Treatment modalities in children with teeth affected by molar-incisor enamel hypomineralisation (MIH): A systematic review N.A. Lygidakis Dept of Paediatric Dentistry, Community Dental Centre for Children, Athens, Greece. Abstract AIM: This was to review the literature concerning the treatment of permanent teeth with molar-incisor hypomineralised enamel (MIH), comment about possible shortcomings and propose areas of future research. METHODS: A search of MedLine, Scopus, ResearchGate, Isis and Google Scholar databases was conducted using all terms relevant to the subject. Relevant papers published in English were identified after a review of their titles, abstracts or full reading of the papers. RESULTS: Of 189 references initially found, 66 papers were included; 34 directly relevant to the subject. From the latter, only 14 concerned laboratory or clinical studies dealing with treatment for MIH. Since 2000 11 reviews evaluated, to a certain extent, treatment options for affected teeth. Analysis of the proposed treatment modalities indicated options for prevention, restorations, and adhesion to hypomineralised enamel, full coronal coverage and extraction followed by orthodontics. Based on these findings, a treatment decision plan is proposed. CONCLUSIONS: Although treatment approaches for MIH have started to be clearer, long-term clinical trials, supported by laboratory studies, should be conducted to further facilitate the clinical management of this dental defect. Introduction Molar incisor hypomineralisation (MIH) is defined as the developmentally-derived dental defect that involves hypomineralisation of 1 to 4 permanent first molars (FPM), frequently associated with similarly affected permanent incisors [Weerheijm et al., 2003; Mathu-Muju and Wright 2006]. The defect is the result of a variety of environmental factors acting systemically, including prenatal, perinatal and childhood medical conditions that affect the developing enamel, while an underlying genetic predisposition could not be excluded [Lygidakis et al., 2008b, Alaluusua, 2010]. MIH presents as demarcated enamel opacities of different colour in the affected teeth that occasionally undergo posteruptive breakdown due to soft and porous enamel, resulting in atypical cavities or even to complete coronal distortion [Weerheijm et al., 2003]. Accordingly the defect reveals serious clinical management problems attracting the attention of the dental profession the last decade [Lygidakis et al., 2003; Mathu-Muju and Wright 2006]. Following the establishment of the presently used diagnostic criteria for MIH [Weerheijm et al., 2003], a number of welldocumented studies have reported on the prevalence of the disorder and were reviewed by Jälevik . Previous studies recorded a prevalence of 5.9-14.3% in Europe, while there are few studies concerning America and other parts of the world [Fleita et al, 2006; Willmott et al., 2008]. Additionally MIH prevalence has a strong positive correlation with the overall prevalence of developmental defects of enamel. Muratbegovic et al.  showed that prevalence of DDE fell after exclusion of MIH patients from 32.8% to 21.4%. Accordingly it is clear that MIH is an important clinical problem often concerning both general dentists and specialist paediatric dentists. As caries rates have declined in western countries, paediatric dental defects have become more apparent, requiring more complex and long-term treatment. As a result over the last few years a limited number of papers have appeared dealing with the treatment of MIH. The aim of this paper was to review the literature concerning the treatment of MIH, comment about possible shortcomings and propose areas of future research. Methodology A broad search of MedLine, Scopus, ResearchGate, Isis and Google Scholar databases was conducted for the years 1980 until 2009, using as index terms ‘treatment or management or therapy or clinical approach’ AND ‘dental enamel defects’, ‘developmental enamel defects’, ‘chronological enamel defects’, ‘molar-incisor-hypomineralisation’, ‘non fluoride hypomineralisation of permanent teeth’, ‘idiopathic hypomineralisation of permanent teeth’, ‘cheese molars’, ‘hypomineralised permanent molars’ and ‘hypomineralised permanent incisors’. Papers other than in English were excluded. All abstracts were read and the full text of relevant ones were then read. The reference list of each of these papers was additionally examined in order to locate any further references that may not have been found in the search engines previously mentioned. Of the 189 initial references, 93 were selected based on their abstracts, the remaining papers dealing with inherited enamel defects. After a reading of each paper, 66 papers were chosen for inclusion, 32 supportive to the review and 34 relevant to the subject. From these 66, those dealing exclusively with Key words: molar, incisor, enamel hypomineralisation, MIH, treatment, review. Postal address: Dr N. A. Lygidakis, 2 Papadiamantopoulou Street, Athens 11528, Greece. Email: [email protected] 65 European Archives of Paediatric Dentistry // 11 (Issue 2). 