Enamel defects in permanent first molars and incisors in individuals with cleft lip and/or palate

Background. Enamel defects are common in deciduous and permanent maxillary incisors of individuals with cleft lip and palate and their occurrence has been associated with the cleft, especially when the alveolus is affected. Objective. To compare the prevalence of enamel defects in permanent maxillary and mandibular central incisors and first molars of individuals with cleft lip and palate, cleft palate and without clefts. Material and methods. 150 individuals (50 with cleft lip and palate, 50 with cleft palate and 50 without clefts), of both genders and aged 6 to 12 years. The frequency, extent and location of enamel alterations on the buccal aspect of teeth were evaluated by the modified DDE index. Results. There was greater manifestation of enamel defects in maxillary incisors and molars in groups with clefts, with statistically significant difference compared with the noncleft group. Conclusions. The occurrence of enamel defects was common in permanent incisors and molars and was significantly associated with clefts.


Introduction
Enamel defects are common in deciduous and permanent maxillary incisors of individuals with cleft lip and palate, and their occurrence has been associated with the cleft, especially when the alveolus is affected.These defects may be classified according to their macroscopic appearance in two main categories: enamel hypoplasia and hypomineralized enamel.While hypoplasia is a quantitative defect, the hypomineralized enamel is a qualitative defect identified upon clinical examination as an abnormality in enamel translucency, also called opacity (1,2).
Even though enamel defects in maxillary incisors are widely investigated in children with clefts, other enamel alterations such as defects in permanent first molars combined with hypomineralized incisors (MIH) are not (1,(3)(4)(5).In children without clefts, the prevalence of this disorder ranges from 2.8% to 40.2% (6)(7)(8)(9)(10)(11).The studies reveal that the more the molars are affected, the higher the relative risk of opacities in incisors (1).In general, more than one permanent first molar is affected, and a typical characteristic of MIH is the asymmetric appearance (i.e. while the enamel of one molar is severely affected, the contralateral molar may be less or unaffected) (1,12).
From a clinical standpoint, MIH represents a serious problem for dental health due to the fast and unexpected development of caries during the eruption of the first molars, difficult reanatomization of MIH, and the approach to be adopted when treatment is indicated.For the affected children, the experience of pain and sensitivity when the enamel is not intact discourages toothbrushing, and individuals also complain about the appearance of their incisors (13).
Thus, the main objective of this study was to compare the prevalence of enamel defects in permanent maxillary and mandibular central incisors and first molars of individuals with cleft lip and palate, cleft palate, and without clefts.

Materials and methods
The Institutional Review Board of the Hospital for Rehabilitation of Craniofacial Anomalies of the University of São Paulo (HRAC/USP) approved the study.Additionally, the parents or caretakers of the children signed an informed consent form agreeing to their participation in the study.
The sample consisted of three groups.Group I included 50 children with unilateral or bilateral complete cleft lip and palate (CLP) (19 females and 31 males).Group II comprised 50 children with cleft palate (CP), 22 females and 28 males, all attending the Pediatric Dentistry Clinic of HRAC/USP.Group III -the control group-included 50 children without clefts (NC), 33 females and 17 males, registered in a single public school in the city of Agudos, São Paulo, Brazil.The evaluation took 1,200 teeth and each tooth was divided in three thirds: incisal-occlusal, middle and cervical.
The inclusion criteria were Caucasoid children, aged 6 to 12 years, with erupted maxillary and mandibular central incisors and permanent first molars, with more than half of the crown exposed in the oral cavity, free of restorations, caries or orthodontic appliances.Individuals with clinical signs of white spot lesions caused by cervical demineralization in proximal and occlusal surfaces, as well as individuals with fluorosis ranging from yellow to dark brown, were symmetrically and bilaterally distributed, normally reaching several teeth.
Clinical examination was performed under artificial light using a dental mirror and dental probe.The buccal surfaces of maxillary and mandibular central incisors and first molars, as well as occlusal surfaces of maxillary and mandibular first molars, were examined after cleaning and drying with gauze to prevent the masking of defects by saliva or dental biofilm.All examinations were conducted by a single observer previously trained and submitted to an intra-rater test (kappa=1).
Defects were classified according to the DDE index (14) in three categories: hypoplasia, demarcated opacities and diffuse opacities.Diffuse opacities presented with normal thickness of the affected enamel, translucence abnormalities, and undefined limits (Figure 1).Hypoplasia was characterized by enamel thickness reduction, and the combination of defects was related to teeth showing the two defects, hypoplasia, and opacities in the same surface (Figure 3).The association between enamel defects and type of cleft was analyzed by the chi-square test (α=0.05).Groups with and without clefts were compared, as well as groups with different types of clefts.

