H rats had impaired glucose response
following glucose gavage (P<0.05) without disturbance of insulin
concentration, associated with a 43% increase in HOMA IR (mean
± SEM: C 1.99 ± 0.43 vs H 2.85 ± 0.77, p = 0.0402). Overall,
CNPRM 2015
triglyceride and HDL concentrations over a 24h period were higher
in H rats (P<0.01 and P<0.05 respectively). Conclusion: This study
shows that transient neonatal O2 exposure induces alterations in
both lipid and glucose metabolism in adult male rats. In particular,
we observed a disruption of day/night insulin efficiency,
suggesting alteration of the circadian regulation of metabolism.
This study provides new perspectives regarding potential
mechanisms involved in the Developmental Origins of Health and
Disease, using chronobiology as a new tool to examine the long
term consequences of prematurity. Acknowledgements: This
project was supported by the Molly Towell fundation. Contact
Information: [email protected]
[445]
EPIGENETIC MECHANISMS OF TRANSGENERATIONAL
PROGRAMMING BY STRESS IN A RAT MODEL. Olena Babenko1,
David M. Olson2, Igor Kovalchuk3, Gerlinde A.S. Metz4
1Canadian Centre for Behavioural Neuroscience, Department of
Biological Sciences, University of Lethbridge, Lethbridge, AB,
Canada, 2Departments of Obstetrics & Gynecology, Pediatrics and
Physiology, University of Alberta, Edmonton, AB, Canada,
3Department of Biological Sciences, University of Lethbridge,
Lethbridge, AB, Canada, 4Canadian Centre for Behavioural
Neuroscience, University of Lethbridge, Lethbridge, AB, Canada
Introduction: Prenatal stress is associated with an increased
vulnerability to neurodevelopmental disorders and mental health,
such as depression, anxiety, autism, and schizophrenia. While the
effects of prenatal stress on the first-generation offspring are well
documented, there is still very limited evidence if stress generates
a transgenerational memory that involves epigenetic signatures
that may predict disease risk later in life. Objective: The objective
of the present study was to investigate the mechanisms of
transgenerational transmission of stress responsiveness in a rat
model. We hypothesized that prenatal stress causes epigenetic
changes in the brain of the offspring, which persist through
generations. Methods: Three generations of prenatally stressed
Long Evans rats were bred (F0-F3). Two maternal lineages of stress
exposure were used. One lineage experienced gestational stress
only in the first generation (F0), but not in subsequent
generations. The second lineage was exposed to cumulative stress
in which pregnant dams experienced gestational stress in each
generation (F0-F2). Assessments included mRNA and miRNA
expression profiling in placentas and pup brains using Illumina
whole-genome expression beadchips and Genome Analyzer IIx,
respectively. Results: Offspring from both lineages whose great
grandmothers were stressed during pregnancy displayed changes
in cortical gene expression in critical neurodevelopmental
pathways, including axonal guidance. The results of miRNA
profiling showed significant changes in the expression of
seventeen miRNAs. mRNA and miRNA expression revealed distinct
transgenerational patterns from one generation to the next
depending on the stress lineage, and similarities were found in the
placentas and cortex. Conclusion: Our results indicate that
prenatal stress generates a transgenerationally heritable
epigenotype. Stress-induced miRNA regulation targets genes
involved in brain development, mental health and stress response.
The findings indicate that placenta reflects many of the changes in
the brain, thus potentially providing a mechanism for the
identification of predictive epigenetic Acknowledgements: This
work was funded by the AIHS Preterm Birth and Healthy Outcomes
Team Interdisciplinary Team Grant #200700595 (GM), Alberta
Innovates – Health Solutions (GM), and the Canadian Institutes of
Health Research (GM). Contact Information:
[email protected]
[457]
ANTENATAL EXPOSURE TO FLUOXETINE HYDROCHLORIDE
AUGMENTS HEPATIC TRIGLYCERIDE SYNTHESIS IN THE
OFFSPRING THROUGH EPIGENETIC MODIFICATIONS AT THE
ELOVL6 PROMOTER. NE De Long1, N Ma2, EJ Barry1, DB Hardy2,
KM Morrison3, VH Taylor4, HC Gerstein5, AC Holloway1
1McMaster University, Department of Obstetrics and Gynecology,
2Western University, Department of Obstetrics and Gynecology,
Physiology and Pharmacology, 3McMaster University, Department
of Pediatrics, 4University of Toronto, Department of Psychiatry,
5McMaster University, Department of Medicine
Introduction: Pregnancy is a window of vulnerability for
depression with prevalence rates in pregnant and postpartum
women estimated to be as high as 20%. As a consequence, many
women take antidepressants during pregnancy. One of the most
commonly prescribed antidepressants for perinatal depression is
the selective serotonin reuptake inhibitor (SSRI) fluoxetine
hydrochloride [Prozac®]. A recent clinical study has demonstrated
that maternal SSRI use is associated with an increased risk of
overweight in exposed children. In humans, obesity is often
associated with fatty liver, dyslipidemia and inflammation.
However the effects of perinatal exposure to SSRIs on markers of
fatty liver and inflammation have not been examined. Objective:
The aim of this study was to examine the effect of antenatal
exposure to fluoxetine hydrochloride (FLX) on hepatic lipid
accumulation, markers of inflammation and epigenetic regulation
of hepatic triglyceride synthesis in offspring. Methods: Female
nulliparous Wistar rats were given vehicle (N=15) or FLX (10
mg/kg/d; N=15) orally for 2 weeks prior to mating until weaning.
At 6 months of age, we assessed liver histology, hepatic lipid levels
and expression of inflammatory markers and components of
hepatic triglyceride biosynthesis pathway in the offspring and
determined whether epigenetic changes may have been
implicated. Results: There was a significant increase in the
number of offspring with mild to moderate NASH in FLX-exposed
offspring relative to controls (p=0.04). Furthermore, FLX exposed
animals had significantly higher hepatic triglyceride levels along
with elevated markers of inflammation compared to controls.
There were no significant differences in the gene or protein
expression of enzymes involved in triglyceride synthesis. However,
SSRI-exposed offspring had a significant increase in the mRNA
expression of Elovl6. ChIP revealed that this enhanced gene
expression was associated with increased acetylation of histone
H3 lysine 9 (a marker of gene activation) surrounding the
promoter region of Elovl6. Conclusion: This is the first study to
demonstrate that antenatal exposure to SSRIs can lead to fatty
liver in the offspring raising concerns regarding the long term
metabolic sequelae. Furthermore, these findings suggest that the
elevated triglyceride observed in SSRI-exposed offspring is due to
long-term posttranslational histone modifications favouring
activation of transcription within the promoter region of Elovl6.
Acknowledgements: Funding for this study was provided by the
Canadian Institutes of Health Research (MOP 119323 and MOP
111001). Salary support for NED was provided by the CIHR
CNPRM 2015
105
Training Program in Reproduction, Early Development and the
Impact on Health (REDIH). Contact Information: Nicole E De Long
[email protected]
[483]
THE IMPACT OF MATERNAL OBESITY ON OFFSPRING OVARIAN
DEVELOPMENT AND FUNCTION IN RATS. Tsoulis MW, Connor KL,
Vickers MH and Sloboda DM1
1McMaster University, Department of Biochemistry and
Biomedical Sciences
Introduction: Maternal obesity predisposes offspring to noncommunicable disease and reproductive dysfunction. We have
previously shown that female rat offspring born to mothers fed a
high fat (HF) diet throughout pregnancy and lactation enter
puberty early and display aberrant reproductive cyclicity. It is
currently unknown what mechanisms are driving this reproductive
phenotype. Objective: We hypothesize that maternal HF diet
induced obesity impairs perinatal ovarian development and the
functioning of the ovary later in life in female rat offspring.
Methods: Wistar rats were randomized to be fed either a control
or HF diet throughout pregnancy and lactation. All offspring were
fed a control diet post weaning. Offspring of HF fed mothers were
assessed at 4 different time points: embryonic day 20 (E20),
postnatal day (P) 4, P27, and P120 (fetal, neonatal, prepubertal,
and adulthood, respectively). Ovarian histological analysis was
conducted at each time point to determine oocyte and follicle
counts. Key factors regulating ovarian processes were investigated
using ELISA, IHC and qPCR. Results: Fetuses of HF fed mothers
had a 20% loss of oocytes at E20. At P4, when the primordial
follicle pool is established in rats, HF offspring had more primordial
follicles assembled and demonstrated decreased AMH and AMHRII
protein expression. At P27, prepubertal offspring born to HF fed
mothers had smaller secondary follicles, an increased number of
atretic follicles and decreased circulating E2. At P120, adult
offspring born to HF fed mothers had an increased number of
atretic follicles and an increased circulating FSH:E2 ratio. Adult HF
offspring also demonstrated decreased mRNA levels of the oocytesecreted factor, GDF9, as well as estrogen receptor . These
changes were also accompanied by elevated AMH protein
expression levels in antral follicles. Changes in ovarian follicle
dynamics were not associated with increased oxidative stress or
the induction of inflammation at P27 and P120. Conclusion: The
present study demonstrates that in rats, offspring born to HF-fed
mothers have impaired ovarian function likely stemming from
altered ovarian development early in life. Given the high rates of
obesity in female populations worldwide and the growing concern
of trans-generational inheritance of disease risk, future studies are
needed to fully delineate the molecular mechanisms mediating
ovarian dysfunction induced by a maternal obesogenic diet.
Acknowledgements: I would like to thank members of my lab.
Contact Information: [email protected]
[484]
THE AAR PATHWAY MEDIATES IGFBP-1
HYPERPHOSPHORYLATION IN RESPONSE TO LEUCINE
DEPRIVATION. N Malkani1, T Jansson2, M B Gupta3
1University of Western Ontario/Department of Biochemistry,
2University of Colorado Denver/Dept of OB/GYN, 3University of
Western Ontario/Departments of Biochemistry and Paediatrics
Introduction: Insulin-like growth factor-I (IGF-I) is the key
regulator of fetal growth. IGF-I bioavailability is strongly influenced
by the phosphorylation of IGF-binding protein-1 (IGFBP-1), which
increases the affinity of IGFBP-1 for IGF-I resulting in its decreased
bioavailability. Intrauterine Growth Restriction (IUGR) is associated
with marked IGFBP-1 hyperphosphorylation in circulation and in
the liver, the primary source of IGFBP-1 in the fetus, suggesting
that IGFBP-1 hyperphosphorylation plays an important role in the
106
development of IUGR. However, the mechanisms underlying
IGFBP-1 hyperphosphorylation in IUGR remain unknown. IUGR is
characterized by decreased amino acid availability, which activates
the amino acid response (AAR) and inhibits mechanistic target of
rapamycin (mTOR) signaling. We hypothesized that inhibition of
mTOR signaling and activation of the AAR increases IGFBP-1
secretion and phosphorylation in response to amino acid
deprivation. Objective: This study aims to elucidate the
mechanisms involved in mediating IGFBP-1 phosphorylation under
nutrient restriction. Methods: HepG2 cells, a model of fetal
hepatocytes, were cultured with or without leucine (450/0 µM)
and treated with mTOR inhibitor rapamycin (100 nM) or AAR
inhibitor U0126 (10 µM) for 24 hours. Alternatively, cells were
transfected with siRNA to alter mTOR and AAR signaling. 24 hours
later cells were cultured with or without leucine for additional 72
hours. IGFBP-1 secretion and phosphorylation was determined
using antibodies against phosho-Ser101, 119 and 169 IGFBP-1.
ANOVA, Dunnet’s Multiple Comparison Post-Test was used (n=3
each). Results: Leucine deprivation alone or combined with
mTOR inhibition decreased mTORC1 (p70-S6KThr389, -60%) and
mTORC2 (pAktSer473, -65%) activity while inducing IGFBP-1
secretion (+300%). mTOR inhibition increased IGFBP-1
phosphorylation (+300%) but was less pronounced than in leucine
deprivation alone (+300-1100%). Activation of mTORC1+C2
attenuated leucine deprivation-induced IGFBP-1 secretion but not
phosphorylation. Conversely, inhibition of AAR prevented both
IGFBP-1 secretion and phosphorylation in response to leucine
deprivation. Conclusion: mTOR and AAR independently regulate
IGFBP-1 secretion and phosphorylation. We speculate that limited
amino acid availability contributes to IUGR by increasing secretion
and phosphorylation of IGFBP-1 mediated by mTOR inhibition and
AAR activation in the fetal liver (Figure 1). Acknowledgements:
This work was supported by grants from the National Institute of
Health (HD 078313 to MBG and TJ) and the Lawson Health
Research Institute (to MBG). NM received the Department of
Pediatrics (UWO) Graduate Student Scholarship. Contact
Information: Niyati Malkani [email protected]
[485]
MECHANISMS UNDERLYING IGFBP-1 PHOSPHORYLATION IN
NUTRIENT DEPRIVATION: A KINASE SURVEY. N Malkani1, M B
Gupta2
1University of Western Ontario/Department of Biochemistry,
2University of Western Ontario/Departments of Biochemistry and
Paediatrics
Introduction: Insulin-like growth factor-I (IGF-I) is a key regulator
of fetal growth and is regulated by IGF-binding protein-1 (IGFBP1), the key circulating IGFBP during gestation. Phosphorylated
IGFBP-1 displays a marked increase in affinity of IGFBP-1 for IGF-I,
further sequestering the mitogenic peptide. Intrauterine Growth
CNPRM 2015
Restriction (IUGR) is associated with IGFBP-1
hyperphosphorylation in fetal circulation and liver, which is the
primary source of fetal IGFBP-1. IGFBP-1 hyperphosphorylation
may therefore contribute to the pathogenesis of IUGR, however,
the mechanisms underlying IGFBP-1 hyperphosphorylation in IUGR
remain unknown. In this study, we conduct a survey of potential
kinases that may be involved in IGFBP-1 phosphorylation in
nutrient restricted conditions which are central to IUGR onset. We
hypothesize that inhibition of CK2 and PKC, two kinases for which
IGFBP-1 contains consensus sequences, will attenuate IGFBP-1
phosphorylation(Ser101,119,169), but not secretion, in response
to amino acid deprivation. Objective: This study aims to elucidate
the mechanisms involved in mediating IGFBP-1 phosphorylation
under nutrient restriction. Methods: HepG2 cells, a model of
fetal hepatocytes, were cultured with or without leucine (450/0
µM) and treated with FGF inhibitor su54042 (10 µM), PKA inhibitor
PKI (100 nM), PKC inhibitor Bisindolylmalemide (BIS) (5 µM), or
CK2 inhibitor TBB (1 µM). IGFBP-1 secretion and phosphorylation
was determined using antibodies against phosho-Ser101, 119 and
169 IGFBP-1 in cell media. ANOVA, Dunnet’s Multiple Comparison
Post-Test was used (n=3 each). Results: Leucine deprivation
consistently increased IGFBP-1 secretion (+300%) and
phosphorylation (Ser101: +1000%, Ser119: +300%, Ser169:
+1100%). FGF or PKA inhibition in the presence of leucine
deprivation induced IGFBP-1 secretion and phosphorylation to the
same extent as leucine deprivation alone, suggesting that neither
kinase is able to attenuate IGFBP-1 phosphorylation. Conversely, a
decrease in IGFBP-1 phosphorylation (-50%) at all three sites was
observed when cells were treated with BIS or TBB regardless of
leucine status. Further, neither BIS nor TBB were able to prevent
leucine deprivation-induced IGFBP-1 secretion. Conclusion: PKC
and CK2 independently regulate IGFBP-1 phosphorylation but not
secretion in leucine deprivation. We speculate that limited amino
acid availability contributes to IUGR by increasing IGFBP-1
mediated via activation of PKC and CK2 in the fetal liver.
Acknowledgements: This work was supported by grants from the
National Institute of Health (HD 078313 to MBG and TJ) and the
Lawson Health Research Institute (to MBG). NM received the
Department of Pediatrics (UWO) Graduate Student Scholarship.
Contact Information: Niyati Malkani [email protected]
[374]
PERINATAL FACTORS AFFECTING FOXP3 DNA METHYLATION AND
EXPRESSION IN UMBILICAL CORD BLOOD TREGS AND
MONONUCLEAR CELLS. Elizabeth Lee1, Michelle North1,2,
Vanessa Omana1, Julie MacIsaac3, Jeffrey Brook4,
Meaghan J. Jones3,5, Michael Kobor 3,5, and Anne K. Ellis 1,2
1) Departments of Medicine and Biomedical & Molecular Science,
Queen's University, Kingston, ON, 2) Allergy Research Unit,
Kingston General Hospital, Kingston, ON, 3) Centre for Molecular
Medicine & Therapeutics, Child & Family Research
Institute,Vancouver, BC, 4) Environment Canada, Toronto, ON, 5)
Department of Medical Genetics, University of British Columbia,
Vancouver, BC
Introduction: Previous research has shown that maternal
exposure to various perinatal factors can epigenetically affect the
newborn’s genes through DNA methylation. Regulatory T Cells
(Tregs) are important immunomodulatory cells thought to
influence the development of allergy and asthma. The Forkhead
Box Protein 3 (FOXP3) transcription factor is essential for Treg
function and is regulated by DNA methylation. Examining the
effects of various perinatal factors on FOXP3 DNA methylation and
gene expression may thus contribute to better understanding the
cause of allergic symptoms in newborns. Objective: We
hypothesized that prenatal exposure to cigarette smoke, maternal
allergy, mode of delivery, gestational age and the newborn’s
gender affect FOXP3 DNA methylation in umbilical cord blood
Tregs and mononuclear cells (MNCs). We additionally
hypothesized that FOXP3 gene expression at baseline and upon
stimulation with IL-5 may be affected by these perinatal factors.
Methods: The Kingston Allergy Birth Cohort (KABC) was
established to investigate prenatal and early-life factors and
epigenetic biomarkers that may be related to childhood allergy
and asthma. In a subset of 86 mother/child pairs, Tregs were
isolated from fresh cord blood using magnetic sorting. DNA
methylation at FOXP3 was assessed in Tregs and matching
mononuclear cells (MNCs) by pyrosequencing. In a subset of 45
mother/child pairs, MNCs were further processed to non-adherent
mononuclear cells (NAMCs), and stimulated with IL5. Baseline, 24h
and 72h samples were collected. RNA was extracted for each time
point, and FOXP3 expression was assessed by qPCR. Results: DNA
methylation at FOXP3 was significantly associated with gestational
age at birth, and the sex of the child. In all participants, FOXP3
gene expression was significantly down regulated at 24h and 72h
by IL5 stimulation in NAMCs. However, there was no difference at
baseline or after stimulation based on gender, maternal allergy,
maternal exposure to smoke during pregnancy, or mode of
delivery. FOXP3 expression increases with gestational age and
correlates significantly with weeks gestation at baseline and after
24h of IL-5 stimulation. Conclusion: Results emerging from the
KABC study indicate that preterm birth may be related to
epigenetic changes in the key immune cell population of Tregs.
Gestational age at birth also demonstrated effects on FOXP3
expression after IL5 stimulation in umbilical cord blood NAMCs.
Prenatal and early-life factors may affect the risk of childhood
allergies and asthma, potentially mediated through epigenetic
mechanisms. Umbilical cord blood provides a window into the
prenatal environment and potentially contains epigenetic
biomarkers that precede allergic disease.
Perinatal Brain Injury
[371]
MATERNAL IMMUNE ACTIVATION INDUCED BY INACTIVATED
GROUP B STREPTOCOCCUS: CHORIOAMNIONITIS AND FETAL
INFLAMMATORY RESPONSE DRIVEN BY INTERLEUKIN-1? AND
MATRIX-METALLOPROTEASES THAT COULD LEAD TO AUTISM
SPECTRUM DISORDERS FEATURES. Julie D Bergeron1, Djorjde
Grbic1, Louis-Charles Fortier2, Claire Poyart3, Guillaume Sébire1
1Université de Sherbrooke & McGill University, Department of
pediatrics , 2Université de Sherbrooke, Department of
microbiology, 3Université de France, Institut de Cochin
Introduction: A high incidence of neurobehavioral disorders, such
as autism spectrum disorders, occurs in children born to mothers
who experienced infections during pregnancy. Objective: Our
goal is to study the role of the group B streptococcus (GBS)
induced maternal immune activation in placental lesions and
offspring subsequent neurobehavioral disabilities. Methods: We
designed a pre-clinical animal model in which dams were injected
every 12 hours with inactivated GBS (109 CFU) from serotype 1a
GBS, versus saline, from gestational day (G) 19 to G22. C-sections
were performed to remove GBS-exposed placentas and fetal
brains for immunohistochemical studies and proteins analysis
(ELISA). Results: GBS-exposed placentas presented
polymorphonuclear infiltration located within the
decidual/maternal side of the placenta at 24 and 48h following
GBS challenge and placental overexpression of IL-1 at 72h postGBS as compared to control. Preliminary results showed elevated
levels of IL-1 in fetal blood and increased expression of MMP-2
mRNA, a metalloprotease that could be implicated in blood brain
barrier breakdown, in GBS-exposed fetal brains. Autistic-like
CNPRM 2015
107
behavior was found predominantly in males in this animal model.
Conclusion: Our results show for the first time that materno-fetal
inflammatory response to inactivated GBS plays a role in the
induction of chorioamnionitis and neurobehavioral disabilities in
offspring. Chorioamnionitis may spread through a foetal
inflammatory reaction syndrome (FIRS) affecting certain
developmental processes of the offspring’s brain, thereby
increasing its susceptibility to ASD, especially in males.
Acknowledgements: This work was supported by a scholarship
from Fonds de la Recherche du Québec-Santé (FRQ-S), a grant
from the Canadian Institutes of Health Research (CIHR) and a grant
from the Heart and Stroke Foundation. Contact Information:
[email protected],ca
[380]
MILD INFLAMMATORY WHITE MATTER INJURY INDUCED
INCREASED BILATERAL FUNCTIONAL CONNECTIVITY IN
NEONATAL RAT BRAINS ASSESSED BY RESTING-STATE OPTICAL
INTRINSIC SIGNAL (RSOIS) IMAGING. Chen Jin1, Edgar Guevara2,
Parikshat Sirpal3, Maxime Abran3, Irene Londono1, Philippe
Pouliot4, Frédéric Lesage3, Gregory A. Lodygensky5
1CHU Sainte-Justine, 2Universidad de las Américas Puebla, 3École
Polytechnique de Montréal, Montreal Heart Institute, 4École
Polytechnique de Montréal, Montreal Heart Institute, 5CHU SainteJustine, University of Montreal, Montreal Heart Institute
Introduction: Intracallosal lipopolysaccharide (LPS) injection in
neonatal rats mimics diffuse white matter injury commonly
observed in preterm infants. A reduced functional connectivity
(FC) assessed by MRI has been shown in preterm infants with
white matter injury (Inder et al. 2005). Objective: The aim of the
study was to assess the long term effect of inflammation on FC in
neonatal rat brains using a novel approach, rsOIS imaging, that
allows for higher temporal and 2D special resolution and to assess
its impact in light of high-resolution ex vivo DTI analysis.
Methods: We injected 0.8 mg/kg of LPS in the left corpus callosum
of six P3 rat pups and compared them to six saline controls. RsOIS
was performed on P24 at 2Hz under illumination of 630 nm;
imaging sessions of 6 min were carried out under urethane (2
mg/g). Data were processed according to previously published
methodology (Guevara et al. 2013). All seeds (~0.3 mm radius)
were manually placed using the coordinates corresponding to left
and right motor and somatosensory cortices. The metric used to
evaluate FC was a bilateral functional correlation z(r). Statistical
significance was computed assuming non-Gaussian distributions
(p<0.05). Following transcardial perfusion, brains were extracted
for ex vivo DTI with a native resolution of 109x73x300 µm. Blinded
to group attribution, regions of interest were placed on fractional
anisotropy (FA) maps in both external capsules and in the corpus
callosum on coronal sections at the level of injection. Results:
There was an increased FC in the motor area of the LPS group (LPS
0.49±0.14; saline -0.12±0.16, p=0.015); the increased FC in the
somatosensory cortex was not significant (LPS 0.23±0.23; saline 0.42±0.11, p=0.065). Increased FA was observed for the
contralateral external capsule (ec) though did not quite reach
statistical significance (LPS 0.75±0.01; saline 0.65±0.02, p=0.057).
FA values in the corpus callosum and the ipsilateral ec did not
show significant differences between saline and LPS animals.
Conclusion: Surprisingly, LPS exposure at P3 induced an increase in
inter-hemispheric connectivity together with an increased
contralateral FA at P24. As it has been demonstrated that LPS preexposure can induce protective effects on subsequent brain
hypoxia-ischemia (Mallard et al. 2007), this reflects a possible
compensatory mechanism to overcome the effects of
inflammatory insult. Using rsOIS, we demonstrated a non-invasive
approach of using rsOIS to assess cerebral changes in response to
inflammatory white matter injury. Acknowledgements: CIHR,
108
Institute of Human Development, Child and Youth Health (IHDCYH)
(Grants #126790 and #136908) the Fonds de recherche en santé
du Québec (FRSQ) and the CHU Ste-Justine. Contact Information:
Gregory A. Lodygensky [email protected]
[381]
USING HIGH RESOLUTION EX VIVO DIFFUSION TENSOR IMAGING
AND TRACT-BASED SPATIAL STATISTICS TO EVALUATE INJURY
AND PLASTICITY OF THE NEONATAL RAT BRAIN FOLLOWING AN
INFLAMMATORY EXPOSURE. Chen Jin1, Julie Tremblay1, Philippe
Pouliot2, Irene Londono 1, Frédéric Lesage2, Gregory A.
Lodygensky3
1CHU Sainte-Justine, 2École Polytechnique de Montréal, Montreal
Heart Institute, 3CHU Sainte-Justine, University of Montreal,
Montreal Heart Institute
Introduction: Cerebral injury following a local inflammatory insult
in neonatal rats mimics diffuse white matter injury commonly
observed in preterm infants (Inder et al. 2005). High-resolution
diffusion tensor imaging (DTI) is a powerful diagnostic tool for
noninvasive measurement of cerebral microarchitecture. A
common analytical approach uses manual selection of regions of
interest (ROI); however, the bias of this approach compromises
optimal analysis if used solely. Tract-based spatial statistics (TBSS)
compensates for such weaknesses by allowing for a more userindependent quantification of changes in microarchitecture.
Objective: Using ex vivo DTI, we aimed to study microstructural
changes in white matter tracts following an inflammatory insult in
neonatal rat brains by means of TBSS and manual segmentation.
Methods: Six rats received 0.8mg/kg lipopolysaccharide (LPS)
injection in the left corpus callosum on P3 and were compared to
six saline controls. On P24, brains were extracted and immersed in
Fomblin for DTI. An average FA skeleton of white matter fiber
tracts was created. Aligned FA map from each brain was projected
onto the mean skeleton and voxel-wise statistical analysis using
TBSS was then performed to find differences between the two
groups. Confirmation of TBSS findings was then computed by
manually selecting ROI on native and isotropic FA maps, blinded to
group attribution. Results: TBSS results show a significant
increase in FA in the LPS group in the contralateral external
capsule (ec) on both isotropic (Fig 1) and native FA maps. Manual
selection of ROI on isotropic and native FA maps showed coherent
findings with TBSS: increased FA for the contralateral ec, but not
the ipsilateral ec nor the corpus callosum (Table 1). Conclusion:
Using ex vivo DTI, we found an increased FA in the contralateral ec
of neonatal rat brains 21 days following inflammatory white
matter injury. The increased FA may be attributed to an increased
plasticity of the developing brain in response to mild injury. It has
been shown that exposure to LPS can elicit preconditioning effects
on subsequent brain hypoxia-ischemia (Mallard et al. 2007).
Furthermore, it has been shown that some neurobehavioral
deficits in neonatal rats, following a cerebral inflammatory insult,
improve with development, possibly suggesting a role of inherent
plasticity of the developing rodent brain (Fan et al. 2005). Ex vivo
DTI on whole rat brains, combined with TBSS, allows for a more
automated approach of evaluating injury and possibly plasticity of
the developing brain. Acknowledgements: CIHR, Institute of
Human Development, Child and Youth Health (IHDCYH) (Grants
#126790 and #136908) the Fonds de recherche en santé du
Québec (FRSQ) and CHU Ste-Justine. Contact Information:
Gregory A. Lodygensky [email protected]
CNPRM 2015
defective communication, disorganized exploratory behavior,
impaired sensory integration and social behavior impairments, as
compared to control. Conclusion: GBS-induced inflammation
results in gender dichotomic neurodevelopmental and behavioral
impairments. Further neurobehavioral characterization and
inflammatory mechanistic studies of this new preclinical animal
model will help to target future neuroprotective strategies.
Acknowledgements: Grants from Fond de Recherche du Québec Santé, Canadian Institutes of Health Research, Heart & Stroke
Foundation. Contact Information: [email protected]
[385]
SELF-LIMITED MATERNAL END-GESTATIONAL GROUP B
STREPTOCOCCUS INFECTION INDUCES GENDER SPECIFIC
FOREBRAIN INJURIES AND AUTISTIC-LIKE BEHAVIORAL
IMPAIRMENTS IN THE OFFSPRING. Marie-Julie Allard1, Julie
Bergeron1, Louis-Charles Fortier2, Claire Poyart3, Guillaume Sébire4
1Université de Sherbrooke, Département de pédiatrie, 2Université
de Sherbrooke, Département de microbiologie, 3Université René
Descartes, Département de Maladies Infectieuses, 4McGill
University, Department of pediatrics; Department of neurology
and neurosurgery
Introduction: Group B streptococcus (GBS) infection occurs in 1030% of pregnant women. GBS is one of the major causes of
chorioamnionitis, associated to cerebral injuries in the newborn.