2010 N.A. Lygidakis treatment options and outcomes to MIH, either laboratory or clinical comprised only 14 for final evaluation. An additional 9 publications dealt with structural properties of MIH enamel, dentine and pulp, relevant to treatment. Since 2000, 11 reviews evaluated and described, to a certain extent, the treatment options of such defective teeth. The following reviews were used in the present paper: Croll, ; Wray and Welbury, ; Mahoney, ; Fayle, ; Williams and Gowans ; Mathu-Muju and Wright, ; William et al. [2006a]; Sapir and Shapira, ; Fitzpatrick and O'Connell, ; Willmott et al. ; Daly and Waldron, . rom this limited number of studies, even though they had F shortcomings, it was evident that a 'treatment guidelines flow-diagram', based on SIGN methodology, is presently impossible to be made for MIH. According to the SIGN criteria, the grade of recommendation from all studies was moderate (C-D) [Sign, 50]. Results Clinical problems in MIH. Patient and parents concerns related to MIH include aesthetics, rapid wear and enamel loss, increased susceptibility to caries, sensitivity, and finally tooth loss [Leppaniemi et al., 2001; Jälevik and Klingberg, 2002; Willmott et al., 2008]. When post-eruptive breakdown occurs in MIH teeth, the porous sub-surface enamel and even the dentine are exposed, resulting in teeth sensitive to cold air, warm water and food and tooth brushing [Jälevik and Klingberg, 2002]. Poor oral hygiene favours plaque retention and promotes rapid caries development [Leppaniemi et al., 2001; Mahoney, 2001]. Children with MIH receive much more dental treatment than unaffected children [Kotsanos et al., 2005; Chawla et al, 2008]. Affected molars usually require extensive treatment and might create serious problems for both patient and clinician, as they can frequently be difficult to anaesthetise and to restore adequately. The porous exposed subsurface enamel and the dentine may promote bacteria penetration into the dentine resulting to chronic inflammation of the pulp, complicating the use of local analgesia [Rodd et al., 2007; Fargell et al., 2008]. Research has shown that by the age of 9-years, children affected with MIH teeth had undergone dental treatment on their FPM nearly 10 times more frequently than unaffected controls and that each affected tooth had been treated on average twice [Jälevik and Klingberg, 2002]. A considerable proportion of treatment needs for MIH patients was the treatment of affected FPM [Leppaniemi et al., 2001; Muratbegovic et al., 2007]. In addition, it was found that the actual treatment needs were probably underestimated by evaluating only carious, restored and extracted teeth; these patients would also require further restorative, orthodontic and preventive care [Leppaniemi et al., 2001]. Finally for the 18-year-olds there was an additional treatment need in almost half of the patients who had had their FPM restored previously [Mejare et al., 2005]. 66 European Archives of Paediatric Dentistry // 11 (Issue 2). 2010 Apart from the restorative difficulties faced by clinicians, children with MIH have considerable behaviour management problems; dental fear and anxiety are more commonly found in these children. Behaviour problems can be related to pain experienced by the patients during multiple treatment appointments, as many of them were either inadequately anesthetised or even had treatment without local analgesia [Jäalevik and Klingberg, 2002]. A clinical approach for treating MIH. A very useful 6-step management approach for MIH has been proposed recently by William et al. [2006a]: l Risk l Early identification, diagnosis, l Remineralisation (a better term may be mineralisation; the tooth was never ‘completely’ mineralised during development although there may also be an element of demineralisation from enamel caries, superimposed upon the hypomineralised areas) and desensitisation, l Prevention of dental caries and post eruptive enamel breakdown, l Restorations or extractions, l Maintenance. Additionally a valuable treatment decision tree was created by Mathu-Muju and Wright  who proposed a treatment approach according to the level of defect severity (mild, moderate, severe) and to the length of treatment time needed (short and long term). According to those authors the following clinical criteria should be considered in order to divide the defects in the 3 different severity levels: l Mild MIH: Demarcated opacities are in non-stress-bearing areas of FPM, there are isolated opacities, no enamel loss from fracturing is present in opaque areas, there is no history of dental hypersensitivity, there are no caries associated with the affected enamel, and incisor involvement is usually mild if present. l Moderate MIH: Intact atypical restorations can be present, demarcated opacities are present on occlusal/ incisal third of teeth without posteruptive enamel breakdown, posteruptive enamel breakdown/caries are limited to 1 or 2 surfaces without cuspal involvement, dental sensitivity is generally reported as normal, aesthetic concerns are frequently expressed by the patient or parent l Severe MIH: Posteruptive enamel breakdown is present and frequently occurs as the tooth is emerging, there is a history of dental sensitivity, often widespread caries is associated with the affected enamel, crown destruction can readily advance to involve the dental pulp, defective atypical restoration is present, aesthetic concerns are expressed by the patient or parent. Treatment in molar-incisor-hypomineralisation In assessing the review of William et al. [2006a], although it is very informative and suggestive, the clear cut treatment decision tree proposed by Mathu-Muju and Wright  gives a better way of dealing with MIH clinically and for the long term. The division, however of the severity of the defects into 3 categories is complicated and might not help the clinician. Another way of categorizing the defect should be investigated, evaluated and agreed upon. technique [Lygidakis et al., 2009]. FS in the former case recorded 70.2% full retention compared with 25.5% in the later (Table 1a). Finally, for partially erupted FPM with MIH, glass ionomer cements (GIC) can be used as FS, providing temporarily, caries and sensitivity protection and minimizing break-downs; as retention of such materials is poor, these should be replaced as soon as the tooth is fully erupted with resin-based sealants [William et al., 2006a]. Overall