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Etiological Factors Involved in Molar-Incisor Hypomineralization in 7 to 12-Year-Old Children in Tehran

Objectives: Molar-incisor hypomineralization (MIH) lesions are common in children. The prevalence of MIH is variable in different communities. However, information regarding the prevalence of MIH in the Iranian population is limited. This study sought to assess the prevalence and etiological factors of MIH in 7-12-year-old children in Tehran. Materials and Methods: This descriptive, cross-sectional study evaluated 1028 elementary students between 7-12 years, selected from different districts of Tehran in 2017. The frequency of MIH in the maxillary and mandibular molars and incisors was determined by clinical examination. In order to assess the role of different factors in the development of MIH, a questionnaire was filled out by the mothers regarding problems during their pregnancy, medical history of children, and age of occurrence of systemic conditions (if any). The effect of different factors on the development of MIH was analyzed by the logistic regression test. Results: The prevalence of MIH was found to be 25.6%. The delivery condition of the mother (P<0.001), history of urinary tract infection (P<0.011), history of chickenpox (P<0.018), and frequent use of amoxicillin during childhood (P<0.041) significantly affected the occurrence of MIH. The most commonly involved teeth were the mandibular left first molars. Conclusion: The prevalence of MIH in our study population was within the range reported in the literature. Considering the relatively high prevalence of MIH in 7-12-year-old children, pediatric dentists should pay special attention to treatment of MIH.


INTRODUCTION
Enamel hypomineralization is a developmental anomaly, which may occur alone or in association with dysplasia in other tissues, some systemic conditions, or genetic/ environmental factors [1]. Molar-incisor hypomineralization (MIH) refers to enamel defects in one or more permanent molars with/without incisors [2]. According to another definition, MIH often involves one or more permanent first molars with a minimum of one hypomineralized incisor [3]. MIH of molars is not related to fluoride and the teeth are referred to as cheese molars [4]. Localized enamel opacities in MIH are different from the more diffuse opacities related to fluorosis [5]. The involved porous teeth have higher susceptibility to plaque accumulation and are at higher risk of caries and fracture after eruption. The influential factors in the etiopathology of MIH include medical problems (before, during and after birth), environmental pollutants, and genetic factors.
The term MIH was first used in 2001 to describe permanent first molars with white or yellow-brown discoloration, which were often associated with hypomineralized permanent incisors [6]. Enamel defects in MIH have a systemic origin and can affect a number of teeth. Unlike tetracycline discoloration or linear enamel hypoplasia, MIH does not have chronological manifestations. Unlike amelogenesis imperfect it does not affect the entire dentition [7]. In MIH, the enamel structure is soft and porous. Thus, unusual cavities may develop, and enamel destruction may occur in the occlusal surface. Defective enamel structure also results in development of hypersensitivity, secondary caries, suboptimal restorative treatments, restoration loss, and eventual tooth loss [8,9]. The reported prevalence of MIH varies from 4% to 25%. However, most previous studies on this topic have been conducted in European countries [10,11]. Ahmadi et al. [12] evaluated the prevalence of MIH and its correlation with systemic conditions in a group of Iranian children and showed that the prevalence of this condition was 12.7%. Mehran et al. [13] studied 1400 elementary students in Tehran and reported that 34.2% of females and 30.1% of males had enamel defects in their permanent incisors and first molars. Despite the significance of MIH, studies regarding its prevalence in Iran are limited. Thus, we sought to assess the prevalence and etiological factors of MIH in 7-12 year-old children in Tehran.

