The Journal of M aternal- F etal and N eonatal M edicine, 2010; Early Online, 1–5 Placental abruption: critical analysis of risk factors and perinatal outcomes GALI PARIENTE1, ARNON WIZNITZER1, RUSLAN SERGIENKO2, MOSHE MAZOR1, GERSHON HOLCBERG1, & EYAL SHEINER1 J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of British Columbia on 09/23/10 For personal use only. 1 F aculty of H ealth Sciences, Department of Obstetrics and G ynecology, Soroka University M edical Center, Ben- Gurion University of the N egev, Beer-Sheva, Israel and 2 F aculty of H ealth Sciences, Department of Epidemiology and H ealth Services E valuation, Soroka University M edical Center, Ben- Gurion University of the N egev, Beer-Sheva, Israel (Received 5 F ebruary 2010; accepted 23 July 2010) Abstract Objective. To investigate risk factors and pregnancy outcome of patients with placental abruption. M ethods. A population-based study comparing all pregnancies of women with and without placental abruption was conducted. Stratified analysis using multiple logistic regression models was performed to control for confounders. Results. During the study period there were 185,476 deliveries, of which 0.7% (1365) occurred in patients with placental abruption. The incidence of placental abruption increased between the years 1998 to 2006 from 0.6 to 0.8%. Placental abruption was more common at earlier gestational age. The following conditions were significantly associated with placental abruption, using a multivariable analysis with backward elimination: hypertensive disorders, prior cesarean section, maternal age, and gestational age. Placental abruption was significantly associated with adverse perinatal outcomes such as Apgar scores 5 7 at 1 and 5 min and perinatal mortality. Patients with placental abruption were more likely to have cesarean deliveries, as well as cesarean hysterectomy.Using another multivariate analysis, with perinatal mortality as the outcome variable, controlling for gestational age, hypertensive disorders, etc., placental abruption was noted as an independent risk factor for perinatal mortality. Conclusions. Placental abruption is an independent risk factor for perinatal mortality. Since the incidence of placental abruption has increased during the last decade, risk factors should be carefully evaluated in an attempt to improve surveillance and outcome. Keywords: Placental abruption, perinatal mortality, trends, pregnancy outcome Introduction Placental abruption is defined as the partial or complete separation of a normally implanted placenta from the uterine wall before delivery of the fetus . It is an important cause of maternal morbidity and perinatal mortality . Despite its clinical significance, there are no reliable diagnostic tests or biomarkers to predict or prevent the occurrence of abruption. The clinical hallmarks of abruption include painful vaginal bleeding accompanied by tetanic uterine contractions, uterine hypertonicity, and a non-reassuring fetal heart rate patterns . Placental abruption complicates roughly 1 in 100 to 200 (0.5–1%) pregnancies [3,4] and evidence from the United States and Norway indicate that the frequency is increasing [5,6]. The rate of placental abruption varies by gestational age at delivery with the rate being 10-fold higher at very preterm gestations and sharply declining as pregnancy progresses toward term, with a rate of abruption of 5.4 and 0.3% at preterm and term gestations, respectively [7,8]. Despite extensive research, the majority of placental abruption cases are of unknown cause . A number of epidemiologic and clinical studies have identified several predisposing risk factors for this condition. Our group  found the following factors to be independently associated with the occurrence of placental abruption in term pregnancies: gestational hypertension, intrauterine growth restriction (IUGR), nonvertex presentation, hydramnios, and advanced maternal age. Other risk factors for the occurrence of placental abruption included multiparity , intrauterine infection [5,11], premature rupture of membranes (PROM) [9,11–13], and smoking during pregnancy . Placental abruption is associated with a variety of maternal complications, including disseminated intravascular coagulation, hemorrhagic shock, uterine rupture, hysterectomy, acute renal failure, and maternal death [15– 20]. Although its rarity, placental abruption contributes disproportionately to excessively high rates of preterm birth , fetal growth restriction , and perinatal mortality [7,8]. This study was designed to investigate trends over the years, timing during pregnancy, risk factors and pregnancy outcomes of patients with placental abruption. We hypothesized that most cases of abruption will Correspondence: Eyal Sheiner, Department of Obstetrics and Gynecology, Soroka University Medical Center, P. O. Box 151, Beer-Sheva, Israel. Tel: þ972-54-804-5074. Fax: þ972-8-627-5338. E-mail: [email protected] Presented in part at the Society of Maternal Fetal Medicine (SMFM) 30th Annual Scientific Meeting, Chicago, USA, 1–6 February 2010. ISSN 1476-7058 print/ISSN 1476-4954 online ! 