Prenatal exposure to bisphenols, metals, and risk of fetal chromosome numerical abnormalities in high-risk pregnancies: Independent, combined, and interactive effects.

Prenatal exposure to bisphenols and metals has raised significant concerns regarding their potential impact on fetal development, particularly the risk of fetal chromosome numerical abnormalities (CNA). In this case-control study, we analyzed bisphenol and metal concentrations in amniotic fluid of high-risk pregnant women undergoing amniocentesis. Concentrations of bisphenols and metals were measured using ultra-performance liquid chromatography-tandem mass spectrometry and inductively coupled plasma-mass spectrometry, respectively. Logistic regression and quantile-based g-computation were applied to evaluate individual and combined effects, while dose-response relationships were assessed using restricted cubic splines. Our findings indicated that bisphenol S (BPS), bisphenol Z (BPZ), bisphenol AF (BPAF), antimony (Sb), and vanadium (V) were significantly associated with an increased risk of CNA when analyzed individually, whereas manganese, iron, copper (Cu), nickel (Ni), and zinc (Zn) were significantly and inversely associated with CNA risk. Combined exposure to bisphenol and metal mixtures was associated with an increased risk of CNA in multi-pollutant models. Cu and Ni exhibited a positive additive interaction. Furthermore, BPS, BPZ, and BPAF were individually associated with an increased risk of Down syndrome, while Zn was associated with a decreased risk of Down syndrome. BPS, Sb, V, and Zn were individually associated with an increased risk of Klinefelter syndrome. These findings underscore the potential role of prenatal bisphenol and metal exposure in the pathogenesis of fetal CNA, highlighting both additive and synergistic effects.