Prevalence and Aetiology of Molar Incisor Hypomineralization in Children: A Cross- Sectional Study

Prevalence and Aetiology of Molar Incisor Hypomineralization in Children: A Cross- Sectional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Prevalence and Aetiology of Molar Incisor Hypomineralization in Children: A Cross- Sectional Study Selin Sena YILMAZ, Ilhan UZEL, Fahinur ERTUĞRUL, Şule GÖKÇE, Burçe DÖRTKARDEŞLER, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6888304/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Nov, 2025 Read the published version in BMC Oral Health → Version 1 posted 10 You are reading this latest preprint version Abstract Background: Molar Incisor Hypomineralization (MIH) is a qualitative enamel defect affecting first permanent molars often involving incisors. It presents clinical challenges including hypersensitivity, rapid caries, and restorative difficulties. Though its etiology is unclear, systemic and environmental factors have been implicated. Objective : This study aimed to determine the prevalence and aetiology of MIH and to assess the risk factors. Methods : A cross-sectional study was conducted on children aged 6-12 years. Among 700 children examined, 50 diagnosed with MIH were included in the case group, while 50 healthy children formed the control group. Parental interviews assessed sociodemographic, prenatal, perinatal, postnatal factor. Biochemical parameters were analyzed appropriate statistical tests. Results : MIH prevalence was 12% and 76% had severe defects (MIH-2), and 24% had mild opacities (MIH-1). Significant associations were observed with socioeconomic status, maternal employment, birth weight, antibiotic use and respiratory infections (p <0.005). Exclusive breastfeeding duration was longer in controls (p = 0.020). Conclusion : MIH is a multifactorial condition influenced by systemic and environmental factors. Early diagnosis and prevention are essential. Longer breastfeeding duration may offer a protective effect. Larger longitudinal studies are needed to better understand MIH etiology. Molar Incisor Hypomineralization Nutrition Etiology of MIH Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 INTRODUCTION Molar Incisor Hypomineralization (MIH) is a developmental enamel defect that primarily affects the first permanent molars and frequently the incisors. Clinically, MIH leads to rapid dental caries, hypersensitivity, aesthetic concerns and compromised restorative outcomes, presenting a significant challenge for pediatric dental care [ 1 ]. Despite global recognition of MIH and its increasing prevalence, the etiology remains complex and multifactorial, involving systemic, genetic, and environmental influences during critical stages of tooth development [ 2 ].The etiology of MIH is multifactorial, involving systemic, genetic, and environmental factors during the prenatal, perinatal, and postnatal stages [ 3 , 4 ]. Numerous international studies have investigated MIH prevalence and risk factors; however, there is a limited body of region- spesific evidence from Turkey, particularly concerning the western urban region of İzmir. Previous studies from Turkey have reported varying prevalence rates and heterogeneous risk associations, indicating a need for localized epidemiological data that accounts for sociodemographic, perinatal and systemic health variables [ 5 – 7 ]. Although no clear causal relationship has been established, risk factors include vitamin D deficiency, antibiotic use, childhood infection illnesses, and atopic diseases such as dermatitis and asthma[ 3 , 8 – 10 ]. Globally, MIH affects approximately 12.9% of children, with regional variations[ 11 ]. In Turkey, its prevalence ranges from 9.1–14.2%, with severity classified as mild (limited opacities) or severe (post-eruptive breakdown or restorations)[ 5 – 7 ]. Therefore, this study aims to determine the prevalence of MIH among school-aged children in İzmir amd to identify associated etiological factors, contibuting context-specific insights to the global understanding of MIH. MATERIALS AND METHOD This quantitative, descriptive study was conducted at Ege University Faculty of Dentistry, Department of Pediatric Dentistry, and Faculty of Medicine, Department of Pediatrics, Division of General Pediatrics, between September 2023 and January 2024. Ethics Ethics committee approval was obtained from the Ege University Faculty of Medicine Medical Research Ethics Committee. Informed consent was secured from parents, and assent was obtained from children. Study population Between September 2023 and January 2024, 700 patients visited the Department of Pedodontics at Ege University Faculty of Dentistry for examination, and MIH was diagnosed in 84 of them. Out of these 84 patients, 50 volunteers who met the inclusion criteria and consented to participate were randomly selected for the study. The control group consisted of 6–12-year-old patients with fully erupted molars who had no MIH diagnosis. The MIH examination was conducted in the dentistry polyclinic under natural daylight. During the procedure, the children sat upright in a chair. The dentists moistened the teeth and used a dental mirror and probe to eliminate any food debris if necessary. Each tooth (4 first permanent molars, 8 incisors and 4 canines ) was assessed based on the EAPD criteria for MIH. For MIH diagnosis, at least one affected first permanent molar must be present and frequently associated with affected incisors. Questionnaire Evaluation The potential aetiological factors were assessed with a questionnaire comprised of 29 questions and were sent to parents/caretakers in addition to the study consent form. A total of 100 questionnaires were completed and returned. A questionnaire was specifically developed for this study. The English version of the questionnaire is available as Supplementary File 1. The questionnaire contained following sections: Demographic data (child’s age, gender, place of birth), whether the mother was healthy or taking any medicines during pregnancy, how was the baby delivered, whether there were any complications during or before childbirth and child’s birth weight, average breastfeeding period, child’s medical history of first three years (diarrhea, tonsillitis, pharyngitis, digestive system diseases, atopic diseases, pneumonia, respiratory tract infections, asthma, frequent high fever (39 C), otitis media, chronic renal failure, urinary infections and childhood diseases as a rubella, scarlet fever, chickenpox). Exclusion criteria included systemic diseases, dental anomalies, orthodontic treatment, and missing permanent teeth. Clinical Evaluation The oral examinations of these 50 MIH-diagnosed patients were repeated at the Department of Pedodontics at Ege University Faculty of Dentistry to determine which teeth and how many teeth in total were affected by MIH, and the findings were recorded. Patients were categorized into MIH-1 and MIH-2 groups based on the severity criteria defined by Kılınç et al[5]. (2019). Patients were classified as MIH-1 if they had well-defined opacities on one or more permanent first molars or incisors (Fig. 1-2-3). Those who had at least one permanent first molar or incisor with post-eruptive enamel breakdown (Fig.4,5), atypical restoration (Fig.6), or a missing permanent first molar due to MIH were classified as MIH-2. All parents and children received oral hygiene education and were informed about MIH. The affected teeth were documented with photographs. As shown in Figure 5 and 6, patients requiring treatment were referred to our clinic. Statistical Analysis The statistical analysis was performed using SPSS version 25.0 (IBM, New York, USA). Descriptive statistics were presented as frequency (n) and percentage (%) for categorical variables, median (min–max) for non-normally distributed data, and mean ± standard deviation for normally distributed variables. The Shapiro-Wilk test was used to evaluate the assumption of normality, and the Levene test was used to assess variance homogeneity. Dependent Variables Teeth affected by MIH: Categorized using FDI notation[12]. Severity: MIH-1: Limited opacities (Figure 1,2,3) MIH-2: Post-eruptive enamel breakdown, caries, atypical restorations, or extractions¹³'¹⁴ (Figure 4,5,6) Independent Variables Sociodemographic Factors: Age, gender, parental education, income, family type, employment, and smoking. Systemic Factors: Respiratory conditions, atopic conditions, infections, neonatal jaundice, and antibiotic use before age 3. Prenatal/Perinatal Factors: Pregnancy complications, delivery type, birth weight, birth length, gestational