2010 Informa UK, Ltd. DOI: 10.3109/14767058.2010.511346 2 G . Pariente et al. J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of British Columbia on 09/23/10 For personal use only. occur preterm, that major risk factors for placental abruption would be maternal age and hypertensive disorders, and that in an era where women tend to delay pregnancies later to their reproductive life, the rate of this critical complication will increase over the years. We also wanted to investigate whether placental abruption is an independent risk factor for perinatal mortality or whether the risk is attributed to other preexisting conditions. During 20-year period, we were able to examine a relatively large number of women with placental abruption who delivered in the southern part of Israel. Materials and methods A population-based study comparing all pregnancies of women with and without placental abruption was conducted. Deliveries occurred during the years 1988–2008 at the Soroka University Medical Center. This is the sole hospital in the Negev, the southern part of Israel, which serves the entire obstetric population in this region. Data were collected from the computerized perinatal database that consists of information recorded directly after delivery by an obstetrician. Only four skilled medical secretaries examine the information routinely before entering it into the database. Coding was done after assessing the medical prenatal care records, as well as the routine hospital documents. These procedures assure maximal completeness and accuracy of the database. The following clinical characteristics were evaluated: ethnicity (i.e. Jewish or Bedouin Arabs), maternal age, parity, gestational age, birth weight, small for gestational age (birth weight below the 10th percentile, using local standards), and gender. The following obstetric risk factors were examined: smoking, previous cesarean delivery, recurrent abortions (two or more consecutive pregnancies resulting in spontaneous abortion), fertility treatments, vasa previa, hypertensive disorders [23,24], gestational diabetes mellitus , and premature rupture of membranes. The following labor characteristics and perinatal outcomes were assessed: second trimester bleeding, placenta accreta, cesarean delivery, Apgar score at 1 and 5 min less than 7, congenital malformations, perinatal mortality, postpartum hemorrhage, pathological presentation, IUGR, cesarean hysterectomy, maternal sepsis, and maternal packed cell transfusions. The local ethics institutional review board approved the study. Statistical analysis was performed with the SPSS package (SPSS, Chicago, IL). Statistical significance was calculated by using the X 2 for differences in qualitative variables and the Student t-test for differences in continuous variables. A multivariable logistic regression model, with backward elimination, was constructed to find independent risk factors associated with placental abruption. Since we had special interest in the association between abruption and perinatal mortality, another multivariable model was constructed with perinatal mortality as the outcome variable. Odds ratios (ORs) and their 95% confidence intervals (CIs) were computed. A value of P 5 0.05 was considered statistically significant. Results During the study period, there were 184,111 deliveries, of which 1365 (0.7%) occurred in patients with placental abruption. The incidence of placental abruption increased between the years 1998 and 2008 from 0.6 to 0.8%. Placental abruption was more common in elderly women and in lower gestational age (Table I, Figure 1). Accordingly, abruption was associated with lower birth weight as compared to pregnancies without placental abruption (Figure 2). Obstetric risk factors are presented in Table II. There were higher rates of hypertensive disorders, previous cesarean delivery, infertility treatment, habitual abortions, and PROM among parturients with placental abruption as compared with the comparison group. No significant differences were noted between the groups regarding smoking. Placental abruption was significantly associated with adverse perinatal outcomes such as congenital malformations, vasa previa, Apgar scores at 1 and 5 min less than 7, and perinatal mortality (Table III). Patients with placental abruption were more likely to have sepsis, cesarean deliveries, and cesarean hysterectomies (Table III). Using a multivariate analysis with backward elimination, the following conditions were significantly associated with placental abruption (Table IV): advanced maternal age, lower gestational age, prior cesarean delivery, and hypertensive disorders. Gestational age was entered to the multiple logistic regression model as a continuous variable. The risk is presented for every week . Likewise, maternal age was entered to the model as a continuous variable, and the risk was calculated for every year. The other risk factors were dichotomous (i.e. yes/no hypertensive disorders, etc). Using another multivariate logistic regression model, with perinatal mortality as the outcome variable, controlling for gestational age, hypertensive disorders and congenital malformations placental abruption was noted as an independent risk factor for perinatal mortality (weighted OR: 2.7; 95% CI: 2.2–3.3; P 5 0.001; data not shown in a table). Table I. Clinical characteristics of women with and without placental abruption. Maternal age 5 20 years 20–29 years 30–34 years More than 35 years Ethnicity Jewish Bedouin Gestational age 5 36 weeks 37–41 weeks More than 42 weeks Birth weight 500–1500 g 1500–2500 g 2500–4000 g 4000–5000 g Gender Male Female Placental abruption (n ¼ 1365) No placental abruption (n ¼ 184,111) 3.2% 47.7% 25.7% 23.4% 4.1% 55.7% 23.6% 16.5% 50.% 49.2% 54.% 46.% 56.