preventive approach and advice. It is very important to start approaching the affected children and their parents with the appropriate dietary and preventive advice. As it has been proposed in a recent extensive review by Willmott et al , if a child is still using a low-fluoride children’s toothpaste then the parents should be encouraged to change to one with a higher fluoride level of at least 1,000 ppm F [EAPD, 2009]. Other topical fluorides may also be useful; amongst these are topical fluoride varnishes, e.g. Duraphat® 22,600ppm F (Colgate Oral Care) and Gelkam® 1,000ppm F (Colgate Oral Care). Although there is no research at present to evaluate their efficacy in MIH patients, all these products may help to reduce sensitivity and enhance mineralisation of the hypomineralised areas. Comments on prevention. The reviews by William et al. [2006a] and Willmott et al.  deal with the subject of MIH prevention extensively and adequately providing sensible suggestions. However, the information provided is empirical and anecdotal as there are no clinical or laboratory studies on MIH teeth and suggestions are mainly based on studies of ‘normal’ teeth. Prospective clinical trials will help to evaluate the use of fluoride products to minimize hypersensitivity. Any CCP-ACP effect on MIH teeth should be especially evaluated, as the clinical outcome on this promising product is still controversial [Azarpazhooh and Limeback, 2008]. In addition, although stannous fluoride gel has been demonstrated to reduce dentine sensitivity [Thrash et al., 1994], this effect has yet to be confirmed by clinical trials in hypomineralised teeth. Another product that might be also useful for MIH patients and requires further research [William et al., 2006a; Willmott et al., 2008] is Casein (Phosphopepetide-Amorphous Calcium Phosphate, CPP-ACP). This product has been shown to create and stabilise a super saturated solution of calcium and phosphate followed by deposition at the enamel surface. CPP-ACP has been incorporated into sugar-free chewing gum and encourages remineralisation of the sub-surface carious lesions [Shen et al., 2001]. Following these findings it has been empirically suggested that home application of a CPP-ACP containing cream will help seal, desensitise and act as a source of bio-available calcium and phosphate for an erupting tooth with MIH [Willmott et al., 2008; Chawla et al, 2008]. Finally the use of 0.4% stannous fluoride gels on a daily basis have also been proposed to be helpful for reducing sensitivity in defective teeth [Fayle, 2003]. Fissure sealants (FS) may also be useful for FPM with mild defects, not sensitive and without breakdown, particularly when they are regularly monitored and replaced when lost [Fayle, 2003; Mathu-Muju and Wright 2006; William et al., 2006a]. Mathu and Wright  suggested that if the fissures appeared opaque or yellow-brown then a 60 second pre-treatment with 5% sodium hypochlorite might be beneficial in that it might remove intrinsic enamel proteins. Limited clinical information on using FS in affected teeth comes from the study by Kotsanos et al.  who reported that FS in 35 MIH molars had to be retreated after a shorter period of time than FS in a control group. However, a recent long term clinical study in 54 children with MIH and defective molars with occlusal opacities, reported that FS appeared to have greater retention when applied using 5th generation adhesive prior to FS, compared with the conventional Concerning FS, Mathu-Muju and Wright  repeated a possibly valuable suggestion for pre-treatment that has been noted previously for defective enamel in amelogenesis imperfecta cases by Venezie et al. ; however at the time of that report, modern adhesives did not exist, therefore the use of 5% sodium hypochlorite might not be as useful nowadays. The only available research for FS is a recent prospective clinical study [Lygidakis et al., 2009] indicating that in MIH molars with occlusal opacities, FS appear to have greater retention when applied using adhesive prior to sealant. Restoring one or more surfaces of hypomineralised permanent molars. Having solved the difficulties in achieving local analgesia and managing a child’s behaviour, restoration of the affected FPM can be further complicated by difficulties in defining the cavity margins and the choice of the suitable replacement material. Concerning the former, two empirical approaches have been proposed: removal of all defective enamel until sound surfaces are reached [William et al., 2006a; Mathu-Maju and Wright, 2006] or removal of the porous enamel only, until resistance to the bur or to the probe is felt [Lygidakis et al., 2003; Fayle, 2003]. The first approach means that a lot of tooth material is lost but is better if an adhesive material is to rely upon bonding to enamel. The second approach is less invasive, but it can mean that the defective enamel may continue to chip away. There are many restorative materials/options available to the dental surgeon treating these patients: GIC, Resin Modified Glass Ionomer Cements (RMGIC), Polyacid modified composite resins (PMCR), Composite resins (CR), and amalgam. 67 European Archives of Paediatric Dentistry // 11 (Issue 2). 