age, parity, and supplement use. Feeding: Exclusive and total breastfeeding duration. Biochemical Parameters: Categorized using reference ranges from Clinical Biochemistry Laboratory. A complete blood count was performed using Sysmex XN3100 analyzers. Iron levels, ferritin, total iron-binding capacity (TIBC), and creatinine were measured photometrically. Vitamin B12 and total IgE levels were analyzed using immunochemistry methods. The Westergren technique was used to measure the sedimentation rate. For comparisons between two independent groups, normally distributed variables were analyzed using the Independent Samples T-test, while non-normally distributed variables were compared using the Mann-Whitney U test. The Pearson Chi-Square test was used to examine relationships between categorical variables when the expected value assumption (>5) was met; otherwise, Fisher’s Exact test was applied. RESULTS A) Case group and control group Out of 700 examined pediatric patients, 84 were diagnosed with MIH, indicating a prevalence rate of 12%. Within the case group, 24% (n=12) were classified as MIH-1 (mild opacities) (Fig. 1-2-3) and 76% (n=38) as MIH-2 (severe defects) (Fig. 4-5-6). The average number of affected teeth was significantly higher in the MIH-2 group (8.71 ± 3.39) compared to the MIH-1 group (4.17 ± 2.98). The most frequently affected teeth were the maxillary right first molar (16) and the mandibular left first molar (36). Among the case group, 72% (n=36) had both maxillary first molars affected, while 66% (n=33) had both mandibular first molars affected. Regarding permanent incisors, the upper left central incisor (21) was the most affected. Additionally, 64% (n=32) had both maxillary central incisors affected, 58% (n=29) had both mandibular central incisors affected, and 24% (n=12) had both maxillary lateral incisors affected. The mandibular right canine (43) showed the highest frequency of MIH among permanent canine. 8% (n=4) having both mandibular canines affected, while 92% (n=46) had no maxillary canines affected. The study included 100 participants: 50 patients diagnosed with MIH in the case group (34 parents did not agree to participate in the study) and 50 healthy controls for comparison analyses. The case group comprised 33 females (66%) and 17 males (34%), with a mean age of 9.18 ± 1.67 years. The control group included 26 females (52%) and 24 males (48%), with a mean age of 9.14 ± 2.08 years. Patients in the case group had a mean BMI of 17.52 ± 3.92. Among them, 80% were classified as normal weight, 4% as underweight (BMI ≤ -2 SDS), and 16% as obese (BMI ≥ +2 SDS). In contrast, 98% of the control group had normal weight, with only 2% classified as obese. The majority (84%) of the case group lived in nuclear families, while 16% lived in extended families. When analyzing the distribution of MIH by gender, no significant difference was found between gender, age and MIH. However, a significant association was observed between economical status and the presence of defects. The prevalence of MIH was found to be higher in children from families with low economic status compared to those from families with normal or high economic status (p<0.001). In parallel with this situation, there was a higher prevalence in the malnourished group as having MIH (p=0.009). In the case group, 26% of mothers had primary education, and 74% were unemployed. Among fathers, 30% had primary education, and 96% were employed. Regarding birth-related factors, 54% (n=27) of the case group were delivered via normal spontaneous vaginal delivery (NSVD), while 46% (n=23) were born by cesarean section (p> 0.05). Prematurity (≤37 weeks) was more common in the case group (22%) than in the control group (12%). Birth prematurity, number of births, exposure to cigarette smoke, diarrhea frequency, upper airway system infections, urinary tract infections, antibiotic use and age were found to be significantly associated with MIH. Similarly, having had chickenpox, gastroenteritis hand and foot mouth disease were also linked with MIH etiology (p < 0.005). There were significant associations (p<0.05) between patient groups and BMI, income level, parental education, maternal employment, birth weight, gestational age, number of births, household smoking, feeding method, respiratory diseases (tonsillitis, bronchitis, asthma), febrile conditions, allergic rhinitis, atopic dermatitis, urinary tract infections, neonatal jaundice, hand-foot-mouth disease, acute gastroenteritis, cardiac disease, age of illness onset, and antibiotic use. The case group had higher rates of borderline obesity, lower income, unemployed mothers, and parents with primary education. Birth weight ≥3.5 kg, gestational age <37 weeks, and a higher number of maternal births were also more common in the case group. Household smoking and mixed feeding (breast milk and complementary foods) were more frequent. Respiratory diseases, febrile conditions, allergic rhinitis, atopic dermatitis, urinary tract infections, neonatal jaundice, acute gastroenteritis, and cardiac disease were predominantly observed in the case group. Early illness onset and antibiotic use before age three were also more common. Regarding breastfeeding, 58% (n=29) of the case group were exclusively breastfed for 6 months, while 12% (n=6) received breast milk with formula and 12% (n=6) with complementary feeding. The onset of illness occurred before the age of 3 in 82% of cases. Among 49 respondents, 91.8% used antibiotics before the age of 3, while 8.2% used them only after the age of 3. Statistical analysis revealed a significant association (p < 0.05) between the presence of MIH, antibiotic use, and the age at onset of illnesses before 3 years. Comparison of demographic and clinical characteristics among patient groups and control groups, and the relationships between these characteristics were shown in Table 1. A significant difference was found in the average breastfeeding period between children with and without MIH. Table 2 indicates that children exclusively breastfed during the first six months exhibit a higher prevalence of molar incisor hypomineralization (MIH) compared to their non-exclusively breastfed counterparts. [5,02±2,4 vs. 6,44±2,52] (p<0.05) (Table 2). B) MIH-1 and MIH-2 groups Among 50 MIH-positive patients, when teeth affected by MIH were categorized as MIH-1 and MIH-2 using the FDI notation, no significant differences were found between the groups in terms of BMI, mode of delivery, birth weight, economic status, maternal education, and feeding patterns before the age of 1 (Table-3). No significant associations were found with gender, family type, father’s employment, cesarean section, pregnancy complications, birth length, vitamin supplementation, otitis, food allergies, sepsis, intellectual disability, measles, chickenpox, or pneumonia (p>0.05). A statistically significant difference (p<0.05) was observed in exclusive breastfeeding duration between the case and control groups, with the control group having a longer breastfeeding duration. No significant differences were found in age, maternal age, paternal age, or total breastfeeding duration (p>0.05). When the biochemical findings were compared between MIH-1 and MIH-2 patients, significant differences were observed in urea, total iron-binding capacity (TIBC), lymphocyte, monocyte, and eosinophil levels (p < 0.05), with the MIH-2 group exhibiting higher lymphocyte, monocyte, and eosinophil levels. However, no significant differences were found between the groups in terms of ALP, creatinine, calcium, phosphorus, iron, leukocytes, neutrophils, basophils, erythrocytes, hemoglobin, hematocrit, MCV, MCH, MCHC, platelets, erythrocyte sedimentation rate, total IgE, ferritin, vitamin B12, PTH, and vitamin D levels (p > 0.05) (Table-4) DISCUSSION Molar Incisor Hypomineralization (MIH) is an increasingly recognized global dental health concern, characterized by enamel defects that lead to dental hypersensitivity, rapid caries progression, masticatory dysfunction, and aesthetic concerns. The multifactorial etiology of MIH remains a subject of ongoing investigation, with genetic, systemic, and environmental factors playing potential roles [ 10 , 13 ]. Our study, which examined MIH prevalence and etiological risk factors among patients attending the Ege University Faculty of Dentistry, found an MIH prevalence rate of 12%, aligning with previous studies conducted in Turkey[ 5 – 7 ]. Consistent with the literature, the maxillary first molars and central incisors were the most affected teeth, while mandibular molars were less frequently involved [ 6 , 14 ]. Several studies have highlighted the role of socioeconomic factors in MIH prevalence, suggesting that lower socioeconomic status is associated with a higher risk of MIH[ 15 ]. In our study, significant associations were found between MIH prevalence and lower parental education levels, maternal unemployment, higher birth order, and household smoking exposure. These findings align with existing research indicating that limited access to healthcare, inadequate oral hygiene practices, and poor nutrition may contribute to MIH development. Systemic and perinatal factors have also been linked to MIH. Our study found a significant association between preterm birth and MIH, consistent with findings from Silva et al.