Antibiotics administered to colonized mothers during labor protect
the newborn against GBS infection, but do not prevent the
maternofetal immune activation induced by alive and then
antibiotic-inactivated GBS. Our hypothesis is that GBS-induced
gestational infection has a deleterious neurodevelopmental
impact on offspring through a maternofetal inflammatory
response. Objective: Our goal is to study, with a new preclinical
animal model, the impacts of GBS-induced gestational
inflammation on the neurodevelopmental features in the
offspring. We will characterize physiological parameters,
behavioral outcomes and cerebral histology. Methods: Pregnant
rats were intra-peritoneally injected at gestational day 19 with
serotype 1a GBS (10^8 CFU) or saline. The maternofetal
inflammatory response was studied by ELISA and
immunohistochemistry. Brains were collected at postnatal day 40
(P40) for histological studies. Behavioral tests were performed
from P7 to P40 to assess maternal attachment and neonatal
communication, exploratory abilities, sensory integration and
social interactions. Results: GBS infection of the dams is selflimited and paucisymptomatic. A mild decrease in body weight
gain of dams exposed to GBS was noticed. A transient intrauterine growth retardation was present in GBS-exposed male –
but not female - pups from P1 to P4. GBS-exposed placentas
displayed a decidual chorioamnionitis featured by infiltration of
polymorphonuclear cells (PMN), which was significantly more
prominent in male than female. At P40, GBS-exposed male
showed a reduced thickness of periventricular white matter. GBSexposed male – but not female - showed autistic-like traits:
[397]
NEUROPROTECTIVE EFFECT OF HYPOTHERMIA IN A MODEL OF
NEONATAL ENCEPHALOPATHY (NE) RESULTING FROM E. COLIINDUCED INFLAMMATION PLUS HYPOXIA-ISCHEMIA (HI).
Mathilde Chevin1, Alexandre Savard1, Guillaume Sébire2
1Laboratoire de neurologie, Département de pédiatrie, Université
de Sherbrooke, 2Laboratoire de neurologie, Département de
pédiatrie, Université de Sherbrooke and Child neurology division,
McGill University, QC, Canada.
Introduction: NE which affects 2-9/1000 full term newborn leads
to life threatening symptoms and can cause permanent brain
damage such as cerebral palsy (CP). The two main risk factors of
NE are perinatal infection-inflammation (e.g. E. coli-induced
chorioamnionitis) and HI. The standard treatment is therapeutic
mild hypothermia (body cooling of 33-34°C for 72h) providing a
partial neuroprotection in moderate to severe NE. Such
neuroprotective effect of hypothermia remains unclear when NE
result from pathogen-induced inflammation combined to HI.
Otherwise, the anti-inflammatory interleukine-1 receptor
antagonist (IL-1ra) has a well-proved neuroprotective effect in
preclinical models of perinatal inflammation induced by pathogens
and/or HI. We hypothesize that the combination of mild
hypothermia plus IL-1ra results in additive or synergistic
neuroprotection. Objective: We first characterised the impact of
hypothermia on the expression of cerebral inflammatory markers
(cytokines, chemokines) and on the prevention of cerebral
damage. Methods: We used an animal model of rat pups (Lewis)
at postnatal day 12 (P12). P12 corresponds to the level of cerebral
development of the human full term newborn. Inflammation is
induced by injecting the rat pups intraperitonealy, with 200 µg/kg
of lipopolysaccharide (LPS) from E.coli. Four hours (h) later, the
right common carotid artery is ligated, then hypoxia is induced (8%
O2, 1 h 30 min). Finally, rat pups are submitted to hypothermia
(32° +/- 0.5°C, 4 h). Pups are euthanized at different time points in
order to perform histological analysis and cytokine titration.
Results: Our results show that hypothermia alleviated brain
damage in the LPS+HI-exposed cerebral cortex and hippocampus.
This protective effect only occurred in the brain areas affected by
ischemic penumbra, but not core injuries; penumbra corresponds
histologically to an association of pyknotic and healthy neurons,
without destruction of extracellular matrix or ischemic cavitation.
This neuroprotective effect did not result from a down-regulation
of the neurotoxic neuroinflammatory response mediated by IL-1
or TNF-. Conclusion: Our results demonstrate a neuroprotective
effect of hypothermia on LPS+HI-induced brain damage in a model
of NE. This beneficial effect of hypothermia is not mediated by IL1 down-regulation meaning that IL-1ra administration might
reinforce the hypothermic neuroprotective effect. This project
could open new therapeutic avenues to prevent CP.
Acknowledgements: This work is supported by grants from CIHR,
FRQ-S, Heart and Stroke Foundation, Faculté de Médecine de
l’Université de Sherbrooke (MSc scholarship), and Foundation of
Stars. Contact Information: [email protected]
CNPRM 2015
109
[487]
NEURAL PROGENITOR CELLS ISOLATED FROM A
BRONCHOPULMONARY DYSPLASIA (BPD) MODEL SHOW SIGNS
OF INJURY. Marissa Lithopoulos BSc1, Alysen Clark MSc2, Nastaran
Ahmadi BSc3, Ruth Slack PhD4, Arul Vadivel PhD5, Bernard Thébaud
MD PhD6
1University of Ottawa/ Cellular and Molecular Medicine, Ottawa
Hospital Research Institute , 2University of Ottawa/ Cellular and
Molecular Medicine, 3University of Ottawa/Cellular and Molecular
Medicine, 4University of Ottawa/ Celluler and Molecular Medicine
, 5University of Ottawa/ Cellular and Molecular Medicine, Ottawa
Hospital Research Institute, 6University of Ottawa/ Cellular and
Molecular Medicine, Ottawa Hospital Research Institute,
Children’s Hospital of Eastern Ontario Research Institute
Introduction: BPD, the chronic lung disease of prematurity
resulting from oxygen and mechanical ventilation, remains the
main complication in this patient population. Adverse
neurodevelopmental outcomes affect many BDP patients. The
mechanism of associated brain damage is poorly understood. We
hypothesized that neural progenitor cell function is perturbed in
experimental BPD. Objective: 1) To isolate neural progenitor cells
from the subventricular zone and hippocampus of mouse pups
and culture them as neurospheres. 2) To examine whether or not
neural progenitor cells are injured in BPD by comparing the
morphology and proliferative ability of neural progenitor cells
isolated from normoxia-exposed mouse pups to age-matched
hyperoxia-exposed mice. Methods: Newborn mice were exposed
to room air or 80% oxygen (BPD model) for 10 days. The
subventricular zone and hippocampus were isolated. Neural
progenitor cells were harvested by enzymatic digestion and
cultured as neurospheres. Differences in spontaneous
differentiation and proliferation capacity were assessed. Results:
Neural progenitor cells isolated from the BPD model appeared to
have a higher rate of spontaneous differentiation than those
isolated from the normoxia mice. Additionally, by the fourth
passage, the hyperoxia neural progenitor cells were less capable of
proliferating, as indicated by the lower cell numbers. Conclusion:
The greater ability to spontaneously differentiate and the
decreased proliferative capacity of the hyperoxia-exposed
neurospheres are both indications of damage to the neural
progenitor cells in the BPD model. Further observations are
required to confirm this damage, such as differences between the
normoxia and hyperoxia groups with regard to colony-forming
potential. However, these results are an important first step, as
they will aid in the understanding of the cognitive defects caused
by BPD, which will in turn help to find an effective treatment to
protect the brain of infants with BPD. Acknowledgements: ML is
supported by The Stem Cell Network (SCN). RS is supported by The
Canadian Institutes of Health Research (CIHR), The Heart and
Stroke Foundation of Ontario, The Canada Foundation for
Innovation (CFI), Brain Canada, Krembil Foundation, Canadian
Stroke Network, and Canadian Partnership for Stroke Recovery. BT
is supported by SCN, CIHR, CFI, and The Canadian Thoracic Society.
Contact Information: Marissa Lithopoulos [email protected]
110
[417]
THE EFFECTS OF WORKING MEMORY TRAINING ON CHILDREN
BORN EXTREMELY PRETERM. Clara Lee1, Jacqueline Pei2, Kimberly
Kerns3, Gail Andrew4, Carmen Rasmussen5
1University of Alberta/ Department of Educational Psychology,
2UUniversity of Alberta/ Department of Educational Psychology,
3University of Victoria/ Department of Psychology , 4Glenrose
Rehabilitation Hospital, 5University of Alberta/ Department of
Pediatrics and Glenrose Rehabilitation Hospital
Introduction: Research shows that working memory (WM) training
has positive and lasting effects on the WM of various populations.
However, it is unclear if these same training effects will be found
in children born preterm. Objective: This study had 4 aims: (i) to
investigate the effect of a WM training program (Cogmed R) on
the WM of preterm children after 5 weeks of training, (ii) to
explore whether the positive training effect on WM can be
CNPRM 2015
transferred to other non-trained cognitive function (i.e.,
attention), (iii) to examine whether the training effect on WM
remains present at a 5-week follow-up, and (iv) to investigate
whether preterm children respond similarly to age-matched fullterm children on WM training. Methods: Participants. Two
groups of children were recruited. The Preterm group included 14
children (mean age = 71.79 months, SD = 16.14; mean GA = 28.21
weeks, SD = 2.12; mean BW = 1112.00 grams, SD = 378.21) and the
age-matched full-term Control group included 14 children (mean
age = 75.21 months, SD = 18.27; mean GA = 38.86 weeks, SD =
1.70; mean BW = 3125.50 grams, SD = 590.92). Measures. The
Automated Working Memory Assessment (AWMA) was
administered to measure WM. The Test of Variables of Attention
(TOVA) was conducted to measure attention. Tests were
administered before training (T1), immediately after training (T2),
and five weeks post-training (T3). Training. Children in both groups
were asked to do training at home for 5 days a week across 5
weeks. Results: When comparing the performance at T1 and T2,
repeated measures MANOVA showed an insignificant group
difference between the Preterm and Control groups(p > .05).
However, there was a significant Time effect (F (1, 26) = 7.890, p <
.001), which means both groups changed over time, preterm and
control children improved in their WM after training. The
interaction effect was not significant (p > .05), suggesting the
groups showed a similar pattern of change. Although both groups
improved in attention over time, there were no significant effects
of Group, Time,and Group and Time interaction (all ps >.05). When
examining the lasting effect, there was a significant Time effect (F
(1, 26) = 4.137, p < .001), suggesting both groups changed over
time, better performance was found at T3 than at T1. A quadratic
WM pattern for the Control group and a linear WM trend for the
Preterm group were found across the 3 time points respectively.
Conclusion: Working memory training has beneficial effects on the
WM of children born extremely preterm, which can last for at least
5 weeks and can be transferred to attention. Acknowledgements:
This study was supported by the Women and Children’s Health
Research Institute Innovation Grant. Contact Information: Clara
Lee [email protected]
Family Centered Care – Developmental
Outcomes and Interventions
[393]
BE SWEET TO BABIES: PILOT EVALUATION OF A BRIEF PARENTTARGETED VIDEO TO IMPROVE PAIN MANAGEMENT PRACTICES.
Catherine Larocque1, Denise Harrison1, JoAnn Harrold2, Cheryl
Aubertin 2, Jessica Reszel3
1University of Ottawa & Children’s Hospital of Eastern Ontario
Research Institute, 2Children’s Hospital of Eastern Ontario, NICU,
3Children’s Hospital of Eastern Ontario Research Institute
Introduction: Newborns have blood work for screening in their
first days of life, and preterm or sick hospitalized infants need
many more needle-related procedures. These procedures cause
pain, distress, and contribute to long-term adverse developmental
and cognitive outcomes. There are three effective, simple, and
safe ways to minimize pain in newborns during painful procedures:
breastfeeding (BF), skin to skin care (SSC), or giving sweet
solutions (sucrose or glucose). Studies of neonatal pain
management practices in Canada, and throughout many other
parts of the world, consistently show infrequent use of these
strategies. Objective: To pilot test a parent-targeted knowledge
translation (KT) intervention, the BSweet2Babies video
(http://tinyurl.com/BSweet2newborns), which demonstrates BF,
SSC, and sucrose for pain management during blood work for
neonates. The study aimed to: i) evaluate the feasibility of making
the video accessible to parents of newborns in neonatal intensive
care units (NICUs) and ii) determine parents’ perceptions of the
acceptability, usefulness, and preliminary effectiveness of the
video in influencing intent and use of BF, SSC, and sucrose for
newborns during blood work. Methods: A survey consisting of
seven questions and one comment box. All parents of eligible
infants at the Children’s Hospital of Eastern Ontario (CHEO) NICU
were approached to obtain informed consent. The parents were
shown the BSweet2Babies video by the research assistant during
their infant’s stay in the NICU. After watching the video the
parents completed the survey. Descriptive statistics were used to
analyze all data from the survey and content analysis was used to
analyze the comments. Results: Between July 3, 2014 and
November 21, 2014, 25 mothers and 12 fathers were enrolled
(n=34). Results indicate that prior to watching the video, n=34
parents had not used breastfeeding, n=33 had not used SSC, and
n=12 had not used sucrose to reduce procedural pain in their
newborn. After viewing the video n=35 parents intended to
advocate for BF, SSC, or sucrose and n=31 said they would
recommend the video to other parents. Conclusion: Preliminary
results show that: i) the video increased parents’ knowledge and
intention to use BF, SSC, and sucrose, and ii) this KT intervention is
feasible, acceptable, and useful to parents of neonates in the
NICU. This pilot study will inform the design of a planned full-scale
randomized controlled trial to further establish the effectiveness
of this intervention in improving use of BF, SSC, and sucrose during
blood work in neonates. Acknowledgements: Chantal Horth,
Melissa Allaire, Chantalle Clarkin, Lucia Figueredo (CHEO Media
House), Cynthia Joly. Contact Information:
[email protected]
[402]
INFANT FEEDING AND MATERNAL GUILT: THE APPLICATION OF A
FEMINIST FRAMEWORK TO GUIDE CLINICIAN PRACTICES IN
BREASTFEEDING PROMOTION
Britney Benoit, RN, MScN1, Lisa Goldberg, RN, PhD2, Marsha
Campbell-Yeo, PhD, NNP-BC1
1Dalhousie
University School of Nursing; Centre for Pediatric Pain
Research, IWK Health Centre, Halifax, NS, Canada, 2Dalhousie
University School of Nursing, Halifax, NS, Canada
Introduction: Breastfeeding is recognized as a means of providing
optimal nutritional and immunological support for infant growth
and development. As such, breastfeeding promotion programs are
being implemented internationally to enhance breastfeeding. The
promotion of breastfeeding has been identified as a source of
maternal guilt, and literature suggests that fear of inducing guilt is
a barrier to clinician promotion of breastfeeding. It is thus
necessary to identify practices by which clinicians can provide
breastfeeding support without instilling feelings of guilt.
Objective: This work aimed to examine the issue of breastfeeding
promotion and maternal guilt through a feminist framework to
inform breastfeeding support practices in the perinatal period.
Methods: A feminist framework provided a guide to critically
examine breastfeeding promotion practices and how they
influence maternal experiences of guilt and choice in infant
feeding in the context of gender, power, and hierarchical
relationships often imposed within healthcare institutions. These
findings informed the proposal of practices aimed at minimizing
the guilt associated with breastfeeding promotion. Results:
Mothers are often expected to breastfeed without consideration
of the personal, professional, or social constraints that would
prevent them from doing so. While the benefits of breastfeeding
are well established, clinician promotion of breastfeeding may
suppress maternal experience of having choice in infant feeding.
Educating mothers on the benefits of breastfeeding is an
intervention recommended in breastfeeding promotion programs.
CNPRM 2015
111
However, educating without assessing the complex nature of
factors that influence a mother’s decision to breastfeed may be a
practice that imposes guilt. A feminist position suggests that
clinicians must provide their care from the place of the mother. By
exploring each mother’s lived experience and the process by
which she came to her infant feeding decision, clinicians can
provide individualized care. Such mother-centered care aims to
ensure an informed choice while minimizing guilt by optimizing
maternal voice, choice, and autonomy in her breastfeeding
decision. Conclusion: Breastfeeding promotion has been
identified as a source of maternal guilt. Given the known benefits
of breastfeeding, it is imperative that barriers to breastfeeding
education and support are minimized. Viewing the mothers voice
as critical in informing breastfeeding promotion interventions
could minimize guilt by promoting maternal experience of
autonomy and choice. Acknowledgements: Britney Benoit is
supported by the Nova Scotia Graduate Scholarship, Helen Watson
Memorial Scholarship, and Dalhousie University School of Nursing
Doctoral Scholarship. Contact Information: [email protected]
[410]
DO PRETERM TWINS MOUNT AN EMPATHETIC RESPONSE WHEN
BEING NEAR THEIR CO-TWIN UNDERGOING A PAINFUL
PROCEDURE? Marsha Campbell-Yeo1, Celeste Johnston 2, KS
Joseph3, Nancy Feeley4, Christine Chambers5, Keith Barrington6
1School of Nursing, Dalhousie University, Department of
Pediatrics, IWK Health Centre, Halifax, Nova Scotia, 2Department
of Pediatrics, IWK Health Centre, Halifax, Nova Scotia, 3Obstetrics
and Gynaecology, University of British Columbia, Vancouver BC ,
4Nursing, Ingram School of Nursing, McGill University, Montreal,
Quebec, 5Departments of Pediatrics and Psychology &
Neuroscience, Dalhousie University, Halifax, Nova Scotia ,
6Department of Pediatrics, Université de Montréal, Montreal,
Quebec
Introduction: Despite acceptance that animals and infants are
capable of prosocial behaviour and emotional contagion which are
precursors to empathy, evidence that some element of
empathetic response and capacity for true self-awareness felt to
be necessary to be empathetic is scarce (Keenan et al. 2003;
Landford, 2006; Campbell-Yeo, Latimer, Johnston, 2007).
Objective: The purpose of this randomized trial was to determine
the behavioral and cortisol response of a co twin by contrasting
preterm twins stratified in pairs by gestational age (≤31 6/7 weeks
or ≥32 weeks) and site and then randomly assigned to receive
either co-bedding, n=36, (cared for in the same incubator or crib)
or a standard care group, n=31, (cared for in a separate incubator
or crib) while their twin underwent a tissue breaking procedure.
Methods: Co twin response was collected simultaneously as their
twin underwent a medically indicated heel lance. Pain response
was determined by physiologic and videotaped facial reaction in
accordance with the Premature Infant Pain Profile (PIPP).
Additional outcomes included physiologic time to recovery,
alterations in salivary cortisol, heart rate variability (HRV), and
adverse events. Results: Simultaneous response of the twin not
undergoing the heel lance whether they were co-bedding with
their twin or in a separate incubator with respect to PIPP scores,
facial action, time to recovery, salivary cortisol, HRV or adverse
events were not significantly different between the groups.
Conclusion: Our lack of co-twin response is consistent with others
reporting that empathy is a learned process that develops over
time with maturation of the pre frontal cortex and the attainment
of self-awareness. Thus, clinicians concerns regarding increased co
twin distress while providing skin-to-skin comfort to their twin
undergoing procedural pain do not appear to be warranted.
Whether unconscious neuronal changes in response to being near
their twin experiencing pain occur in the absence of
112
biobehavioural or physiologic response remains unknown.
Acknowledgements: The study was supported by operating and
salary support from the Nova Scotia Health Research Foundation
(NSHRF), the Groupe de Recherche Interuniversitaire en
Interventions en Sciences Infirmieres du Quebec (GRIISIQ),
Canadian Nurses Foundation, Pain in Child Health (CIHR Strategic
Training Initiative in Health Research), the IWK Health Centre, and
the Canadian Institutes of Health Research (CIHR). Contact
Information: [email protected]
[446]
REDUCTION OF NICU LIGHT AND NOISE levels DURING KMC:
ACCEPTABILITY BY NEONATAL NURSES. Marilyn Aita1, Robyn
Stremler2, Nancy Feeley3, Keith Barrington4, Anne Monique Nuyt4
1Université de Montréal, 2University of Toronto, 3McGill
University, 4CHU Sainte-Justine
Introduction: Light and noise may influence outcomes of preterm
infants and their mothers when they are experiencing kangaroo
mother care [KMC] in the NICU. A dimmed and quiet environment
during KMC may then be beneficial for infants and their mothers.
A pilot study of a randomized control trial [RCT] was designed to
evaluate the feasibility and acceptability of reducing light and
noise levels combined to KMC in the NICU. As nurses have a
strategic position in the NICU to reduce infants’ exposure to
inappropriate light and noise levels, as well as to encourage KMC,
it was also pertinent to evaluate in this pilot study their
acceptability as to the reduction of light and noise levels during
KMC. Objective: Specific objectives were to: a) describe how
acceptable neonatal nurses found the reduction of light and noise
levels during KMC in a NICU, and b) describe if the reduction of
light and noise levels during KMC interfered with their care
delivery. Methods: Pilot study where 24 neonatal nurses from a
level III NICU of a Mother and Child University Hospital Center
were recruited so far. To participate, nurses had to provide care in
the room where infants and their mothers were experiencing the
KMC, which lasted one-hour. Following consent and when the
KMC ended, the nurses completed a questionnaire evaluating on a
5-point Likert scale if they found acceptable the reduction of light
and noise levels in general during KMC and in regards to 9
interventions reducing light and noise levels. Two questions with a
5-point Likert scale were also evaluating if they found that
reducing light and noise levels during the KMC interfered with
their care delivery. Results: Preliminary results reveal that the
majority of the nurses (69.6%) found totally acceptable the
reduction of light and noise levels during KMC in general. For
specific interventions reducing light and noise levels, all nurses
found acceptable that the ceiling lights were closed during the
KMC along with the room's door. More than 60% of the nurses
responded, for both the reduction of light and noise levels during
KMC, that it did not interfere with their care delivery.
Conclusion: Findings confirm that neonatal nurses found
acceptable the reduction of light and noise levels during the KMC
and may support a full-scale RCT. Findings provide incentive
toward the implementation of guidelines relating to KMC as well
as to the reduction of NICU light and noise levels.
Acknowledgements: Thank you to: CIHR Team Research and
Training Program Sleep and Biological Rhythms Toronto, the
Quebec Nursing Intervention Research Network [RRISIQ] and the
Canadian Association of Perinatal and Women’s Health Nurses
[CAPWHN] for research funding as well as to CIHR for the RCT
Mentoring Program. Contact information:
[email protected]
[458]
THE EXPERIENCE OF TRANSITIONING INTO MOTHERHOOD:
MOTHERS WITH VERY LOW BIRTH WEIGHT BABIES. Katherine
Bright PhD(c)1, Dr. Cynthia Mannion1
CNPRM 2015
1University
of Calgary Faculty of Nursing
Introduction: During the neonatal period, mothers of preterm
very low birth weight (VLBW) babies experience heightened levels
of psychological distress which are greater than those of mothers
with full-term babies. Mothers of VLBW babies have a multitude of
difficulties to overcome on their attachment journey with their
infants. This early postpartum period is a crisis situation for
mothers of these VLBW babies. Objective: The purpose of this
study was to gain an understanding from the mother\'s
perspective of what happens to them during their early
postpartum period. From this understanding, a theoretical model
of the transition into motherhood for women with VLBW babies
was developed. Methods: Grounded theory was the
methodology chosen for this research study because of its
inductive nature and the ability to generate a theoretical
framework rather than testing previous theories (Glaser & Strauss,
1967). The theory that evolved through this research method was
illustrated as a set of concepts, which were distinct but also
connected. From these concepts a theory emerged that provided
an entirely new way of understanding the observations. A
purposive approach to sampling was used to obtain participants.
Results: From the data, four social processes were concluded and
they were categorized as: 1) Mother-Baby Relationship; 2)
Maternal Development; 3) Maternal Care Giving and Role
Reclaiming Strategies; and 4) Baby’s Developmental Milestones.
Although these four processes were distinct they were not
mutually exclusive, rather the processes inform one another and
often occurred simultaneously. The processes were not linear, but
rather could go forward and backward as the situation or reality
presents itself for these mothers. The core variable of
Reconstructing Normal emerged from the data and was informed
by the basic social processes. Conclusion: For mothers of VLBW
babies nothing about their situations were normal – not their
pregnancies, not their deliveries, and not their babies. So how
does one cope with these “not normal” or expected outcomes?
For the mothers of VLBW babies they began Reconstructing
Normal, that is, they took their reality, the situation they were in,
their knowledge of what was happening and then learned about
what would be an expected outcome for their situation. They
assimilated this into what would now be normal and expected for
them. Their current state became their reconstructed normal. For
the mothers in this study, these reconstructions and
transformations were a part of an ongoing, never-ending process
and allow them to reduce their levels of distress and move
forward. Acknowledgements: Funding for this study was received
from the ARNET and the Faculty of Nursing. Contact Information:
Katherine Bright [email protected]
[473]
EFFECTS OF CYCLED LIGHTING VERSUS NEAR DARK LIGHTING ON
THE PHYSIOLOGICAL STABILITY AND MOTOR ACTIVITY LEVEL OF
PRETERM INFANTS. Valérie Lebel1
1Faculty of nursing, University of Montreal
Introduction: After birth, preterm infants evolve in the neonatal
intensive care unit (NICU) characterized by a high and variable
lighting which differs significantly from the dimmed intra-uterine
environment. Exposure to high or variable NICU lighting can create
physiological instability in preterm infants as well as increasing
their motor activity level. An appropriate control of the NICU
lighting can prevent the adverse effects of exposing infants to
inadequate levels of lighting. To date, it appears that two methods
of lighting control have been discussed and studied: near dark
lighting and cycled lighting. At the same time, it is acknowledged
that there is ambiguity about the results of studies which have
evaluated these two NICU lighting methods. Therefore, the
optimal NICU lighting remains unknown and further research is
needed to identify the lighting mode witch promote preterm
infant’s adaptation to the NICU environment. Objective: The
objective of this research is to evaluate the effects of cycled
lighting versus near dark lighting on the physiological stability and
motor activity level of preterm infants. Methods: A randomized
controlled trial (RCT) allowed the assessment of the preterm
infants' physiological stability and motor activity level. 38 preterm
infants born between 28 to 32 weeks of gestational age were
recruited from a level III NICU university affiliated hospital. Each
infant were randomly allocated to one of the following groups for
24 hours: cycled lighting or near dark lighting. Physiological
stability was assessed by the score of Stability of the Cardio
Respiratory System in Premature Infants (Fischer et al., 1998),
while the motor activity level was evaluated by an accelerometer.
The light intensity level was continuously measured with a light
meter to ensure that the lighting mode assigned was respected.
Results: The analysis conducted indicates no significant difference
between the two intervention groups in regard to physiological
stability and the motor activity level. This lack of significant
difference between the two groups indicates that the participants
in the two groups demonstrated a comparable physiological
stability state and a comparable level of motor activity when
exposed to near dark lighting or cycled lighting. Conclusion:
Premature infants are physiologically stable and their motor
activity is low when exposed to cycled lighting or near dark
lighting. Acknowledgements: Faculty of nursing, University of
Montreal; Gustav Levinschi Foundation, CHU Sainte-Justine;
Canadian Institute of Health Research (CIHR); Groupe de
Recherche Interuniversitaire en Interventions en Sciences
Infirmières du Québec (GRIISIQ); FRESIQ MELS-University Program.
Contact Information: [email protected]
[478]
FACTORS RELATED TO WOMEN'S EXPERIENCES AND
SATISFACTION WITH PRENATAL CARE. Patricia Gregory, RN, PhD1
1Red River College/Department of Nursing; University of
Manitoba/College of Nursing
Introduction: There is substantial observational evidence that
prenatal care provides numerous maternal and infant health
benefits. Prenatal care is more likely to be effective if women
begin receiving care early and continue prenatal care throughout
pregnancy. Patient satisfaction is recognized as a predictor of
adherence to medical recommendations and utilization of care.
Objective: The purpose of this study was to identify the factors
associated with women's satisfaction with prenatal care in
Winnipeg. Methods: A cross-sectional, descriptive, correlation
design examined the relationships between expectations,
interpersonal processes of care, quality of prenatal care, personal
CNPRM 2015
113
characteristics, and the type of provider with satisfaction. In
addition to overall satisfaction various dimensions of satisfaction
were measured including: satisfaction with information, provider
care, staff interest, and system characteristics. Donabedian's
(2003) structure, process, and outcome framework guided the
study. A convenience sample of 216 pregnant women in the late
third trimester, from diverse socioeconomic backgrounds was
surveyed using self-administered questionnaires. Multiple linear
regression analyses identified the predictors of satisfaction.
Results: Participants received prenatal care from a variety of types
of providers including obstetricians (58.2%), midwives (15.9%),
family physicians (13.9%), nurse practitioners (4.8%), or mixed
(7.2%). Perceived quality of care was a significant predictor of
overall satisfaction and in all of the dimensions of satisfaction. In
terms of interpersonal processes of care, the provider's
interpersonal style was a significant predictor in all of the
satisfaction measures with the exception of satisfaction with
information, where patient-centered decision making was
significant. Receiving prenatal care from a midwife was a predictor
of satisfaction with system characteristics. Expectations for
prenatal care were unrelated to satisfaction. Although most of the
participants in this study were satisfied with prenatal care, 5-20%
reported dissatisfaction with the various dimensions of
satisfaction. Conclusion: The findings of this study provide
empirical support for the Donabedian's hypothesized associations
between structural and process factors and satisfaction.
Identification of the factors related to the various dimensions of
satisfaction provided valuable and actionable information to
improve the experience and satisfaction of women receiving
prenatal care. Implications for policy, education, and future
research have been identified. Acknowledgements: Funding:
Manitoba Centre for Nursing and Health Research, research grant
Kathleen and Winnifred Ruane Student Research Grant for Nurses.
