Prenatal Exposure to Bisphenol A and Bisphenol S and Neurodevelopment in Children at 2 Years of Age: Results from The APrON Cohort Study

Abstract

Background/Aim: Bisphenol A (BPA) is an endocrine disruptor highly detected in human biofluids. Experimental laboratory evidence and epidemiology studies suggest that BPA is a neurodevelopmental toxicant with sex-specific effects. Bisphenol S (BPS), as an alternative BPA, has already been widely used in commercial products and frequently detected in human samples with a lower exposure level compared to BPA. It has similar structure compared to BPA and equally affects neurodevelopment in animal experiment, yet epidemiology study of BPS remains limited. We examined the effects of prenatal exposure of BPA and BPS, adjusting for maternal nutrients status, co-exposure of heavy metals and hypothesizing sex-specific effects. Method: Total BPA and BPS were detected in spot urine samples collected during 2nd and 3rd trimesters from 402 pregnant women, who also provided blood samples for detecting nutrients status and co-exposure level of heavy metals. The development of children at 2 years of age was evaluated using Bayley III scales. Associations between prenatal exposure of BPA and BPS and development of children were estimated using multiple regression models with adjustments for potential confounders, which were selected from a pool of covariates including co-exposure of heavy metals and maternal nutrients status during pregnancy. The selected confounders are those remaining significantly correlated (p<0.05) with at least one of the Bayley III composite scores. Results: Significant interaction (p<0.05) was observed between prenatal BPA exposure (log10 transformed BPA after creatinine adjustment) and child sex on Social Emotional. The prenatal BPA exposure was negatively associated with the scores of Social Emotional for boys [β=-5.2; 95% confidence interval (CI): -9.8, -0.62]. This association for boys remained significant after adjusting family income, ethnicity, maternal status of vitamin B12, folate, copper, manganese, selenium and co-exposure of cadmium at 2nd trimester of pregnancy (β=-4.5; 95% CI: -8.9, -0.07). No significant association between prenatal BPA exposure and Bayley III scores was observed among girls. Significant interaction (p<0.05) was also observed between prenatal BPS exposure and sex on Language. High prenatal BPS exposure (upper quartile vs. other three quartiles) was associated with significantly lower composite scores of Language (β=-4.8; 95% CI: -9.5, -0.23) for girls, while no significant association was observed among boys. The estimate of this association for girls remained negative after adjusting confounders (β=-3.4; 95% CI: -7.8, 1.1), but the p-value increased to 0.136. Conclusions: The results suggest negative association between prenatal exposure of BPA and BPS and development of children at 2 years of age, with different effects among boys and girls.