[ 13 ] and Wu et al.[ 16 ] which suggest that premature birth may disrupt enamel mineralization during critical developmental phases. Additionally, early childhood illnesses, particularly respiratory infections, high fever episodes, and gastrointestinal disorders, were significantly associated with MIH, supporting prior evidence of their impact on ameloblast function[ 1 , 17 – 19 ] The role of breastfeeding in MIH remains controversial. While some studies suggest that prolonged breastfeeding may have a protective effect[ 20 ], others indicate a potential risk for enamel defects [ 21 ]. Our study found that the duration of exclusive breastfeeding was significantly longer in the healthy control group, suggesting a possible protective effect against MIH. However, further research with more cases is needed to clarify the underlying mechanisms. The relationship between MIH and vitamin and mineral deficiencies has been debated. Our study did not find significant associations between MIH severity and serum levels of calcium, phosphorus, parathyroid hormone (PTH), vitamin B12, or hemoglobin. However, increased total iron-binding capacity (TIBC) levels in mild MIH cases and elevated eosinophil and monocyte levels in severe cases suggest a potential role of systemic inflammation [ 22 ]. These findings warrant further investigation into the inflammatory aspects of MIH pathogenesis. While previous research, including a systematic review and meta-analysis by Hujoel et al., has suggested that vitamin D supplementation in early life may be associated with reduced caries risk, our study did not find a statistically significant association between MIH and the use of vitamin D or multivitamin supplements [ 23 ]. Notably, although the number of individuals receiving vitamin D supplementation was higher in the healthy control group compared to those diagnosed with MIH, this difference was not statistically significant. These findings suggest that, within the limitations of our sample, vitamin D supplementation alone may not be a protective factor against MIH development. The results of this study were consistent with those of other studies in the literature and there was no statistically significant relationship between the vitamin D levels of the severity groups. However, vitamin D levels of the patients in the case group were significantly and mildly moderately low (median = 17 ng/mL). Genetic susceptibility has been increasingly explored in MIH research. Bussaneli et al.[ 24 ] identified associations between TGFBR1 gene polymorphisms and severe MIH cases, highlighting potential genetic contributions. Moreover, studies have demonstrated links between MIH and allergic conditions such as atopic dermatitis and allergic rhinitis [ 20 , 25 ] findings that are consistent with our study results. Finally, the potential role of antibiotic exposure in MIH development has been well-documented. Our study found a significant association between antibiotic use in the first three years of life and MIH, corroborating previous findings that early-life antibiotic exposure may alter enamel formation [ 13 , 26 ] While this study identifies significant associations, further research is required to determine causal relationships between these factors and MIH development. In conclusion, our findings support the hypothesis that MIH etiology is multifactorial, with significant contributions from socioeconomic, systemic, perinatal, and genetic factors. Future research should focus on large-scale longitudinal and genetic studies to elucidate the multifactorial etiology of MIH and identify potential preventive strategies. CONCLUSION In this cross-sectional study conducted in İzmir, Turkey, the prevalence of molar incisor hypomineralization (MIH) among children aged 6–12 who presented to the Department of Pediatric Dentistry at Ege University was found to be 12%. The study identified that MIH predominantly affected the lower left and upper right first permanent molars, with a significant increase in the number of affected teeth in more severe cases (MIH-2). Several associations were observed between MIH and nutritional habits, systemic health conditions, and perinatal risk factors. Notably, the duration of exclusive breastfeeding was longer in the healthy control group, supporting WHO recommendations and highlighting a potential protective effect against MIH. Children diagnosed with MIH were more likely to have experienced respiratory diseases, atopic conditions, and early antibiotic exposure, suggesting these factors may negatively influence enamel development. Prenatal (e.g., prematurity), perinatal (e.g., low birth weight, cesarean delivery), and postnatal factors (e.g., infections, atopy) were significantly associated with MIH occurrence, whereas no significant association was found between MIH and prenatal vitamin or mineral deficiencies. Although serum vitamin D levels were generally lower in the MIH group, no statistically significant relationship was found between MIH presence and vitamin or multivitamin supplementation. Given the multifactorial etiology of MIH, a multidimensional approach is required. Raising awareness among parents and health professionals, emphasizing exclusive breastfeeding during the first six months, and implementing preventive dental strategies—such as fluoride application and fissure sealants—are essential. Early diagnosis through routine dental check-ups, along with interprofessional collaboration, particularly between pediatricians, allergists, and pediatric dentists, is critical. Unnecessary antibiotic prescriptions in children should be minimized. This study provides an important contribution to the growing body of literature on molar incisor hypomineralization (MIH) by offering new epidemiological data from a large pediatric population in İzmir, Turkey—a region where comprehensive MIH data remains limited. By examining both prevalence and a broad set of potential etiological risk factors, including prenatal, perinatal, and postnatal influences, this research presents a more nuanced understanding of the multifactorial nature of MIH. The findings highlight the importance of early-life systemic health conditions such as respiratory diseases, atopy, and antibiotic use, as well as nutritional factors like the duration of exclusive breastfeeding, in the development of MIH. These results align with and expand upon previous studies by reinforcing the potential protective role of exclusive breastfeeding and pointing to systemic illnesses as modifiable risk factors that may be targeted through public health interventions. Moreover, the study’s identification of affected tooth patterns and the correlation between lesion severity and the number of involved teeth add to the clinical understanding of MIH’s progression. While vitamin D deficiency was prevalent among children with MIH, the lack of a statistically significant association with supplementation highlights the need for further investigation into the role of micronutrients. By integrating clinical findings with sociodemographic and systemic health data, this study advocates for a multidisciplinary, prevention-oriented approach to MIH management. It also underscores the necessity of national surveillance and the development of targeted educational programs for both caregivers and healthcare providers. As such, the study lays the groundwork for future longitudinal research and contributes valuable region-specific insights to the global MIH discourse. Abbreviations · MIH: Molar Incisor Hypomineralization · BMI: Body Mass Index · SDS: Standardized Deviation Score · FDI: Fédération Dentaire Internationale · ALP: Alkaline Phosphatase · TIBC: Total Iron Binding Capacity · PTH: Parathyroid Hormone · IgE: Immunoglobulin E · MCV: Mean Corpuscular Volume · MCH: Mean Corpuscular Hemoglobin · MCHC: Mean Corpuscular Hemoglobin Concentration · SPSS: Statistical Package for the Social Sciences · NSVD: Normal Spontaneous Vaginal Delivery · EAPD: European Academy of Paediatric Dentistry Declarations Ethics Approval and Consent to Participate This study was approved by the Ethics Committee of Ege University Medical Research EThics Board (Approval number: 24-8T/124, date of approval: January 4, 2024.) Written informed consent was obtained from all participants and their legal guardians prior to data collection. Consent for Publication The images used in the manuscript show only anonymized intraoral views with no identifiable patient information. Therefore, we believe that patient consent for publication is not required. However, we are ready to obtain written consent if the journal deems it necessary. Availability of data and materials The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Competing Interests The authors declare that they have no competing interests. Funding This research received no external funding. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Authors’ contributions Dr. Yılmaz, Dr. Uzel and Dr. Ertuğrul contributed to the study design, formation of the control and study groups, clinical examinations, and collection of clinical materials. Dr. Dörtkardeşler and Dr. Gökçe were responsible for the development of the questionnaire and the evaluation of the survey results. Dr. Ak contributed to the collection of biochemical samples and the interpretation of biochemical findings. All authors read and approved the final version of the manuscript. Acknowledgements The authors would like to thank all the participating children and their families for their valuable contributions to this study. We also gratefully acknowledge the support of the Ege University Departments of General Pediatrics, Biochemistry, and Pediatric Dentistry for their assistance throughout the research process. **Clinical trial number:** Not applicable. References Bekes K. Molar Incisor Hypomineralization A Clinical Guide to Diagnosis and Treatment. 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Prevalence and Possible Etiological Factors of Molar-Incisor Hypomineralization (MIH) in Population of Silesian Children in Poland: A Pilot Retrospective Cohort Study. Int J Environ Res Public Health 2022;19. https://doi.org/10.3390/ijerph19148697. Alaluusua S, Lukinmaa P-L, Koskimies M, Pirinen S, Hölttä P, Kallio M, et al. Developmental dental defects associated with long breast feeding. European Journal Of Oral Science 1996;104:493–7. Frascino S, Frascino A, Rezende KM, Imparato JC, Pignatari S. Molar-incisor enamel hypomineralization cross-sectional prevalence evaluation in oral-breathing allergic children. Clinical and Laboratorial Research in Dentistry 2018. https://doi.org/10.11606/issn.2357-8041.clrd.2017.134317. Hujoel PP. Vitamin D and dental caries in controlled clinical trials: Systematic review and meta-analysis. Nutr Rev 2013;71:88–97. https://doi.org/10.1111/j.1753-4887.2012.00544.x. Bussaneli DG, Restrepo M, Fragelli CMB, Santos-Pinto L, Jeremias F, Cordeiro RDCL, et al. Genes Regulating Immune Response and Amelogenesis Interact in Increasing the Susceptibility to Molar-Incisor Hypomineralization. Caries Res 2019;53:217–27. https://doi.org/10.1159/000491644. Hernandez M, Boj J, Espasa E, Planells P, Peretz B. Molar-incisor hypomineralization: Positive correlation with atopic dermatitis and food allergies. Journal of Clinical Pediatric Dentistry 2018;42:344–8. https://doi.org/10.17796/1053-4625-42.5.4. Wuollet E, Laisi S, Salmela E, Ess A, Alaluusua S. Molar–incisor hypomineralization and the association with childhood illnesses and antibiotics in a group of Finnish children. Acta Odontol Scand 2016;74:416–22. https://doi.org/10.3109/00016357.2016.1172342. Tables Tables 1 to 4 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Table1articleMIH.docx Table2articleMIH.docx Table3IJPD.docx Table4MIHBMCOralHealth.docx Supplementaryfile1.docx Cite Share Download PDF Status: Published Journal Publication published 25 Nov, 2025 Read the published version in BMC Oral Health → Version 1 posted Editorial decision: Revision requested 04 Aug, 2025 Reviews received at journal 02 Aug, 2025 Reviewers agreed at journal 30 Jul, 2025 Reviews received at journal 28 Jul, 2025 Reviewers agreed at journal 28 Jul, 2025 Reviewers invited by journal 09 Jul, 2025 Editor assigned by journal 09 Jul, 2025 Editor invited by journal 09 Jul, 2025 Submission checks completed at journal 08 Jul, 2025 First submitted to journal 08 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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2","display":"","copyAsset":false,"role":"figure","size":401063,"visible":true,"origin":"","legend":"\u003cp\u003eMIH-1: Limited opacities on mandibular incisors and canines\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6888304/v1/1ac8d25e3e46bea60b9aa228.png"},{"id":86663202,"identity":"3d8de0a9-4b10-4f22-afe9-280a61f5ceaa","added_by":"auto","created_at":"2025-07-14 10:47:58","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":597636,"visible":true,"origin":"","legend":"\u003cp\u003eMIH-1: Limited opacities on a maxillary first permanent molar\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6888304/v1/b8946939f2c3217f6d1523da.png"},{"id":86663208,"identity":"b328f3bb-08c7-4901-bffa-a86bed5b8e0a","added_by":"auto","created_at":"2025-07-14 10:47:58","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":640309,"visible":true,"origin":"","legend":"\u003cp\u003eMIH-2: Post-eruptive enamel breakdown on maxillary first permanent molar\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6888304/v1/3d54c60904f1ca409c16c59f.png"},{"id":86664862,"identity":"a250415b-427d-4a8e-ba06-e97c5565d540","added_by":"auto","created_at":"2025-07-14 10:55:58","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":428443,"visible":true,"origin":"","legend":"\u003cp\u003eMIH-2: Post-eruptive enamel breakdown and caries on mandibulary first permanent molar\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-6888304/v1/f56a2617a40daa4bb2fc83bd.png"},{"id":86665557,"identity":"87a3f0ac-cb63-4996-88c7-d2c32ee0ad0a","added_by":"auto","created_at":"2025-07-14 11:03:58","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":611152,"visible":true,"origin":"","legend":"\u003cp\u003eMIH-2: \u0026nbsp;Atypical composite restoration on maxillary first permanent molar\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-6888304/v1/72113e09ea3919b7de3bccd7.png"},{"id":97178777,"identity":"bad7ef57-2f44-47bb-a58d-c3b0bdd897fc","added_by":"auto","created_at":"2025-12-01 16:13:34","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5059981,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6888304/v1/8f144f3e-0e69-4b6c-b8aa-071725ba7660.pdf"},{"id":86665555,"identity":"3a9d2777-9c4c-4079-a0d1-ee1b8ac95332","added_by":"auto","created_at":"2025-07-14 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10:55:58","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":30754,"visible":true,"origin":"","legend":"","description":"","filename":"Table3IJPD.docx","url":"https://assets-eu.researchsquare.com/files/rs-6888304/v1/32832db6da01d01b4176d256.docx"},{"id":86664861,"identity":"b6736b08-8f1b-4f6f-bb4a-e046f814d6ad","added_by":"auto","created_at":"2025-07-14 10:55:58","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":21597,"visible":true,"origin":"","legend":"","description":"","filename":"Table4MIHBMCOralHealth.docx","url":"https://assets-eu.researchsquare.com/files/rs-6888304/v1/53e95698b32bcce88a5b64ec.docx"},{"id":86664860,"identity":"740cfb03-1449-4cca-93a9-cc3c994b96af","added_by":"auto","created_at":"2025-07-14 10:55:58","extension":"docx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":37391,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementaryfile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6888304/v1/1848fda9279dc3044b53c586.