Contact Information: Dr. Patricia Gregory [email protected]
[481]
OUTCOMES ASSOCIATED WITH PLANNED PLACE OF BIRTH IN
LOW-RISK WOMEN ATTENDED BY MIDWIVES IN ONTARIO, 20062009: A RETROSPECTIVE COHORT STUDY. AdrianaCappalletti1,
Angela Reitsma2, Julia Thorpe2, Jordyn Horne3, Eileen Hutton4
1McMaster University/ Health Science Program, 2McMaster
University/ Midwifery Education Program, 3McMaster University/
Life Science Program, 4Department of Obstetrics & Gynecology
Introduction: In Ontario, Canada, midwifery is regulated for the
care of low-obstetric risk women intending birth both in hospital
and at home. Objective: This study aimed to compare the risk of
perinatal/neonatal mortality and morbidity and intrapartum
interventions in Ontario women based on planned place of birth.
Methods: We used a retrospective cohort design to study of
54,026 midwife attended births. Our primary outcome was a
composite of perinatal and neonatal mortality or serious
morbidity. We compared all women indicating planned home birth
at the onset of labour to a similarly low risk group of women
planning hospital birth, matched by parity and previous Caesarean
sections (CS). Results: We compared outcomes of 11,492 women
planning home births with 11,429 women, randomly selected and
matched on parity and prior CS, who planned hospital births. We
found no differences in perinatal/neonatal mortality or morbidity
in our primary analysis for women planning home (6.7%)
compared to hospital (6.5%) (RR [95% CI]: 1.01 [.096-1.107]).
Women who planned a home birth were at significantly lower risk
of all intrapartum interventions studied. Conclusion: Overall,
women planning either home or hospital birth under midwifery
care had good outcomes and those planning home birth had fewer
interventions. Acknowledgements: We would like to thank the
Ministry of Health and Long-Term Care for providing the data to
114
conduct this study and Rashid Ahmed for his insight on the data
cleaning process. Contact Information: Julia Thorpe
[email protected]
[368]
BREAST MILK EXPRESSION AT PRETERM INFANT'S BEDSIDE MOTHERS’ ACCEPTABILITY AND EXPERIENCES. Marjolaine Héon1,
Linda Bell2, Renée Flacking3, Céline Catelin4
1Université de Montréal/Faculté des sciences infirmières,
2Université de Sherbrooke/École des sciences infirmières, 3Dalarna
University/School of Health and Social Studies, 4Université de
Sherbrooke/Faculté de médecine et des sciences de la santé
Introduction: Mothers who give birth prematurely struggle to
establish and maintain a sufficient breast milk production.
Insufficient breast milk production is one of the major barriers that
jeopardize breastfeeding in preterm infants. Breast milk
expression at the preterm infant’s bedside is recommended to
enhance breast milk production, although there is limited
evidence supporting this intervention. To date, no study has
evaluated mothers’ acceptability of breast milk expression at their
preterm infant’s bedside or described their experiences.
Objective: The aim of this pilot study with a mixed method
evaluation is to assess mothers’ acceptability and explore their
experiences of breast milk expression at their preterm infant’s
bedside. Methods: A total of 40 mothers of preterm infants born
at <30 weeks of gestation and admitted to a NICU of a university
health center are being recruited and randomly assigned either to
the control (breast milk expression in room reserved for this
purpose, according to usual care) or experimental (breast milk
expression at the preterm infant’s bedside) group. At the end of
the study, mothers’ acceptability of the experimental intervention
is evaluated through the Treatment Acceptability and Preference
Questionnaire (Sidani et al., 2009). Their experiences of breast
milk expression at their preterm infant’s bedside are assessed with
an adapted version of the Personal Experience Subscale of the
Breast Milk Expression Experience Questionnaire (Flaherman et
al., 2013). In order to further assess mothers’ acceptability of
breast milk expression at their preterm infant’s bedside and
explore their related experiences, an individual semi-structured
interview with open-ended question is conducted with mothers.
Interviews are recorded and transcribed for conventional content
analysis. Results: Preliminary results indicate that the
experimental intervention seems to be acceptable and convenient
for mothers. Mothers report that it optimizes their presence at the
bedside, increases their physical and emotional closeness, and
promotes their attachment and involvement in care. They also
report that the most challenging aspects of expressing at their
preterm infant’s bedside are the lack of intimacy, frequent
interruptions, and stressful neonatal unit environment.
Conclusion: This pilot study has the potential to contribute to the
development of knowledge on breast milk expression at the
preterm infant’s bedside, enlighten clinical practice, and guide
future research on the support of breast milk production in
mothers of preterm infants. Acknowledgements: Thanks to
RRISIQ and Centre de recherche clinique Étienne-Le Bel for their
support. Contact Information: [email protected]
Canadian Maternal Fetal Medicine Society
[361]
PSYCHOSOCIAL STRESS DURING PREGNANCY AND LENGTH OF
GESTATION IN A LOW-RISK CANADIAN COHORT: THE 3-D STUDY.
Gabriel D. Shapiro1, Jean R. Séguin1, Gina Muckle2, Emmanuel
Bujold2, William D. Fraser3
CNPRM 2015
1Université
de Montréal, 2Université Laval, 3Université de
Sherbrooke
Introduction: While preterm birth (PTB) is a problem of great
public health concern, its determinants are not well explained.
Psychosocial stress during pregnancy (PSP) has been identified as a
potential predictor of PTB. Objective: We measured four forms of
psychosocial stress and explored their associations with length of
gestation in a large Canadian pregnancy cohort (3-D Study). We
hypothesized that: 1) among pregnancy stress measures,
pregnancy anxiety and perceived stress would exhibit the
strongest relationships with length of gestation; 2) first-trimester
stress would have the strongest association with length of
gestation; and 3) PSP would be most strongly associated with
length of gestation among women of lower socioeconomic status
and those from minority racial groups. Methods: Three of the
psychosocial stress measures (general perceived stress, pregnancy
anxiety and stress in the partner relationship) were assessed
following prenatal study visits in each trimester of pregnancy (8-14
weeks, 20-24 weeks, 32-35 weeks), and stressful life events were
measured in the second trimester only. Length of gestation was
estimated from the last menstrual period and ultrasound data,
collected from a postpartum chart review. Bivariate correlations
were obtained between psychosocial stress variables and length of
gestation, and in the presence of significant associations,
multivariate regression models adjusting for potential confounding
variables were constructed. Results: Of 2366 participating
women, 1593 had spontaneous labour onset or spontaneous
rupture of membranes leading to a live birth. The mean length of
gestation was 39.2 weeks. There were 113 spontaneous preterm
births (7.1%) and 355 spontaneous early term (37-39 weeks) births
(22.3%). After controlling for confounders and testing for
moderators, only third-trimester pregnancy anxiety was related to
the length of gestation, which was decreased by 0.08 weeks for
each standard deviation increase in the pregnancy anxiety scale.
None of the stress measures was significantly associated with
spontaneous preterm or early term birth in multivariate analyses.
Conclusion: Besides an association of small magnitude between
third-trimester pregnancy anxiety and length of gestation, we
found little evidence to support the hypothesis that psychosocial
stress is a clinically significant contributor to risk of PTB or reduced
length of gestation. This conclusion is strengthened by our use of a
range of psychosocial stress measures administered at three time
points in pregnancy, thus overcoming several limitations of
previous research. Acknowledgements: The 3-D Study is
supported by a grant from CIHR. Contact Information:
[email protected]
[366]
CAN WE SAFELY RECOMMEND GESTATIONAL WEIGHT GAIN
BELOW THE GUIDELINES FOR OBESE PREGNANT WOMEN?
Christina K. Park1, Mufiza Z. Kapadia2, Joseph Beyene3, Lucy Giglia4,
Cindy Maxwell5, Sarah D. McDonald2
1McMaster University/Faculty of Health Sciences, 2McMaster
University/Department of Obstetrics and Gynecology, 3McMaster
University/Department of Clinical Epidemiology and Biostatistics,
4McMaster University/ Department of Pediatrics, Division of
General Pediatrics, 5University of Toronto/Division of Maternal
Fetal Medicine
Introduction: One third of women of reproductive age are obese,
increasing their risk of complications during pregnancy, including
pre-eclampsia, gestational diabetes, and cesarean birth. Infants
born to obese women also have increased risks such as preterm
birth and large for gestational age. To try to reduce these risk of
pregnancy complications, some have suggested that obese
pregnant women should gain less than recommended by the
Institute of Medicine/Health Canada gestational weight gain
(GWG) guidelines. However, a comprehensive, unbiased synthesis
of the evidence is required. Objective: We conducted a
systematic review and meta-analysis to examine the association
between GWG below (0-4.9 kg) compared to within (5-9 kg) the
guidelines and the risk of adverse pregnancy outcomes in obese
women (body mass index ≥30 kg/m2). Secondly, we checked for a
gradient effect across classes of obesity. Methods: Medline,
Embase, Cochrane Register, CINHAL and Web of Science databases
were searched from 1 January 2009 to 31 July 2014. A modified
Newcastle-Ottawa scale was used to assess study quality. Primary
outcomes were preterm birth (<37 weeks gestation), small for
gestational age (SGA, <10th percentile) and large for gestational
age (LGA, >90th percentile). Secondary outcomes included other
adverse infant or maternal outcomes. Results: Eighteen cohort
studies with almost 100,000 women were included. Compared to
obese women who gained within the guidelines, those who gained
below had higher odds of preterm birth (adjusted odds ratio [AOR]
1.46; 95% CI 1.07-2.00) and SGA (AOR 1.24; 95 % CI 1.13-1.36), and
lower odds of LGA (AOR 0.77; 95% CI 0.73-0.81). There were no
notable gradients in outcomes across obesity classes. There were
reduced odds of macrosomia, caesarean birth, preeclampsia and
gestational hypertension associated with GWG below the
guidelines. Conclusion: GWG below guidelines cannot be safely
recommended for all obese women but may be individualised for
certain women with caution, accounting for known risk factors of
adverse pregnancy outcomes such as gestational diabetes and
hypertension. Acknowledgements: This work was supported by a
grant from CIHR. SDM is supported by a CIHR New Investigator
Salary Award. We thank Neera Bhatnager, B.Sc., M.L.I.S., Head of
Systems, Coordinator of Research & Graduate Education Support,
Health Sciences Library, McMaster University, for her assistance in
developing the search strategies. Contact Information: Christina
K. Park [email protected]
[367]
THE IMPACT OF GESTATIONAL WEIGHT GAIN ON PERINATAL
OUTCOMES IN ADOLESCENT MOTHERS: A RETROSPECTIVE
COHORT STUDY. Kayla Balderston1, Emily Whelan1, Dr. Christy
Woolcott2
1Dalhousie University, Faculty of Medicine Class of 2017,
2Dalhousie University, Obstetrics & Gynaecology and Pediatrics
Introduction: Gestational weight gain (GWG) recommendations
made by the Institute of Medicine are qualified by the statement
that there may be some variation due to age as many adolescent
women grow themselves throughout pregnancy. Objective: We
examined the associations between GWG and perinatal outcomes
in adolescent women aged <20 years and determined whether
they differed from the associations among adult women aged 2035 years. Methods: A retrospective cohort study was conducted
within the Atlee Perinatal Database. Included were all live born,
singleton deliveries to mothers <=35 years in Nova Scotia between
2003 and 2013. Gestational weight gain was categorized as below,
within or above the recommendations. Primary outcomes
included preterm birth (<37 weeks), small for gestational age
(SGA; <10th percentile), large for gestational age (LGA; >90th
percentile) and Caesarean delivery. Logistic regression was used to
estimate adjusted odds ratios (OR) with 95% confidence intervals
(CI). To examine whether the GWG-outcome associations differed
between adolescent and adult women, the significance of the
interaction term between GWG and maternal age was
determined. Results: This study included 3,243 adolescent and
43,979 adult women. Adolescent mothers who gained above the
recommendations (relative to mothers who gained within), were
at increased odds of having an LGA neonate (OR, 2.12; 95% CI,
1.50-2.98) and Caesarean section (OR, 1.31; 95% CI, 1.01-1.69),
while the odds of having an SGA neonate decreased (OR, 0.65;
CNPRM 2015
115
95% CI, 0.49-0.85). Adolescent mothers with low GWG had
decreased odds of having an LGA neonate (OR, 0.40; 95% CI, 0.210.76) and increased odds of having an SGA neonate (OR, 1.73; 95%
CI, 1.27-2.35). The GWG-outcome associations observed among
adolescent women were similar to those observed among adult
women for SGA, preterm birth, and Caesarean section (pinteraction=0.99, 0.25, and 0.70, respectively). However, the ORs
for the association between GWG and LGA among adult women
(OR 1.94; 95% CI, 1.80-2.08 for low GWG and OR 0.64; 95% CI,
0.57-0.72 for high GWG) were less substantial than the ORs among
adolescent women (p-interaction=0.045). Conclusion: Among
adolescent women, GWG was significantly associated with SGA,
LGA, and Caesarean delivery. The difference in the strength of the
association between GWG and LGA in adolescent versus adult
women does not suggest that the recommended GWG be
increased for adolescent women. More research considering other
outcomes is needed to determine the optimal GWG for adolescent
women. Acknowledgements: Ms. Balderston received a
Dalhousie Medical Research Foundation Lalia B. Chase Summer
Research Studentship. Data were provided by the Nova Scotia
Reproductive Care Program. Contact Information:
[email protected]
[373]
MAFF TRANSCRIPTION FACTOR DEPENDENT REGULATION OF
MYOMETRIAL CELLS. Vera Solovieva1, Fangshi Lu1, Anna Derjuga1,
Volker Blank1
1Lady Davis Institute and McGill University
Introduction: The myometrium, the smooth muscle layer of the
uterus, contracts during birth. Evidence from various laboratories
suggested that proinflammatory cytokines are involved in the
events that lead to preterm labor, particularly in association with
infection. Previous studies have shown that MAFF transcription
factor transcripts are present in term myometrium, but not in
early gestation and non-pregnant myometrium. We found that
MAFF protein is rapidly induced upon cytokine treatment of
hTERT-C3 myometrial cells. Here, we assessed MAFF dependent
gene regulation in this myometrial cell model. Objective: In this
study, we further explored the link between MAFF transcription
factor, proinflammatory cytokine signaling and myometrial cell
function. Methods: We examined hTERT-C3 myometrial cells
following siRNA mediated MAFF knockdown and/or interleukin1beta (IL-1beta) treatment by RNA-sequencing. We confirmed
differential gene expression of candidate genes by qPCR and/or
immunoblot analysis, and analyzed the transcriptome data by
ingenuity pathway analysis (IPA). Results: We showed that the
MAFF transcription factor is rapidly induced by IL-1beta in hTERTC3 myometrial cells. We analyzed the transcriptome of hTERT-C3
cells upon MAFF knockdown and/or IL-1beta exposure by RNAseq. We used IPA to assess the biological functions and cellular
networks of differentially expressed genes. We found that MAFF
inhibition has an effect on genes that are involved in inhibition of
matrix metalloproteinases, cell cycle damage checkpoint
regulation and cell cycle control of chromosomal replication. IL1B
treatment showed an effect on gene groups participating in NFkappaB signaling as well as apoptotic signaling such as death
receptor and tumor necrosis factor signaling pathways. We
identified genes differentially expressed upon MAFF transcription
factor knockdown, including prostaglandin-endoperoxide synthase
(PTGS2, previously COX2) and inhibitor of metallopeptidases 3
(TIMP3). This is of interest, as PTGS2 plays key roles during
parturition and labor, and TIMP3 is involved in collagen membrane
rupture. Our data show that MAFF plays a role in myometrial cell
gene regulation and suggest that the transcription factor may
participate in the control of parturition and/or labor. Conclusion:
We found that alteration of MAFF transcription factor levels in
116
myometrial cells leads to changes in the expression of genes
involved in parturition and labor. Dissecting the MAFF dependent
transcriptional network in uterine smooth muscle cells may help in
the design of novel diagnostic and treatment options for infection
driven preterm birth. Acknowledgements: We thank François
Lefebvre for help with bioinformatics. This research was funded by
NSERC. Contact Information: Volker Blank
[email protected]
[378]
NEWBORN OUTCOMES AFTER CAESAREAN SECTION FOR NONREASSURING FETAL STATUS IN BRITISH COLUMBIA. Patricia
Janssen1, Kevin Jenniskens2
1School of Population and Public Health, University of British
Columbia, 2Nijmegen Medical Centre, Radboud University, The
Netherlands
Introduction: Non-reassuring fetal status is among one of the
most prevalent indications for primary cesarean section. Electronic
fetal monitoring remains the primary instrument to assess fetal
status in labour. SOGC has revised parameters for diagnosis and
management of NRFS in their 2007 guidelines 2007. The National
Institute for Health and Care Excellence (NICE) in the UK has called
for large scale studies looking at the ability of EFM to predict
outcomes such as cord blood gases and Apgar scores as well as
longer term outcomes such as, hypoxic ischaemic encephalopathy,
respiratory problems and length of neonatal intensive care unit
stay. Objective: To assess the incidence of severe morbidity in
neonates delivered by caesarean section for non-reassuring fetal
status in the Province of British Columbia and describe the
accuracy of Apgar score and umbilical cord gases in predicting
severe neonatal morbidity. Methods: We assessed rates of
hypoxic ischaemic encephalopathy, neonatal intensive care unit
stay, ventilator days individually and as a composite outcome with
neonatal death among a total of 8466 term singletons delivered by
caesarean section for non-reassuring fetal status between January
1st 2007 and December 31st 2011. We calculated the predictive
accuracy of Apgar scores and umbilical cord blood gases using area
under the receiving operator curve, sensitivity and specificity for
each outcome. Results: The incidence of Apgar score at 1 minute
and 5 minutes < 4 were 8.0% and 0.6%, and for umbilical cord pH <
7.10 and base-excess < -12 were 6.5% and 2.9% respectively.
Apgar at 1 minute < 7 demonstrated highest predictive accuracy
for the composite outcome at 81% for both sensitivity and
specificity. The area under the receiver-operator curve for Apgar
at 1 minute and 5 minutes and umbilical cord pH and base-excess
were 0.87, 0.86, 0.76 and 0.78 respectively. Conclusion: The
incidence of abnormal Apgar score and umbilical cord gas values is
very low among neonates delivered by caesarean section for nonreassuring fetal status in British Columbia. One minute Apgar score
< 7 is a good predictor of severe neonatal morbidity. Electronic
fetal monitoring remains a non-specific method for detection of
fetal compromise in the intrapartum period. Acknowledgements:
This work was funded through a CIHR Partnerships for Health
Systems Improvement Grant for Optimal Birth BC. Contact
Information: [email protected]
[387]
OUTCOMES OF PRIMARY MATENITY CARE IN THE NORTHWEST
TERRITORIES. Patricia Janssen, PhD1, Caitlin Frame, MSc1, Lesley
Paulette, RM, RN2, Gisela Becker, RM, MA3, Vicki van Wagner, RM,
PhD4, Saraswathi Vedam, RM, MSN, Sci D. 5
1School of Population and Public Health, University of British
Columbia, 2Fort Smith Midwifery Program, Northwest Territories,
3Fort Smith Midwifery Progarm, Northwest Territories, 4Midwifery
Education Programme, Ryerson University, 5Midwifery Program,
Faculty of Medicine, University of British Columbia
Introduction: In northern Canada women residing in rural
CNPRM 2015
communities without local access to maternity care must evacuate
at 36-37 weeks gestation to await labour in a city with a regional
hospital. Midwifery services are expanding to rural areas of
Canada, yet there are few studies that evaluate the safety of rural
and remote midwifery compared to routine evacuation for birth.
Objective: To compare the outcomes of community birth with the
Fort Smith Midwifery Program to those of Hay River, where
evacuation from the community for birth is mandatory, and those
of community-based maternity services in the Eastern Arctic.
Methods: A retrospective cohort study was conducted to compare
birth outcomes from the Fort Smith Midwifery Program (n=281)
to: 1) the Inuulitsivik Midwifery Program in Nunavik (n=1388), and
2) the community of Hay River (n=143). Maternal and newborn
outcomes were compared among the three comparison groups
using univariate and multivariate logistic regression. Results:
There were no statistically significant differences in the odds of 5minute APGAR scores less than 7. The odds of 1-minute APGAR
scores below 7 in Fort Smith were increased compared to Nunavik,
however the rate was similar to those of newborns of women who
resided in Hay River and delivered in Yellowknife. In Fort Smith
compared to Nunavik, the odds of induction of labour, use of
epidural analgesia, cesarean section and episiotomy were
increased; the excess occurred among women who elected to
deliver outside of Fort Smith. Fort Smith had decreased rates of
preterm birth and induction of labour compared to Hay River.
Conclusion: The Fort Smith Midwifery Program was not associated
with increased risk of adverse maternal or newborn outcomes.
The findings of this study support the development and evaluation
of midwife-led models of maternity care in rural and remote
communities. Acknowledgements: This work was funded through
a grant from the Alva Foundation. Contact Information:
[email protected]
[390]
ABSENT DUCTUS VENOSUS – IS IT A MARKER OF UMBILICAL
CORD COMPLICATIONS? Rania Okby1, Hadar Rosen2, Shannon
Murphy3, Anne Berndl4
1Advanced Obstetrics Fellow, Sunnybrook Health Science Center,
University of Toronto, 2Maternal Fetal Medicine fellow , University
of Toronto , 3Obstetrical Ultrasound Center, Sunnybrook Health
Science Center, 4Maternal Fetal Medicine, Sunnybrook Health
Science Center, University of Toronto
Introduction: The clinical significance of true umbilical cord knots
is unclear. The incidence varies from 0.04% to 3% of all deliveries,
with an associated perinatal morbidity reaching as high as 11%.
Objective: At 31 weeks of gestation, the patient was referred
because of reduced fetal movements and a non-reactive
cardiotocogram. Methods: An ultrasound (US) examination
showed viable fetus, in transverse lie, normal amniotic fluid index,
but the fetal movement, tone and diaphragm movements were
absent. There was a small ascites and small pleural effusion. Blood
flow in umbilical artery and middle cerebral artery were normal
and there was no ductus venosus flow. Results: Given the non
reassuring fetal heart rate with biophysical profile of 2/8 and
absence of ductus venusus flow Cesarean section was done. A
tight true knot of cord was seen close to the umbilicus was seen.
The postnatal echocardiogram showed a normal cardiovascular
anatomy. Conclusion: Absent ductus venosus with reduced fetal
movement maybe a sign of umbilical cord complications such as a
true knot of cord or cord wrapped around the neck. Contact
Information: Rania Okby [email protected]
[395]
REVIEW OF INDICATIONS OF LABOUR INDUCTION PRACTICES IN
TERM PREGNANCIES AT A TERTIARY REFERRAL CENTRE: ARE
THERE EDUCATIONAL OPPORTUNITIES TO ENSURE WE ARE
EVIDENCE BASED AND FOLLOWING CURRENT GUIDELINES?
Jessica Rollings-Scattergood1, Patricia Smith1, Anne Berndl2
1McMaster University , 2Sunnybrook Health Science Centre
Introduction: The aim of this project was to look at indications for
induction of labour (IOL) at term and identify opportunities for
physician education to ensure that all IOL preformed at McMaster
are evidence-based and/or follow practice guidelines. Objective:
To assess the indications for induction of labour in term
pregnancies in order to identify areas of improvement and
education. Methods: After research ethics board approval was
obtained, a retrospective chart review of all patients undergoing
IOL after 37 weeks gestation, at McMaster University from July
2011 to December 2011 was completed. Results: A total of 299
patient charts were reviewed including 9 twin gestations. The
most common indication for IOL was post dates (31%), followed by
term rupture of membranes (21%). Twenty five percent of patients
were induced for maternal indications, including 6% for diabetes
and 6% for hypertensive complications. Intrauterine growth
restriction was the most common fetal indication for IOL (9%). Five
percent of patients were induced because of concerns around
safety at time of delivery. Only two patients had a social/nonmedical indication. The caesarean delivery rate was 21%.
Conclusion: The majority of the inductions followed best evidence
or practice guidelines. We were able to identify small discrete
areas where evidence based practice was lacking. The largest was
post dates, where 10% of patients were only post term (40.2-40.6
weeks). Other identified areas were: isolated oligohydramnios,
gestational diabetes, macrosomia, dichorionic/diamniotic twin
pregnancies and social inductions. The literature supports
reduction in non indicated inductions through processes of audit,
system review and physician education. This audit has identified
areas for physician education to reduce IOL rates for non-evidence
CNPRM 2015
117
based indications at term. Acknowledgements: McMaster
University. Contact Information: [email protected]
[408]
ANALYSIS OF MATERNAL MEDICAL CONDITIONS, PREGNANCY
COMPLICATIONS AND ADVERSE PERINATAL OUTCOMES BY
PREVIOUS MODE OF DELIVERY. Mary Kwakyepeprah1, Mark
Walker2, Ann Sprague3, Doug Coyle1, Shi Wu Wen2
1University of Ottawa/Department of Epidemiology, 2Ottawa
Hospital Research Institute (OHRI), Ottawa, 3Better Outcomes
Registry & Network (BORN), Ontario
Introduction: Background In 1996, 20.7% of babies were born by
cesarean section in the United States (US). This rate increased to
32.9% by 2009 (an increase of nearly 60%), and declined slightly to
32.8% in 2012. Given this remarkable increase, it is important to
evaluate maternal chronic medical conditions, pregnancy
complications and adverse perinatal outcomes related to cesarean
birth. Objective: Objective To examine maternal chronic medical
problems, pregnancy complications and adverse perinatal
outcomes occurring in second pregnancy in women who had
cesarean delivery in the first pregnancy in relation to vaginal
delivery in the first pregnancy. Methods: Method This is a
retrospective cohort study. Data for the study was obtained from
the National Center for Health Statistics, linked birth/death data in
the US. The study population included 981,779 mothers who
delivered in their second pregnancy, singleton live births with
gestational age at 20 weeks and more with no congenital anomaly,
in 2005 and 2006. The rates of maternal medical and pregnancy
complications as well as perinatal outcomes in the second
pregnancy were compared between women who had cesarean
delivery in the first pregnancy versus vaginal delivery in first
pregnancy using chi square tests, with a p-value of <0.05
considered significant. Main outcomes studied include chronic
medical problems, pregnancy complications and adverse perinatal
outcomes. Results: Results Women who had cesarean delivery in
their first pregnancy compared with vaginal delivery had
statistically significantly more medical problems like renal disease,
acute lung disease, diabetes, chronic hypertension (p<0.05);
pregnancy complications like cephalopelvic disproportion,
prolonged labor, dysfunctional labor (p<0.05); and adverse
perinatal outcomes like low (0-6) five-minute Apgar scores,
neonatal death and fetal distress (p<0.05) in the second
pregnancy. There was no significant difference among the two
delivery groups with respect to birth weight <2500 grams
(p=0.2352), incompetent cervix (p=0.1028), anemia disease
(p=0.0531) and uterine bleeding (p=0.1458) occurring in the
second pregnancy. Conclusion: Conclusion Mothers with first
cesarean birth relative to first vaginal birth had higher rates of
medical, and pregnancy complications as well as adverse perinatal
outcomes in the second pregnancy, with the exception of birth
weight <2500g, anemia disease, incompetent cervix and uterine
bleeding during pregnancy. This finding may inform level of care to
help reduce risk of complications associated with cesarean birth.
Acknowledgements: National Center for Health Statistics, United
States. Contact Information: Mary Kwakyepeprah
[email protected]
[413]
PGF2A AND IL-1B PROMOTE UTERINE TRANSFORMATION
THROUGH POSITIVE FEEDBACK INTERACTIONS AND SYNERGY IN
HUMAN MYOMETRIUM SMOOTH MUSCLE CELLS (HMSMC).
Kelycia B Leimert1, Barbara Verstraeten1, Rojin Nemati2, Xin Fang3,
David M Olson4
1Physiology, University of Alberta, Edmonton, Alberta, 2Biological
Sciences, University of Alberta, Edmonton, Alberta, Canada,
3Ob/Gyn and Pediatrics, University of Alberta, Edmonton, Alberta,
118
4Physiology,
Ob/Gyn and Pediatrics, University of Alberta,
Edmonton, Alberta
Introduction: Uterine transformation is essential to parturition,
involving interactions between a series of ‘birth cascade’ pathways
to transform the uterus of pregnancy into the contractile uterus of
delivery. We have condensed the complex process of uterine
transformation into three stages: positive feedback, synergy and
amplification. PGF2a is a key signaling mediator in parturition; we
have discovered that PGF2a not only induces uterine contraction
but is also involved in the induction of uterine transformation
through positive feedback and synergistic interactions. Objective:
Previously we demonstrated that PGF2a stimulates COX-2 and IL-6
mRNA and protein abundance in HMSMC via its receptor, PTGFR,
and that IL-1B stimulates PTGFR, COX-2 and IL-6 mRNA and
protein abundance in HMSMC. We hypothesized that IL-1B
elevation of PTGFR would correspondingly increase the ability of
PGF2a to stimulate uterine transformation. Methods: HMSMC
were treated for 24h with DMEM only, followed by 6h PGF2a (10-5
M), 12h IL-6 (5 ng/mL) or 12h IL-1B (5 ng/mL) and extracted for
mRNA abundance determination by real-time RT-PCR. A second
set of cells were treated for 24h with IL-1B (5 ng/mL) then washed
and treated for another 6h with PGF2a (10-5 M) or DMEM alone.