2010 N.A. Lygidakis Table 1a: Papers/studies reported on clinical modalities in hypomineralised molars (MIH). Study No of children No of MIH teeth evaluated Study design Age* Restoration Methods Duration** Results Koch and GarciaGodoy  12 41 molars; 25 with opacities 12 enamel hypoplasia, 4 hypomineralised AI Clinical prospective 6-8 29 gold crowns 4 composite crowns 8 ceramic crowns 2-5 100% retention Excellent (39) or acceptable (2) in: Marginal Adaptation Supragingival Margins At the end of the study: all teeth vital, no secondary caries Zagdwon et al  17 42 molars with DDE and AI 18 cases, clinical prospective, 24 cases, split mouth 6-16 19 PMC 23 nickel chrome alloy adhesive casts Mean = 1.6 (range 1-2) 94.7% acceptable 91.3% acceptable, Adhesive casts 4 times more expensive than PMCs Kotsanos et al  36 + 36 controls 136 molars Retrospective with controls 7.7 ± 1.3 35 sealants 18 amalgam fillings 59 composite fillings 24 PMC 33.0 (± 25.7) 32.3 (± 30.3) 48.3 (± 30.6)− 87.1% acceptable 38.9% acceptable 74.6%acceptable 100% acceptable Lygidakis et al  46 49 molars Prospective 8-10 49 Composite resin (18 two surfaces, 31 three surfaces) 4 100% full retention, Ryge A: Surfaces appearance 93.8% Colour match 79.5% Marginal adaptation 100% Anatomic form 91.8% 0/49 with pulp necrosis at the end Mejare et al  76 153 molars Retrospective 6-17, mean (8.5 ± 2.16) 63 GIC 14 compomer 34 composite 32 amalgam 1 SSC 9 castings 5.2 (±3.29) 49.2% acceptable 64.3% acceptable 85.3%acceptable 78.1% acceptable 100% acceptable 100%acceptable 5/153 with pulp necrosis Lygidakis et al  47 47 sets of molars 21 maxilla 26 mandible Prospective, half mouth double blind 6-7 Adhesive FS (group A) vs conventional (Group B) 4 Group A: 70.2% were fully sealed, 29.7% partly sealed, none unsealed. Group B: 25.5% fully sealed, 44.6% partly sealed, 29.7% unsealed * age in years at time of first examination; ** years; NR – not recorded; DDE – dental developmental defects; PMC – preformed metal crown Amalgam is a non-adhesive material and its use in these atypically shaped cavities is not indicated; the inability to protect the remaining structures usually results in further enamel breakdown [Croll 2000; Fayle, 2003; William et al., 2006a]. The few existing clinical studies of amalgam restorations in MIH molars support this view as they report lower success rates when compared with CR [Kotsanos et al., 2005; Mejare et al., 2005]. Regarding other restorative materials and options there is very little evidence to support their use [Fayle, 2003; MathuMaju and Wright, 2006]. Restorations with GIC, RMGIC and PMCR are not recommended in the stress bearing areas of FPMs and they can only used as intermediate approach until a definite restoration is placed [Mahoney 2001; William et al., 2006a; Willmott et al., 2008]. GIC has been additionally proposed as an intermediate layer restoring the dentinal contours, prior to composite placement, in cases that the cavity involves large areas of dentine [Mathu- Maju and Wright, 2006]. 68 European Archives of Paediatric Dentistry // 11 (Issue 2). 2010 The only material that appears to be usable for one or more surfaces restorations in MIH molars is CR. There are 3 clinical studies dealing with the outcome of such restorations in MIH molars (Table 1a). Lygidakis et al.  evaluating the success rate of CR restorations placed on two or more surfaces including cusps of affected molars, reported good/ acceptable results after 4 years. Following a strict clinical procedure, none of 49 restorations (18 two/31 three surfaces) needed replacement by the end of the study. Mejare et al.  followed 76 children with various types of restorations for a period of 5.2±3.29 years. In FPMs, GIC had the lowest and CR the highest success rate, amalgam and compomers being in the middle. From the 34 CR placed, 29 (85.3%) had a good/acceptable outcome, the remaining needing replacement. Finally Kotsanos et al.  reported a 74.4% success rate of CR restorations placed on MIH molars in children aged 7.7±1.3 after 48±30.6 months of follow-up. These authors also reported that restorations and FS in affected children had over 3 times greater probability of needing re-treatment than interventions on children of a control group. Treatment in molar-incisor-hypomineralisation Comments on materials. In commenting on the restorative approaches it is still unclear which approach is better for cavity preparation and further laboratory research is required. From the 3 existing clinical studies only one mentions clearly the cavity preparation technique, stating ‘removal of all carious tissues together with possible previous, failed amalgam restoration and enamel easily penetrated by probe’ [Lygidakis et al., 2003]. From all available restorative materials, many reviews [Fayle, 2003; Mathu-Muju and Wright 2006; William et al., 2006a; Willmott et al., 2008], agree on the superior properties of CR, combined with the new adhesive materials. The 3 clinical studies available have particular limitations. Kotsanos et al.  was retrospective with no defined treatment procedure and methodology criteria and a very wide time-span of evaluation (48±30.6 months). Similar limitations apply to Mejare et al.  study that is also unclear about patients’ ages and year of treatment (meaning different restorative materials). The Lygidakis et al.  study dealt with the previous problems adequately but it had no controls for evaluation. Further long-term clinical trials should be organised, preferably multi-centre, in order to finalise this approach and the type of composite material most appropriate. Adhesion to hypomineralised enamel. The use of various adhesive resin systems has certain limitations in MIH teeth as a result of defective enamel. A recent study by William et al. [2006b] demonstrated that adhesion to MIH enamel is possible, but the enamel-adhesive interface of defective enamel was porous with cracks, had decreased bond strength, and a higher likelihood of cohesive failure compared with sound enamel. This possible ability of adhesion to MIH enamel was found by the study of William et al. [2006b], strenghtens the previous findings by Seow and Amaratunge , in AI variants, which reported that the etching patterns in hypomineralized types of AI may occasionally resemble those of normal enamel despite the presence