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Prevalence and Aetiology of Molar Incisor Hypomineralization in Children: A Cross- Sectional Study","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eMolar Incisor Hypomineralization (MIH) is a developmental enamel defect that primarily affects the first permanent molars and frequently the incisors. Clinically, MIH leads to rapid dental caries, hypersensitivity, aesthetic concerns and compromised restorative outcomes, presenting a significant challenge for pediatric dental care [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Despite global recognition of MIH and its increasing prevalence, the etiology remains complex and multifactorial, involving systemic, genetic, and environmental influences during critical stages of tooth development [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].The etiology of MIH is multifactorial, involving systemic, genetic, and environmental factors during the prenatal, perinatal, and postnatal stages [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Numerous international studies have investigated MIH prevalence and risk factors; however, there is a limited body of region- spesific evidence from Turkey, particularly concerning the western urban region of İzmir. Previous studies from Turkey have reported varying prevalence rates and heterogeneous risk associations, indicating a need for localized epidemiological data that accounts for sociodemographic, perinatal and systemic health variables [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Although no clear causal relationship has been established, risk factors include vitamin D deficiency, antibiotic use, childhood infection illnesses, and atopic diseases such as dermatitis and asthma[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Globally, MIH affects approximately 12.9% of children, with regional variations[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In Turkey, its prevalence ranges from 9.1\u0026ndash;14.2%, with severity classified as mild (limited opacities) or severe (post-eruptive breakdown or restorations)[\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTherefore, this study aims to determine the prevalence of MIH among school-aged children in İzmir amd to identify associated etiological factors, contibuting context-specific insights to the global understanding of MIH.\u003c/p\u003e"},{"header":"MATERIALS AND METHOD","content":"\u003cp\u003eThis quantitative, descriptive study was conducted at Ege University Faculty of Dentistry, Department of Pediatric Dentistry, and Faculty of Medicine, Department of Pediatrics, Division of General Pediatrics, between September 2023 and January 2024.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics committee approval was obtained from the Ege University Faculty of Medicine Medical Research Ethics Committee. Informed consent was secured from parents, and assent was obtained from children.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBetween September 2023 and January 2024, 700 patients visited the Department of Pedodontics at Ege University Faculty of Dentistry for examination, and MIH was diagnosed in 84 of them. Out of these 84 patients, 50 volunteers who met the inclusion criteria and consented to participate were randomly selected for the study. The control group consisted of 6–12-year-old patients with fully erupted molars who had no MIH diagnosis. The MIH examination was conducted in the dentistry polyclinic under natural daylight. During the procedure, the children sat upright in a chair. The dentists moistened the teeth and used a dental mirror and probe to eliminate any food debris if necessary. Each tooth (4 first permanent molars, 8 incisors and 4 canines ) was assessed based on the EAPD criteria for MIH. For MIH diagnosis, at least one affected first permanent molar must be present and frequently associated with affected incisors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQuestionnaire Evaluation \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe potential aetiological factors were assessed with a questionnaire comprised of 29 questions and were sent to parents/caretakers in addition to the study consent form. A total of 100 questionnaires were completed and returned.\u0026nbsp;A questionnaire was specifically developed for this study. The English version of the questionnaire is available as Supplementary File 1.\u003c/p\u003e\n\u003cp\u003eThe questionnaire contained following sections: Demographic data (child’s age, gender, place of birth), whether the mother was healthy or taking any medicines during pregnancy, how was the baby delivered, whether there were any complications during or before childbirth and child’s birth weight, average breastfeeding period, child’s medical history of first three years (diarrhea, tonsillitis, pharyngitis, digestive system diseases, atopic diseases, pneumonia, respiratory tract infections, asthma, frequent high fever (39 C), otitis media, chronic renal failure, urinary infections and childhood diseases as a rubella, scarlet fever, chickenpox).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eExclusion criteria included systemic diseases, dental anomalies, orthodontic treatment, and missing permanent teeth.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Evaluation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe oral examinations of these 50 MIH-diagnosed patients were repeated at the Department of Pedodontics at Ege University Faculty of Dentistry to determine which teeth and how many teeth in total were affected by MIH, and the findings were recorded. Patients were categorized into MIH-1 and MIH-2 groups based on the severity criteria defined by Kılınç et al[5]. (2019). Patients were classified as MIH-1 if they had well-defined opacities on one or more permanent first molars or incisors (Fig. 1-2-3). Those who had at least one permanent first molar or incisor with post-eruptive enamel breakdown (Fig.4,5), atypical restoration (Fig.6), or a missing permanent first molar due to MIH were classified as MIH-2. All parents and children received oral hygiene education and were informed about MIH. The affected teeth were documented with photographs. As shown in Figure 5 and 6, \u0026nbsp;patients requiring treatment were referred to our clinic.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe statistical analysis was performed using SPSS version 25.0 (IBM, New York, USA). Descriptive statistics were presented as frequency (n) and percentage (%) for categorical variables, median (min–max) for non-normally distributed data, and mean ± standard deviation for normally distributed variables. The Shapiro-Wilk test was used to evaluate the assumption of normality, and the Levene test was used to assess variance homogeneity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDependent Variables\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTeeth affected by MIH: Categorized using FDI notation[12].\u003c/p\u003e\n\u003cp\u003eSeverity:\u003c/p\u003e\n\u003cp\u003eMIH-1: Limited opacities (Figure 1,2,3)\u003c/p\u003e\n\u003cp\u003eMIH-2: Post-eruptive enamel breakdown, caries, atypical restorations, or extractions¹³'¹⁴ (Figure 4,5,6)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIndependent Variables\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSociodemographic Factors: Age, gender, parental education, income, family type, employment, and smoking.\u003c/p\u003e\n\u003cp\u003eSystemic Factors: Respiratory conditions, atopic conditions, infections, neonatal jaundice, and antibiotic use before age 3.\u003c/p\u003e\n\u003cp\u003ePrenatal/Perinatal Factors: Pregnancy complications, delivery type, birth weight, birth length, gestational age, parity, and supplement use.\u003c/p\u003e\n\u003cp\u003eFeeding: Exclusive and total breastfeeding duration.\u003c/p\u003e\n\u003cp\u003eBiochemical Parameters: Categorized using reference ranges from Clinical Biochemistry Laboratory. A complete blood count was performed using Sysmex XN3100 analyzers. Iron levels, ferritin, total iron-binding capacity (TIBC), and creatinine were measured photometrically. Vitamin B12 and total IgE levels were analyzed using immunochemistry methods. The Westergren technique was used to measure the sedimentation rate.\u003c/p\u003e\n\u003cp\u003eFor comparisons between two independent groups, normally distributed variables were analyzed using the Independent Samples T-test, while non-normally distributed variables were compared using the Mann-Whitney U test. The Pearson Chi-Square test was used to examine relationships between categorical variables when the expected value assumption (\u0026gt;5) was met; otherwise, Fisher’s Exact test was applied.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cstrong\u003eA)\u0026nbsp;\u0026nbsp;Case group and control group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOut of 700 examined pediatric patients, 84 were diagnosed with MIH, indicating a prevalence rate of 12%. Within the case group, 24% (n=12) were classified as MIH-1 (mild opacities) (Fig. 1-2-3) and 76% (n=38) as MIH-2 (severe defects) (Fig. 4-5-6). The average number of affected teeth was significantly higher in the MIH-2 group (8.71 ± 3.39) compared to the MIH-1 group (4.17 ± 2.98). The most frequently affected teeth were the maxillary right first molar (16) and the mandibular left first molar (36). Among the case group, 72% (n=36) had both maxillary first molars affected, while 66% (n=33) had both mandibular first molars affected. Regarding permanent incisors, the upper left central incisor (21) was the most affected. Additionally, 64% (n=32) had both maxillary central incisors affected, 58% (n=29) had both mandibular central incisors affected, and 24% (n=12) had both maxillary lateral incisors affected. The mandibular right canine (43) showed the highest frequency of MIH among permanent canine. 