N=4-8 patients, statistical analysis was performed on Log10transformed data: ANOVA followed by Tukey post hoc testing or
independent samples t-test (p<0.05). Results: 6h of PGF2a
treatment (alone) increased relative mRNA abundance for COX-2
by 4.8-fold (p<0.01) and IL-6 by 8.2-fold (p<0.001). Cells treated
with 24h IL-1B followed by 6h DMEM increased relative mRNA
abundance for PTGFR by 3.6-fold, COX-2 by 19.4-fold (p<10-5), and
IL-6 by 36-fold (p<10-5). Conversely, both PGF2a and IL-1B
treatment increased mRNA expression of IL-1B receptor IL-1R1
(p<0.001). 12h IL-1B treatment increased mRNA expression of IL6R (p<0.01), but IL-6 treatment did not drive expression of IL-6R.
IL-1B treatment for 24h followed by 6h of PGF2a treatment
increased COX-2 mRNA abundance synergistically 35-fold (p<10-6)
and increased IL-6 mRNA abundance by 104-fold (p<10-6).
Conclusion: IL-1B treatment followed by subsequent PGF2a
stimulates extremely large synergistic increases in COX-2 and IL-6
mRNA abundance. These data suggest that in vivo preconditioning
with IL-1B increases myometrial responsiveness to PGF2a
tremendously thereby promoting a feed-forward amplification
that activates the uterus for labour. Positive feedback interactions
involving PGF2a, IL-1B and other signaling intermediates
contribute to the process of uterine transformation.
Acknowledgements: March of Dimes, CIHR, Global Alliance for the
Prevention of Prematurity and Stillbirth, an initiative of Seattle
Children's. Contact Information: Kelycia Leimert
[email protected]
[419]
ASSESSMENT OF THE TIME-COURSE OF PREGNANCY LOSS IN A
RAT MODEL OF ADVANCED MATERNAL AGE. Alison S. Care1,
Stephane L. Bourque2, Sandra T. Davidge1
1Department of Obstetrics and Gynaecology, Women and
Children’s Health Research Institute; University of Alberta,
Edmonton, 2Department of Anesthesiology and Pain Medicine,
Women and Children’s Health Research Institute; University of
Alberta, Edmonton
Introduction: The age at which women deliver their first child has
increased steadily in recent years, particularly in Western
societies. Aging is associated with poor pregnancy outcomes, and
studies have shown that changes in the uterine microstructure
affect implantation success. Little is known about age-related
changes occurring between the peri-implantation period and term
pregnancy. Here, we investigated pregnancy loss at several
periods throughout gestation in young and aged rats to enable
CNPRM 2015
detailed mechanistic investigations into causes of age-related
pregnancy loss. Objective: To investigate the time-course of
pregnancy loss in a rat model of advanced maternal age.
Methods: Aged female Sprague Dawley rats (9.5 months;
approximately equivalent to a 35 year old woman) and young
controls (4 months) were mated with young males. Implantation
was assessed on gestational day (GD)5, GD8, GD15, and GD20.
Results: On GD5 pregnancy success was lower in aged rats (young:
100%; aged: 66%), although preliminary data suggest that of the
rats that were pregnant, the number of implantation sites
between young and aged dams was not different. On GD8, 9/9
young dams were pregnant, compared to 7/11 aged (P<0.05 by
Chi-square test). Aged pregnant dams had 39% fewer implantation
sites (young=15.2±0.8, vs. aged=9.3±1.7, P<0.01), and of those
implantation sites, more of them were undergoing various stages
of resorption (young=0 vs. aged=5.6±2.0 resorptions, P<0.01);
similar results were observed on GD15. Overall, by GD20, aged
dams had a reduced capacity to carry a viable pregnancy to term
(young=90% vs. aged=50%), and had reduced litter sizes
(young=15.0±0.57 pups vs. aged=8.5±1.6 pups, P<0.01).
Conclusion: Pregnancy in aged dams is impaired early, which was
attributed to both implantation failure and miscarriage. These
results are dramatic given the aged rats used in this study are
otherwise healthy, without existing comorbidities. This model of
advanced maternal age will enable the assessment of mechanisms
underpinning the pregnancy loss, including those pertaining to
oocyte quality, embryo developmental competence, spiral
remodelling and depth of trophoblast invasion.
Acknowledgements: This work is funded by grants from CIHR and
WCHRI. ASC is supported by fellowships from HSFC and AIHS.
Contact Information: Alison Care [email protected]
[421]
THE ASSOCIATION BETWEEN GESTATIONAL WEIGHT GAIN AND
PERINATAL OUTCOMES IN MOTHERS WITH CLASS I, II, AND III
OBESITY. Whelan E, Balderston K, Woolcott C1
1Dalhousie University, Obstetrics & Gynaecology and Pediatrics
Introduction: The 2009 Institute of Medicine recommendations
for gestational weight gain (GWG) advise that women with obesity
should gain 5–9 kg, but do not distinguish between the three
classes of obesity. Objective: Our objective was to examine the
association between GWG and perinatal outcomes, by class of
maternal obesity. Methods: This retrospective cohort study used
data from the Nova Scotia Atlee Perinatal Database and included
women with obesity who had singleton pregnancies resulting in
live births between 2003–2013. Class of obesity was defined by
body mass index: I, 30.0–34.9 kg/m2; II, 35.0–39.9 kg/m2; and III,
40.0 kg/m2. We categorized GWG as below, within, or above the
recommendations. The primary outcomes were small for
gestational age (SGA; <10th percentile), large for gestational age
(LGA; >90th percentile), preterm birth (<37 weeks), and Caesarean
delivery. Odds ratios (OR) with 95% confidence intervals (CI) for
the association between GWG (below and above the
recommendations relative to within) and each outcome were
estimated with logistic regression adjusting for length of gestation
and other confounders. The significance of the interaction terms
between obesity class and GWG were determined to examine if
the GWG-outcome associations varied by obesity class. Results:
Included were 6071, 2974, and 1973 pregnancies to women with
class I, II, and III obesity, respectively. Most women gained more
than the recommendations (70.7%, 58.4%, 45.4% for class I, II, and
III obesity, respectively). The association between GWG and having
an LGA infant was modified by obesity class (P-interaction= 0.04):
the association with high GWG diminished with increasing obesity
class (OR 1.8, CI 1.5–2.2; OR 1.6, CI 1.3–2.0; and OR 1.1, CI 0.8–2.0
for class I, II, and III, respectively) but the association with low
GWG was similar across the obesity classes (OR 0.7, CI 0.5–0.9; OR
0.6, CI 0.4–0.8; and OR 0.6, CI 0.5–0.8 for class I, II, and III,
respectively). No effect modification by obesity class was observed
for the associations between GWG and SGA, preterm birth, and
Caesarean delivery. Analyses conducted among all women with
obesity suggested that low GWG increased the odds of preterm
birth (OR 1.4, CI 1.1–1.9) whereas high GWG reduced the odds of
SGA (OR 0.6, CI 0.5–0.7) and increased the odds of Caesarean
delivery (OR 1.3, CI 1.1–1.4). Conclusion: The data suggested that
class of obesity modified the association between GWG and LGA
but the nature of this effect modification would not support
recommending lower GWG for women of higher classes of obesity.
Acknowledgements: Ms. Whelan was supported by a Dalhousie
Faculty of Medicine Summer Research Studentship. Contact
Information: [email protected]
[427]
SALMONELLA ENTERICA TYPHIMURIUM INFECTION AND
DISRUPTION OF PREGNANCY. Shuhiba Mohammad1, Barbara
Anne Croy1, Kristina Wachholz2, Lakshmi Krishnan2, Shawn P.
Murphy3
1Department of Biomedical and Molecular Sciences, Queens
University, 2National Research Council of Canada, University of
Ottawa , 3Department of Microbiology and Immunology,
University of Rochester Medical Center
Introduction: Salmonella species are Gram-negative, facultative,
intracellular bacteria of emerging global health concern.
Pregnancy confers increased susceptibility to infection that can
cause adverse pregnancy complications and severe neonatal and
maternal illness. Mouse models have shown that Salmonella
enterica serovar Typhimurium (ST) infection during pregnancy
causes significant placental destruction and maternal lethality.
Mouse strains resistant to S.enterica express a functional NRAMP1
(natural resistance-associated macrophage protein 1) gene, while
infection in susceptible strains such as C57BL6/J do not.
Objective: The purpose of this study is to examine the effects of
background strain and antibacterial pathways on ST infectability of
pregnant females and on fetal survival. Methods: Control
C57BL6/J (B6) and congenic mice expressing Nramp, a bacterial
resistance gene (B6.NRAMP+/+) were infected with 1 X 103 ST by
tail vein injection on gestational day (gd) 12. After 48 h, mice were
euthanized and implantation sites were harvested, fixed, paraffinembedded, sectioned, and stained for histological analysis using
H&E staining. Percent resorption was calculated to determine fetal
loss. ST presence was determined by immunohistochemical
staining using an anti-Salmonella antibody (Abcam, Cambridge,
MA, ab156656). Matched gd 14 naïve pregnancies were used as
controls. Results: Percent resorptions were higher in infected B6
and B6.NRAMP+/+ compared to controls (16-fold and 3-fold
increase respectively, however not statistically significant).
Implantation sites from infected mice of both strains showed overt
inflammation and destruction of the placental labyrinth, with a
massive immune infiltration. ST was detected in histological
sections usually contained within maternal blood vessels,
surrounded by immune cells. Conclusion: Preliminary findings at
gd 14 of mouse 19 day gestation, confirm profound placental
destruction and fetal loss 48 hours after ST infection in susceptible
and resistant strains of C57BL6/J mice during mid-pregnancy.
Although percent resorptions were lower in mice with a functional
NRAMP gene, ST infection and loss of placental integrity was still
observed, indicating that fetal loss was imminent but the process
of pathogenesis was slower. Further investigation is required to
deduce the pathogenesis of Salmonella species during pregnancy.
Acknowledgements: We acknowledge the National Institutes of
Health (NIH) for funding support. Contact Information: Shuhiba
Mohammad [email protected]
CNPRM 2015
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[434]
METHODS OF CERVICAL RIPENING PRIOR TO INDUCTION OF
LABOUR AT TERM: A SURVEY OF CANADIAN PRACTITIONERS.
Anne Berndl1, Kellie Murphy2, Anthony Armson3, Sarah McDonald4
1University of Toronto, Department of Obstetrics and
Gynaecology, Division of Maternal Fetal Medicine, 2University of
Toronto, Department of Obstetrics and Gynaecology, Division of
Maternal Fetal Medicine, Departments of Clinical Epidemiology
and Health Policy Management and Evaluation, 3Dalhousie
University, Department of Obstetrics and Gynaecology, Division of
Maternal Fetal Medicine, 4McMaster University, Department of
Obstetrics and Gynaecology, Division of Maternal Fetal Medicine,
Departments of Clinical Epidemiology and Biostatistics, and
Diagnostic Imaging
Introduction: Induction of labour is a common obstetrical
intervention. A meta-analysis found high volume (compared to
low volume) Foleys used for cervical ripening were associated with
greater cervical favorability and less time to delivery, and a slight
trend towards decreased risk of cesarean section. Objective:
Prior to a clinical trial to assess if high volume Foleys are
associated with decreased cesarean section risk, it is necessary to
assess current practice patterns, interest level, and possible
barriers to evaluate feasibility and inform protocol development.
Methods: A survey was distributed electronically to Canadian
obstetricians in all 10 provinces to evaluate interest in trial
participation, current cervical ripening practices, and barriers to
trial success. Results: A total of 136 surveys were returned from
eight provinces. Interest in an RCT was high, with 76% of
respondents expressing interest. Prostaglandins are used most
often for cervical ripening by 83% of respondents and Foleys are
used most often by 15% of respondents. Modifiable barriers to
trial success were identified, including presumed patient
preferences (37%) and lack of resident familiarity with Foley
insertion (25%). Conclusion: There is interest in participating in a
trial comparing high and low volume Foleys for cervical ripening.
However, current practice in Canada is heavily weighted towards
use of prostaglandins. Therefore, this survey reveals that a trial
comparing prostaglandins to high volume Foley catheters with
cesarean section as an outcome is more relevant to Canadian
obstetrical practice. The barrier assessment has resulted in the
early designs of a cervical ripening training model. Contact
Information: [email protected]
[443]
DELIVERY OUTCOMES IN WOMEN WITH EPILEPSY IN BRITISH
COLUMBIA. Kristi McIntosh, MPH1
1University of British Columbia/School of Populaiton and Public
Health
Introduction: Increased rates of cesarean section and induction
have been previously documented in women with epilepsy
compared to women without epilepsy. However, little explanation
for these differences have been given. Objective: In our study,
we review the indications for various delivery outcomes in women
with and without epilepsy. Methods: 643 pregnant women
identified as having epilepsy at labour admission by ICD were
compared to an equal number of pregnant women identified as
not having epilepsy at labour admission who gave birth in a British
Columbia hospital between since from 1/1/2000 – 31/12/2010
using the British Columbia Perinatal Database Registry. Results:
The only significant differences in maternal characteristics
between women with epilepsy and without were parity
(nulliparous; 58.9% vs. 51.6%) and smoking status (current; 16.9%
vs. 10.1%). Significant pregnancy complications in women with
epilepsy compared to women without epilepsy included
hypertensive disorders (6.2% vs. 2.8%), proteinuria (4.4% vs.
0.7%), intrauterine growth retardation (5.3% vs. 2.6%), and
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premature delivery (15.6% vs. 7.5%). Women with epilepsy were
significantly more likely to require a cesarean delivery compared
to women without epilepsy (30.8% vs. 19.3%; OR, 1.87; 95% CI,
1.41–2.47) with the top indication being “Other” (31.6%).
However, when select maternal characteristics and pregnancy
complications were reviewed, no significant differences were
found between the two groups. Induction of labour was more
likely to occur in women with epilepsy compared to women
without epilepsy (31.3% vs. 21.8%; OR, 1.63; 95% CI, 1.19–2.24)
with the most common indication listed as “Maternal condition”
(36% vs. 19.8%). Compared to women without epilepsy, women
with epilepsy were more likely to receive epidural anesthesia
when delivering vaginally (36.9% vs. 23.6%; OR, 1.89; 95% CI,
1.41–2.47), more likely to have assisted vaginal delivery (21.5% vs.
11.1%; OR, 1.83; 95% CI, 1.23–2.74) and more likely to receive
general anesthetic during cesarean delivery (12.5% vs. 3.8%; OR,
3.61; 95% CI, 1.20–10.82) before adjustment using variables
reflecting more urgent situations. Conclusion: Epilepsy is not an
indication for induction or for cesarean delivery. A review of the
literature suggests that less than 2% of women with epilepsy
experience a seizure during labour. The increased rate of epidural
anesthesia in women with epilepsy may be unecessary. The
increased rate of general anesthesia in women with epilepsy
undergoing a cesarean delivery is of concern and deserves further
study. Acknowledgements: Drs. Patricia Janssen, Tim Oberlander,
Jan Friedman, Autumn Klein. Contact Information:
[email protected]
[456]
GESTATIONAL DIABETES AND THE FOLATE-METHIONINE CYCLE.
Eran Barzilay1, Ashley Moon2, Lesley Plumptre2, Shannon Masih2,
Carly Visentin2, Anna Ly2, Kyoung-Jin Sohn2, Andrea Lausman1,
Ruth Croxford3, Deborah L. O’Connor4, Young-In Kim2, Howard
Berger1
1Department of Obstetrics & Gynecology, St. Michael’s Hospital &
University of Toronto, Toronto, ON, Canada, 2Keenan Research
Center for Biomedical Science of St. Michael’s Hospital, Toronto,
ON, Canada, 3Institute for Clinical Evaluative Sciences, Toronto,
ON, Canada, 4Department of Nutritional Sciences, University of
Toronto. Physiology & Experimental Medicine Program, Hospital
for Sick Children, Toronto, ON, Canada
Introduction: Modifications in the Folate-Methionine cycle have
been suggested to be associated with gestational diabetes mellitus
(GDM). Studies have shown that Folic acid uptake by
CNPRM 2015
syncytiotrophoblast is affected by gestational diabetes and that
GDM is associated with low plasma vitamin B12. Objective: To
examine the association between gestational diabetes and
components of the Folate-Methionine cycle. Methods: The study
was nested in a study examining the effects of prenatal Folic acid
exposure on DNA Methylation in the newborn. Pregnant women
were recruited from St. Michael’s Hospital at 11-16 weeks
gestation. Maternal baseline clinical, obstetric, demographic and
dietary information were collected from study participants.
Women were allocated to the GDM group or the control group
following a glucose challenge test and a subsequent oral glucose
tolerance test, if needed. Maternal blood was collected at study
recruitment (11- 16 weeks of gestation). At the time of delivery,
both maternal blood and cord blood were collected. Levels of
plasma and RBC folate, B12, homocysteine, serum B6 and
unmetabolized folic acid were compared between the two groups.
Results: 366 women were included in the study, of them 17 (4.6%)
were diagnosed with gestational diabetes. There was no
significant difference in median BMI between the GDM group and
the control group (23.3 vs. 25.5, respectively, p=0.129). The
plasma level of B6 In the umbilical cord was higher in the GDM
group (422 vs. 301 nmol/L, p=0.018), umbilical cord betaine levels
were lower in the GDM group (17.1 vs. 21 nmol/L, p=0.024) and
umbilical cord trimethylamine oxide levels were higher in the GDM
group (2.7 vs. 1.4 nmol/L, p=0.036). However, these differences
lost statistical significance after correction for multiple
comparisons. All other comparisons did not show a difference
between GDM and control groups. Conclusion: In this study we
did not find a statistically significant difference in components of
the Folate-Methionine cycle between women with and without
GDM. Contact Information: [email protected]
[461]
THE TWIN BIRTH STUDY: INCIDENCE OF CESAREAN DELIVERY IN
THE INDUCTION OF TWIN PREGNANCIES. Elad MEI-DAN1,
Elizabeth V. ASZTALOS1, Andrew R. WILLAN2, Jon F.R. BARRETT1
1Women and Babies Program, Sunnybrook Health Sciences Centre,
Sunnybrook Research Institute, Toronto, ON, Canada., 2Child
Health Evaluative Sciences, SickKids Research Institute, University
of Toronto, Toronto, ON, Canada.
Introduction: The Twin Birth Study demonstrated that in a
planned vaginal birth between 32 and 38 weeks gestation, where
the first twin was a cephalic presentation, there was no difference
in neonatal outcomes from a planned cesarean section. The Twin
Birth Study protocol necessitated induction of labor for women in
the planned vaginal delivery group between 37+5 and 38+6 weeks
of gestation. Published data regarding optimal method for
induction of twins is limited. Objective: The objectives of this
secondary analysis was first to assess baseline factors that might
predict the choice of induction agent used (prostaglandin versus
no prostaglandin). Secondly we wished to analyze the probability
of an unplanned cesarean section in women induced by
prostaglandin compared to no prostaglandin. Finally we wished to
analyze the effect of the method of induction on neonatal and
maternal mortality or serious morbidity. Methods: 368 women,
who were randomized to planned vaginal delivery in the initial
study and had labor induction, were included in our secondary
analysis. Of these women, 153 (41.5%) were induced by
prostaglandin (prostaglandin group) and 215 (58.5%) were
induced by amniotomy and/or oxytocin (no prostaglandin group).
Results: Of the baseline factors, only the country’s perinatal
mortality rate was significantly associated with method of
induction. For the countries with a perinatal mortality rate
<10/1000, 45.7% of the mothers were induced using
prostaglandin, compared to 32.5% for the countries with a higher
perinatal mortality rate (p= 0.017). In total, 149/368 (40.5%)
women underwent a cesarean delivery after induction; the
incidence in the two methods of induction was similar: 62/153
(40.5%) in the prostaglandin group and 87/215 (40.5%) in the no
prostaglandin group (p=0.99). Nulliparity, late maternal age, noncephalic presentation of twin B and high country’s perinatal
mortality rate were found to be independent predictors for the
induction to end with an unplanned cesarean section. There were
no significant differences between the two methods of induction
with respect to maternal or neonatal morbidity. Conclusion: The
method of induction in twins (prostaglandin or no prostaglandin)
had no effect on the incidence of cesarean delivery or an
abnormal neonatal or maternal outcome. Acknowledgements:
Steering Committee (Twin Birth Study): J. Barrett (Chair), E.
Asztalos, A. Willan, M. Hannah, E. Hutton, A. Allen, A. Armson, A.
Gafni, KS. Joseph, A. Ohlsson, S. Ross. Contact Information: Elad
Mei-Dan [email protected]
[462]
SERIAL CERVICAL LENGTH DETERMINATION IN TWIN
PREGNANCIES REVEALS FOUR DISTINCT PATTERNS WITH
PROGNOSTIC SIGNIFICANCE FOR PRETERM BIRTH. Nir Melamed1,
Alex Pittini1, Ori Nevo1, Noor Niyar N. Ladhani1, Howard Cohen1,
Dini Hui1, Anne Berndl1, Elizabeth V. Asztalos2, Jon Barrett1
1Division of Maternal Fetal Medicine, Sunnybrook Health Sciences
Centre, University of Toronto, 2Department of Neonatology,
Sunnybrook Health Sciences Centre, University of Toronto
Introduction: There is limited evidence regarding the role of serial
measurements of cervical length (CL) in twin pregnancies.
Furthermore, in most studies conducted to date the analysis was
limited to only two sequential measurements. Information on the
optimal interpretation and integration of multiple serial
measurements is lacking. Objective: To identify distinct patterns
of change in sonographic cervical length (CL) as a function of
gestational age in twin gestations and to determine their
prognostic value. Methods: This was a retrospective study of all
women with twin pregnancies followed in the Twins Clinic in a
tertiary referral medical centre between 2012-2014. All women
underwent routine measurement of CL at mid gestation (18-22
weeks) and every 2-4 weeks thereafter until 28-32 weeks of
gestation. Pregnancies complicated by any of the following
conditions were excluded: monoamniotic twins, birth weight
<500g, gestational age at delivery <24 weeks, stillbirth of one or
both fetuses, genetic or structural anomalies, less than 4
measurements of CL along gestation, cervical cerclage or uncertain
pregnancy dating. Longitudinal changes in CL along gestation were
analyzed and classified into distinct patterns. The association
between each of the patterns and their characteristics with the
risk of preterm birth (PTB) was analyzed. Results: 1) We
identified 441 women with twin pregnancies who underwent
serial measurements of CL (median (IQ range) of 6 (5-8)
measurements). 2) There were 4 distinct patterns of changes in CL
over time (Figure): Pattern I (Stable Cervix)-cervix remained long
until 32 weeks; Pattern II (Early Shortening)–persistent shortening
of CL starting at mid-gestation; Pattern III (Delayed Shortening)–
persistent shortening of CL starting at late 2nd trimester; Pattern
IV (Transient Shortening)–transient early shortening of CL until
reaching a new stable plateau. 3) The rate of PTB<34 weeks was
lowest for Pattern I (11.7%), followed by Pattern IV (14.4%) and
Pattern III (20.2%), and was highest for Pattern II (44.4%,p<0.001)
(Figure). 4) For Pattern II, the main factor affecting the risk of PTB
was the shortening rate (AUC 0.67), while for Pattern III it was the
week at which shortening began (AUC 0.74). The main factors that
affected the risk of PTB in cases of Pattern IV were the initial
shortening rate (AUC 0.63) and the new final plateau of CL (AUC
0.68) (Figure). Conclusion: The study of CL in twin gestations over
time may assist clinicians in assessing the risk of PTB. Whether
CNPRM 2015
121
these distinct patterns reflect a difference in the underlying
pathogenic mechanism for PTB or different degrees of cervical
insufficiency deserves further investigation. Contact Information:
[email protected]
[464]
WHAT IS THE LIKELIHOOD OF SPONTANEOUS CHANGE OF FETAL
PRESENTATION FOLLOWING 3RD TRIMESTER ULTRASOUND IN
TWIN PREGNANCIES? Nir Melamed1, Hadar Rosen1, Ori Nevo1,
Noor Niyar Ladhani2, Howard Cohen1, Dini Hui1, Anne Berndl1,
Elizabeth Asztalos3, Jon Barrett1
1Division of Maternal Fetal Medicine, Sunnybrook Health Sciences
Centre, University of Toronto, 2Division of Maternal Fetal
Medicine, Sunnybrook Health Sciences Centre, University of
TorontoDivision of Maternal Fetal Medicine, Sunnybrook Health
Sciences Centre, University of Toronto, 3Department of
Neonatology , Sunnybrook Health Sciences Centre, University of
Toronto
Introduction: Information on the likelihood of spontaneous
change in fetal presentation during the 3rd trimester in twin
pregnancies is major importance as it may influence the timing of
sonographic assessment of fetal presentation. Unfortunately,
available data are scarce and conflicting. Objective: To determine
the likelihood of spontaneous change of fetal presentation
following 3rd trimester ultrasound in twin pregnancies, and to
identify factors that affect the likelihood of spontaneous fetal
version. Methods: This was a secondary analysis of the data of
the “Twin Birth Study” in which women presenting with twin
pregnancies after 32 weeks of gestation with the first twin in
vertex presentation were randomized to planned cesarean section
or planned vaginal delivery. In the current study we analyzed the
likelihood of a spontaneous change in twins presentation between
sonographic assessment at the time of presentation and delivery.
Multivariable regression analysis was used to identify factors
associated with spontaneous fetal version. Results: 1) A total of
2612 women with twin pregnancies were included in the analysis.
2) The mean gestational age at the time of presentation was
34.5±1.9 weeks and the mean presentation to delivery interval
was 15.6±12.8 days. 3) The overall likelihood of change in the
presentation for twin A was 3.1% and was related to the time to
delivery interval (2.3% (interval <1 week) vs. 6.7% (interval 5
weeks), p<0.001). 4) The overall likelihood of change in the
presentation for twin B was 24.8% and was related also to the
time to delivery interval (18.4% (interval <1 week) vs. 37.6%
(interval >5 weeks), p<0.001). 5) Vertex presentation twin B and a
higher estimated weight of twin B were associated with the lowest
likelihood of change in presentation for twin A (1.7% and 1.9%,
respectively) and twin B (18.0% and 20.5%, respectively). 6)
Nulliparity was associated with a lower risk of change in
presentation for twin B (21.5% vs. 27.0%, p=0.002) but not for
twin A (3.0% vs. 3.2%, p=0.7). Conclusion: The likelihood of
change in presentation after 32 weeks is relatively low when twin
A is in the vertex presentation, even though this small risk persists
even after 36 weeks. The risk is much higher for twin B. This
information as well as the factors affecting the likelihood of
change in presentation can be used to determine the need for
repeat sonographic assessment during the 3rd trimester,
especially in settings in which the presentation of twin B affects
the decision regarding mode of delivery due to limited experience
in maneuvers such as fetal breech extraction. Contact
122
Information: [email protected]
[476 –477]
EXPRESSION AND LOCALIZATION OF PERIOSTIN IN PREGNANT
MYOMETRIUM. Oksana Shynlova1, Anna Dorogin 2, Xuesen Dong3,
Stephen Lye4
1University of Toronto, Department of Ob/Gyn, 2Mount Sinai
Hospital, 3Vancouver Prostate Centre, University of British
Columbia, 4University of Toronto, Department of Ob/Gyn &
Physiology
Introduction: The molecular mechanisms regulating preparation
of the uterus for labor are not fully understood. We have
previously reported that mechanical stretch of the uterine wall by
the growing fetus plays a direct role in the regulation of major
components of the extracellular matrix in late pregnant rat
myometrium. As was shown by others, periostin (POSTN), an
extracellular matrix protein involved in the process of fibrosis and
myofibroblast differentiation, is expressed in tissues subjected to
mechanical stress. However, the expression of POSTN in human or
animal myometrium during gestation and its response to uterine
stretch has not yet been investigated. Objective: Using (1)
primary human myometrial cells (HMCs) derived from the lower
uterine segment (LUS) and fundus, (2) human myometrium
collected before and during labour from LUS and (3) a unilaterally
tubal-ligated rat model, we examined gestational variations and
the effect of mechanical stretch on POSTN expression. Methods:
Gene expression was examined by Real-time PCR, protein
expression and localization - by Western immunoblotting and
immunohistochemical (IHC) staining, static mechanical stretch was
applied by Flexcell 5 unit. Results: : Using HMCs, we found that
under control conditions POSTN mRNA and protein levels in cells
derived from lower uterine segment were higher as compared to
cells derived from uterine fundus of the same term non-laboring
patient. When cells from LUS were subjected to static mechanical
stretch (Flexcell 5, 25% elongation for 24 hours), POSTN transcript
levels were significantly up-regulated but only in HMCs also
expressing high levels of desmin, a marker of muscle cell terminal
differentiation. Cells derived from the fundal uterine region did
not react to mechanical stretch. We found that myometrial
expression of the POSTN gene was significantly up-regulated in rat
myometrium at late gestation (gestational day(GD)17-21) and
during term labour (GD23) as compared to early gestation.
Importantly, most changes in POSTN gene expression occurred
specifically in the gravid horn but not in the empty horn of
unilaterally pregnant animals, indicating the effect of gravidity.
Immunostaining for POSTN was highly elevated in both muscle
layers of late pregnant rat myometrium compared to early
gestation and was more pronounced in the gravid horn.