of hypomineralisation abnormalities and morphological changes at the crystallite level. A number of studies dealing with the ultrastructure and biochemical make-up of MIH enamel [Jälevik et al., 2001a, 2005; Jälevik and Norén 2000; Fearne et al., 2004; Mahoney et al., 2004; Al-Dobiyan et al., 2006] and dentine [Fearne et al., 2004; Heijs et al., 2007] indicated that the ‘full thickness enamel’ surrounding the clinically defective lesions is less affected and the underlying dentine has no major structural changes. These findings may explain the acceptable results for adhesive CR restorations in molars with MIH, if all apparently defective enamel is removed. The type of adhesive used should also play a role. William et al. [2006b] suggested that self-etching adhesives (SEA) have superior bond strength to hypomineralised enamel compared with all-etch single-bottle alcohol containing adhesives (SBA) possibly attributed to omiting rinsing thus eliminating the contamination of residual water on the bond and micromechanical and chemical bonding to hydroxyapatite of the SEA, as compared with micromechanical only for the SBA. However the hydrophilic properties of acetone included in some other SBA systems, may play the same role for removing the residual water from the etched enamel surface enhancing the enamel-adhesive interface. An acetone-containing adhesive system that was used prior to CR and FS in two of the clinical studies in MIH molars, mentioned previously, revealed good long-term results regarding adhesion [Lygidakis et al, 2003, 2009]. An additional procedure prior to etching in order to enhance adhesion to hypomineralised enamel has been proposed by Mathu-Maju and Wright, . They recommend pre-treatment of the enamel with 5% sodium hypochlorite in order to remove intrinsic proteins encasing the hydroxyapatite and therefore facilitate etching and resin penetration. Comments on adhesion. The study by William et al. [2006b] covers the subject well and makes some valuable suggestions for the clinician. However, there is a limitation namely that the absence of cavity preparation prior to material placement means that results apply to defective enamel exclusively and not to ‘less defective’ enamel and the ‘normal’ dentine surrounding the lesion. Additionally, the MIH affected FPM examined for adhesion revealed yellow-brown demarcated opacities with posteruptive breakdown. This was given as the reason for failure, being a cohesion failure within the enamel, while high microshear bond strength was found in some specimens having milder whitish-creamy defects. Further laboratory research in that area is required followed by clinical trials applying the suggestions regarding the adhesive types most effective in MIH. Furthermore, the suggestion of Venezie et al.  and Mathu-Maju and Wright , on pre-treatment, should be evaluated in vitro and in clinical trials. It should be noted however that at the time of the original publication in 1994 there were no adhesive agents and their widespread use today might reduce the clinical value of the 5% sodium hypochlorite pre treatment. Restoring hypomineralised permanent molars with full coronal coverage. Preformed metal crowns (PMC) for use on FPM have been used for many years to cover molars with defective enamel and they are still recommended as a treatment option for MIH posterior teeth [Fayle, 2003; William et al., 2006a; AAPD, 2008]. They prevent further tooth loss, control sensitivity, establish correct interproximal and proper occlusal contacts, are not costly and require little time to prepare and insert. Kotsanos et al.  reported that no replacement was needed for PMC placed on 24 molars with MIH, for a period of 3-5 years (Table 1a). Zagdwon et al.  reported good success rate with only one failure of 19 PMC placed over a 2 year-period; they also found that there were no significant differences between the longevity and success rates for PMC and cast adhesive copings (nickel chrome alloy) (Table 1a). Adhesive cast copings conserved more tooth tissue but were more technique sensitive and time consuming; additionally in young children 69 European Archives of Paediatric Dentistry // 11 (Issue 2). 2010 N.A. Lygidakis there are short clinical crowns and large pulps and a child’s cooperation might be questionable [William et al., 2006a]. From another clinical study similar acceptable results were reported for laboratory-fabricated crowns on defective molars, either gold in 29 teeth or tooth-coloured in 12 teeth [Koch and Garcia-Godoy, 2000]. From the 41 crowns placed with a modified technique for crown preparation, in children aged 6-8 years, only 2 recorded minor marginal problems, the remaining 39 being in good condition 2-5 years post placement (Table 1a). Restoring hypomineralised permanent incisors. As the recent research on MIH has shown, up to 71.6% of affected children may have incisors as well as FPM involved [Jälevik et al 2001b; Chawla et al, 2008; Lygidakis et al., 2008a]. In addition the most frequent (23.5%) combination of affected teeth in children with all 12 ‘index’ teeth erupted is 4 molars/2 incisors [Lygidakis et al., 2008a]. Some of these children have serious aesthetic problems that require treatment. Unfortunately the literature lacks evidence-based results for the management of such defects for the anterior teeth (Table 1b). Comments on coronal coverage. Although PMC have been used for many years by our specialty, there are only 2 clinical studies evaluating their use in MIH molars. The study of Zagdwon et al.  was prospective, very well conducted with clear methodology and a detailed technique procedure, although the follow-up period was limited to 2 years (usually the time requirement for PMC maintenance is up to 10 years) and there were