8% (n=4) having both mandibular canines affected, while 92% (n=46) had no maxillary canines affected.\u003c/p\u003e\n\u003cp\u003eThe study included 100 participants: 50 patients diagnosed with MIH in the case group (34 parents did not agree to participate in the study) and 50 healthy controls for comparison analyses. The case group comprised 33 females (66%) and 17 males (34%), with a mean age of 9.18 ± 1.67 years. The control group included 26 females (52%) and 24 males (48%), with a mean age of 9.14 ± 2.08 years. Patients in the case group had a mean BMI of 17.52 ± 3.92. Among them, 80% were classified as normal weight, 4% as underweight (BMI ≤ -2 SDS), and 16% as obese (BMI ≥ +2 SDS). In contrast, 98% of the control group had normal weight, with only 2% classified as obese. The majority (84%) of the case group lived in nuclear families, while 16% lived in extended families.\u0026nbsp;When analyzing the distribution of MIH by gender, no significant difference was found between gender, age and MIH. However, a significant association was observed between economical status and the presence of defects. The prevalence of MIH was found to be higher in children from families with low economic status compared to those from families with normal or high economic status\u0026nbsp;(p\u0026lt;0.001).\u0026nbsp;In parallel with this situation, \u0026nbsp;there was a higher prevalence in the malnourished group as having MIH (p=0.009). In the case group, 26% of mothers had primary education, and 74% were unemployed. Among fathers, 30% had primary education, and 96% were employed. Regarding birth-related factors, 54% (n=27) of the case group were delivered via normal spontaneous vaginal delivery (NSVD), while 46% (n=23) were born by cesarean section (p\u0026gt; 0.05). Prematurity (≤37 weeks) was more common in the case group (22%) than in the control group (12%).\u0026nbsp;Birth prematurity, number of births, exposure to cigarette smoke, diarrhea frequency, upper airway system infections, urinary tract infections, antibiotic use and age were found to be significantly associated with MIH. \u0026nbsp;Similarly, having had chickenpox, gastroenteritis hand and foot mouth disease were also linked with MIH etiology (p \u0026lt; 0.005). There were significant associations (p\u0026lt;0.05) between patient groups and BMI, income level, parental education, maternal employment, birth weight, gestational age, number of births, household smoking, feeding method, respiratory diseases (tonsillitis, bronchitis, asthma), febrile conditions, allergic rhinitis, atopic dermatitis, urinary tract infections, neonatal jaundice, hand-foot-mouth disease, acute gastroenteritis, cardiac disease, age of illness onset, and antibiotic use. The case group had higher rates of borderline obesity, lower income, unemployed mothers, and parents with primary education. Birth weight ≥3.5 kg, gestational age \u0026lt;37 weeks, and a higher number of maternal births were also more common in the case group. Household smoking and mixed feeding (breast milk and complementary foods) were more frequent. Respiratory diseases, febrile conditions, allergic rhinitis, atopic dermatitis, urinary tract infections, neonatal jaundice, acute gastroenteritis, and cardiac disease were predominantly observed in the case group. Early illness onset and antibiotic use before age three were also more common.\u003c/p\u003e\n\u003cp\u003eRegarding breastfeeding, 58% (n=29) of the case group were exclusively breastfed for 6 months, while 12% (n=6) received breast milk with formula and 12% (n=6) with complementary feeding. The onset of illness occurred before the age of 3 in 82% of cases. Among 49 respondents, 91.8% used antibiotics before the age of 3, while 8.2% used them only after the age of 3. Statistical analysis revealed a significant association (p \u0026lt; 0.05) between the presence of MIH, antibiotic use, and the age at onset of illnesses before 3 years.\u0026nbsp;Comparison of demographic and clinical characteristics among patient groups and control groups, and the relationships between these characteristics were shown in Table 1. A significant difference was found in the average breastfeeding period between children with and without MIH.\u0026nbsp;Table 2 indicates that children exclusively breastfed during the first six months exhibit a higher prevalence of molar incisor hypomineralization (MIH) compared to their non-exclusively breastfed counterparts.\u003c/p\u003e\n\u003cp\u003e[5,02±2,4 vs. 6,44±2,52] (p\u0026lt;0.05) (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eB)\u0026nbsp;\u0026nbsp;MIH-1 and MIH-2 groups\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong 50 MIH-positive patients, when teeth affected by MIH were categorized as MIH-1 and MIH-2 using the FDI notation, no significant differences were found between the groups in terms of BMI, mode of delivery, birth weight, economic status, maternal education, and feeding patterns before the age of 1 (Table-3).\u0026nbsp;No significant associations were found with gender, family type, father’s employment, cesarean section, pregnancy complications, birth length, vitamin supplementation, otitis, food allergies, sepsis, intellectual disability, measles, chickenpox, or pneumonia (p\u0026gt;0.05). A statistically significant difference (p\u0026lt;0.05) was observed in exclusive breastfeeding duration between the case and control groups, with the control group having a longer breastfeeding duration. No significant differences were found in age, maternal age, paternal age, or total breastfeeding duration (p\u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003eWhen the biochemical findings were compared between MIH-1 and MIH-2 patients, significant differences were observed in urea, total iron-binding capacity (TIBC), lymphocyte, monocyte, and eosinophil levels (p \u0026lt; 0.05), with the MIH-2 group exhibiting higher lymphocyte, monocyte, and eosinophil levels. However, no significant differences were found between the groups in terms of ALP, creatinine, calcium, phosphorus, iron, leukocytes, neutrophils, basophils, erythrocytes, hemoglobin, hematocrit, MCV, MCH, MCHC, platelets, erythrocyte sedimentation rate, total IgE, ferritin, vitamin B12, PTH, and vitamin D levels (p \u0026gt; 0.05) (Table-4)\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eMolar Incisor Hypomineralization (MIH) is an increasingly recognized global dental health concern, characterized by enamel defects that lead to dental hypersensitivity, rapid caries progression, masticatory dysfunction, and aesthetic concerns. The multifactorial etiology of MIH remains a subject of ongoing investigation, with genetic, systemic, and environmental factors playing potential roles [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur study, which examined MIH prevalence and etiological risk factors among patients attending the Ege University Faculty of Dentistry, found an MIH prevalence rate of 12%, aligning with previous studies conducted in Turkey[\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Consistent with the literature, the maxillary first molars and central incisors were the most affected teeth, while mandibular molars were less frequently involved [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSeveral studies have highlighted the role of socioeconomic factors in MIH prevalence, suggesting that lower socioeconomic status is associated with a higher risk of MIH[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In our study, significant associations were found between MIH prevalence and lower parental education levels, maternal unemployment, higher birth order, and household smoking exposure. These findings align with existing research indicating that limited access to healthcare, inadequate oral hygiene practices, and poor nutrition may contribute to MIH development.\u003c/p\u003e\u003cp\u003eSystemic and perinatal factors have also been linked to MIH. Our study found a significant association between preterm birth and MIH, consistent with findings from Silva et al.