Conclusion: We identified the differential expression of POSTN by
human myometrial cells in the uterine fundus vs lower segment
and established spatiotemporal expression patterns of POSTN in
the pregnant rat myometrium, but its function during gestation is
largely unknown. Additional studies are in progress to examine the
role of POSTN in myometrial differentiation. Acknowledgements:
CIHR (MOP-37775). Contact Information: Oksana Shynlova
[email protected]
CNPRM 2015
[488]
MATERNAL AND INFANT MORBIDITY ASSOCIATED WITH UTERINE
RUPTURE. Yasser Sabr1, Sarka Lisonkova2, Ayesha Al-Nashwan3,
Giulia Muraca4, Carmen Young5, KS Joseph6
1Department of Obstetrics and Gynaecology, King Saud University,
Riyadh, Saudi Arabia/University of British Columbia, Vancouver,
Canada., 2Department of Obstetrics and Gynaecology/University
of British Columbia, Vancouver, Canada., 3Department of
Obstetrics and Gynaecology/ King Saud University, Riyadh, Saudi
Arabia., 4School of Population and Public Health, University of
British Columbia, Vancouver, Canada., 5Department of Obstetrics
and Gynaecology, University of Alberta, Edmonton, Canada.,
6Department of Obstetrics and Gynaecology, School of Population
and Public Health, University of British Columbia, Vancouver,
Canada.
Introduction: Uterine rupture is one of the most feared obstetric
complications, carrying an increased risk of maternal and perinatal
morbidity and mortality. Objective: To determine the incidence,
risk factors, and maternal and perinatal morbidity associated with
uterine rupture. Methods: We carried out a retrospective,
population-based cohort study of all singleton deliveries in the
United States between 2009 and 2012 with information from the
natality files of the National Center for Health Statistics. Risk
factors and morbidity associated with uterine rupture and severe
uterine rupture (i.e., with blood transfusion) were quantified.
Logistic regression was used to obtain adjusted odds ratios (AOR)
and 95% confidence intervals (CI) after adjustment for relevant
factors. Results: The study included 11,905,571 deliveries; there
were 3,184 cases of uterine rupture (26.7 per 100,000 deliveries),
of which 471 required transfusion (3.96 per 100,000). Risk factors
moderately associated with uterine rupture (AOR <2.0) included
non-white race, smoking, grand multi-parity, diabetes, labor
induction/augmentation, and repeat caesarean without a trial of
labour; protective factors included nulliparity, obesity, and
hypertension. Factors strongly associated with uterine rupture
included previous cesarean (AOR 4.20, 95% CI 3.29-5.36), forceps
(AOR 3.54 95% CI (2.31-5.42), vacuum (AOR 2.17, 95% CI 1.662.83), primary caesarean (AOR 6.46, 95% CI 5.81-7.17), and repeat
cesarean after trial of labour (AOR 14.0, 95% CI 10.9-18.1). The
strongest risk factors for uterine rupture with transfusion were
primary caesarean (AOR 11.8, 95% CI 8.82-15.9), previous
caesarean (AOR 8.43, 95% CI 5.26-13.5), vacuum (AOR 7.40, 95%
CI 4.62-11.8) and repeat caesarean after trial of labor (AOR 5.37,
95% CI 3.13-9.24). Uterine rupture was associated with high rates
of maternal and perinatal morbidity including hysterectomy, ICU
admission, low 5-minute Apgar scores, neonatal seizures and
assisted ventilation (Table 1). Conclusion: Uterine rupture
remains a rare but serious obstetric complication. There are
distinct differences between risk factors for uterine rupture and
severe uterine rupture. Acknowledgements: Drs. Sabr and
Lisonkova are supported by a Canadian Institutes of Health
Research Team grant in severe maternal morbidity (MAH-115445).
Dr. Sabr is also supported by a new faculty award from the King
Saud University, Saudi Arabia. Dr. Joseph holds a Canadian
Institutes of Health Research Chair in maternal, fetal and infant
health services research and his work is also supported by the
Child and Family Research Institute. Contact Information: Yasser
Sabr [email protected]
[490]
PRETERM PREMATURE RUPTURE OF MEMBRANES IN TWIN
PREGNANCY: COMPARISON BETWEEN PPROM IN PRESENTING
VERSUS NON-PRESENTING TWIN
Elad Mei-Dan1, Mark Osmond1, Susan Pakenham2, Eugene Ng3, Jon
Barrett2, Ori Nevo2
1Department of Obstetrics and Gynaecology, Mount Sinai Hospital,
Toronto, Ontario, Canada 2Department of Obstetrics &
Gynaecology, University of Toronto, Sunnybrook Health Sciences
Centre, 3Department of Newborn and Developmental Paediatrics,
Sunnybrook Health Sciences Centre. Objective: To compare the
latency from membrane rupture to delivery and neonatal outcome
in twin gestations complicated by prolonged preterm premature
rupture of membranes (PPROM) of Twin A (presenting sac) versus
Twin B (non-presenting sac)….Methods: We identified 76 women
with twin pregnancies who were diagnosed as having PPROM and
a latency period to delivery greater than 24 hours between 2004
and 2010. Demographic characteristics and risk factors for
preterm labour and PPROM were evaluated for all women. We
compared the length of time from rupture of membranes to
delivery and subsequent neonatal morbidity and mortality
resulting from PPROM of twin A versus PPROM of twin B. Neonatal
adverse outcomes include: sepsis, necrotizing enterocolitis (NEC),
patent ductus arteriosis (PDA), retinopathy of prematurity (ROP),
intraventricular hemorrhage (IVH), persistent newborn pulmonary
hypertension (PPHN) and death. …Results:The median latency
periods from PPROM to delivery were 10.7 days (N = 66) when the
sac of twin A ruptured and 41.3 days (N=10) when twin B’s sac
ruptured (p < 0.05). Twins were more likely to be complicated by
ROP (57% vs. 19%, p<0.05) but less likely to have PPHN (0% vs
25%, p<0.05) when the twin A sac ruptured in comparison to the
twin B sac, respectively. Neonatal Death was significantly higher
with PPROM of twin A when compared with PPROM of twin B
(21.4% VS 0%, p=0.05, respectively). These differences persisted
after adjusting for other factors, such as gestation, birth weights
and maternal characteristics. The rates of other neonatal adverse
outcomes were similar between the two
groups….Conclusions:This is the first study to our knowledge
comparing clinical outcomes of PPROM in the presenting (A) to
that in the non-presenting twin (B). The etiology and mechanism
for PPROM in the two sacs may be different. Patients with PPROM
of the non-presenting twin might be reassured by the longer
anticipated latency to delivery and decreased incidence of
neonatal complications. Contact information: [email protected]
CNPRM 2015
123
Chronic Lung Disease of Prematurity
[424]
ANTI-FIBROTIC PROPERTIES OF SILDENAFIL IN NEWBORN RAT
PULMONARY ARTERY SMOOTH MUSCLE CELLS CULTURED IN
FLUCTUATED OXYGEN CONDITION . Karen Belen, M.D.1
1University of Manitoba
Introduction: Sildenafil, an inhibitor of phosphodiesterase type 5,
has been used orally for long-term management of preterm
infants who suffered bronchopulmonary dysplasia associated
pulmonary hypertension (BPD-PH). Negative results in older
children for sildenafil clinical trials led banning the use of Sildenafil
in all children by US FDA.We previously found that newborn pups
exposed to 60% O2 for 14 days challenged with intermittent
hypoxia 1 hr per day for 14 days developed BPD-PH compared to
60% O2 exposure alone (BPD). Sildenafil had no acute dilatation
effects on constricted pulmonary arteries on precision cut lung
slices of D14 pups stimulated by U46619, a thromboxane
antagonist. Objective: Our objective is to test the beneficial role
of Sildenafil in newborn pulmonary vascular remodelling process,
via regulating extracellular matrix assembly machinery in the
cultured pulmonary artery smooth muscle cells (PASMCs).
Methods: 2nd to 3rd generation PASMCs from 7-day old rats were
serum starved to synchronize in contractile phenotype then
exposed in four conditions: 1. air (21% O2:A); 2. hyperoxia (60%
O2: H); 3. 1-hour hypoxia (10% O2:L) + 23-hour air; 4. 1-hour
hypoxia + 23-hour hyperoxia (H+L) for 72 hours. Half of each
condition was suspended with Sildenafil. Cell survival was
measured by MTT and Calcein assay. Label free images of elastin
and collagen were localized in PASMCs using multimodal nonlinear
optical (NLO) microscope. Western blot and real time qPCR were
performed to identify the extracellular matrix proteins and RNA
expressions of tropoelastin, elastin, collagen I, II, III, IV and lysyl
oxidase 1, 2, 3, 4. Results: Different O2 tensions had no effects on
PASMC viability. Sildenafil markedly ameliorated elastin
production via inhibition of lysyl oxidase expression in H+L
exposed PASMCs, which was further confirmed by NLO
microscope. Conclusion: Production of Elastin and tropoelastin,
but not collagens, was exacerbated by intermittent hypoxia
challenges on chronic hyperoxia exposed newborn pup PASMCs.
Sildenafil inhibited excessive ECM deposition of elastin in PASMCs
by down-regulating lysyl oxidase expression. We speculate that
fluctuated O2 tension stimulates PASMCs secrete ECM constituent
proteins that contributes to pulmonary artery medial wall
thickness and stiffness. Sildenafil reverses the remodelling process
via regulating ECM reconstruction. Acknowledgements: Special
thanks to MICH and Biology of Breathing Laboratory. Contact
Information: Karen Belen [email protected]
[490]
INDUCED PLURIPOTENT STEM CELLS (IPSCS) PREVENT
HYPEROXIA-INDUCED LUNG INJURY. Mehdi Shafa1, Lavinia
Ionescu2, Arul Vadivel1, Jennifer Collins1, Lakshmi Puttagunta2,
Bernard Thébaud1
1Ottawa Hospital Research Institute (OHRI), Sprott Centre for Stem
Cell Research, Ottawa, Ontario , 2Women and Children’s Health
Research Institute, University of Alberta, Edmonton, Alberta
Introduction: Bronchopulmonary dysplasia (BPD), a chronic lung
disease characterized by arrested lung growth and impaired
angiogenesis, is the most common complication in extreme
premature infants that follows mechanical ventilation and oxygen
therapy. There is no treatment for BPD. Alveolar epithelial type 2
cells (AEC2) are putative distal progenitor cells. AEC2s are
impaired in BPD. Objective: We hypothesized that iPSCs prevent
lung injury in experimental BPD model. Methods: Newborn mice
were exposed to room air or 85% oxygen (BPD model) for 10 days.
124
Airway delivery of iPSCs was performed at day 4 (prevention) or
day 14 (repair). Lung structure and function were assessed two
weeks after treatment. Results: Both, undifferentiated miPSCs
and episomal hiPSCs prevented, but did not rescue hyperoxiainduced arrested alveolar growth as assessed by lung function
testing and lung morphometry. At long term follow-up (18
months), 3/5 miPSCs recipients developed malignant tumours
while at 7.5 months post hiPSC injection, only 1/5 mice developed
a lung teratoma. We then established a highly efficient method to
differentiate hiPSCs into a homogenous population of AEC2 using
5% hypoxic condition, signaling pathways agonists and Fibronectin
matrix. hiPSCs acquired an AEC2 phenotype and were positive for
NKX2.1, SPB, SPC. NKX2.1+ cells (day 12) were treated with
PluriSIn#I to eliminate undifferentiated iPSCs. Fully differentiated
cells (day 25) were also purified through FACS using Lysotrackergreen. Airway delivery of differentiated and purified hiPSCs
improved lung function. Conclusion: Undifferentiated iPSCs
prevent oxygen-induced lung injury, but form tumors. hiPSCs can
be differentiated into AEC2 and improve lung function in this
model. Long term follow up will determine if differentiated lung
iPSCs is safe and efficient. Acknowledgements: MS is supported
by CTS and TPRM. BT is supported by SCN, CIHR, CFI and CTS.
Contact Information: [email protected]
Neonatal Nutrition
[258]
MATERNAL OMEGA-3 SUPPLEMENTATION REDUCES APNEA
DURATION INDUCED BY LARYNGEAL CHEMOREFLEX
STIMULATION IN RAT PUPS. Cécile Baldy1, Océane Mercier1,
Luana Tenorio Lopes1, Tommy Seaborn1, Richard Kinkead1, Isabelle
Marc1
1Medicine faculty/Laval University/Department of Pediatrics
Introduction: The laryngeal chemoreflex (LCR) is a series of
responses activated when fluids or solids come into contact with
the laryngeal mucosa to prevent their aspiration into the airways.
In preterm infants LCR triggers apneas, bradycardias, and O2
desaturations that can be life threatening. Objective: Because
fatty acids omega-3 (-3) benefit brain development, we tested
the hypothesis that -3 reduces the deleterious cardio-respiratory
consequences resulting from LCR stimulation in rat pups.
Methods: Experiments were performed on pups (10-11 days old).
Pups were raised by mothers that were either fed a normal diet
(control; 0,3g/kg of -3) or received a Fish oil enriched diet
(13g/kg of -3) from birth to day 10-11. Pups were anesthetized
(chloralose 20mg/kg + urethane 1mg/kg). A tracheotomy was
performed below the larynx to place a water filled catheter near
the larynx. Breathing was monitored with an EMG electrode on
the intercostals muscle. O2 saturation and heart rate were
monitored with pulse oxymetry. Following baseline measurements
of cardio-respiratory variables, each pup received 10 µL injection
of water near the larynx. This procedure was repeated 3 times
with a 5 min recovery period between injections. Results: By
comparison with controls, maternal -3 supplementation
significantly raised -3 levels in the blood and brainstem of the
pups and reduced apnea duration elicited by LCR stimulation by
32%. Conclusion: These data suggest that -3 supplementation
accelerates development of the brainstem circuits that regulate
breathing. Subsequent work will evaluate the effect on respiratory
variables in intact pups. These results suggest that maternal -3
supplementation may alleviate cardio-respiratory complications
associated with neurological immaturity. Acknowledgements:
This research was supported by CIHR RK and IM. Contact
Information: [email protected]
CNPRM 2015
[261]
PARENTERAL FISH-OIL LIPID EMULSIONS IN THE PREVENTION OF
SEVERE RETINOPATHY OF PREMATURITY: A SYSTEMATIC REVIEW
AND META-ANALYSIS. Sakeer Vayalthrikkovil1, Rani A Bashir1,
Yacov Rabi2, Harish Amin3, Abhay Lodha4
1Section of Neonatology, Department of Pediatrics, University of
Calgary, Calgary AB, 2Section of Neonatology, Department of
Pediatrics, University of Calgary; Alberta Children's Hospital
Research Institute, Calgary, Canada, 3Section of Neonatology,
Department of Pediatrics, University of Calgary;Calgary, Canada,
4Section of Neonatology, Department of Pediatrics, University of
Calgary; Alberta Children's Hospital Research Institute;
Department of Community Health Sciences, University of Calgary,
Calgary, Canada
Introduction: Docosahexaenoic acid (DHA) is an omega-3
polyunsaturated fatty acid that is anti-inflammatory and
contributes to both retinal and brain development. Preterm
infants are deficient in DHA as fetal accretion occurs in the last
trimester of pregnancy. The role of parenteral fish oil lipid
emulsions in the prevention of severe retinopathy of prematurity
(ROP) is unclear. Objective: To evaluate whether early
administration of parenteral fish oil lipid emulsion (FLE) prevents
severe ROP in preterm infants Methods: We conducted a
systematic search of MEDLINE, EMBASE, PUBMED, SCOPUS and
Cochrane Library until October 2014. Studies that compared
parenteral FLE to soy-based lipid emulsions (SLE) in infants <33
weeks gestational age (GA) were included. Both lipid emulsions
were started within 24 hours after birth. Primary outcome was
severe ROP (stage III or laser therapy). Secondary outcomes were
cholestasis, sepsis, necrotizing enterocolitis (NEC), intraventricular
hemorrhage (IVH), bronchopulmonary dysplasia (BPD) and
mortality. We determined risk ratios (RR) with 95% confidence
intervals (CI) and test for overall effect. Results: Four studies
were included in the final analysis, involving 292 and 339 infants in
the FLE and SLE groups, respectively. The FLE group had a lower
risk of severe ROP than the SLE group (RR 0.44; 95% CI 0.28, 0.70,
NNT 11) (figure1). The RR of developing either ROP stage II (RR
0.92; 95% CI 0.46, 1.8), sepsis (RR 1.17; 95% CI 0.96, 1.43), IVH
grade III (RR 1.28; 95% CI 0.75, 2.18), all IVH (RR 0.93; 95% CI
0.68, 1.27) and mortality (RR 0.86; 95% CI 0.65, 1.13). Conclusion:
Early parenteral fish oil lipid emulsion supplementation appears to
be effective in preventing severe ROP stage III and laser
treatment in preterm infants. Acknowledgements: We
acknowledge Dr. Majeeda Kamaluddeen. Contact Information:
Rani Bashir [email protected]
[324]
CYCLED ENTERAL ANTIBIOTICS (CEA) IN SUSPECTED SMALL
BOWEL BACTERIAL OVERGROWTH SYNDROME (SBBO) - A
REVIEW OF OUR PRACTICE. Allison Callejas1, Claudia Olivera1,
Amitava Sur1, Julia Panczuk1
1UBC/Department of Pediatrics/Neonatal Perinatal Medicine
Introduction: In Canada the overall incidence of Short Bowel
Syndrome is 24.5/100000 live births. SBBO complicates 60% of
these, leading to colonization of the small intestine by pathological
flora. In our NICU, a large tertiary center in Vancouver dealing with
complex abdominal surgeries and post-operative rehabilitation,
SBBO is often treated with cycled enteral Gentamicin for 1 week,
Metronidazole for 1 week, followed by 1 week off. Treatment may
be based on features like high conjugated bilirubin (CB), loose
stool/stoma outputs leading to dehydration and growth failure, or
abnormal Xrays. However markers of SBBO are largely non-specific
in pediatric literature, particularly among neonates, and there is a
lack of treatment guidelines. Objective: 1. To review our practice
of using cycling oral antibiotics to treat suspected SBBO 2. To
review clinical, laboratory or radiological parameters that led to
the use of cycling oral antibiotics, and analyze their trend pre/post
antibiotic administration. Methods: We retrospectively reviewed
medical charts of all infants between 2009-14 who received CEA.
We collected relevant laboratory data including serum chemistries
and CB at 3 time points: within 2 weeks prior to starting CEA, 1
week and 6 weeks post-initiation, and reviewed abdominal
radiographs within 1 week prior to CEA for the presence of dilated
bowel loops. We used descriptive statistics for depicting data such
as diagnosis, presence or absence of stoma, and used paired ttests to compare means. Results: A total of 36 patients received
CEA, among which the commonest pathology was NEC or NECrelated strictures (28%) and intestinal atresia (20%). Gentamicin
was the most commonly used first drug (83%). 50% of patients had
a stoma before starting CEA. Mean serum ph values pre- and postCEA were 7.38 (+/-0.07) and 7.4 (+/-0.07) and mean HCO3 was
27.12. Mean pre-antibiotic CB (44µmol/L) and Urea (5.3 mmol/L)
were both elevated. 63.9% had abdominal xrays prior to starting
antibiotics, and all of them had dilated bowel loops Paired sample
mean analysis of CB values at 1 week prior and 6 weeks post CEA
were significant (p= 0.001. The mean weight of patients 1 week
before and 4 weeks after were not significantly different.
Conclusion: We found an inconsistent diagnostic workup for SBBO,
and no single parameter was consistently identified prior to
treatment with CEA, though CB and Urea were significantly
elevated and dilated bowel loops were found for many. CB also
significantly decreased 6 weeks post initiation of CEA.
Development of a comprehensive assessment scale to guide
consistent practice is recommended to identify suitable candidates
for CEA. Acknowledgements: We acknowledge the pharmacy and
health records departments. Contact Information: Amitava Sur
[email protected]
[411]
CAN OSMOLALITY OF TARGET FORTIFIED BREAST MILK FOR
PRETERM INFANTS BE PREDICTED? Arum Choi1, Gerhard Fusch1,
Niels Rochow1, Christoph Fusch1
1Department of Pediatrics, McMaster University, Hamilton, ON
Introduction: Breast milk (BM) is the best source of nutrition for
preterm infants. Due to inter- and intra-individual macronutrient
variations in BM, target fortification of BM (TFO) might become a
desirable strategy to reduce macronutrient variations. However,
fortifying BM with standard milk fortifier and additional
CNPRM 2015
125
macronutrients might increase osmolality. High osmolality has
been implicated as potential risk factor of feeding intolerance and
NEC. Thus, it would be beneficial if osmolality of fortified BM could
be predicted prior to milk preparation. Objective: 1) To establish
and validate an osmolality prediction model within clinically
relevant ranges for each macronutrient 2) To test feasibility using
TFO samples for a post-validation in a clinical setting 3) To test
change in osmolality after 24h storage at 4°C. Methods: 1)
Prediction model: samples of pooled breast milk (n=10) was
gradually fortified with Polycose (P: 0.5-2.0g), Beneprotein (B: 0.22.0g), Microlipid (M: 0.5-4.0g), and Aptamil protein (A: 0.2-2.0g). A
best-fit equation was generated for each component. Validation:
fortified BM with each macronutrient (n=5) and combinations of
macronutrients (n=10) were tested in a set with separate samples.
2) Post-validation: TFO samples (n=700) were tested. 3) BM
samples with P were stored at 4°C for 24h. Results: 1) Prediction:
linear correlation (R2= 0.89, R2= 0.65, R2= 0.98 for P, B, A,
respectively). Validation: linear correlation between measured and
predicted osmolality values [(R2= 0.76, R2= 0.82, R2= 0.99 for each
P, B, A, respectively) and (R2= 0.93 for combinations of
macronutrients, Figure 1)] 2) Predicted and measured osmolality
values for TFO samples were in agreement with a precision of
±10mOsmol/kg. 3) 24h storage led to increase of average
20mOsmol/kg. Conclusion: These models can predict osmolality
of each macronutrient, combinations of macronutrients, and TFO
samples and are applicable for these products above. It may be
utilized as a simple quality assurance tool prior to feeding of
preterm infants. Acknowledgements: C. Fusch holds the
Hamilton Health Sciences Foundation – Jack Sinclair Chair in
Neonatology at McMaster University. Contact Information:
Christoph Fusch [email protected]
obstetric emergencies are lacking. Objective: We examined rates
of stillbirth due to cord prolapse and placental abruption, two
obstetric emergencies potentially responsive to medical
intervention, for Haitians and non-Haitians in the province of
Quebec, Canada. We assessed how rates compared with stillbirth
due to congenital anomaly, a cause less responsive to emergency
obstetric care. Methods: Data from singleton birth registration
certificates on 10,287 stillbirths and 2,482,364 live births were
extracted from 1981 through 2010 in Quebec, Canada. We
computed stillbirth rates due to cord prolapse, placental abruption
and congenital anomalies, and estimated hazard ratios (HR) and
risk differences (RD) for Haitians relative to non-Haitians, with 95%
confidence intervals (CI). To examine differences over the duration
of pregnancy, we calculated the cumulative stillbirth risk at each
week of gestation. Results: Stillbirth rates were higher for
Haitians than non-Haitians, particularly for cord prolapse (HR 1.87,
95% CI 1.10-3.18) and placental abruption (HR 2.84, 95% CI 1.954.15). The rate of stillbirth due to congenital anomalies was similar
for Haitians and non-Haitians. Overall, Haitians had an excess of
2.93 (95% CI 1.69-4.17) stillbirths per 1000 births compared to
non-Haitians, with placental abruption alone contributing one
excess stillbirth (RD 0.98 per 1000, 95% CI 0.38-1.57). Risks due to
cord prolapse and abruption were higher for Haitians at every
week of gestation in both the late second and third trimesters
(Figure 1). Conclusion: Stillbirth rates in Haitians are
disproportionately high in Quebec, particularly for fetal death due
to cord prolapse and placental abruption, causes potentially
responsive to emergency obstetric care. A better understanding of
risk factors for stillbirth due to placental abruption and cord
prolapse is needed for vulnerable minorities. Research is required
to determine whether optimizing emergency obstetric care can
reduce rates of stillbirth in Quebec, and possibly other Canadian
provinces. Acknowledgements: This project was funded by
Health Canada via the McGill Training and Retention of Health
Professionals Project. Contact Information:
[email protected]
Perinatal Epidemiology and Randomized Trials
[311]
OBSTETRIC EMERGENCIES AND RISK OF STILLBIRTH IN QUEBEC
Nathalie Auger MD MSc FRCPC1, André Costopoulos PhD2, Ashley I.
Naimi PhD3, Fulvia Bellingeri MSc MScPH1, William D. Fraser MD
MSc FRCSC4
1Institut national de santé publique du Québec, and University of
Montreal Hospital Research Centre, 2Department of Anthropology,
McGill University, 3Department of Obstetrics and Gynecology,
McGill University, 4Department of Obstetrics and Gynecology,
University of Sherbrooke
Introduction: Minorities in Canada have high rates of stillbirth, and
strategies to reduce inequalities are needed. Some stillbirths may
be prevented through emergency obstetric care, but studies
indicating that minorities have higher rates of stillbirth during
126
[320]
REGIONAL VARIATIONS IN THE PREVALENCE OF MAJOR
CONGENITAL MALFORMATIONS IN QUEBEC: THE IMPORTANCE
OF FETAL GROWTH ENVIRONMENT. Jinping Zhao1, Odile Sheehy2,
Anick Bérard1
1Faculty of Pharmacy, University of Montreal, Sainte-Justine
CNPRM 2015
University Hospital Research Center, Montreal, Quebec, Canada,
2Sainte-Justine University Hospital Research Center, Montreal,
Quebec, Canada
Introduction: Congenital anomalies are the consequence of a
complex interaction between genetic predisposition and fetal
environment. Based on the Congenital Anomalies Surveillance in
Canada between 1998 and 2007, the rate of congenital heart
defects in Quebec was significantly higher than the Canadian
average; no other data on the prevalence of congenital anomalies
for Quebec or data on regional variations in any province are
available. Objective: We aim to estimate the prevalence of major
congenital malformations in 17 administrative regions of Quebec.
Methods: Using data from Quebec Pregnancy Cohort, we included
infants if they were born between 01/01/1998 and 12/31/2008.
Major congenital malformations were identified within infant’s
first year of life using validated International Classification of
Diseases (ICD)-9 and ICD-10 codes. The rate of major congenital
malformations was calculated and stratified on Quebec’s
administrative regions. Results: Among 152,353 eligible infants,
the prevalence of major congenital malformations was 36.6 (per
1,000 live births). The regions with the highest rate of major
congenital malformations were Lanaudiere (48.1/1,000 live
births), Laval (45.8/1,000 live births), and Mauricie (45.1/1,000 live
births). Regions with the lowest rate were Outaouais (13.4/1,000
live births), Côte-Nord (19.1/1,000 live births), AbitibiTémiscamingue (27.5/1,000 live births), Gaspésie-îles-de-laMadeleine (27.9/1,000 live births), and Saguenay-Lac-Saint-Jean
(28.9/1,000 live births). Congenital heart defects (10.3/1,000 live
births) and musculoskeletal anomalies (12.6/1,000 live births)
were the most common. Laval had the highest rate of heart
defects (16.1/1,000 live births), and Lanaudière had the highest
rate of musculoskeletal anomalies (22.0/1,000 live births).
Conclusion: The central regions of Quebec had high rates of major
congenital malformations, whereas the genetically relatively
homogenous peripheral regions of Quebec had lower rates of
major congenital malformations, suggesting the importance of
fetal growth environment in the etiology of major congenital
malformations in Quebec. Acknowledgements: Dr. Anick Bérard is
the recipient of a career award from the Fonds de la recherche du
Québec – Santé (FRQ-S), and is on the endowment research Chair
of the Famille Louis-Boivin on ‘Medications, Pregnancy and
Lactation’ at the Faculty of Pharmacy of the University of
Montreal. This study was supported by the FRQ-S and the Réseau
québécois de recherche sur les médicaments (RQRM). Contact
Information: [email protected]
[354]
FACTORS ASSOCIATED WITH PRETERM BIRTH: A POPULATIONBASED STUDY IN MANITOBA. Maureen Heaman1, Dawn
Kingston2, Marni Brownell3, Michael Helewa4, Shelley Derksen5,
Kari-Lynne McGowan6
1College of Nursing, University of Manitoba, 2Faculty of Nursing,
University of Alberta, 3Manitoba Centre for Health Policy,
Department of Community Health Sciences, University of
Manitoba, 4Department of Obstetrics, Gynecology and
Reproductive Sciences, College of Medicine, University of
Manitoba, 5Manitoba Centre for Health Policy, University of
Manitoba, 6formerly Manitoba Centre for Health Policy, University
of Manitoba
Introduction: Preterm birth (livebirth < 37 weeks gestation) is the
leading cause of neonatal and infant mortality and incurs
substantial costs to the health, social and educational systems. A
variety of demographic, psychosocial, behavioral, and
medical/obstetric risk factors are related to preterm birth. Recent
systematic reviews provide support for the association of
socioeconomic disparities measured at both individual and
neighborhood levels with adverse birth outcomes such as preterm
birth. Objective: The objective of this population-based study
was to explore the association of a variety of demographic,
medical/obstetric, psychosocial and behavioral factors (including
those not typically found in administrative databases) with
preterm birth (PTB) in Manitoba. We measured socio-economic
disadvantage at both the neighborhood and individual level.
Methods: We used administrative databases in the Repository at
the Manitoba Centre for Health Policy: population registry,
hospital discharges, physician claims, pharmaceuticals dispensed,
Census, social assistance, and Families First program (social risk
data). We studied live births from 2005/06 to 2008/09 (N=55,253).
Multivariable logistic regression was used to estimate adjusted
odds ratios. Results: The PTB rate was 7.7%. Factors significantly
associated with PTB included maternal age >35 years, lone parent,
high parity (>3), hypertension, diabetes, multiple birth, previous
PTB, and male sex of newborn. Women having a cesarean birth or
induction were more likely to have PTB compared to spontaneous
vaginal delivery. Protective factors included intensive prenatal
care, and living in rural or northern region of province compared
to Winnipeg. Neighborhood income quintile was not significant. In
a second model incorporating social assistance and Families First
data (N=36,915), additional predictors were prenatal smoking and
maternal receipt of income assistance, while young maternal age
(<19 years) became a protective factor and region of residence
and lone parent status were no longer significant. Conclusion:
These models help identify women at increased likelihood of PTB
and have implications for policy and programs. The addition of an
individual-level income measure was important in identifying
socioeconomic disparities in PTB, whereas neighborhood-level
income was not a significant predictor in this study.