Results
For maxillary incisors, the cervical and middle thirds were the most affected in incisors on the cleft side.The incisal third was also affected, as well as incisal and middle thirds in the contralateral incisor in unilateral right and left cleft lip and palate, respectively.In the CP and NC groups, the incisal and middle thirds were the most affected.Both hypoplasia and opacities occurred more frequently in individuals with clefts, especially with alveolar involvement.
For mandibular incisors, there was a low occurrence of enamel defects in all groups, and opacity was the most common defect affecting the three thirds.There was only one case of hypoplasia in the NC group affecting the incisal third.Maxillary molars demonstrated marked occurrence of defects affecting all three thirds.Opacity was common for all groups with clefts ranging from 15% to 38%, affecting teeth related or not to the cleft.Hypoplasia was observed only in individuals with clefts.In the NC group only one case of opacity was observed, affecting the occlusal third.
In mandibular molars the occlusal and middle thirds were the most affected.Opacity was predominant in both molars, while hypoplasia was observed only in the mandibular right first molar.The prevalence of structural enamel defects considering at least one affected tooth was 12% for the NC group, 50% for the CP group and 94% for the CLP group.The prevalence of MIH, with at least one incisor and one molar affected, was 4% for the NC group, 22% for the CP group, and 42% for the CLP group.Figure 4 shows the data on the prevalence of MIH defects.There was a statistically significant association when groups with clefts were compared with the NC group, indicating that the anatomical defect of the cleft might influence the occurrence of MIH defects in the three studied groups (Table 1 When comparisons were applied only for groups with clefts, there was no statistically significant association for the molars.This fact could suggest that anterior teeth might be more likely to be affected by the MIH defects, possibly because of their proximity to the cleft, and also the severity of the defect.

Discussion
This study investigated enamel defects of central incisors and permanent first molars (MIH) in children with different types of clefts compared to individuals without clefts.A control group was included for better understanding of enamel defects, and to analyze the possible correlation with the different types of clefts.
The buccal surface was selected because of its susceptibility to enamel defects (15,16), with division in thirds to facilitate the report of the extent or severity of defects and assess the probable period when the injury occurred during formation of tooth enamel (17).
Involvement of the cervical and middle thirds by the different types of enamel defects was higher in incisors related to the cleft, yet the incisal third was also affected.This demonstrates the importance of the cleft region in the occurrence of dental structural defects, suggesting that rehabilitation procedures in early stages of life (18)(19)(20)(21) may contribute to the occurrence of defects in the structure of developing teeth (22,23).Those results highlight the relationship of more severe clefts with dental defects in this region (24,25).
Involvement of the three thirds of maxillary molars and occlusal and middle surfaces of mandibular molars suggests that the damage, in lower proportion for the mandibular incisors, may have occurred throughout the period of tooth formation, comprising the first three years of life (1).It seems that there is no relationship between the type of defects and side of the cleft for maxillary molars because opacity was common for all groups with clefts, in percentages ranging from 15% to 38%, affecting teeth related or not to the cleft side.Hypoplasia was found only in individuals with clefts, supporting the hypothesis that dental development may be compromised by the cleft.For mandibular molars, opacity was the predominant defect.The structural defects of enamel in incisors, molars or both showed increasing prevalence in the NC, CP and CLP groups, which indicates that increasing the anatomic severity of the cleft causes a gradual increase in the defects, as well as in the severity of injuries.So far, molecular biology studies (26,27) have not isolated specific genes related to the development of structural enamel defects.However, considering that odontogenesis occurs by epithelial-mesenchymal inductions, which present several regulatory genes that are repeatedly expressed in different stages of dental development,.iIt may be inferred that any interference in these interactive sequential events might cause problems in tooth formation.
In conclusion, the findings strongly suggest that the cleft has an important role in the occurrence, distribution, and severity of enamel lesions, especially in maxillary permanent incisors and molars.Further investigations are needed to better understand the process of enamel development and the factors that interfere with this mechanism, thereby contributing to prevent the occurrence of MIH defects and their clinical consequences.

Figure 4 .
Figure 4. Prevalence of MIH defects in all studied groups.

Table 1 .
). Chi-square test for comparison of groups.