Tracing impacts of prenatal exposure to bisphenol analogues on child anogenital distance development: A birth-cohort study

Prenatal exposure to bisphenol analogues (BPs) is increasingly common and may affect children's reproductive development. However, human evidence is limited and inconsistent. Based on the Shanghai-Minhang Birth Cohort Study that enrolled participants in 2012 at Minhang Maternal and Child Health Hospital in Shanghai, China, we measured BPs in maternal urine samples collected during late pregnancy and children's anogenital distance (AGD: boys, AGDAP (anus-penis), AGDAS (anus-scrotum); girls, AGDAC (anus-clitoris), AGDAF (anusfourchette)) from birth to 48 months as an indicator of reproductive development. A total of 545 mother-child pairs were included. Boys with detected maternal bisphenol A (BPA), bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF) tended to have increased AGDAP at 6 months, while at 12 months, BPA, BPS, and BPAF were associated with a marginal decrease in AGDAP. In girls, higher levels of BPA, BPF and BPS were associated with longer AGD at 48 months and higher risks of rapid AGD growth. Bayesian kernel machine regression models showed significant associations between BPs mixtures and AGD in both sexes, with BPF and BPS identified as major contributors. Our study revealed the lasting, sex-specific impacts of prenatal exposure to BPA and its alternatives on children's reproductive development.