Acknowledgements: This work was supported through funding
provided by the Department of Health of the Province of Manitoba
to the University of Manitoba. The results and conclusions
presented are those of the authors. No official endorsement by
Manitoba Health is intended or should be inferred. Contact
Information: Maureen Heaman, RN, PhD
[email protected]
[357]
PREDICTORS OF PRENATAL AND POSTPARTUM PSYCHOLOGICAL
DISTRESS: A POPULATION-BASED STUDY IN MANITOBA.
Maureen Heaman1, Dawn Kingston2, Marni Brownell3, Michael
Helewa4, Shelley Derksen5, Kari-Lynne McGowan6
1College of Nursing, University of Manitoba, 2Faculty of Nursing,
University of Alberta, 3Manitoba Centre for Health Policy,
Department of Community Health Sciences, University of
Manitoba, 4Department of Obstetrics, Gynecology and
Reproductive Sciences, College of Medicine, University of
Manitoba, 5Manitoba Centre for Health Policy, University of
Manitoba, 6formerly Manitoba Centre for Health Policy, University
of Manitoba
Introduction: Maternal psychological distress (depression and
anxiety) is a common morbidity in the prenatal and postnatal
periods, and has serious adverse effects on mothers and children.
Although interventions aimed at improving maternal mental
health can reduce the risk of adverse outcomes, early
identification of prenatal and postnatal distress remains a
challenge. Few studies have explored predictors of prenatal
psychological distress, and most studies that examined predictors
of prenatal and postnatal distress used small sample sizes and
maternal self-report measures. Objective: The objective of this
study was to determine factors associated with prenatal and
postnatal psychological distress using population-based data and
objective measures of maternal psychological distress. Methods:
We used administrative databases in the Repository at the
CNPRM 2015
127
Manitoba Centre for Health Policy: population registry, hospital
discharges, physician claims, pharmaceuticals dispensed, income
assistance, and Census. We studied mothers giving birth from
2007/08 to 2008/09. Cases with depression/anxiety were
identified using diagnostic codes and prescriptions. Multivariable
logistic regression was used to estimate adjusted odds ratios
(aOR). Results: The prevalence of prenatal and postpartum
psychological distress was 7.5% and 13.8% respectively. Factors
significantly associated with prenatal distress (N=28,037) included
maternal age, region of residence, income quintile, marital status,
being on income assistance, maternal hypertension, and
antepartum hemorrhage. Psychological distress prior to pregnancy
had the largest effect on prenatal distress (aOR 9.79, 95% CI 8.8910.77), after adjusting for other variables in the model. Factors
significantly associated with postpartum distress (N=29,269)
included maternal age, region of residence, marital status, being
on income assistance, antepartum hemorrhage, newborn
admission to NICU, and having a low birth weight or preterm
infant. Prenatal psychological distress had the largest effect on
postpartum distress (aOR 8.11, 95% CI 7.50-8.77). Conclusion:
Women who experienced prenatal psychological distress were
eight times more likely to experience psychological distress in the
postpartum period. Screening for anxiety and depression and
intervening to improve maternal mental health in the
preconception, pregnancy and postpartum periods may
ameliorate the risk of poor maternal, child, and family outcomes.
Acknowledgements: This work was supported through funding
provided by the Department of Health of the Province of Manitoba
to the University of Manitoba. The results and conclusions
presented are those of the authors. No official endorsement by
Manitoba Health is intended or should be inferred. Contact
Information Maureen Heaman, RN, PhD
[email protected]
[363]
MORTALITY, MORBIDITY AND RESOURCE USE AMONG INFANTS
WITH TRISOMY 21(TR21) ADMITTED TO LEVEL III (L3) NICUS. Dr
Mary Angela Woodward1, Dr Connie Williams1, Dr Abhay Lodha2,
Dr Prakesh S Shah3, Dr Sandesh Shivananda1
1Division of Neonatology, Department of Pediatrics, McMaster
Childrens Hospital, Hamilton, Ontario, 2Division of Neonatology,
Department of Pediatrics, Alberta Childrens Hospital,Calgary,
Alberta, 3Department of Pediatrics, Mount Sinai Hospital,
University of Toronto, Torronto, Ontario
Introduction: TR 21 is by far the most common and well known
chromosomal disorder in humans and a common cause of
intellectual disability. However, the lack of outcome and resource
utilization details among infants with TR 21 admitted to Level 3
NICU’s precludes effective antenatal counseling, anticipation of
hospital course and resource planning. Objective: To determine
(i) the mortality, morbidity and resource utilization among infants
with TR 21 admitted to L3 NICU (ii) Factors associated with
mortality during hospital stay. Methods: A retrospective cohort
study on infants admitted to the NICU’s participating in the
Canadian Neonatal Network for the epochs 2004-2009 and 20102013 was conducted. Data on demography, resource utilization
and outcomes during hospital stay were collected. Association
between outcomes (death, length of stay and oxygen at discharge)
and predictors (gestational age, gender, outborn, severity of illness
(SNAP score), mechanical ventilation (MV) and inotrope use were
analyzed. Results: 482 and 438 infants with TR 21 during the two
epochs (1 % each of all L3 NICU admissions) were identified. The
mean (SD) gestational age was 36.5(3) and 36.4(3) weeks
respectively in the two epochs. In the second epoch, 21 (5%)
infants died, 21(5%) of the infants required inhaled nitric oxide
and 14(3%) infants had late onset sepsis. The odds of higher
128
deaths of TR 21infants were associated with the use of inotropes.
On logistic regression analysis, SNAP score, MV and inotrope use
had fair association with death, [odds ratio (95 % confidence
interval) 0.98(0.94,1.03), 11.1(0.95,129.7) and 75.1(10.7,530)
respectively. Conclusion: Infants with Trisomy 21 admitted to L3
NICU have a significant mortality rate and receive a fair degree of
intensive care support. Results could be used for improving
effectiveness of antenatal counseling, planned serial cardiac
function monitoring as well as facilitating resource planning at
various levels of health care administration. Contact Information:
Mary Angela Woodward [email protected]
[389]
COMBINING DATA SOURCES TO ENHANCE THE SURVEILLANCE OF
6 CONGENITAL ANOMALIES IN ONTARIO. Erin Graves1, Heather
Ramshaw1, Julian Little2, Aidenn Moore3, Ann Sprague1
1BORN Ontario, 2University of Ottawa/Department of
Epidemiology and Community Medicine, 3Hospital for Sick
Kids/University of Toronto/Paediatrics
Introduction: BORN has partnered with the Public Health Agency
of Canada (PHAC) to enhance the surveillance of congenital
anomalies in Ontario. The BORN Information System (BIS) has
developed data capture methods for anomalies detected in the
fetus and newborn during clinical encounters before (antenatal
specialty, prenatal screening) and at the time of birth (including
the delivery and NICU admissions). Objective: Using a
combination of the Canadian Institute for Health Information’s
(CIHI) Discharge Abstract Database (DAD) and the BIS, we jointly
ascertained the rates of 6 congenital anomalies in Ontario for
2012-13 and 2013-14: Down syndrome, neural tube defects,
congenital heart defects, orofacial clefts, limb deficiency defects
and gastroschisis. Methods: The two databases were linked
together using a combination of deterministic linkage by health
card number and probabilistic linking techniques to identify
anomalies collected in either, or both databases. Data from BORN
includes fetal anomalies detected through prenatal screening and
care from an antenatal specialty clinic, along with newborn
anomalies identified prior to discharge from hospital or midwifery
care. DAD includes hospital records from birth through to one year
of age (including termination, stillbirth and live birth records).
Results: Combined prevalence rates for all 6 anomalies in Ontario
are lower than the national average and lower than Alberta (with a
robust anomalies surveillance system); however they are higher
than those reported using either data source alone. Preliminary
analyses were conducted using only live births. For anomalies such
as cleft lip (with or without cleft palate) we expect our overall
prevalence of 0.67 per 1,000 in 2012-2013 to remain similar after
we extend our analysis to include terminations and stillbirths. In
contrast, we expect our overall prevalence of 0.93 per 1,000 in
2012-2013 for Down syndrome to increase when we extend our
analysis to include terminations and stillbirths. Prevalence rates
calculated using terminations and stillbirths from both databases
is ongoing. Conclusion: In this investigation of 6 congenital
anomalies, using a combination of data sources improved the
CNPRM 2015
ascertainment of congenital anomalies in Ontario. BORN is
working to expand our ascertainment of congenital anomalies and
all pregnancy outcomes (including terminations and stillbirths) to
be able to provide even more accurate congenital anomalies rate
estimates. Acknowledgements: We would like to thank the PHAC
for their support, as well as the members of the Ontario
Congenital Anomalies Committee (OCAC) for their time and
expertise in directing us in this work. Contact Information:
[email protected]
[398]
MATERNAL POLYBROMINATED DIPHENYL ETHER LEVELS IN
EARLY PREGNANCY AND BIRTH WEIGHT IN THE CANADIAN BIRTH
COHORT GESTE. SERME Yasmine1, Nadia Abdelouahab2, Jeans
Charles Pasquier3, Alan A Cohen4, Larissa Takser2
1Université de Sherbrooke/Département de Physiologie,
2Université de Sherbrooke/Département de Pédiatrie, 3Université
de Sherbrooke/Département de Gynécologie Obstétrique,
4Université de Sherbrooke/Département de Médecine de Famille
Introduction: Polybrominated diphenyl ethers (PBDEs) are a group
of environmental contaminants used as flame retardants. Their
levels have increased in human adipose tissue, milk and serum
over the last ten years, raising concerns about their consequences
on human health. Although some animal studies suggest that
PBDEs can affect growth through the disruption of insulin-like
growth factor 1 (IGF-1), epidemiologic studies are few and
inconclusive. Objective: This study evaluates the association
between the most common PBDEs in maternal sera (BDE-47, 99,
100 and 153) measured in early pregnancy and fetal growth
represented by birth weight (BW). Methods: Plasma levels of
PBDEs were measured in 349 women during their first prenatal
care visit at the Centre Hospitalier Universitaire de Sherbrooke
(CHUS) in Quebec, Canada, between 2007 and 2008. Birth weight
was collected from medical records. Other environmental
pollutants that are likely to interact with fetal growth
(polychlorinated biphenyls (PCBs), mercury, lead, cadmium and
manganese) were also measured and controlled for. Data were
analyzed on SAS version 9.3 and R software. Results: Despite
careful consideration of risk factors known to affect fetal growth,
there was no statistically significant association between BW and
PBDEs. Conclusion: Our results suggest that there is no clinically
consistent PBDEs effect on fetal growth. Acknowledgements:
This study was financed by grant 12397 from the Fonds de
Recherche du Québec–Santé (FRQS) and grant MOP- 84551 from
the Canadian Institutes of Health Research (CIHR). We thank the
personnel of the Centre hospitalier universitaire de Sherbrooke
(CHUS) maternity service for their active participation in the
collection of samples at delivery. We gratefully acknowledge the
help of members of the CHUS Department of Family Medicine,
especially Dr. Donna Cherniak, in organizing the recruitment of
pregnant women. Contact Information:
[email protected]
[399]
MARRIAGE POSITIVELY IMPACTS BIRTH OUTCOMES IN URBAN,
LOW SOCIOECONOMIC POPULATION. Jennifer J. Barr1
1Department of Obstetrics and Gynecology, State University of
New York at Buffalo, Sisters of Charity Hospital
Introduction: Preliminary reports show paternal involvement
during pregnancy impacts birth outcomes. Previously surrogates
for paternal involvement such as birth certificate data have been
used. This study utilized specific questions to gauge the type of
relationship and level of paternal involvement during pregnancy.
Objective: To assess the role of parental relationship and paternal
support in pregnancies in an urban, low socioeconomic
population. Methods: Charts were obtained from adult women
with singleton pregnancies receiving prenatal care at Sisters
Ob/Gyn Center (Buffalo, NY, USA) between 2002 and 2012 who
delivered after 20 weeks gestation. A social work interview was
used to obtain relationship between parents of the baby, the
mother of the baby’s attitude toward pregnancy, the father of the
baby’s attitude toward pregnancy, and if the patient anticipated
support of the father. Age, race, parity, and ethnicity were
recorded. Outcome measures were low birth weight, preterm
delivery, compliance with diabetes screening, and breastfeeding at
time of delivery. Outcomes were compared based on relationship
between the parents using chi-squared statistics. Other variables
were then controlled for using a Mantel-Haenszel analysis.
Results: We identified 2285 pregnancies. The type of relationship
between the parents impacted rates of low birth weight (married
5.6%, cohabitating 8.0%, romantically involved 9.6%, no
relationship 10.1%, p=0.048), compliance with diabetes screening
(married 90.4%, cohabitating 87.0%, romantically involved 88.3%,
no relationship 78.9%, p<0.001), and breastfeeding rates (married
75.2%, cohabitating 55.6%, romantically involved 48.5%, no
relationship 49.8%, p<0.001). The parental relationship did not
influence rates of preterm delivery (married 7.1%, cohabitating
10.3%, romantically involved 9.6%, no relationship 10.9%, p=0.21).
Adjusting for attitude of the father, the impact of marriage
remained significant for low birth weight (chi-square (1, N=2203) =
5.008, p=0.025) and breastfeeding rates (chi-square (1, N=1739) =
64.034, p<0.001). Adjusting for a commitment by the father of the
baby to support the pregnancy, marriage remained significant for
rates of low birth weight (chi-square (1, N= 2263) = 5.685,
p=0.017) and breastfeeding rates (chi-square (1, N=1774),
p<0.001). Conclusion: The relationship between parents during
pregnancy impacts rates of low birth weight, compliance with
routine screening, and breastfeeding rates. Even after adjusting
for the father of the baby’s attitude toward the pregnancy,
mothers who were married had lower rates of low birth weight
infants and higher rates of breastfeeding. Acknowledgements:
Department of Obstetrics and Gynecology, Sisters of Charity
Hospital. Contact Information: [email protected]
[400]
MATERNAL CAFFEINE INTAKE AND RISK OF SMALL FOR
GESTATIONAL AGE: RESULTS FROM THE APRON STUDY.
Mohammadreza Pakseresht1, Jessica Hamilton1, Andrea
Patterson1, Shira Wickenheiser1, Linda McCargar1, Rhonda C. Bell1,
The ENRICH and APrON Research Teams1
1University of Alberta/ Department of Agricultural, Food &
Nutritional Science
Introduction: Infants defined as small for gestational age (SGA) are
at increased risk for mortality and morbidity. Studies have
implicated several lifestyle factors as increasing the risk for SGA
birth, including excessive caffeine intake during pregnancy.
However, there is still controversy around this relationship; effects
may vary across international settings due to differences in
patterns of caffeine consumption as well as other factors that
affect risk of SGA. Little is known about this relationship among
Canadian women. Objective: To determine the pattern of
caffeine intake prior to and during pregnancy and to explore any
association between caffeine intake and risk of SGA among
Albertan women. Methods: The Alberta Pregnancy Outcomes
and Nutrition (APrON) study is a cohort study of ~2200 pregnant
women and their infants. Women enrolled were 16 yrs old and
26 weeks’ gestation when recruited from Calgary and Edmonton
between June 2009 and June 2012. Pre-pregnancy food and
beverage intake was measured using a food frequency
questionnaire. Dietary information during pregnancy was assessed
using a 24-hr recall collected during each trimester. Demographic
and general health status information was also collected. Results:
Data was available for 2086 women (mean age=31.5±4.5 yr).
CNPRM 2015
129
Seventy-nine % of participants reported caffeine intake before
pregnancy (236±246 mg/d, median 161 mg/d). Mean daily caffeine
intake at pre-pregnancy was higher for Caucasians compared to
non-Caucasians and for women with family income >$100,000/yr
compared to those with a lower income (P=0.03). The prevalence
of caffeine consumers decreased to 64% and 70% in the 2nd and
3rd trimesters of pregnancy, respectively. Caffeine intake was
dramatically reduced to 67 ± 77 mg/d (median 50 mg/d) in the 2nd
trimester and to 72 ± 75 mg/d (median 50 mg/d) in the 3rd
trimester. There was no difference in caffeine intake between
ethnic groups during pregnancy. Caffeine intake in 2nd and 3rd
trimesters of pregnancy was not associated with risk of SGA.
However, poor weight gain in the 2nd and 3rd trimesters were
associated with at least a 37-fold increase in risk of SGA (p=0.003).
Caucasian women were at 63% lower risk of SGA (p=006). No
interaction between smoking and caffeine intake and risk of SGA
was observed. Conclusion: Pregnant women reduced
consumption of caffeine by one third after becoming pregnant.
There was no association between caffeine intake and SGA,
probably due to low power, since only 3% of the pregnant women
consumed daily caffeine >200 mg/d and only 3% reported
smoking. Acknowledgements: This project was supported by
Alberta Innovates-Health Solutions. Contact Information:
[email protected]
[415-416]
TEMPORAL TRENDS IN OBSTETRIC TRAUMA AND SURGERY FOR
PELVIC FLOOR DISORDERS: AGE-PERIOD-COHORT ANALYSIS.
Sarka Lisonkova 1, Innie Chen 2, Giulia Muraca-Muir3, Geoffrey
Cundiff4, KS Joseph 1
1University of British Columbia, Dpt. of Obstetrics and
Gynaecoogy, 2University of Ottawa, Dpt. of Obstetrics and
Gynaecoogy, 3University of British Columbia, School of Population
and Public Health, 4University of British Columbia,Dpt. of
Obstetrics and Gynaecoogy
Introduction: Obstetric trauma during childbirth is a major risk
factor for subsequent urinary and fecal incontinence and pelvic
organ prolapse. We carried out a population- based study to
explore the temporal association between trauma during
childbirth and pelvic floor disorders. Objective: We examined
age-specific temporal trends in vaginal and cesarean delivery,
obstetric trauma, and surgery for urinary and fecal incontinence
and pelvic organ prolapse in Washington state, USA, between
1987 and 2009. Methods: we used ICD-9 diagnostic and related
procedure codes to identify obstetric trauma (including 3rd and
4th degree perineal tears, high vaginal lacerations, anal sphincter
tear, and inversion of the uterus) and surgery for pelvic floor
disorders in the Comprehensive Hospital Abstract Reporting
System (CHARS) dataset that included all hospitalizations in
Washington state. The number of pregnant and non-pregnant
women in each age group was used as the denominator for all
rates and obtained from Vital Statistics and census data. We used
the Cochran-Armitage test to assess temporal trends, and ageperiod-cohort effect analysis to quantify the experience of women
born between 1920 and 1980. Results: The rate of cesarean
delivery increased by 49.2% from 12.4 in 1987 to 18.5 per 1,000
women aged 15-44 years in 2009, while the vaginal delivery rate
remained stable (approximately 45 per 1,000 women). However,
the rate of instrumental vaginal delivery declined from 6.2 in 1987
to 5.1 per 1,000 women in 2009, with a substantial 9-fold drop in
the rate of mid-pelvic forceps (from 0.4 to 0.05 per 1,000 women).
Similarly, the rate of obstetric trauma decreased by 55.6% from
1.8 in 1987 to 0.8 per 1,000 women aged 15-44 years in 2009, with
the largest decline observed among women <25 years of age. The
rate of surgery for pelvic organ prolapse decreased steadily from
2.3 in 1987 to 1.4 per 1000 women aged 20-84 years in 2009, and
130
a similar trend was observed in surgery for urinary incontinence
(46.7% decline from 1.5 in 1987 to 0.8 per 1,000 women aged 2084 years in 2009). All trends were statistically significant (p<0.01).
The rate of surgery for fecal incontinence remained relatively
stable between 0.3 and 0.1 per 10,000 women aged 20-84 years.
Age-period-cohort analysis showed that consecutive cohorts of
women were less likely to experience obstetric trauma and require
surgery for incontinence and pelvic organ prolapse. Conclusion:
The temporal increase in cesarean delivery and the concomitant
drop in instrumental vaginal delivery has resulted in significant
declines in obstetric trauma and consequent reductions in surgery
for urinary and fecal incontinence and pelvic organ prolapse.
Acknowledgements: Research supported by CIHR. Contact
Information: Dr Sarka Lisonkova [email protected]
[432]
PRENATAL VITAMIN D SUPPLEMENTATION AND INFANT
GROWTH. Wei Guang Bi1, Anne-Monique Nuyt2, Line Leduc1, Shu
Qin Wei1
1Department of Obstetrics and Gynecology, Saint-Justine Hospital,
University of Montreal, Montreal, Canada, 2Department of
Pediatrics, University of Montreal
Introduction: Vitamin D deficiency is common in pregnant women.
Prenatal vitamin D deficiency is associated with low birth weight
or small for gestational age (SGA). However, it is unknown if
vitamin D supplementation during pregnancy might improve
infant’s growth and health outcomes. Objective: To determine
the effects of vitamin D or related compounds, with or without
calcium, during pregnancy on infants growth and health outcomes.
Methods: This is a systematic review and meta-analysis. We
searched electronic databases of the literature in PubMed, the
Cochrane Library up to November, 2014 and reference lists of
articles using the following keywords: ‘vitamin D’ and ‘pregnancy’.
We included randomised or quasi-randomised trials that
compared vitamin D or related compounds, alone or with calcium,
against placebo, standard care, no intervention or calcium alone,
and that reported vitamin D supplementation during pregnancy
and infants outcomes including infants’ weight, length, head
circumference, skin fold, low birth weight or small-for-gestational
age (SGA) from newborn baby until 12 months old. Two authors
independently assessed trial risk of selection bias and aspects of
methodological quality, and extracted data. Data were pooled,
where possible, using the fixed-effect model, or the randomeffects model when heterogeneity between studies appeared
substantial. Results: Seven RCTs involving 1004 women were
included in this study. The pooled data shows that women who
received vitamin D supplements during pregnancy had a higher
mean birth weight (g) (mean difference 125.53, 95% CI 104.90 to
146.16), larger body length (cm) (mean difference 0.30, 95% CI
0.19 to 0.42), larger head circumference (cm) (mean difference
0.59, 95% CI 0.42 to 0.76). Vitamin D supplementation had
increased skin fold (mean difference 0.20, 95% CI 0.17 to 0.23).
There were less frequently had a baby with a birth weight below
2500 grams in women with vitamin D supplementation than those
women receiving standard care or placebo (RR 0.38, 95% CI 0.21
to 0.66). Follow-up the infants to 3month, 6 month, 1-year-old,
vitamin D supplementation was associated with infants growth.
Conclusion: Vitamin D supplementation during pregnancy may
increase infant growth. However, the trials included were small.
These finding support the need for a single larger trial with enough
power to validate this effect. Acknowledgements: Dr. SQ Wei
was a recipient of Award of Fonds de Recherche en Santé du
Québec, and Dr. WD Fraser by a CIHR Canada Research Chair
award. Contact Information: Shu Qin Wei
[email protected]
CNPRM 2015
[460]
NEONATAL MORTALITY AND MORBIDITY IN EARLY PREMATURE
SECOND TWIN. Elad Mei-Dan1, Jyotsna Shah 1, Anne Synnes1,
Sandesh Shivananda1, Greg Ryan1, Prakesh Shah1, Kellie E.
Murphy1
1Department of Obstetrics and Gynaecology, Mount Sinai Hospital,
Toronto, Ontario, Canada
Introduction: Compared with first twins, second twins born at
term or late preterm are known to be at increased risk of adverse
neonatal outcomes. Objective: The aim of this study was to
determine the effect of birth order on neonatal morbidity and
mortality in a population of very preterm twin pregnancies.
Methods: A retrospective cohort study using data from the
Canadian Neonatal Network, between 2005 and 2012. Risk of
mortality and adverse outcomes of second twins relative to firstborn co-twins were examined by matched-pair analysis. Main
outcomes measures included: a composite outcome of neonatal
death or one of the following severe injuries, intraventricular
haemorrhage, periventricular leukomalacia, bronchopulmonary
dysplasia, retinopathy of prematurity (ROP), Necrotizing
enterocolitis. Furthermore a multivariable analysis was performed
to control for the, following covariates: gestational age, small for
gestational age (SGA), gender and SNAPII score>20. Results: In
total 6636 twin pregnancies, born between 24-32 weeks of
gestation, were included in this analysis. There was no difference
in the composite outcome between the second and the first-born
twin (Odd ratio [OR] 1.07, 95% confidence interval [CI] 0.95, 1.20).
Furthermore, the mortality rate was higher for the first twins
compared to the second twins (5.3% vs. 4.3%, p=0.02). The rate of
SGA was higher in the second twins compared to the first twins
(6.0 vs. 10.3, p=0.01). In a multivariable analysis, being the first
born twin was found to be an independent predictor for neonatal
death (OR 0.75; 95% CI 0.59, 0.95), whereas being the second born
twin was associated with ROP and respiratory distress syndrome
(OR 1.46; 95% CI 1.07, 2.01 and OR 1.40, 95% CI 1.29, 1.52,
respectively). There was no association between birth order and
other adverse outcomes. Conclusion: In very preterm twins, the
second twin is not at greater risk of neonatal death or severe
neurologic injury as compared to the first. This is in contrast to the
supported literature for the outcomes of term and late preterm
second twins. Acknowledgements: For the Canadian Neonatal
Network. Contact Information: Elad Mei-Dan
[email protected]
[470]
A RANDOMIZED TRIAL OF AIR FILTERS AND FETAL GROWTH:
PRELIMINARY RESULTS FROM THE ULAANBAATAR GESTATION
AND AIR POLLUTION RESEARCH (UGAAR) STUDY. Prabjit Barn 1,
Enkhjargal Gombojav2, Bolor Beejin2, Buyantushig Boldbaatar2,
Chimedsuren Ochir2, Bayarkhuu Laagan3, Tsogtbaatar Byambaa1,
Craig Janes1, Patricia A. Janssen4, Bruce P. Lanphear1, Young Man
Roh5, Tim Takaro1, Scott A. Venners1, Glenys M. Webster1, Ryan
W. Allen1
1Simon Fraser University/Faculty of Health Sciences, 2Mongolian
National University of Health Sciences/School of Public Health ,
3Sukhbaatar District Health Center, 4University of British
Columbia/School of Population and Public Health, 5Hanyang
University
Introduction: Exposures to fine particulate matter (PM2.5) air
pollution during pregnancy may impair fetal growth. Portable high
efficiency particulate air (HEPA) filters can reduce residential
PM2.5 concentrations, but little research exists on the use of
filters among vulnerable populations in highly polluted cities.
Objective: In an ongoing randomized trial, we are evaluating of
HEPA filters on indoor air quality and the relationship between
PM2.5 exposures during pregnancy and fetal growth among
pregnant women in Ulaanbaatar, Mongolia, one of the world’s
most polluted cities. Methods: Recruitment of non-smoking
women in the 1st trimester of pregnancy began in January 2014.
We aim to recruit 500 participants all of whom will be randomized
into an intervention (use of 2 HEPA filters from enrollment to
childbirth) or control (no filters) group. Air pollution exposure and
health measurements are being collected for each participant at
approximately 12 and 30 weeks gestation. Exposure
measurements include continuous indoor PM2.5 (over 1 week
periods), hair nicotine and blood lead, cadmium and mercury. The
primary health outcome is gestational age-adjusted birth weight;
secondary outcomes include maternal blood pressure and Creactive protein, an indicator of systemic inflammation.
Information on housing characteristics, behaviours, reproductive
history, and birth outcomes is obtained via questionnaire and
clinical records. Our primary analysis will be intention to treat.
Secondary analyses will evaluate relationships between PM2.5 and
health outcomes. Results: Initial indoor air pollution sampling has
been conducted in 230 homes and 57 births have occurred.
Baseline characteristics, including age, pre-pregnancy BMI and
blood pressure, are similar among intervention and control
groups. Over half of the participants live with a smoker. Median
(interquartile range) indoor PM2.5 concentrations were highest in
winter [36 (34) µg/m3 in intervention and 86 (46) µg/m3 in control
homes] compared to spring and summer when median
concentrations were below 31 µg/m3. Filter effectiveness,
comparing median PM2.5 concentrations in intervention to
control homes, was highest in winter (58%) compared to spring
(26%), summer (5%) and fall (-4%). Higher indoor median PM2.5
concentrations were seen in homes with smokers in both
intervention and control homes. Conclusion: HEPA filters reduce
indoor PM2.5. Effectiveness is highest in winter, likely due to less
opening of windows. Additional data will allow for evaluation of
longer-term HEPA filter performance and investigation of the
effect of filter use on health outcomes. Acknowledgements: This
study is funded by the Canadian Institutes for Health Research.
Contact Information: Prabjit Barn [email protected]
[474]
OUTCOMES AND PATTERNS OF MIDWIFERY CARE RECEIVED BY
WOMEN AND THEIR INFANTS IN ONTARIO BETWEEN 2006-2009.