% 42.2% 1.8% 7.5% 87.8% 4.7% 5 0.001 23.7% 31.2% 43.3% 1.3% 1.1% 6.5% 87.7% 4.6% 5 0.001 53.8% 46.2% 51.2% 48.8% 0.063 P value 5 0.001 0.191 J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of British Columbia on 09/23/10 For personal use only. Placental abruption Figure 1. Incidence of placental abruption by gestational age. Figure 2. Percent of placental abruption by birth weight. 3 4 G . Pariente et al. Table II. Obstetric risk factors of patients with or without placental abruption. Risk factor Placental abruption (n ¼ 1365) No placental abruption (n ¼ 184,111) OR 95% CI P value 1.2% 4.1% 19.4% 8.9% 15.3% 8.6% 7.3% 1.3% 1.9% 11.6% 5.4% 5.9% 6.8% 6.8% 0.927 2.25 1.84 1.72 2.86 1.29 1.09 0.5–1.4 1.72–2.95 1.61–2.11 1.42–2.07 2.46–3.32 1.07–1.56 0.89–1.33 0.758 5 0.001 5 0.001 5 0.001 5 0.001 0.007 0.401 J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of British Columbia on 09/23/10 For personal use only. Smoking Infertility treatment Prior cesarean delivery Habitual abortions Hypertensive disorders PROM Diabetes mellitus Table III. Pregnancy and labor complications and outcomes associated with placental abruption. Placental abruption (n ¼ 1365) No placental abruption (n ¼ 184,111) OR 95% CI P value 0.8% 2.3% 0.8% 14.9% 0.3% 19.1% 0.7% 16.9% 19.4% 44.6% 21.6% 67.7% 0.1% 0.4% 8.1% 0.1% 1.3% 0.5% 1.2% 0.% 5.3% 0.1% 5.0% 1.1% 5.7% 2.5% 12.8% 0.% 0.1% 2.1% 15.9 1.8 1.5 14.3 17.4 4.2 6.99 3.8 20.8 13.3 10.8 14.3 15.8 7.9 4.2 8.4–29.7 1.2–2.6 0.8–2.7 12.2–16.7 6.1–49.5 3.6–4.8 3.69–13.2 3.3–4.4 18.1–23.9 11.9–14.8 9.5–12.4 12.7–16.0 3.6–68.8 3.4–18.1 3.4–5.1 5 0.001 0.001 0.18 5 0.001 5 0.001 5 0.001 5 0.001 5 0.001 5 0.001 5 0.001 5 0.001 5 0.001 5 0.000 5 0.001 5 0.001 Second trimester bleeding Placenta accreta Post partum hemorrhage Maternal blood transfusion Maternal sepsis Pathological presentation Vasa previa Congenital malformation Perinatal mortality Apgar score at 1 min 5 7 Apgar score at 5 min 5 7 Cesarean section Subtotal hysterectomy Hysterectomy IUGR Table IV. Multiple logistic regression with back ward elimination of factors associated with placental abruption. Maternal age (years) Gestational age (weeks) Prior cesarean section Habitual abortions Hypertensive disorders Second trimester bleeding Odds ratio 95% CI P 1.02 0.77 1.38 1.18 2.0 3.1 1.01–1.03 0.76–0.78 1.2–1.6 0.97–1.45 1.7–2.4 1.5–6.3 5 0.001 5 0.001 5 0.001 0.092 5 0.001 0.02 The initial model included, in addition, fertility treatments and premature rupture of membranes. Discussion The present population-based study includes a large number of patients with placental abruption (n ¼ 1365), enabling us to describe independent risk factors associated with this critical condition. Importantly, the incidence of placental abruption is increasing over the years. Although causes of temporal increase could be varied and numerous, it is likely that the increase in cesarean section rate  may have contributed much to these trends. In accordance to previous studies, placental abruption was significantly more common among preterm deliveries. Disease patterns at term may differ from those occurring at preterm gestations. Conditions associated with acute inflammation are more common at preterm pregnancies. Indeed, Nath et al.  confirmed the association of histologic chorioamnionitis with placental abruption in both preterm and term pregnancies. In this study PROM and maternal sepsis were significantly more common among parturitions with placental abruption, reflecting acute inflammation associated conditions. Small-for-gestational age and hypertensive disorders, reflecting chronic processes associated with vascular dysfunction, were found to be in strong association with placental abruption, in accordance to the literature . Ananth et al.  has postulated that there are acute and more often chronic disease processes reflected in the known associated risk factors for placental abruption. While the frequency of acute inflammation associated conditions decline steadily with gestational age, in both women with and without placental abruption, rates of chronic processes increase with advancing gestation steadily up to term, among women with placental abruption, in contrast to women without placental abruption where the rate began to decline much earlier. Conditions associated with chronic disease processes are present throughout the pregnancy, and it should be targeted and carefully evaluated to recognize pregnancies with risk of placental abruption. Our study has several inherent weaknesses because of its retrospective design. Differences in the severity of the condition could not be evaluated since we did not have such data. Nevertheless, during 20-year period, we were able to examine a large number of women and to state that Placental abruption J Matern Fetal Neonatal Med Downloaded from informahealthcare.com by University of British Columbia on 09/23/10 For personal use only. placental abruption is independently associated with perinatal mortality. With such large database, it is possible to find statistically significant findings that are not clinically significant. For this reason, we have constructed the multivariate logistic regression model, to define independent risk factors for placental abruption. In conclusion, placental abruption is an independent risk factor for perinatal mortality. Since the incidence of placental abruption has increased during the last decade, risk factors should be carefully evaluated in an attempt to improve surveillance and outcome. Declaration of interest: The authors report no conflicts of interest. 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