no follow up periapical radiographs to evaluate possible pathology. The study by Kotsanos et al. , although it does provide very good results, was retrospective with no defined treatment procedure and methodology criteria and a very wide time-span of evaluation (50.2 ± 23.3 years). Therefore long-term (>7 years) prospective clinical trials are needed in order to evaluate their performance in such teeth. According to Jälevik and Noren  the yellow or brownish-yellow defects are of full thickness and more porous, whilst those that are creamy-yellow or whitish-creamy are less porous and variable in depth, located in the inner part of the enamel. As a result, the former defects may respond occasionally to bleaching with carbamide peroxide, while microabrasion using abrasive paste and 18% hydrochloric acid might be effective only in shallow patchy whitish defects (Table 1b) [Fayle, 2003; William et al., 2006a; Mathu-Muju and Wright, 2006; Joiner, 2006]. More pronounced enamel defects might be dealt with by combining the two methods [Sundfeld et al., 2007]. Both techniques are however questionable in immature teeth as microabrasion involving aggressive reduction of the enamel resulting from duration, number, and intensity of applications may occur [Sapir and Shapira, 2007]. An alternative method of polishing with pumice and etching with 37.5% phosphoric acid has been proposed to overcome these problems, but again this has not been studied on immature anterior teeth [Peariasamy et al., 2001] (Table 1b). Additionally, bleaching with 10% – 38% carbamide peroxide for brownish-yellow defects is not recommended in immature teeth as it is frequently followed by side effects, such as sensitivity, mucosal irritation and enamel surface alterations, while symptoms are frequently increased with higher concentrations [Joiner 2006; AAPD, 2009]. These techniques for tooth whitening are described in detail in the UK Clinical Guidelines [Wray and Welbury, 2001], while the long-term experience with microabrasion is thoroughly evaluated in the review by Sundfeld et al. . The use of cast adhesive copings, as proposed by Harley and Ibbetson,  for other dental defects, namely AI and DI, do seem to have a potential for the treatment of MIH molars as shown by Zagdwon et al. . Further clinical research is, however, needed in order to justify their long-term use and evaluate further the possibility of using alternative toothcoloured materials instead of various alloys. With the use of laboratory fabricated full crowns there is still great concern for the destructive nature of crown preparation to these immature teeth. The study by Koch and GarciaGodoy, , although presenting good results, evaluated a very limited number of coloured crowns, as compared in addition to much larger sample of gold crowns. The use of the latter however would not be well accepted by parents nowadays. Additionally, there is the transitional stage of the occlusion that children undergo during the years involved in the placement of such restorations must be considered. Finally, as Koch and Garcia-Godoy,  stated: “Placement may be difficult owing to short crowns, large pulps, previous loss of enamel and subgingival placement of crown margins. The impression material must allow for good wetting of dental surfaces. Polyether impression materials (which appear to be ideal for these cases) require a long setting time. The treatment requires the fabrication of a temporary crown, and the patient must cooperate, maintain a good oral hygiene status and, preferably, have a low risk of developing caries” 70 European Archives of Paediatric Dentistry // 11 (Issue 2). 2010 It should be noted that all these methods, discussed above, have mainly been studied in diffuse fluorotic opacities or post-orthodontic white spots, therefore their application to hypomineralised MIH enamel should be with caution. MIH has morphological differences and distinct characteristics from the former other defects [Jäalevik et al, 2001a, 2005]. An interesting approach, namely etch-bleach-seal technique, has been suggested by Wright . According to this conservative approach for yellow-brown defects the lesions are etched with 37% phosphoric acid for 60 s, bleached with 5% sodium hypochlorite for 5-10 min, re-etched and covered with a FS over the surface to occlude porosities and prevent re-staining. Acceptable clinical results were reported for a 5 years period. Recently the technique was evaluated in 33 children aged 8-12 years, but with diffuse fluorotic opacities Treatment in molar-incisor-hypomineralisation Table 1b: Papers/studies reporting on clinical modalities in hypomineralised incisors (MIH). Study No of No of MIH teeth Study design children evaluated Age * Restoration Methods Duration* Results Welbury  66 52 incisors/ canines with 'hypoplasia' (from a group of 289 teeth***) prospective 6-18 Composite resin veneers with feathered or bevelled or overlapped incisal edge. 0.5-2.5 86% acceptable Failures due to partial or complete loss of composite, adhesive failure, poor colour match. Ashkenazi and Sarnat  5 NR. Teeth presented brown or white DDE resembling hypo-maturation Prospective observation 9-11 Microabrasion with pumice and 37% HCl Up to 4 ‘surprising’ satisfactory results Peariasamy et al  NR 30 molars with demarcated or diffuse opacities Experimental with controls NR Pumicing for 30-35 sec and etching for 1 or 2 min with 37.5% phosphoric acid. NR Removal of 34±4 μm of the surface enamel without mineral loss in the subsurface. Formation of a ‘new’ mineralized surface 22±3 μm, with favorable optical properties Wong and Winter  15 out of 32 *** 30 central incisors with demarcated white/yellow opacities Prospective NR Microabrasion with Prèma abrasive paste and 18% HCl 0.5 Statistically