Prenatal bisphenol A exposure, fetal thyroid hormones and neurobehavioral development in children at 2 and 4 years: A prospective cohort study

Findings about the association between prenatal Bisphenol A (BPA) exposure and neurobehavioral development in children are still inconsistent. In addition, whether fetal thyroid hormones (THs) mediate the reported association remains unclear. The present study aimed to examine the association between prenatal BPA exposure and risks of child behavioral problems at 2 and 4 years of age and whether the association could be explained by alteration of fetal THs as measured in cord plasma. Using the Shanghai-Minhang Birth Cohort Study (S-MBCS), BPA concentration was measured in maternal urine samples collected at 12-16 weeks of gestation. Children's neurobehavioral development was assessed using the Child Behavior Checklist/1.5-5 (CBCL), at 2 and 4 years of age. Using generalized estimating equation (GEE) models, 745 mother-pairs were included to examine associations of BPA with CBCL scores, Using multiple linear regression models, 348 mother-pairs were included to evaluate the association between maternal BPA and THs in cord plasma. A mediation analysis was conducted to explore the potential mediating role of THs. After adjusting for potential confounders, prenatal BPA level was associated with increased risks of Emotionally Reactive problem, Anxious/Depressed problem, having Somatic Complaints, exhibiting Aggressive Behavior, and Internalizing and Externalizing Problems: compared to the lowest tertile, the risks in the highest tertile and middle tertile, ranged between 1.55-fold (95% CI: 1.09, 2.21) and 2.59-fold (95% CI: 1.52, 4.42). The association was more pronounced among boys. None of the associations reached statistical significance among girls. An inverse association between prenatal BPA and fetal TH level was also observed. However, the observed neurotoxic effects of prenatal BPA exposure did not appear to be mediated by THs levels. The current findings suggest that prenatal exposure to BPA may disrupt fetal THs levels and may induce long-lasting behavioral alterations, especially in boys.