MATERIALS AND METHODS
This descriptive cross-sectional study was conducted on 7-12 year-old children residing in Tehran, who were selected from elementary schools in different municipal districts by cluster sampling. The parents signed informed consents prior to the participation of their children in the study. The sample size was calculated to be 1028 students considering the prevalence range of MIH to be 0.5% to 40.2% and its global prevalence of 14.2% [14], and assuming P=0.12, d=34%, power of 90% and effect size of 2. The students were selected by random cluster sampling such that one girls' school and one boys' school were chosen from different municipal districts of Tehran. For sample selection, first male and female students were separated by stratified sampling, and the required number of males and females was calculated. We categorized Tehran into 5 areas of north, west, south, and center, and one district was randomly selected from each area. By doing so, the obtained results could be generalized to the entire population of Tehran. Ten schools were randomly selected from each district (5 girls' schools and 5 boys' schools). One class was chosen from each school (with averagely 20 students in each class). Prior to clinical examination, the examiner (a senior dental student) received instructions regarding the clinical manifestations of MIH and other enamel defects, and the kappa coefficient of agreement was calculated to assess the intraobserver agreement, which was found to be 0.9, indicating good agreement. Students in the first school were examined by both the senior dental student and a faculty member pedodontist. Their results were compared and the disagreements were resolved by discussion until the inter-observer agreement reached 1. The students in the remaining schools were examined by the senior dental student alone. The inclusion criteria were age range of 7-12 years, willingness for participation in the study, and cooperation during clinical examination. The exclusion criteria were presence of enamel or dentin defects in all teeth, chronological hypoplasia, history of trauma, and history of infection in primary incisor teeth. For clinical examination, first the surface of maxillary and mandibular permanent first molar and incisors was cleaned with a gauze and then wetted and inspected for presence of opaque spots, surface destruction, and caries using a dental explorer and cap flashlight. Also, in order to determine the possible predictive factors for MIH, a questionnaire was filled out by the mothers to collect information regarding the health status of their children in the preschool years, their demographics, possible confounders related to development of MIH such as the delivery method, problems during pregnancy and delivery such as pregnancy diabetes, difficult vaginal delivery, etc. The questionnaire also asked some questions regarding birth weight, febrile infectious diseases, antibiotic use, renal diseases, asthma, respiratory problems, diabetes mellitus, etc. This information was collected from the mothers by asking them to fill out a form in this respect. Data were analyzed using SPSS version 23 (SPSS Inc., IL, USA). The frequency and percentage of variables were calculated and reported. The prevalence of MIH was calculated in general, and separately for each maxillary and mandibular molar and incisor tooth. The binary logistic regression (backward step-wise LR model) was applied to assess the effect of different variables on the occurrence of MIH in general, and separately for each tooth. Type 1 error was considered to be 0.05.
In total, our results revealed higher prevalence of MIH in our study population compared with most other populations. The prevalence of MIH in our study was close to the value reported in 6-11-year-olds by Lucheng district, Wenzhou city, China, which was 25.5% [15]. Other reported values were mostly lower than that found in the present study. Ahmadi et al. [12] reported the prevalence of MIH to be 12.7% in a group of Iranian children, which was lower than our value while Mehran et al. [13] evaluated 1400 elementary students in Tehran and reported that 34.2% of females and 30.1% of males had enamel defects in their permanent incisor and first molar teeth. Difference in the prevalence of MIH in different geographical areas is probably due to the effect of environmental (before and after birth), sociodemographic, and behavioral factors (socioeconomic status, nutrition, and lactation), method of assessment (examination under light, retrospective, prospective or longitudinal study design), and rate of caries in the study population [16,17]. Genetics and age may also play a role in development of MIH [18]. By an increase in age over 10 years, a significant drop is noted in the prevalence of MIH [19]. Also, children younger than 10 years have higher prevalence of MIH compared with those over 10 years of age; however, since aging increases the rate of destruction of teeth, older children may show more severe signs and symptoms [20]. Also, higher rate of utilization of preventive and therapeutic dental care services by older children may decrease the prevalence of MIH in them.
The results of regression test in our study revealed that the delivery condition of the mother, history of urinary tract infection, history of chickenpox, and history of frequent use of amoxicillin during childhood had significant impacts on development of MIH. The risk factors of MIH in previous studies included the use of penicillin or macrolides in the first year of life, use of amoxicillin in the first 3 years of life, history of acute earache [21], Prenatal and postnatal factors such as systemic diseases of the mother, medication intake during pregnancy, birth-related complications or premature birth, history of fever, asthma, or respiratory infections during infancy, alcohol consumption by the mother, race [22], history of infectious diseases before and after birth, [20]low birth weight, history of urinary tract infection, chickenpox or allergy [23], age [19], preterm delivery and respiratory disorders at birth [24], history of asthma, fever or antibiotic intake during childhood [25], low socioeconomic class [26], medical problems of the mother and child before, during or after birth [12], teenage pregnancy [27], and use of amoxicillin [28].