significant (p=0.03) immediate and long term satisfaction with the result by patients and parents Wright  NR NR Prospective observation Children with young permanent incisors Surface etched with 37% phosphoric acid for 60 s, b) bleached with 5% sodium hypochlodite for 5-10 min, c) re-etched and covered with a sealant Up to 5 Good results with ‘no-staining after resin perfusion’ * age in years at time of first examination; ** years; ***Remaining patients or teeth revealed different type of defects; NR – not recorded; DDE – dental developmental defects in their incisors and good results for colour improvement were obtained [Cardenas Flores et al., 2009]. Some other authors have suggested that aesthetic improvement can be achieved when any enamel reduction is followed by opaque resins and direct CR veneering [Fayle, 2003; Weerheijm, 2004]. Opaque resins as intermediate layers are also quite frequently necessary in order to mask the reflection of the deep discoloured lesions [Fayle, 2003]. Restorations with CR and veneers are an alternative choice for anterior MIH defective teeth in children and adolescents with larger enamel defects that require treatment [Wray and Welbury, 2001]. The choice between direct and indirect veneers depends upon a clinician’s personal choice and skill and the implicated cost. It should however, be kept in mind that in the majority of cases immature teeth with large pulps are involved and therefore a conservative approach is required. Additionally, the continuous recession of the gingival margin of the anterior teeth during development implies later problems with aesthetics of full coverage veneers. Wakiaga et al.  undertook a systematic review of direct versus indirect CR veneers for intrinsic dental stains and found 6 acceptable papers all in adolescents and adults but none in children. They concluded that there was no reliable evidence to show that either approach was superior to the other with regard to longevity. In the only study in young patients, Welbury  looked at directly placed CR veneers in children and adolescents and found that after three years 14% had failed (Table 1b). At the time of that research there were no modern adhesives available and therefore the study, although the only one in the literature, does not reflect the present situation. Veneers using CR in long term may suffer from susceptibility to discolouration, wear and marginal fractures, reducing thereby the aesthetic long-term result [Peumans et al., 1997a,b]. In such cases and in older children and adolescents porcelain veneers are indicated [Wray and Welbury 2001; AAPD, 2008] Comments on incisal MIH treatments. There are no studies at all evaluating the success rate of for CR restorations for MIH affected incisors. Indications for their use and success rates can nevertheless be drawn from CR studies in molars, as essentially the same technique is used. Further matters to be addressed in the anterior teeth are the additional use of opaque resins and the different mastication forces involved. The etch-bleach-seal technique [Wright, 2002] should be clinically evaluated further in large samples of MIH incisors, as it appears promising for interceptive early approach in aesthetic problems. Chair-side bleaching with 10% 71 European Archives of Paediatric Dentistry // 11 (Issue 2). 2010 N.A. Lygidakis carbamide peroxide, for brownish-yellow defects should be investigated but only in older children. Note should be taken of the side effects of sensitivity, mucosal irritation and enamel surface alterations [Wray and Welbury, 2001; Dahl and Pallesen, 2003; Joiner, 2006]. Micro-abrasion followed by CR restorations for creamy-whitish defects needs to be evaluated adequately in larger patient groups. Either 18% hydrochloric acid or 37% phosphoric acid can be used as both produce similar results [Berezza et al., 2005]. The replacement of micro-abrasion by local enamel thickness reduction, using high-speed headpiece, should be also evaluated. In any case all these approaches should be delayed as much as possible as clinical experience has shown that defective areas tend to get better in the oral environment. The CR veneers for young children and adolescents with severe defects need clinical evaluation in respect to the new adhesives properties when used on defective enamel as discussed previously. In addition porcelain veneers with the new-age materials should be evaluated but only in adolescents and young adults. Extraction and Orthodontics. In children with MIH severely affected FPM, the first clinical consideration is to decide whether to restore or extract. Although both the profession and the public believe nowadays in a more conservative treatment plan, some thought might still be given for such a radical approach, resulting usually in the extractions of several permanent teeth. Variables affecting this decision include the child’s age, orthodontic considerations, presence of other dental anomalies, degree of severity of MIH, pulp involvement, presence of third molar germ(s), restorability of the tooth/teeth and expected long term treatment cost [Mejare et al., 2005; Mathu-Maju and Wright, 2006]. The FPM is not an orthodontist’s first choice for extraction, because later orthodontic treatment may be complicated [Williams and Gowans, 2003]. Therefore, the decision to extract any of the FPM should be seriously evaluated and discussed with an orthodontist as early as possible if a good result is to be anticipated [Williams and Gowans, 2003; Mathu-Maju and Wright, 2006]. If such a decision has been taken the dental age of 8.5-9 years is the ideal time for their extraction. A full clinical examination and a panoramic radiograph will help to evaluate particular contributory signs for acceptable results [Williams and Gowans, 2003]. Complete crown formation and initiation of the calcification of the bifurcation of the permanent second molar, particularly in the mandible, has the potential to help the eruption of the second molar into a good contact with the second premolar, especially when crowding is present. When there is little or no crowding, a space will remain and fixed appliance treatment will be required at a later stage for closure. Considerations should be given also for further FPM extractions in the maxilla for compensation and to the contralateral molar or premolar of the same jaw for balancing, particularly 72 European Archives of Paediatric Dentistry // 11 (Issue 2). 