Jordyn Horne1, Angela Reitsma2, Julia Thorpe2, Adriana
Cappalletti3, Eileen Hutton4
1McMaster University/ Life Science Program, 2McMaster
University/ Midwifery Education Program, 3McMaster University/
Health Science Program, 4McMaster University/ Department of
Obstetrics & Gynecology
Introduction: In Ontario, midwives provide prenatal, intrapartum
and postpartum care to low-risk pregnant women. Objective: The
purpose of this study was to determine the outcomes of women
entering midwifery care between 2006-2009, and to describe the
patterns of care. Methods: Data was obtained from the Ministry
of Health and Long Term Care. Using SPSS, we stratified by parity
and used descriptive statistics to describe outcomes. Results:
Between 2006 and 2009, 54,026 women received care from
midwives in Ontario. The majority of women were between 25
and 34 years of age and resided in southern urban areas of
Ontario; 35.9% were previous Ontario midwifery clients and 56.0%
were multiparous. Median age at booking was 11 weeks. The
incidence of miscarriage or termination of pregnancy was 3.6%;
preterm birth was 5.0%. At the onset of labour 23.6% planned
home birth (19.3% nulliparae; 27.0% multiparae) and 19.0% gave
birth at home (11.8% nulliparae; 24.6% mulitparae). Analgesic pain
relief during labour was utilized during 34.2% of births; 15.8% of
women gave birth by Caesarean section (22.8% nulliparae; 10.4%
multiparae). Median length of stay for infants was 1.03 days. At
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discharge from care, 81.6% of infants were exclusively breastfed.
Conclusion: Outcomes of midwifery clients from 2006 to 2009
reflected low rates of intervention and positive outcomes. For
example, the rate of Caesarean section and preterm birth were
lower, while the rate of breastfeeding at discharge was higher
among midwifery clients than that of the Canadian population as a
whole. Acknowledgements: We would like to thank the Ministry
of Health and Long-Term Care for providing the data to conduct
this study and Rashid Ahmed for his insight on the data cleaning
process. Contact Information: Julia Thorpe
[email protected]
[482]
POPULATION ATTRIBUTABLE RISK FRACTIONS OF MATERNAL
OBESITY FOR ADVERSE PERINATAL OUTCOMES. Natasha
MacInnis1, Stefan Kuhle1
1Perinatal Epidemiology Research Unit, Dalhousie University
Introduction: In Canada, 13% of women of childbearing age are
obese with Atlantic Canada having the highest rates in the country
(23%). Compared to normal weight women, obese women are at
higher risk of developing pregnancy complications such as
gestational diabetes (GDM) and are more likely to require a
cesarean section (CS). Maternal obesity is also associated with
large for gestational age (LGA) birth and admission to the NICU.
However, the extent to which obesity contributes to the
population burden of adverse perinatal outcomes in Canada has
not been examined yet. Objective: The objective of the current
study was to determine the population attributable risk fractions
(PARFs) for maternal pre-pregnancy weight on perinatal outcomes
to determine the reduction in adverse outcomes that may be
achieved if maternal pre-pregnancy weight were reduced.
Methods: We used data from the Nova Scotia Atlee Perinatal
Database (NSAPD) on 51,420 singleton infants and their mothers
born in Nova Scotia between 2004 and 2012. Univariate and
multivariable-adjusted PARFs of maternal pre-pregnancy weight
status were determined for maternal and neonatal outcomes (e.g.
GDM, CS, LGA), under a number of hypothetical scenarios that
reduced the pre-pregnancy weight in overweight and obese
women. Results: The PARFs for GDM, CS, NICU admission, and
LGA assuming that all obese women would become normal weight
were 62.9%, 23.2%, 14.5%, and 26.7%, respectively. Changing the
weight status of overweight women to normal weight would
eliminate 30.4% (GDM), 9.4% (CS), 5.5% (NICU), and 15.1% (LGA)
of adverse perinatal outcomes. Conclusion: A substantial
proportion of GDM, CS, NICU admissions, and LGA births may be
preventable through reductions in maternal pre-pregnancy
weight. The final analysis will present the relative reductions in
adverse perinatal outcomes that may be achieved under different
weight loss scenarios. Acknowledgements: Ms. MacInnis was
supported by a Dr. Carl Tupper Summer Research Studentship
from the Dalhousie Medical Research Foundation. Contact
Information: Stefan Kuhle [email protected]
[355]
IN UTERO EXPOSURE TO A CARDIAC TERATOGEN CAUSES
SUBSEQUENT POSTNATAL CARDIOVASCULAR ABNORMALITIES
DURING PREGNANCY. Kristiina L. Aasa1, Rebecca D. Maciver1,
Shyamlal Ramchandani2, Michael A. Adams1, Terence R.S. Ozolinš1
1Queen's University, 2Analytics for Life
Introduction: Congenital heart defects (CHD) are the most
common birth anomaly, contributing significantly to infant
mortality; however, the life-long burden on survivors is poorly
understood. To address this knowledge gap we developed a rat
model of CHD induced by embryonic exposure to the teratogen
dimethadione (DMO). In our model most DMO-induced structural
defects resolve by weaning, mimicking the clinical scenario. In the
absence of structural defects in adulthood, treated rats exhibit
132
functional deficits under increased cardiac load. The effect of preexisting CHD on the increased cardiovascular (CV) burden of
pregnancy is unknown. Objective: To test the hypothesis that
animals exposed to DMO in utero are predisposed to postnatal
pregnancy-related CV pathologies, even in the absence of
persistent structural defects. Methods: Pregnant rats were
administered distilled water or DMO [300 mg/kg on gestation day
(gd) 9 and 10] and allowed to deliver pups naturally. Treated and
control pups were scanned by echocardiography to identify
functional abnormalities. Reaching adulthood, radiotelemetry
devices were implanted, enabling continuous monitoring of
hemodynamics and cardiac electrophysiology. Adult offspring
were mated and scanned by echocardiography during pregnancy
to assess CV function. On gd 18 maternal hearts were collected
and weighed for further structural and molecular assessment.
Results: Postnatal day 4 echocardiography revealed numerous
differences in treated offspring compared to control; some of
these abnormalities persisted into early adulthood. By 10 weeks of
age no differences existed between treated and control females.
Despite similar cardiac structure and function in virgin rats,
pregnancy revealed differences in cardiac output, left ventricular
mass as well as radial and longitudinal strain. In utero treatment
with DMO also affected the subsequent generation. Gd18 fetal
and placental weights were increased in treated F2 offspring;
however, the ratio of placental/fetal weight was decreased
compared to control. Despite this, there were no alterations in
umbilical artery blood flow or fetal heart rate on gd12 or gd18.
Conclusion: This study demonstrates that teratogenic exposure
may permanently alter the capacity of the postnatal heart to adapt
to pregnancy later in life. Results underscore the need to identify
individuals with pre-existing, but resolved CHD, as they may still be
at higher risk for CV complications. Acknowledgements: We
acknowledge funding from Ontario Centres of Excellence (OCE)
Medical Sciences Proof-of-Principle (MSc PoP) Program and the
Canadian Heart and Stroke Foundation. Contact Information:
Kristiina Aasa [email protected]
[442]
THE ASSOCIATION OF HYPERHOMOCYSTEINEMIA WITH
PREECLAMPSIA AND OTHER PLACENTA-MEDIATED OUTCOMES:
ASSUMPTIONS UNDERLYING CAUSAL ANALYTIC APPROACHES.
Shazia Hira Chaudhry1, Shi-Wu Wen2, Monica Taljaard2, Mark
Walker2
1University of Ottawa, Department of Epidemiology and
Community Medicine, 2Ottawa Hospital Research Institute, Clinical
Epidemiology
Introduction: Preeclampsia, placental abruption, fetal growth
restriction, and stillbirth are pregnancy complications linked to
placental vascular pathology that can have serious consequences
for maternal and infant well-being. Subsequent to findings in
cardiovascular disease research, moderately elevated
homocysteine levels are postulated to play a role in alterations of
the placental vasculature. Homocysteine is an intermediate
metabolite from the breakdown of methionine. Elevated levels,
termed hyperhomocysteinemia, are associated with MTHFR
genotype; deficiency in coenzymes of homocysteine metabolism:
Vitamins B6, B9 (i.e., folic acid), and B12; and lifestyle or
behavioural factors. Meta-analyses of observational studies have
demonstrated an association between hyperhomocysteinemia and
placenta mediated disease, but studies inconsistently account for
factors such as folate supplementation. And though hypothesized
confounders are adjusted for, standard approaches can still lead to
biased exposure effect estimates due to statistical selection that is
uninformed by hypothesized causal mechanisms. Additionally,
methodological approaches have not assessed possible effects of
residual confounding from unmeasured factors. Objective: Our
CNPRM 2015
interest is to study the research question using analytic methods
based on a causal framework for better estimates of the unbiased
effect of hyperhomocysteinemia on placenta-mediated outcomes.
Using causal analytic methods to overcome bias and residual
confounding is subject to verifying underlying methodological
assumptions— some of which are empirically unverifiable. The
most definitive way to verify assumptions for each of these
methods is with subject-matter knowledge of the causal structure
of the association. Methods: The causal analytic approaches of
interest are as follows: I. Regression analyses using selection
informed by directed acyclic graphs (DAGs) of hypothesized causal
mechanisms; II. Regression analyses using propensity scores; and
III. Mendelian randomization using MTHFR genotype as an
instrumental variable. Results: The three causal analytic methods
are presented along with their underlying assumptions. The
assumptions are examined through research literature review and
iterative input of content experts. Conclusion: A comprehensive
and conceptually integrated approach to the knowledge base
plays an important role in studying hyperhomocysteinemia and
the development of placenta-mediated outcomes. Evidence of
causality is necessary to inform primary prevention to reduce the
risk of placenta-mediated disease as a consequence of reduction
in homocysteine levels, thereby leading to improved management
of these conditions. Acknowledgements: CIHR QTNPR. Contact
Information: Shazia Hira Chaudhry [email protected]
Preeclampsia and Placenta Development
[342]
MRNA STABILITY: TIS11 FAMILY AT THE PORCINE MATERNALFETAL INTERFACE. Kasra Khalaj1, Jocelyn M. Wessels2, Rami T.
Kridli3, Mallikarjun Bidarimath4, Jonathan LaMarre2, Chandrakant
Tayade1
1 Department of Biomedical and Molecular Sciences, Queen’s
University, Kingston, Ontario, Canada, K7L 3N6; Department of
Biomedical Sciences, Ontario Veterinary College, University of
Guelph, Guelph, Ontario, 2 Department of Biomedical Sciences,
Ontario Veterinary College, University of Guelph, Guelph, Ontario,
3Department of Animal Production, Faculty of Agriculture, Jordan
University of Science and Technology, Irbid, Jordan, 4 Department
of Biomedical and Molecular Sciences, Queen’s University,
Kingston, Ontario
Introduction: The TIS11 gene family are mRNA destabilizing genes
that bind to cytokines and mediate their degradation. Previous
reports from our laboratory confirmed that elevated proinflammatory cytokines such as TNF-α and IFN-γ and lower levels
of VEGF are associated with conceptus arrest during porcine
pregnancy. The TIS11 family is of primary interest with respect to
porcine spontaneous fetal loss since they are associated with posttranscriptional regulation of several pro-inflammatory genes
including TNF-α and IFN-γ. Objective: This study aims to
investigate association of TIS11 with early and mid-gestational
porcine fetal loss. Methods: Endometrial and fetal trophoblast
samples were collected from gestation day 20 (gd20) and
gestation day 50 (gd50) sows. Transcript expression levels of TIS11
family members were quantified using plate-based real-time PCR.
Western blotting and immunohistochemistry were employed for
detection of protein levels and cellular localization, respectively.
Additional mechanistic studies are currently in progress in JEG-3
and JAR cell lines. Results: With the exception of TTP in
endometrium, all TIS11 transcripts were elevated in healthy
tissues as compared to arresting tissues at gd20 (p<0.05).
Conversely, higher levels of TIS11 transcripts were expressed in
arresting gd50 trophoblast compared to healthy counterparts and
in arresting endometrium (p<0.05). TTP protein was expressed
higher in endometrium from arresting conceptuses compared to
healthy counterpart at gd50 (p<0.05). IHC results indicate TIS11
localization in glandular epithelium, stroma and blood vasculature
throughout the maternal-fetal microarchitecture. Conclusion: All
three members of the TIS11 family are expressed on both sides of
the porcine maternal-fetal interface. A marked shift in transcript
expression was observed for all family members between gd20
and gd50 on the fetal side. TIS11 protein is also expressed at both
sides of maternal-fetal interface. This shift may be due to a variety
of factors and is currently being investigated in our planned
mechanistic studies in cell lines. Acknowledgements: Funded by
NSERC CRD, Ontario Pork, Bioniche Life Sciences Inc, and R.S.
McLaughlin Fellowship. Contact Information:
[email protected]
[344]
THROMBOXANE A2 INDUCES VASOCONSTRICTION BY
ACTIVATION OF THE SPHINGOSINE 1-PHOSPHATE PATHWAY.
Daniel Kerage1, Denise G. Hemmings1
1University of Alberta/Obstetrics and Gynecology, Medical
Microbiology and Immunology
Introduction: Pregnancy disorders like preeclampsia are
associated with increased vascular tone. Sphingosine 1-phosphate
(S1P), a bioactive lipid, produced by sphingosine kinase (SK)
regulates vascular tone. Intracellular S1P is exported by ABC-type
transporters and signals through S1P2/S1P3 receptors on vascular
smooth muscle cells (VMSCs) to stimulate constriction.
Thromboxane A2 (TXA2), a vasoconstrictor, releases S1P from
platelets and is elevated in preeclampsia. Whether TXA2 utilizes
S1P to increase constriction is unknown. Objective: We
hypothesize that TXA2 will activate SK in VSMCs of intact arteries
increasing S1P release. S1P will engage S1P2/S1P3 receptors to
stimulate constriction. Our objective is to investigate this signalling
pathway in murine uterine and mesenteric arteries. Methods:
Isolated and intact arteries mounted on a pressure myograph
were treated in the bath with the TXA2 mimetic, U46619 (1100nM), with or without inhibitors to SK (1µM SK-II), ABC
transporters (1µM F9054, 10µM MK571 or combined), S1P1/S1P3
(1µM VPC23019) or S1P2 (10µM JTE013). Arteries from S1P3-/- or
S1P3+/+ wildtype mice were also used. In some cases
phenylephrine (PE; 0.01-10 µM) replaced U46619. Constriction
was measured by diameter change from baseline. Results:
U46619 treatment of uterine (20nM) and mesenteric (100nM)
arteries induced constriction (70.1±2.2%; 77.1±5.3%) that was
significantly decreased to the following levels by SK-II (20.2±9.2%;
10.7±3.8%), F9054 (34.5±8.2%; 39.6±2.7%), MK571 (6.1±5.2%;
30.8±9.8%), F5094+MK571 (-3.0±4.1%, mesentery), JTE013
(13.3±5.9%; 45.2±12.1%), JTE013+LNAME (37.5±4.7%, uterine
arteries) or VPC23019 (12.7±5.0%; 69.8±5.1%-not significant)
respectively. U46619 or PE-induced constriction was significantly
inhibited in uterine arteries (to 25.2±5.1%; 12.6±7.4% respectively)
from S1P3-/- mice but remained unaffected in mesenteric arteries.
Thus, U46619 or PE signal through the S1P pathway to induce
uterine artery constriction through S1P3 and in part via S1P2 in
mesenteric arteries. Notably, the inhibition of U46619 or PEinduced constriction mediated by JTE013 was partly relieved by
the NOS inhibitor L-NAME, which had no effect in the absence of
JTE013. Thus, JTE013 may activate NOS along with antagonizing
S1P2 receptors. Conclusion: We reveal a novel mechanism
through which U46619 or PE induces constriction with vascular
bed differences. Targeting the S1P pathway may be useful for the
treatment of vascular-related disorders like preeclampsia and
intrauterine growth restriction. Acknowledgements: Supported
by CIHR. Contact Information: Denise Hemmings
[email protected]
CNPRM 2015
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[356]
ARTIFICIAL PLACENTA: DEVELOPING A METHOD FOR
POLYDOPAMINE (PDA) AS A BIOGLUE TO ATTACH COAVALANT
ANTITROMBIN HEPARIN (ATH) COMPLEX FOR
HEMOCOMPATIBILITY. Jennifer Leung1, Leslie Berry2, Rena
Cornelius1, Niels Rochow3, Darren Sandejas4, Gerhard Fusch3, Ravi
Selvaganapathy5, Christoph Fusch3, Anthony Chan2, John Brash1
1Chemical Engineering, McMaster University, Hamilton, Ontario,
2Thrombosis and Atherosclerosis Research Institute, Hamilton,
Ontario, 3Pediatrics, McMaster University, Hamilton, Ontario,
4Biomedical Engineering, McMaster University, Hamilton, Ontario,
5Mechanical Engineering, McMaster University, Hamilton, Ontario
Introduction: Based on the concept of the artificial placenta, we
have developed a lung assist device (LAD) for preterm and term
newborns. The LAD is an array of stacked microfluidic oxygenators
made of polydimethylsiloxane (PDMS). To prevent systemic
coagulation, the blood contacting surfaces must be
hemocompatible. ATH is efficient anticoagulant. Due to the low
binding affinity of PDMS, a new approach to bind ATH must be
developed. In nature PDA is an abundant and strong “bioglue.”
Objective: To examine the stability and efficiency of PDMS using
the oxidation of PDA to adhere the covalent ATH complex.
Methods: Coating PDMS with ATH PDMS disc were incubated in a
5% 125I-labeled ATH solution (0.1mg/mL in PBS, pH 7.4, 3 hrs,
n=6). A second set of discs used PDA as an intermediate. Prior to
ATH incubation, the discs were placed into a dopamine
hydrochloride solution (0.1mg/mL in PBS, pH 8.5, 24 hrs, n=6).
Stability of ATH on PDMS and PDMS-PDA PDMS discs coated with
either ATH (n=6) or PDA-ATH (n=6) were exposed to whole blood
(hematocrit 0.5, 3 days) and ATH surface density was measured.
Bioactivity of ATH on PDMS-PDA PDMS, PDMS-ATH and PDMSPDA-ATH discs were incubated in plasma for 3 hours (n=6). 125Ilabeled antithrombin (AT) was added to plasma as a tracer.
Selective AT adsorption from plasma demonstrates an indirect
measure of anticoagulant activity. Another measure of bioactivity
is Anti-Factor Xa (anti-FXa) activity. PDMS discs were incubated in
AT (10 min, n=8), followed by FXa (5min). Results: As shown in
Figure 1, PDMS-PDA discs bound ATH to the surface much stronger
than PDMS. Originally, 0.25g/cm2 ATH was bound to PDMS-PDA,
which only decreased 30% to 0.17g/cm2 over 3 days.
Comparitively, PDMS discs bound 0.15g/cm2 of ATH and
decreased 84% to 0.04g/cm2. Figure 2 shows that PDMS and
PDMS-PDA bound comparative amounts of AT from plasma, at 4.0
and 3.9g/cm2, respectively. PDMS-PDA-ATH bound 19.9g/cm2
from plasma, indicating selective adsorption of AT. Anti-FXa
activity was highest on PDMS-PDA-ATH, at 6.9% of the equivalent
of 25g/cm2 ATH anti-FXa activity in solution. PDMS-PDA discs had
negligible anti-FXa activity. Conclusion: Polydopamine as a
'bioglue' provides high ATH density, stability and anticoagulant
activity. ATH coating of a complete LAD requires further studies.
Contact Information: Christoph Fusch [email protected]
134
[358]
UTERINE NK CELL DIFFERENTIATION IN NFIL3-/- MICE. Mackenzie
Redhead1, Yvonne Bach 1, Dr. Anne Croy1
1Queen's University/BDMS
Introduction: Uterine natural killer (uNK) cells are the most
abundant lymphocyte in early human and mouse decidua. UNK
cell functions have been deduced by histopathologic comparisons
of implantation sites (IS) between alymphoid (NK-T-B-), NK cell
reconstituted alymphoid (NK+T-B-) and normal NK+T+B+ mice.
C57BL/6 mice genetically ablated for the transcription factor Nfil3
are reported to be NK-T+B+ and to experience midgestation Th17
cell-mediated fetal loss when mated by BALB/c males. Objective:
To characterize the impacts of overall Nfil3-/- deficiency and of
lymphocyte-specific Nfil3-/- deficiency on mouse IS. Methods:
Syngeneic (SN) and allogeneic (AL) Nfil3-/- x Nfil3-/- or UBC-GFP
pregnancies were studied for overall effects. For lymphocyte
restricted effects, alymphoid Rag2-/-/Il2rg-/- mice were engrafted
using Nfil3-/- bone marrow (1:1 donor:recipient; BMR) 3 wk before
mating by an alymphoid or UBC-GFP male. For quantitative
paraffin-embedded histopatholgy, mice were euthanized and
perfused with 4% paraformaldehyde and IS were collected,
processed and stained with H&E, Periodicac Acid Schiff’s (PAS)
reagent for glycoproteins or biotinylated Dolichos biflorus
agglutinin (DBA), a lectin reactive to uNK cells. For whole mount in
situ immunohistochemistry, live hemisected implantation sites
were prepared and incubated with mixtures of fluorescently
conjugated antibodies (CD45, CD31, DBA, CD11c, MHCII) for 1hr at
4°C, mounted on glass slides, examined and photographed under
epifluorescence microscopy. Images were analyzed. Results: IS of
SN mated Nfil3-/- mice contained uNK cells though numbers were
significantly lower at GD6.5 and 15.5 and SA remodeling was
restricted. UNK cell numbers in SN mated BMR mice were
significantly lower at GD6.5, 10.5 and 12.5 but normal at GD8.5. SA
remodeling remained impaired although uNK cells strongly
associated with GD10.5 and 12.5 SA. In AL mated mice, most
(>95%) uNK cells were DBA+PAS+, suggesting Nfil3 is not
expressed by progenitors of angiogenic uNK cells but is expressed
by progenitors of cytokine producing DBA-PAS+ uNK cells. SN and
AL mated mice had more open uterine lumens at GD6.5 and 8.5,
and throughout the decidua unusual CD45+CD11c+ DBA+ cells
were prominent. Conclusion: The presence of uNK cells was
unexpected in Nfil3-/- mice and indicates an Nfil3 independent
sublineage of uNK cells. These cells differentiate to the DBA+ uNK
cell subset only but appear to arise later and die earlier when DBAPAS+ possibly Nfil3-dependent uNK cells cohabit the decidua
basalis. The increased population of morphologically unusual cells
may represent a uNK cell progenitor however further study into
the functional role of these cells is needed. Acknowledgements:
NSERC, CFI, OGS. Contact Information: Mackenzie Redhead
[email protected]
CNPRM 2015
[372]
THE IMPACT OF IN UTERO EXPOSURE TO VENLAFAXINE, AN
ANTIDEPRESSANT USED TO TREAT MATERNAL DEPRESSION, ON
FOETAL AND PLACENTAL DEVELOPMENT IN THE RAT. Laetitia
Laurent1, Sheila Rose Ernest2, Chunwei Huang2, Barbara Hales2,
Cathy Vaillancourt1
1INRS-Institut Armand Frappier et centre de recherche BioMed,
Université du Québec, 2Pharmacology and therapeutic
department, McGill University
Introduction: Depressive disorders occur in about 25 % of
pregnant women. Untreated women present a higher risk to
develop obstetric complications associated with alterations in
placental development. In this context, the first-line choices for
the treatment of depression are selective serotonin (5-HT) and 5HT-norepinephrine (NE) reuptake inhibitors (SSRIs and SNRIs). The
placenta serves as an early source of the 5-HT and NE, which are
critical in programming embryonic and foetal developmental
processes. Objective: We hypothesize that treatment with SNRIs
during pregnancy alters placental development, and 5-HT and NE
function. Methods: To address this hypothesis we have
determined the effects of one of the SNRIs most prescribed for
women during their childbearing years in Québec, namely
venlafaxine (Effexor®), in a rat model. Pregnant Sprague Dawley
rats were treated with vehicle or venlafaxine (3, 10, 30, 100
mg/kg/day) from gestational day 8 to day 21. The rats were
euthanized by CO2 inhalation and decapitation, and placentas and
foetuses were collected by caesarean section. Results: We
observed a decrease in the placenta weights (12-14%) of fetuses
from both sexes following treatment with low doses of venlafaxine
compared to control; no differences in body weight were found,
resulting in an increase in the foetus/placenta weight ratio (1014%). RT-qPCR analyses showed a decrease in MAO-A
(monoamine oxidase A, an enzyme that degrades monoamines)
and SERT (5-HT transporter) mRNA levels, whereas NET (NE
transporter) mRNA levels were not affected in the foetuses
exposed to venlafaxine. Conclusion: Altogether, these data
suggest that venlafaxine treatment decreases 5-HT transport and
degradation in the placenta. Considering that placental 5-HT is
involved in foetal brain development, and that a dysfunction of 5HT systems during early development may be involved in mental
disorders, a better understanding of how antidepressants regulate
the placental 5-HT systems is a priority. Acknowledgements: We
should like to thank FRQS and the « RQR new collaboration »
(Réseau Québécois de la Reproduction) for partially financing this
study and Pfizer for graciously providing the venlafaxine
(Effexor®). Contact Information: [email protected]
form of magnetic resonance imaging (MRI), called hyperpolarised
carbon-13 (13C) MRI, allows real-time examination of metabolic
processes in vivo through injection and subsequent imaging of
hyperpolarised 13C enriched substrates. This method allows
images to be obtained of the injected substrate and its metabolic
by-products. Objective: To test the feasibility of hyperpolarised
13C enriched pyruvate MRI for examination of metabolism and
transport in the fetoplacental unit of guinea pigs. Methods: 7
pregnant guinea pigs (40-55 days of gestation, term 68 days)
carrying a combined 30 fetuses were anaesthetized using
isoflurane and a catheter was placed in a vein in the maternal hind
paw. Scanning was performed using a clinical MRI scanner under a
protocol approved by our Animal Use Subcommittee. Anatomical
images were acquired and then a bolus of hyperpolarised 13C
enriched pyruvate was injected into the catheter. 3D 13C images
of pyruvate and its metabolic by-products were obtained starting
at 10 seconds after the beginning of bolus injection and every 10s
thereafter to 60s. The guinea pigs were recovered after imaging
and allowed to pup spontaneously. Results: Figure 1 displays the
colour 13C images of pyruvate and the metabolic by-product
lactate overlaid on the grey scale anatomical images at 30s post
injection of pyruvate. Figure 2 shows the average time courses of
pyruvate and lactate signal intensities in the placentae and fetal
livers. In the placentae, the lactate signal peaks at 20s while the
pyruvate signal peaks at 10s because the pyruvate enters the
placentae as a bolus and is subsequently metabolised to lactate.
Pyruvate and lactate were seen in all the placentae and fetal livers.
At 30s, the lactate signal in the fetal livers was larger than the
pyruvate signal, suggesting that the lactate in the fetal livers arises
at least in part from transport of lactate from the placentae and
not solely from metabolism of pyruvate within the fetal liver.
Conclusion: Pyruvate and lactate were observed in both the
placentae and fetal livers, demonstrating the feasibility of
hyperpolarised 13C MRI for measuring fetoplacental transport and
metabolism. Acknowledgements: Jenn Hadway, GE Healthcare,
NSERC, CIHR, ORF, CRC Program. Contact Information: Lanette
Friesen-Waldner [email protected]
[384]
FEASIBILITY OF HYPERPOLARISED CARBON-13 MAGNETIC
RESONANCE IMAGING FOR EXAMINATION OF FETOPLACENTAL
METABOLISM AND TRANSPORT. Lanette J Friesen-Waldner1,
Kevin J Sinclair1, Trevor P Wade2, Abraam S Soliman3, Colin M
McCurdy1, Banoub C Michael1, Barbra de Vrijer4, Charles A
McKenzie1, Timothy RH Regnault4
1Medical Biophysics, University of Western Ontario, 2Robarts
Research Institute, Unviersity of Western Ontario, 3Biomedical
Engineering, Unviersity of Western Ontario, 4Obstetrics and
Gynaecology, University of Western Ontario,
Introduction: There is increasing evidence that an adverse in utero
environment leads to fetal programming, which significantly
increases the risk of a variety of diseases after birth. Altered
fetoplacental metabolism and transport is implicated in this
programming. The placenta’s role in mediating interactions
between mother and fetus and in nutrient transport to the fetus
involves not only a passive diffusional barrier, but also a variety of
influx and efflux transporters and metabolising enzymes. A new
CNPRM 2015
135
[396]
A FETO-PLACENTAL CO-CULTURE MODEL SHOWS THE COMPLEX
DISRUPTIVE EFFECTS OF ANTIDEPRESSANT FLUOXETINE AND
METABOLITE NORFLUOXETINE ON ESTROGEN BIOSYNTHESIS.
Andrée-Anne Hudon Thibeault1, Thomas Sanderson2, Cathy
Vaillancourt2
1INRS-Institut Armand-Frappier and BioMed Research Center,
2INRS-Institut Armand-Frappier and BioMed Research Center
Introduction: Depression occurs in up to 25% of pregnant women
and almost a third undergo antidepressant treatment, mainly with
selective serotonin-reuptake inhibitors (SSRIs). SSRIs have been
associated with adverse effects on pregnancy and fetal
development. The effects of one of the most prescribed SSRIs,
fluoxetine, on the endocrine functions of the fetoplacental unit
have never been studied. We have previously shown that
serotonin induces aromatase (CYP19), the enzyme that converts
androgens to estrogens, in placental cell lines. Based on this, we
hypothesize that fluoxetine, by increasing serotonin levels,
stimulates placental estrogen production. Objective: The
objective of this study was to determine the effect of fluoxetine
and its metabolite norfluoxetine on CYP19 activity and gene
expression as well as estrogen production in a coculture of BeWo
(human trophoblast-like) and H295R (human fetal-like
adrenocortical) cells, a model of fetoplacental steroidogenesis.
Methods: The coculture was exposed for 24 h to fluoxetine and
norfluoxetine (0.3, 1 and 3 M) in 0.1% DMSO. CYP19 activity was
determined by tritiated-water release assay using 1-[3H]androstenedione. CYP19 mRNA levels were determined by RTqPCR and normalized using SDHA, PPIA and TOP-1 reference
genes. Hormones were quantified using commercial ELISA kits.
