Prenatal Exposure to Phthalates and Bisphenols in Association with Hypomineralization of Second Primary Molar

Hypomineralized second primary molars (HSPM) affect approximately 6.8% of children. Molars affected by HSPM mineralize between 20 wk of gestation and 15 to 17 mo of age. Experimental studies suggest that exposure to endocrine-disrupting chemicals, including di-2-ethylhexyl phthalate (DEHP) and bisphenol A (BPA), may disrupt enamel formation, but evidence in humans remains limited. This study investigates the association between prenatal exposure to individual phthalates, BPA, and their mixtures and the odds of HSPM in children. It was embedded in the Generation R study, a population-based prospective birth cohort in the Netherlands. Maternal urinary concentrations of BPA and 11 phthalate metabolites were measured each trimester. HSPM was diagnosed at age 6 y based on European Academy of Paediatric Dentistry criteria. Multivariate logistic regression models and Bayesian weighted quantile sum regression were used to assess individual and mixture associations, respectively. Among 1,160 mother-child pairs, 10.2% of children were diagnosed with HSPM. In single-exposure models, higher prenatal concentrations of monobenzyl phthalate (mBzBP) were associated with lower odds of HSPM (odds ratio [OR] = 0.76; 95% confidence interval [CI]: 0.59 to 0.97). Second-trimester exposure to DEHP metabolites showed a nonsignificant trend toward increased HSPM odds (eg, mEOHP OR = 1.15; 95% confidence interval [CI]: 0.91 to 1.45). Sex-specific associations were observed: higher BPA and phthalate concentrations were associated with lower likelihood of HSPM in girls (eg, BPA OR = 0.70; 95% CI: 0.50 to 0.98) and higher odds in boys (p-interaction < 0.10). Mixture analyses showed a nonsignificant inverse association for overall prenatal exposure (OR = 0.84; 95% CI: 0.63 to 1.15), with mBzBP contributing most to the mixture. No overall association was observed for DEHP mixture, although sex-specific trends were consistent with single-exposure results. Prenatal exposure to phthalates and BPA may influence HSPM development. These findings highlight the need to consider early-life endocrine-disrupting chemical mixture exposure in HSPM etiology.