2010 in crowded cases, in order to avoid a midline shift [Williams and Gowans, 2003]. It should be stressed that all the above suggested treatment outcomes are valuable, but only in cases of extractions during the indicated best period of development. In all other cases the expected problems of such an approach (e.g. drifting and rolling of adjacent teeth, periodontal defects, occlusion problems, increased spacing), require full term orthodontic treatment with fixed appliances. Such treatment is usually of much longer duration than the one anticipated in cases of premolar extractions [Williams and Gowans, 2003; Seddon 2004]. However, looking to long term prognosis and treatment outcomes, Mejare et al.  found that at 18-years of age the space closure that had occurred was acceptable in 87% of the individuals with extracted MIH molars, and the sagittal relationships did not differ between individuals with and without extraction, from a sample of 76 individuals that 24% had 1-3 molars extracted and 18% had all four FPM extracted. These results are challenging, particularly if we consider that the average age for extractions was 10·5 years for mandibular and 10·6 for maxillary FPMs, in the cases that received no orthodontic treatment. Additionally, a recent study by Jälevik and Møller  stated that the extraction of severely affected FPM in MIH patients was an adequate treatment alternative to restorative care. They examined the orthodontic status of 20 patients 3.8-8.3 years after extractions and concluded that 15 of them had an acceptable occlusion. Space reduction and favourable development could be expected if the extractions were undertaken prior to the eruption of the permanent second molar teeth. Comments on extractions. When extractions of MIH FPMs have been carried out, the two clinical long term studies reported acceptable results for space closure without orthodontic treatment, if defective FPM extractions are performed in due time. However, both studies present some methodological limitations and additionally it is worth noting that children in these studies were first seen and treated in the 1990s, a period when the profession was not fully aware of MIH and not many options for treatment were available. Further prospective clinical research is obviously needed in order to justify this convenient but still invasive approach in judged as unrestorable cases. Meanwhile taking into account all previously evaluated studies, a treatment decision plan (Table 2) can be proposed in order to help the clinician deal with these MIH defects in his/ her everyday practice. The main concept for this proposal is to ‘define the defect severity by individual tooth’ following an initial overall decision whether to keep or to extract the tooth. Treatment in molar-incisor-hypomineralisation Table 2: Proposed treatment decision plan for MIH teeth. Mild Defects Moderate/Severe Defects Enamel opacities without break-down, no/slight sensitivity, mild aesthetic problems, no caries Enamel break-down, atypical restorations, sensitivity, caries, aesthetic problems Molars Incisors if needed Molars Incisors if needed Fluoride varnish in partially erupted teeth In brownish-yellow defects, etchbleach-seal approach in younger children, or chair-side bleaching with 10% carbamide peroxide in older. Consider extractions Wait until the defect gets better, since a degree of enamel mineralisation may occur in the salivary environment When fully erupted, sealants with prior adhesives In whitish defects, microabrasion followed if needed by CR restoration Fluoride varnish or GIC in partially erupted teeth CR restorations or veneers following micro-abrasion or enamel reduction and intermediate opaque resins CR restorations if break-down or caries occur CR restorations following enamel reduction CR restorations for up to 3 surfaces Porcelain veneers if needed in adulthood Full porcelain crowns, if needed, in adulthood PM crowns or copings for more than 3 surfaces Full porcelain crowns in adulthood Ongoing preventive care for all cases Conclusions The information provided on treatment of MIH in the international literature is limited and empirical, relying mainly on case reports and few clinical studies. However advances in dental materials have provided clinical solutions in cases that were regarded as unrestorable in the past. Intensive individually prescribed preventive programs may postpone the initiation of the actual restorative treatment and reduce in long-term patient’s discomfort. In mild and moderate MIH cases composite restorations using modern adhesives is the treatment of choice and may last for many years until permanent restorations may placed. In severe cases transitional treatment for function and aesthetics can be provided, using the various modalities now available until adolescence when permanent prosthetic approach with crowns in molars and veneers in incisors can be initiated. Long term clinical trials supported by laboratory studies are needed to provide ‘guidelines’ for treating MIH. Aknowledgements. 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