Results: Fluoxetine (1 and 3 M) increased CYP19 activity by 1.6and 2.3-fold, respectively, in BeWo cells and by 1.5-fold at 3 M in
H295R cells. Fluoxetine (1 M) increased CYP19 mRNA levels by
1.9-fold. In contrast, fluoxetine’s metabolite, norfluoxetine (3 M)
acted as a catalytic inhibitor of CYP19 in BeWo cells (Ki = 1.2 M).
In the co-culture, fluoxetine did not alter hormone production.
However, norfluoxetine (3 M) decreased production of the
estrogen precursor androstenedione by 56% compared to control.
Norfluoxetine (0.3, 1 and 3M) reduced estradiol production by
43%, 51% and 72%, respectively, and at 1 and 3 M, it reduced
estrone production by 58 % and 62 %, respectively. Estriol
production was not affected. Conclusion: The BeWo/H295R fetoplacental co-culture demonstrates the complex and contrasting
effects of SSRIs, showing no effect of fluoxetine but a disruption of
androgen and estrogen production by its metabolite. This study
indicates that pregnancy complications associated with fluoxetine
use may be caused by disruption of estrogen biosynthesis in the
fetoplacental compartment. Acknowledgements: This work was
supported by the March of Dimes Birth Defects Foundation (12FY12-179: CV and JTS) and studentships to AAHT from Fonds de
recherche du Québec-Santé and Canadian Institutes of Health
Research. Contact Information: [email protected]
[407]
MELATONIN PROTECT AGAINST INFLAMMATION IN PLACENTAL
TROPHOBLAST EXPOSED TO HYPOXIA-REOXYGENATION. Lucas
Sagrillo-Fagundes1, Eugênia Salustiano2, Laetitia Laurent1, Rodrigo
Ruano2, Regina Markus2, Cathy Vaillancourt1
1INRS - Institut Armand Frappier, 2Universidade de São Paulo
Introduction: The lack of arterial remodelling in preeclamptic
placentas generates an intermittent oxygenation to the
trophoblasts and a consequent state of hypoxia and reoxygenation
(H/R). H/R is the main activator of trophoblastic and maternal
inflammation. Melatonin, its synthesis enzymes and receptors
were well described in villous cytotrophoblasts. Actually, its
136
powerful anti-oxidative effects on placental function have been
widely investigated during the last years. However, its antiinflammatory activity on trophoblasts was never investigated.
Objective: The aim of this research is to investigate if melatonin is
able to alleviate the trophoblastic inflammation caused by H/R, a
model of preeclampsia in vitro. Methods: Placentas were
obtained from pregnancies following vaginal delivery (term).
Primary villous trophoblast were isolated and purified using the
classical trypsin digestions followed by a magnetic cell sorter.
Trophoblasts were maintained under culture for 72 hours to
induce the differentiation from villous cytotrophoblast to
syncytiotrophoblast. Then, cells were cultured for an additional
period of 22h of normoxia or 4h of hypoxia followed by 18h of
normoxia. Cells were treated every 24h with one these
treatments: melatonin (1mM); luzindole (antagonist of melatonin
receptors (1nM)); Melatonin (1mM) + luzindole (1nM); and
pyrrolidinedithiocarbamate (PDTC, inhibitor of NF?B (25µM)).
After the treatments, cell medium was collected and cytokines
(inflammation mediators) (TNF and IL-10) and melatonin levels
were measured by the kit MILLIPLEX MAP and by ELISA,
respectively. Results: The concentration of melatonin was
reduced in trophoblasts exposed to H/R in comparison to
normoxia. When exposed to H/R and also treated with melatonin,
luzindole or with the association of melatonin and luzindole, the
content of melatonin is increased in comparison with cells
exposed to normoxia. TNF is significantly increased in trophoblast
exposed to H/R and under PDTC treatment. IL-10, an antiinflammatory cytokine is significantly increased in cells treated
with melatonin and exposed to H/R. Conclusion: In trophoblasts
exposed to H/R, the reduction of melatonin content confirms the
relationship between preeclampsia and lack of placental
melatonin. The higher levels of IL-10 in trophoblasts exposed to
H/R and treated with melatonin evidence the melatonin
protection against excessive inflammation. In sum, the onset of
clinical trials to treat preeclampsia with melatonin require a
deeper comprehension of the effect of melatonin on trophoblasts
and its modulation on the inflammation caused by H/R and
consequently by preeclampsia. Acknowledgements: This work
was supported by the NSERC and a studentship to LSF from
FRQNT. Contact Information: Lucas Sagrillo Fagundes
[email protected]
[444]
EXPRESSION OF MICRORNAS IN PLACENTAL EXOSOMES
COLLECTED IN THE FIRST TRIMESTER OF PREGNANCIES
COMPLICATED BY PREECLAMPSIA OR INTRAUTERINE GROWTH
RESTRICTION. Giilet Virginie 1, Annie Ouellet2, Andrea Baccarelli3,
Larissa Takser1
1Faculté de médecine et sciences de la santé/Université de
Sherbrooke/Pédiatrie, 2Faculté de médecine et sciences de la
santé/Université de Sherbrooke/Obstétrique-Gynécologie,
3Harvard School of Public Health/ Harvard University /
Environmental Health
Introduction: Common pregnancy complications such as
preeclampsia (PE), intrauterine growth restriction (IUGR) and
gestational diabetes mellitus (GDM) are related to placental
dysfunction. Recent case-control studies have reported that
placenta from pregnancies complicated by preeclampsia and/or
intrauterine growth restriction differentially expressed certain
microRNAs compared to those from uncomplicated pregnancies.
Most of these studies have been conducted on full term placenta
samples following birth, which is not appropriate for early
biomarker discovery. A recent study reported that placentalspecific miRNAs were released into maternal circulation through
exosomes, tissue-specific nanovesicles of 30-10nm diameter
secreted by all types of cells including trophoblastic cells.
CNPRM 2015
Objective: Our objective is to examine the miRNA profile of
placental exosomes in pregnancies complicated by PE, by IUGR,
and GDM using blood samples collected in early pregnancy.
Methods: We performed a case-control study nested in a
prospective cohort of pregnant women enrolled at the first
trimester of pregnancy, in Centre Hospitalier Universitaire,
Sherbrooke, Canada. Five cases of preeclampsia, five cases of
intrauterine growth restriction and twenty three cases of
gestational diabetes were selected and each case was matched for
parity and gestational age at sampling with 2 controls
(uncomplicated pregnancy). Based on literature review, we
selected 20 miRNAs (placenta-specific or not) reported with
placenta altered expression in PE / IUGR / GDM pregnancy. Plasma
exosomes were isolated using exoRNeasy kit and miRNAs were
extracted from purified plasma exosomes. The analysis of relative
expression was done by quantitative real-time polymerase chain
reaction (qRT-PCR). Normalisation was done using a spike-in
miRNA (cel miR-39). Results: We are able to isolate exosomes
including placental exosomes from frozen blood plasma obtained
in the first trimester in case of PE, GDM, IUGR and normal
pregnancy. Results were confirmed by electron microscopy and
immunogold. Results of qRT-PCR for the 17 selected miRNAs
showed differential expression between cases of PE, cases of
GDM, cases of IUGR and controls. Conclusion: Exosomes as well
as miRNAs represent a new avenue in the area of early diagnostic
of pregnancy complications. The miRNA profile of placental
exosomes may be used as an early biomarker of placental
dysfunction. To validate our results we currently conduct a larger
prospective clinical study of placental exosomes using blood and
urine repeated sampling during 1st and 2nd trimesters of
gestation. Acknowledgements: We thanks all womens who have
participated, medical personnel of CHUS, and the principal
investigators : Dr Ouellet and Dr Takser. Contact Information:
[email protected]
[472]
EFFECT OF OLANZAPINE IN THE PLACENTA: IDENTIFICATION OF
RECEPTORS. 1Robyn D. Pereira BSc, 2Alison C. Holloway PhD,
3Valerie H. Taylor MD PhD, 1Sandeep Raha PhD
1Department/Institution: Pediatrics, McMaster University,
2Department/Institution: Obstetrics and Gynecology, McMaster
University, 3Department/Institution: Psychiatry, University of
Toronto
INTRODUCTION: 14% of pregnant women suffer a mental illness
and the atypical antipsychotic, olanzapine (OLN), is commonly
used to treat many of these disorders. OLN exposure during
pregnancy can cause babies to be small or large for gestational
age; risk factors for metabolic syndrome in adulthood. However,
the signaling pathways linking OLN to these changes are unknown.
Since placental function contributes to fetal growth, we evaluated
the expression of receptors for OLN in rat placenta and human
trophoblast cells, HTR8/SVneo. OBJECTIVE: This project
determined which receptors are expressed by HTR8s and rat
placenta at two gestational time points. This identified which
receptors may be important to both placental development
(trophoblast invasion) and adverse OLN-mediated pregnancy
outcomes. METHODS: Quantitative PCR was used to determine
the mRNA expression of OLN receptor targets in HTR8s and rat
placenta at gestational day (GD) 15 and 20 (N=5). HTR8s (N=4)
were treated with a clinically relevant dose of 1μM OLN for 48
hours, and the expression of trophoblast invasion enzymes were
assessed by Western blots. RESULTS: HTR8s, GD15 and GD20 rat
placenta express the following OLN targeted receptors: 1)
serotonin 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2A, 5-HT2B, 5-HT5A, and
5-HT6 2) dopamine D1 3) muscarinic M1, M2, M3, M4 and M5 4)
adrenoreceptor α1A, α1B, α2A, α2B and α2C 5) histamine H1.
HTR8s additionally express OLN targeted serotonin 5-HT1E, 5HT2C, 5-HT3, and dopamine D2, D4 and D5 receptors. Both GD15
and GD20 rat placenta express the serotonin 5-HT7 receptor. The
expression of the following receptors increased significantly
(p<0.05) in GD20 relative to GD15 rat placenta: histamine H1
(5.92- fold), muscarinic M1 (4-fold), muscarinic M4 (2-fold),
serotonin 5-HT1D (1.7-fold), 5-HT2A, (1.86-fold) and 5-HT2B (5.13fold). Additionally, adrenoreceptor α1A expression significantly
decreased (p<0.05) in GD20 rat placenta (4.64-fold). The
expression of a key trophoblast invasion enzyme, matrix
metalloproteinase 2 (MMP2), trended to increase by 21.44±0.03%
in HTR8s treated with 1μM OLN. CONCLUSION: Comparison
between receptor expression in HTR8s and rat placenta identifies
which receptors are trophoblast and species specific. Additionally,
comparing GD15 and GD20 rat placenta elucidates which
receptors are likely important for placental function at various
developmental stages. Furthermore, the presence of OLN
receptors in the placenta suggests that OLN use during pregnancy
can directly influence placental development/function but the
specific trophoblast-mediated effects remain to be determined.
ACKNOWLEDGEMENTS: This project was supported by Natural
Sciences and Engineering Council (NSERC) Discovery and NSERC
Masters Studentship funding. CONTACT INFORMATION : Robyn
D. Pereira [email protected]
Newborn Health
[351]
ARTIFICIAL PLACENTA: SURFACE MODIFICATION OF SINGLE
OXYGENATOR UNITS (SOUS) USING POLYDOPAMINE (PDA) AS
BIO-GLUE FOR ANTICOAGULANT ANTITHROMBIN-HEPARIN (ATH)
COMPLEX. Darren Sandejas1, Rena Cornelius2, Leslie Berry3, Niels
Rochow4, Harpreet Matharoo5, Gerhard Fusch4, Helen Atkinson3,
Anthony Chan3, Ravi Selvaganapathy5, Christoph Fusch4, John
Brash2
1Biomedical Engineering, McMaster University, Hamilton, Ontario,
2Chemical Engineering, McMaster University, Hamilton, Ontario,
3Thrombosis and Atherosclerosis Research Institute, Hamilton,
Ontario, 4Pediatrics, McMaster University, Hamilton, Ontario,
5Mechanical Engineering, McMaster University, Hamilton, Ontario
Introduction: Our “artificial placenta” neonatal lung assist device
is a stacked array of microfluidic polydimethylsiloxane (PDMS)
SOUs. Figure 1 shows a schematic of a SOU. Blood contacting
surfaces within the SOUs need to be hemocompatible, A method
using PDA as a ‘bioglue’ to attach a covalent ATH complex, a
potent anticoagulant, has been developed to achieve
hemocompatibility. Objective: To quantify ATH binding and
bioactivity on PDA modified SOUs. Methods: Quantification and
evaluation of surface bound ATH was carried out through blood
exposure. Two sets of oxygenators (n=6 total) were incubated in
dopamine hydrochloride (1 mg/mL in PBS, pH8.5, 24hrs) which
oxidizes to PDA. Subsequent ATH incubation formed the PDMSPDA-ATH complex (0.1mg/mL in PBS, pH7.4, 24hrs). 125I-labeled
ATH was used as a tracer. One set of SOUs (n=3) was then exposed
whole blood (hematocrit 0.5) for 2 days. The heparin component
of ATH, if active, selectively binds antithrombin (AT); therefore,
the anticoagulant activity of ATH modified SOUs was evaluated by
measuring AT uptake from plasma (3hrs, n=6) to PDMS-PDA-ATH.
125I-labeled AT was added to plasma as a tracer. Results: Initially,
0.23g/cm2 of ATH was bound to the PDMS-PDA oxygenators after
24 hours. This level suggests monolayers were formed.
Subsequent exposure to blood removed 35% after 48 hours, with
0.15g/cm2 of ATH remaining on the surface. This indicates the
binding of ATH to PDMS-PDA was relatively stable. Figure 2 shows
that PDMS-PDA-ATH SOUs bound 48.4ng/cm2 of AT from plasma,
CNPRM 2015
137
significantly higher than the precursor PDMS-PDA, at 0.15ng/cm2.
This demonstrates that the anticoagulant activity of heparin in
ATH remains active when attached through PDA. Conclusion:
PDA, used as an adhesive agent to attach ATH to PDMS
microfluidic SOUs, provides high ATH surface density, increased
stability, and increased anticoagulant activity. Contact
Information: Christoph Fusch [email protected]
[386]
THE USE OF PCR FOR DIAGNOSING EARLY ONSET SEPSIS IN
NEWBORNS- A FEASIBILITY STUDY. Joanna Seliga-Siwecka1, Ioana
Moldovan2, Robert Slinger2, Nick Barrowman3, Thierry LacazeMasmonteil1
1Children's Hospital of East Ontario, Department of Neonatology,
2Children's Hospital of East Ontario, Department of Microbiology,
3Children's Hospital of East Ontario, Research Institute
Introduction: Early Onset Neonatal Sepsis (EONS) is a frequent
disease, mainly caused by Group B Streptococcus (GBS) and E. coli.
Symptoms of neonatal sepsis are nonspecific. Available diagnostic
tools cannot reliably diagnose or rule out EONS before blood
culture results are available. Intrapartum antibiotics, given to GBS
positive mothers or with possible chorioamnionitis, can result in
falsely negative blood cultures in the infant. Objective: To test
the feasibility of using real time polymerase chain reaction (RTPCR) for early detection (less than 24 hours) of GBS and E.coli in
newborns with either confirmed (positive blood culture) or
probable (symptomatic infant born to a mother who received
intrapartum antibiotics) EONS. Methods: Serum samples of 62
preterm and 16 late preterm or term infants were analyzed.
Samples were obtained between 15-21 h of age after initiation of
antibiotics as part of two previous prospective studies. RT-PCR was
performed using 5'exonuclease probe assays. Results: There
were 6 and 75 samples of infants with confirmed or probable
sepsis respectively. In the proven sepsis group, the RT-PCR was
found positive in 100% of samples: 2 GBS and 4 E.coli,
microorganisms were consistent with those grown in blood
cultures. In the probable sepsis population, 70 (93%) samples were
negative for bacterial NA, together with 1 and 4 samples positive
for GBS and E.coli respectively. Conclusion: RT-PCR is feasible and
may allow earlier (before blood cultures yield negative at 48
hours) discontinuation of unnecessary antibiotics in high-risk
infants. A prospective study with a larger sample size is warranted
to determine if, in high risk infants born to mothers who received
intrapartum antibiotics, the duration of antibiotic treatment in the
infant could be reduced with a diagnostic algorithm that includes a
point-of-care RT-PCR performed on a sample drawn in the first
138
hours post birth. Contact Information:
[email protected]
[437]
EFFECT OF THE “MICROSYSTEMS” CARE MODEL ON NOISE
REDUCTION IN THE NICU – FIRST RESULTS. Gerhard Fusch1, Saber
Mohamed2, Ahmed Bakry1, Naif Al Sharari1, David Pogorzelski1,
Carrie-Lynn Meyer1, Linda Alberti1, Salhab El-Helou1, Samir Ziada2,
Sourabh Dutta, Christoph Fusch1
1Department of Pediatrics, McMaster University, Hamilton, ON,
2Department of Mechanical Engineering, McMaster University,
Hamilton, ON
Introduction: There are different organisational models to manage
a NICU. We recently introduced “Microsystems” (MS) and
cohorting of patients according to acuity in our level III unit. One
outcome parameter to assess the impact of this change is the
noise level (NL) as this change will create designated areas with
more and less intensive care within the NICU. We hypothesize that
NLs will be different in both areas before and after introduction.
Objective: 1) To assess the NL before and after implementation of
MS comparing day vs. night times, weekdays vs. weekends and
areas of high and low acuity 2) To investigate the effect of the
implementation of MS on the NLs in the different areas of the
NICU. Methods: Institution: McMaster University NICU, 47-bed
level III; 5 pods with 4 x 10 and 1 x 7 beds. Successful
implementation of MS on May 1st, 2014. Data collection: 24h
noise level measurements (60 days before and 50 days after
implementation) in two representative pods (pod A: increased
acuity, pod D: reduced acuity after implementation) using a
commercial available noise meter (Casella, CEL-246). Meter was
positioned in the center of each of the five pods and moved to the
next pod on a daily schedule. NLs were measured as LAeq in dBA
in 10sec intervals and averaged over 5 min. Different times were
analyzed, daytime (6am-9pm) and nighttime (9pm-6am). Time:
Data was collected during two periods: 1. pre-implementation
phase from March-Apr 2014; 2. post-implementation phase from
Sept-Nov 2014. Results: Weekdays: Pre-implementation: Average
NLs in pod A and D were 61±0.5dBA (day) and 57±0.5dBA (night).
During hand-over time of nurses (morning and evening), average
NLs reach 64±0.5dBA, maximum NLs were 72dBA. Postimplementation: pod A (acute care area): Average NL were
unchanged (61±0.5dBA) during the day and elevated (58±0.5dBA)
during night potentially due to increased need of medical
equipment such as ventilators. Noise peaks during hand-over of
nurses (64±0.5dBA) were similar to before start of MS. Pod D
(intermediate care area): average NLs significantly reduced to
58±0.5dBA (day) and 57±0.5dBA (night). Noise peaks during handover have been reduced to 62±0.5dBA in the morning or
disappeared completely in the evening. Weekends:Compared to
weekdays, average NLs were significantly reduced by at least 3dBA
to 58±0.5dBA (day) and 55±0.5dBA (night). Conclusion: Measured
NLs are higher than current recommendations for NICUs (AAP:
<45dBA). NL seems to be more affected by organisational
conditions (e.g. handover, day/night and weekends). Overall, MS
CNPRM 2015
seems to lower the noise exposition significantly with no increase
in the acute area but reduction in the intermediate area.
Acknowledgements: The project is funded by HAHSO. Contact
Information: Christoph Fusch [email protected]
[448]
EXAMINING THE USE OF WITHDRAWAL OF LIFE-SUSTAINING
THERAPY IN THREE PAEDIATRIC PATIENT POPULATIONS. Dr.
Gillian MacLean1, Ms. Chloee Detchou2, Mr. Nick Barrowman3, Dr.
Anna Theresa Lobos1, Dr. Christina Vadeboncoeur1, Dr. Michelle
Mullen1, Dr. Gregory Moore1
1University of Ottawa/Department of Pediatrics, 2University of
Ottawa, 3University of Ottawa/Research Institute Clinical Research
Unit/Department of Pediatrics
Introduction: A poor prognosis based on mortality or disability
rates can push physicians to discuss withdrawal of life-sustaining
therapy (WLST) for newborns in the NICU. However, WLST may
not be discussed with families of an older child despite a similar
poor prognosis. Three patient populations with overlapping
prognoses include: ventilated extremely premature infants (22-25
weeks) (EPI), ventilated term neonates with hypoxic ischemic
encephalopathy (HIE) and ventilated children with traumatic brain
injury (TBI). Objective: 1) To document the frequency with which
physicians discuss WLST with families in each respective
population; 2) to compare the frequency of discussions between
populations; and, 3) to document the frequency of 5 possible
‘outcomes’ of WLST discussions in each population: WLST ‘late’ in
clinical course, WLST ‘early’ in clinical course, WLST with
‘unexpected survival’, refusal of WLST with survival and refusal of
WLST with death. We hypothesize that the WLST will be most
frequently offered in the EPI population. We hypothesize that the
most common ‘type’ to those offered WLST would be the “late”
WLST (“imminent death”) for all three respective populations.
Methods: Retrospective chart review of cases from January 2003
to December 2013. Included cases met pre-specified inclusion
criteria, see attached data collection form with criteria. Prevalence
of WLST discussions and the outcome after WLST discussions will
be determined using the Wilson score method. Comparisons will
use Fisher's exact test. Results: Of the 300 charts reviewed to
date, 155 were included: 95 EPI, 48 HIE and 12 TBI. WLST was
discussed in 35 of EPI, 24 of HIE and 1 of TBI. For EPI, in 16 cases,
WLST was ‘late’; in 12 cases, WLST was ‘early’; there was 1
‘unexpected survival’. For HIE, in 1 case, WLST was ‘late’; in 16
cases, WLST was ‘early’; there was no ‘unexpected survival’. For
TBI, there was no occurrence of WLST. For EPI, WLST was refused
in 6 cases: 3 died and 3 survived. For HIE, WLST was refused in 2
cases: 1 died and 1 survived. For TBI, WLST was never
recommended and thus never refused. Statistical comparison
between populations will occur after chart review completion. In
55 EPI, 24 HIE and 11 TBI (90/155 cases), no discussion of WLST
was documented. Conclusion: Preliminary data does not
demonstrate a greater frequency of WLST discussions in EPI
compared with HIE; this does not support literature suggesting a
bias against EPI. There was a very low frequency of WLST
discussions and actual WLST in TBI, as per the current literature.
Despite guarded prognoses for these populations, discussion of
WLST is relatively infrequent. Contact Information:
[email protected]
[450
UMBILICAL CORD BLOOD CORTISOL LEVELS AND HEMODYNAMIC
STATUS ON THE FIRST DAY OF LIFE IN PRETERM INFANTS <32
WEEKS GESTATION. S Manickaraj1, S Buddhavarapu1, N Brown1, K
Yusuf1
11Division of Neonatology, Department of Pediatrics, University of
Calgary, Calgary, Alberta, Canada.
Introduction: Adrenal insufficiency is an important contributor to
hemodynamic instability in the first few days of life in preterm
infants. Preterm infants hypotensive on day 1 may have an innate
inability to mount an adrenal response to stress, which could be
studied by measuring umbilical cord cortisol levels. Objective: To
compare cord blood cortisol levels between infants <32 weeks
gestation who need fluid bolus or inotropic support (F/I group) in
the first 24 hours of life and infants who do not need such support
(No F/I group). Methods: This was a prospective observational
study on infants <32 weeks gestation. Blood was drawn from the
umbilical vein within 30 minutes of birth and cortisol was assayed
using ELISA. Use of fluid bolus or inotrope in the first 24 hours of
life was used as a marker for hemodynamic instability. The criteria
for use of fluid boluses and inotropes are consistent in our unit.
Cortisol levels were compared between the F/I and No F/I groups.
Statistical analysis was performed using a two way non-paired
Student t test or Mann-Whitney test and χ2 or Fisher's exact test
as appropriate. Results: Infants in F/I group were more preterm,
smaller, and received less antenatal corticosteroids (ANCS) and
had significantly higher SNAPPE-II scores and rates of IVH, RDS,
and mortality. Umbilical cortisol levels did not correlate with mean
blood pressures at 1, 6, 12 and 24 hours of life. There was no
effect of chorioamnionitis or mode of delivery (MOD) on cortisol
levels. Conclusion: Umbilical cortisol levels in hemodynamically
unstable preterm infants are not different from those in well
preterm infants. We speculate that, unlike what is reported with
term infants, preterm infants do not respond adequately to
stressors like intrauterine infection and labor.
Acknowledgements: Alberta Children's Hospital Research Institute
for Child and Maternal Health. Contact Information: Kamran
Yusuf [email protected]
[452]
EXTENDED INTERVAL DOSING OF GENTAMICIN IN NEONATES <32
WEEKS GESTATION AND >7 DAYS OF AGE. Arun Sundaram1, Belal
Alshaikh1, Albert Akierman1, Deonne Dersch-Mills2, Kamran Yusuf1
1Department of Pediatrics, University of Calgary, Calgary, Alberta,
Canada , 2Pharmacy, Alberta Health Services, Calgary, Alberta,
Canada.
Introduction: Conventional interval dosing (CID) regimens employ
a lower gentamicin dose with shorter dosing interval while
extended interval dosing (EID) regimens employ a higher dose
with longer dosing interval. EID results in better therapeutic levels
in term and preterm infants in the first week of life. However.
clearance, serum half-life, and volume of distribution of
gentamicin change during neonatal period. Limited data exists on
the efficacy of EID in preterm infants <32 weeks and >7 days of
age. Objective: To determine if EID of gentamicin achieves
therapeutic serum trough (<2µg/ml) and peak (5-12µg/ml) levels
compared to CID in preterm infants <32 weeks gestation and >7
days of age. Methods: Infants <32 weeks gestation and >7 days
of age who received gentamicin for suspected/confirmed sepsis
were included. Exclusion criteria included major congenital
anomalies and renal dysfunction. Gentamicin was administered
initially at 5 mg/kg/dose with the dosing interval based on a 22 h
level after the first dose (EID). Trough and peak levels were
CNPRM 2015
139
measured before and after the third dose if the dosing interval
was q 24h and after the second dose if the interval was q 36 h or
48 h. These levels were compared with infants who had received
gentamicin 2.5 mg/kg/dose every 8-24 h (CID). Statistical analysis
was performed using a two way non-paired Student t test and χ2
or Fisher's exact test. Results: 22 infants (56%) in the CID group
had peak levels <5 µg/ml while all infants in EID group had peak
levels >5µg/ml (P <0.01). 5 infants (13%) in CID had trough levels
>2 µg/ml while all infants in EID group had trough levels <2 µg/ml
(P <0.01). There was no effect on urine output or serum creatinine
levels in both regimens. 1 infant in each group had sensorineural
hearing loss. Conclusion: In premature infants <32 weeks
gestation and >7 days of age, EID of gentamicin is safe and
achieves more optimum therapeutic serum peak and trough levels
as compared to CID of gentamicin. Contact Information: Kamran
Yusuf [email protected]
[453]
CORTICOSTEROID THERAPY IN NEONATAL MANAGEMENT OF
SHOCK. Gabriel Altit1, Myriam Vigny-Pau1, Keith Barrington1,
Véronique Dorval1, Anie Lapointe1
1Université de Montréal / CHU Sainte-Justine
Introduction: Controversy exists about the management of
neonatal septic shock. Hydrocortisone (HC) is used during septic
course in older children and adults, but has been rarely studied in
neonates. Objective: To describe hydrocortisone administration
in septic shock in our neonatal intensive care unit and determine if
variations in practice are associated with improved survival.
Methods: The effects of HC therapy for septic shock were
retrospectively evaluated in neonates admitted to our unit
between 2010 and 2013. Data regarding timing of HC
administration and effects on survival were analysed. Results:
Thirty-five infants were treated for neonatal shock during the
study period (80% culture proven sepsis). A total of 23 patients out
of the 35 received HC during the course of their shock (average
cumulative dose of 16 ± 16 mg/kg). The 2 groups (hydrocortisone
vs no-hydrocortisone) did not differ significantly in terms of
gestational age (25.7±1.4 vs 26.8 ± 1.8 weeks, p=0.68), birth
weight (994 ± 194 vs 964 ± 371 grams, p=0.34) and age at onset of
shock (12.2 ± 18 vs 9.9 ± 8.1 days, p=0.93). Exposure to antenatal
steroids (87% vs 100%, p=054) and APGAR scores (6±2 and 6±2,
p=0.69) did not differ significantly between the two groups.
Patients who received hydrocortisone were less likely to survive
(26 vs 83 %, p=0.03) and were sicker in general (vasoactive index
score 48 ± 51 vs 10 ± 8, p=0.000). Timing of hydrocortisone
administration was on average 49 ± 63 hours after the onset of
shock. Although we noted a trend toward later hydrocortisone
administration in survivors (79 ± 92 vs 38±51 hours, p=0,26), this
difference was not statistically significant. Patients that received
hydrocortisone and survived had a trend toward a more prolonged
hospitalisation (age at discharge 47.4 ± 5.8 vs 42 ± 5.3 weeks of
corrected gestational age, p=0.08). Conclusion: In our centre,
hydrocortisone administration in the context of neonatal septic
shock tends to be early and in patients presenting with a more
severe clinical picture. However, this is without any improvement
in survival. Further prospective studies are needed to clarify
hydrocortisone’s role in septic shock management in the term and
preterm newborn. Acknowledgements: Jocelyne Vallée. Contact
Information: Gabriel Altit [email protected]
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