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] and Wu et al.[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] which suggest that premature birth may disrupt enamel mineralization during critical developmental phases. Additionally, early childhood illnesses, particularly respiratory infections, high fever episodes, and gastrointestinal disorders, were significantly associated with MIH, supporting prior evidence of their impact on ameloblast function[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe role of breastfeeding in MIH remains controversial. While some studies suggest that prolonged breastfeeding may have a protective effect[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], others indicate a potential risk for enamel defects [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Our study found that the duration of exclusive breastfeeding was significantly longer in the healthy control group, suggesting a possible protective effect against MIH. However, further research with more cases is needed to clarify the underlying mechanisms.\u003c/p\u003e\u003cp\u003eThe relationship between MIH and vitamin and mineral deficiencies has been debated. Our study did not find significant associations between MIH severity and serum levels of calcium, phosphorus, parathyroid hormone (PTH), vitamin B12, or hemoglobin. However, increased total iron-binding capacity (TIBC) levels in mild MIH cases and elevated eosinophil and monocyte levels in severe cases suggest a potential role of systemic inflammation [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. These findings warrant further investigation into the inflammatory aspects of MIH pathogenesis.\u003c/p\u003e\u003cp\u003eWhile previous research, including a systematic review and meta-analysis by Hujoel et al., has suggested that vitamin D supplementation in early life may be associated with reduced caries risk, our study did not find a statistically significant association between MIH and the use of vitamin D or multivitamin supplements [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Notably, although the number of individuals receiving vitamin D supplementation was higher in the healthy control group compared to those diagnosed with MIH, this difference was not statistically significant. These findings suggest that, within the limitations of our sample, vitamin D supplementation alone may not be a protective factor against MIH development.\u003c/p\u003e\u003cp\u003eThe results of this study were consistent with those of other studies in the literature and there was no statistically significant relationship between the vitamin D levels of the severity groups. However, vitamin D levels of the patients in the case group were significantly and mildly moderately low (median\u0026thinsp;=\u0026thinsp;17 ng/mL).\u003c/p\u003e\u003cp\u003eGenetic susceptibility has been increasingly explored in MIH research. Bussaneli et al.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] identified associations between TGFBR1 gene polymorphisms and severe MIH cases, highlighting potential genetic contributions. Moreover, studies have demonstrated links between MIH and allergic conditions such as atopic dermatitis and allergic rhinitis [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] findings that are consistent with our study results.\u003c/p\u003e\u003cp\u003eFinally, the potential role of antibiotic exposure in MIH development has been well-documented. Our study found a significant association between antibiotic use in the first three years of life and MIH, corroborating previous findings that early-life antibiotic exposure may alter enamel formation [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] While this study identifies significant associations, further research is required to determine causal relationships between these factors and MIH development.\u003c/p\u003e\u003cp\u003eIn conclusion, our findings support the hypothesis that MIH etiology is multifactorial, with significant contributions from socioeconomic, systemic, perinatal, and genetic factors. Future research should focus on large-scale longitudinal and genetic studies to elucidate the multifactorial etiology of MIH and identify potential preventive strategies.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn this cross-sectional study conducted in İzmir, Turkey, the prevalence of molar incisor hypomineralization (MIH) among children aged 6\u0026ndash;12 who presented to the Department of Pediatric Dentistry at Ege University was found to be 12%. The study identified that MIH predominantly affected the lower left and upper right first permanent molars, with a significant increase in the number of affected teeth in more severe cases (MIH-2). Several associations were observed between MIH and nutritional habits, systemic health conditions, and perinatal risk factors. Notably, the duration of exclusive breastfeeding was longer in the healthy control group, supporting WHO recommendations and highlighting a potential protective effect against MIH.\u003c/p\u003e\u003cp\u003eChildren diagnosed with MIH were more likely to have experienced respiratory diseases, atopic conditions, and early antibiotic exposure, suggesting these factors may negatively influence enamel development. Prenatal (e.g., prematurity), perinatal (e.g., low birth weight, cesarean delivery), and postnatal factors (e.g., infections, atopy) were significantly associated with MIH occurrence, whereas no significant association was found between MIH and prenatal vitamin or mineral deficiencies. Although serum vitamin D levels were generally lower in the MIH group, no statistically significant relationship was found between MIH presence and vitamin or multivitamin supplementation.\u003c/p\u003e\u003cp\u003eGiven the multifactorial etiology of MIH, a multidimensional approach is required. Raising awareness among parents and health professionals, emphasizing exclusive breastfeeding during the first six months, and implementing preventive dental strategies\u0026mdash;such as fluoride application and fissure sealants\u0026mdash;are essential. Early diagnosis through routine dental check-ups, along with interprofessional collaboration, particularly between pediatricians, allergists, and pediatric dentists, is critical. Unnecessary antibiotic prescriptions in children should be minimized.\u003c/p\u003e\u003cp\u003eThis study provides an important contribution to the growing body of literature on molar incisor hypomineralization (MIH) by offering new epidemiological data from a large pediatric population in İzmir, Turkey\u0026mdash;a region where comprehensive MIH data remains limited. By examining both prevalence and a broad set of potential etiological risk factors, including prenatal, perinatal, and postnatal influences, this research presents a more nuanced understanding of the multifactorial nature of MIH.\u003c/p\u003e\u003cp\u003eThe findings highlight the importance of early-life systemic health conditions such as respiratory diseases, atopy, and antibiotic use, as well as nutritional factors like the duration of exclusive breastfeeding, in the development of MIH. These results align with and expand upon previous studies by reinforcing the potential protective role of exclusive breastfeeding and pointing to systemic illnesses as modifiable risk factors that may be targeted through public health interventions.\u003c/p\u003e\u003cp\u003eMoreover, the study\u0026rsquo;s identification of affected tooth patterns and the correlation between lesion severity and the number of involved teeth add to the clinical understanding of MIH\u0026rsquo;s progression. While vitamin D deficiency was prevalent among children with MIH, the lack of a statistically significant association with supplementation highlights the need for further investigation into the role of micronutrients.\u003c/p\u003e\u003cp\u003eBy integrating clinical findings with sociodemographic and systemic health data, this study advocates for a multidisciplinary, prevention-oriented approach to MIH management. It also underscores the necessity of national surveillance and the development of targeted educational programs for both caregivers and healthcare providers. As such, the study lays the groundwork for future longitudinal research and contributes valuable region-specific insights to the global MIH discourse.