In the present study, gender and age had no significant impact on development of MIH. However, some previous studies found a difference in the prevalence of MIH in males and females, which was attributed to the difference in time of development and complete formation of tooth crowns, time of tooth eruption, and oral hygiene practice between males and females [16,26]. No consensus has been reached regarding the possible causes of MIH [18,29] [33] showed that developmental defects in teeth were correlated with long-term breastfeeding. Also, evidence shows that use of beta-2 agonists and corticosteroids increases the frequency of severe MIH [34]. Respiratory diseases are also correlated with MIH [35]. Also, respiratory diseases in the first year of life can influence tooth formation by oxygen deprivation [36]. Chickenpox, caused by Varicella zoster affects the epithelial surface and can attack the ameloblasts derived from the epithelium in enamafel development phase and influence their activity [28,36]. Treatment with antibiotics especially amoxicillin in the first 3 years of life is also correlated with development of MIH. It may be due to the direct impact of amoxicillin on active ameloblasts or the infective nature of disease for which, antibiotics have been prescribed [37]. The correlation of some systemic conditions with development of MIH highlights the role of pediatricians in early detection of MIH and early referral of patients to pediatric dentists for in-time management of these lesions.
In the present study, mandibular left first molars had the highest rate of involvement with MIH (26.4%) followed by mandibular right first molars (24.9%), maxillary right first molars (23.3%) and maxillary left first molars (19%). In the study by Buchgraber et al, [38] in south Austria, maxillary and mandibular molar teeth were equally involved while maxillary incisors had a higher rate of involvement than mandibular incisors. Subramaniam et al. [39] reported that mandibular molars had a higher rate of involvement with MIH than maxillary molars (29.41% versus 27.94%). Their results were almost in line with our findings. de Lima et al. [24] reported that maxillary molars had the highest prevalence of MIH (36.1%). Cho et al. [11] evaluated Chinese children in Hong Kong and reported that maxillary permanent first molars were more commonly involved with MIH followed by mandibular permanent first molars and maxillary central incisors.
The results of studies regarding the prevalence of MIH in the maxilla and mandible have been controversial. Some studies found no significant difference between the maxilla and mandible while some other reported higher prevalence of MIH in the maxilla [4,40]. The reason for this difference has not been clearly understood. However, development of mandibular molars starts later than maxillary molars. Thus, factors affecting tooth development during this period may be responsible for development of MIH [11,17]. Considering our adequately large sample size and reliable method of examination, it seems 7 / 8 that our results are generalizable to the entire population of elementary schoolers regard MIH children aged 7 to 10 years old in Tehran. One limitation of this study was absence of a data bank regarding the medical history of children. Thus, we had to ask the mothers to fill out a questionnaire to collect information in this regard. According to the European Academy of Pediatric Dentistry, the best age for clinical examination of teeth for MIH is 8 years of age since the eruption of target teeth is almost complete and the possibility of not detecting MIH lesions due to tooth-colored restorations would be minimal at this age [30]. Thus, we selected patients in the age range of 7 to 12 years. Considering the high prevalence of MIH in our study population, further attempts should be made for detection and restoration of MIH defects. Moreover, this study was conducted in Tehran. There is a lack of validity, as the respondent may be forgetful or not be thinking within the full context of the situation. Further studies on children residing in other cities of Iran are recommended.

CONCLUSION
The prevalence of MIH in our study population was within the range reported in the literature and delivery condition of the mother, history of urinary tract infection, history of chickenpox, and history of frequent use of amoxicillin during childhood, significantly affected the development of MIH. Considering the relatively high prevalence of MIH in 7-12 year-old children, pediatric dentists should pay special attention to treatment of MIH.