Supplementary Material for: Predictors of Developmental Defects of Enamel in Primary Maxillary Central Incisors using Bayesian Model Selection

Introduction Localized non-inheritable developmental defects of tooth enamel (DDE) are classified as enamel hypoplasia (EH), opacity (OP) and post-eruptive breakdown (PEB) using the Enamel Defects Index. To better understand the etiology of DDE, we assessed the linkages amongst exposome variables for these defects during the specific time duration for enamel mineralization of the human primary maxillary central incisor enamel crowns. In general, these two teeth develop between 13-14 weeks in utero and 3-4 weeks’ postpartum of a full-term delivery, followed by tooth eruption at about 1 year of age. Methods We utilized existing datasets for mother-child dyads that encompassed 12 weeks’ gestation through birth and early infancy, and child DDE outcomes from digital images of the erupted primary maxillary central incisor teeth. We applied a Bayesian modeling paradigm to assess the important predictors of EH, OP, and PEB. Results The results of Gibbs variable selection showed a key set of predictors: mother’s prepregnancy body mass index (BMI); maternal serum concentrations of calcium and phosphorus at gestational week 28; child’s gestational age; and both mother’s and child’s functional vitamin D deficiency (FVDD). In this sample of healthy mothers and children, significant predictors for OP included the child having a gestational period > 36 weeks and FVDD at birth, and for PEB included a mother’s prepregnancy BMI < 21.5 and higher serum phosphorus concentration at week 28. Conclusion In conclusion, our methodology and results provide a roadmap for assessing timely biomarker measures of exposures during specific tooth development to better understand the etiology of DDE for future prevention

引言
局限性非遗传性牙釉质发育缺陷（Localized non-inheritable developmental defects of tooth enamel, DDE）依据牙釉质缺陷指数（Enamel Defects Index）可分为三类：牙釉质发育不全（enamel hypoplasia, EH）、牙釉质浑浊（opacity, OP）及萌出后釉质崩解（post-eruptive breakdown, PEB）。为深入阐明牙釉质发育缺陷（DDE）的病因学机制，本研究针对人类上颌乳中切牙釉质冠的釉质矿化特定时期，探究了该类缺陷相关暴露组（exposome）变量间的关联。一般而言，该两枚牙齿的发育始于宫内13~14周，足月儿产后3~4周完成发育，随后于约1岁时萌出。

方法
本研究利用了已有的母婴队列数据集，覆盖妊娠12周至分娩及早期婴儿期阶段，同时纳入了通过上颌乳中切牙萌出后数码影像获取的儿童DDE结局数据。本研究采用贝叶斯建模范式（Bayesian modeling paradigm），对牙釉质发育不全（EH）、牙釉质浑浊（OP）及萌出后釉质崩解（PEB）的关键预测因子进行分析。

结果
Gibbs变量选择法的分析结果显示，一系列关键预测因子包括：母亲孕前体重指数（body mass index, BMI）、妊娠28周时母体血清钙与磷浓度、儿童胎龄，以及母亲与儿童均存在的功能性维生素D缺乏（functional vitamin D deficiency, FVDD）。在本研究的健康母婴队列样本中，与牙釉质浑浊（OP）相关的显著预测因子包括儿童胎龄＞36周及出生时存在功能性维生素D缺乏（FVDD）；而与萌出后釉质崩解（PEB）相关的显著预测因子则为母亲孕前BMI＜21.5，以及妊娠28周时较高的血清磷浓度。

结论
综上，本研究的方法与结果为在牙齿特定发育时期及时检测暴露相关生物标志物提供了研究框架，有助于进一步阐明牙釉质发育缺陷（DDE）的病因学机制，为未来的预防工作提供支撑。