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e· MIH: Molar Incisor Hypomineralization\u003c/p\u003e\n\u003cp\u003e· BMI: Body Mass Index\u003c/p\u003e\n\u003cp\u003e· SDS: Standardized Deviation Score\u003c/p\u003e\n\u003cp\u003e· FDI: Fédération Dentaire Internationale\u003c/p\u003e\n\u003cp\u003e· ALP: Alkaline Phosphatase\u003c/p\u003e\n\u003cp\u003e· TIBC: Total Iron Binding Capacity\u003c/p\u003e\n\u003cp\u003e· PTH: Parathyroid Hormone\u003c/p\u003e\n\u003cp\u003e· IgE: Immunoglobulin E\u003c/p\u003e\n\u003cp\u003e· MCV: Mean Corpuscular Volume\u003c/p\u003e\n\u003cp\u003e· MCH: Mean Corpuscular Hemoglobin\u003c/p\u003e\n\u003cp\u003e· MCHC: Mean Corpuscular Hemoglobin Concentration\u003c/p\u003e\n\u003cp\u003e· SPSS: Statistical Package for the Social Sciences\u003c/p\u003e\n\u003cp\u003e· NSVD: Normal Spontaneous Vaginal Delivery\u003c/p\u003e\n\u003cp\u003e· EAPD: European Academy of Paediatric Dentistry\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Ege University Medical Research EThics Board (Approval number: 24-8T/124, date of approval: January 4, 2024.) Written informed consent was obtained from all participants and their legal guardians prior to data collection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe images used in the manuscript show only anonymized intraoral views with no identifiable patient information. Therefore, we believe that patient consent for publication is not required. However, we are ready to obtain written consent if the journal deems it necessary.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no external funding.\u003c/p\u003e\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors’ contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. Yılmaz, Dr. Uzel and Dr. Ertuğrul contributed to the study design, formation of the control and study groups, clinical examinations, and collection of clinical materials.\u003c/p\u003e\n\u003cp\u003eDr. Dörtkardeşler and Dr. Gökçe were responsible for the development of the questionnaire and the evaluation of the survey results.\u003c/p\u003e\n\u003cp\u003eDr. Ak contributed to the collection of biochemical samples and the interpretation of biochemical findings.\u003c/p\u003e\n\u003cp\u003eAll authors read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the participating children and their families for their valuable contributions to this study. We also gratefully acknowledge the support of the Ege University Departments of General Pediatrics, Biochemistry, and Pediatric Dentistry for their assistance throughout the research process.\u003c/p\u003e\u003cp\u003e**Clinical trial number:** Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBekes K. Molar Incisor Hypomineralization A Clinical Guide to Diagnosis and Treatment. Vienna: Springer; 2020. https://doi.org/https://doi.org/10.1007/978-3-030-31601-3.\u003c/li\u003e\n\u003cli\u003eKoch G, Hallonsten A, Ludvigsson N, Hansson B, Holst A, Ullbro C. Epidemiologic study of idiopathic enamel hypomineralization in permanent teeth of Swedish children. Community Dent Oral Epidemiology 1987;15:279\u0026ndash;85. https://doi.org/https://doi.org/10.1111/j.1600-0528.1987.tb00538.x.\u003c/li\u003e\n\u003cli\u003eGarot E, Rouas P, Somani C, Taylor GD, Wong F, Lygidakis NA. 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Int J Environ Res Public Health 2022;19. https://doi.org/10.3390/ijerph19148697.\u003c/li\u003e\n\u003cli\u003eAlaluusua S, Lukinmaa P-L, Koskimies M, Pirinen S, H\u0026ouml;ltt\u0026auml; P, Kallio M, et al. Developmental dental defects associated with long breast feeding. European Journal Of Oral Science 1996;104:493\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eFrascino S, Frascino A, Rezende KM, Imparato JC, Pignatari S. Molar-incisor enamel hypomineralization cross-sectional prevalence evaluation in oral-breathing allergic children. Clinical and Laboratorial Research in Dentistry 2018. https://doi.org/10.11606/issn.2357-8041.clrd.2017.134317.\u003c/li\u003e\n\u003cli\u003eHujoel PP. Vitamin D and dental caries in controlled clinical trials: Systematic review and meta-analysis. Nutr Rev 2013;71:88\u0026ndash;97. https://doi.org/10.1111/j.1753-4887.2012.00544.x.\u003c/li\u003e\n\u003cli\u003eBussaneli DG, Restrepo M, Fragelli CMB, Santos-Pinto L, Jeremias F, Cordeiro RDCL, et al. Genes Regulating Immune Response and Amelogenesis Interact in Increasing the Susceptibility to Molar-Incisor Hypomineralization. Caries Res 2019;53:217\u0026ndash;27. https://doi.org/10.1159/000491644.\u003c/li\u003e\n\u003cli\u003eHernandez M, Boj J, Espasa E, Planells P, Peretz B. Molar-incisor hypomineralization: Positive correlation with atopic dermatitis and food allergies. Journal of Clinical Pediatric Dentistry 2018;42:344\u0026ndash;8. https://doi.org/10.17796/1053-4625-42.5.4.\u003c/li\u003e\n\u003cli\u003eWuollet E, Laisi S, Salmela E, Ess A, Alaluusua S. Molar\u0026ndash;incisor hypomineralization and the association with childhood illnesses and antibiotics in a group of Finnish children. Acta Odontol Scand 2016;74:416\u0026ndash;22. https://doi.org/10.3109/00016357.2016.1172342.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1 to 4 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Molar Incisor Hypomineralization, Nutrition, Etiology of MIH","lastPublishedDoi":"10.21203/rs.3.rs-6888304/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6888304/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eMolar Incisor Hypomineralization (MIH) is a qualitative enamel defect affecting first permanent molars often involving incisors. It presents clinical challenges including hypersensitivity, rapid caries, and restorative difficulties. Though its etiology is unclear, systemic and environmental factors have been implicated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e: This study aimed to determine the prevalence and aetiology of MIH and to assess the risk factors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: A cross-sectional study was conducted on children aged 6-12 years. Among 700 children examined, 50 diagnosed with MIH were included in the case group, while 50 healthy children formed the control group. Parental interviews assessed sociodemographic, prenatal, perinatal, postnatal factor. Biochemical parameters were analyzed appropriate statistical tests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: MIH prevalence was 12% and 76% had severe defects (MIH-2), and 24% had mild opacities (MIH-1). Significant associations were observed with socioeconomic status, maternal employment, birth weight, antibiotic use and respiratory infections (p \u0026lt;0.005). Exclusive breastfeeding duration was longer in controls (p = 0.020).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e: MIH is a multifactorial condition influenced by systemic and environmental factors. Early diagnosis and prevention are essential. Longer breastfeeding duration may offer a protective effect. Larger longitudinal studies are needed to better understand MIH etiology.\u003c/p\u003e","manuscriptTitle":"Prevalence and Aetiology of Molar Incisor Hypomineralization in Children: A Cross- Sectional Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-14 10:47:53","doi":"10.21203/rs.3.rs-6888304/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-04T09:11:34+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-02T07:21:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"319553473394659623906932597716426645739","date":"2025-07-30T10:37:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-28T10:58:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"191232740957332390183596987684570341310","date":"2025-07-28T10:08:27+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-09T12:30:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-09T12:28:13+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-09T05:25:03+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-08T20:48:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Oral Health","date":"2025-07-08T20:44:36+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"31cee5d5-1128-41a0-9a14-c942c47bc712","owner":[],"postedDate":"July 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-12-01T16:07:21+00:00","versionOfRecord":{"articleIdentity":"rs-6888304","link":"https://doi.org/10.1186/s12903-025-07071-2","journal":{"identity":"bmc-oral-health","isVorOnly":false,"title":"BMC Oral Health"},"publishedOn":"2025-11-25 15:57:15","publishedOnDateReadable":"November 25th, 2025"},"versionCreatedAt":"2025-07-14 10:47:53","video":"","vorDoi":"10.1186/s12903-025-07071-2","vorDoiUrl":"https://doi.org/10.1186/s12903-025-07071-2","workflowStages":[]},"version":"v1","identity":"rs-6888304","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6888304","identity":"rs-6888304","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}