Gestational Exposure\nto Endocrine-Disrupting Chemicals\nof Emerging Concern and the Risk of Developing Gestational Diabetes\nMellitus: A Comprehensive Investigation of Sex-Specific and Trimester-Specific\nAssociations

Gestational diabetes mellitus (GDM) is a type of diabetes\nthat\narises during pregnancy, leading to long-term adverse consequences\nfor maternal health and fetal development. However, the specific role\nof endocrine-disrupting chemicals (EDCs) in the pathogenesis of GDM\nremains controversial. This prospective cohort study sought to investigate\nhow coexposure to bisphenols, parabens, triclosan (TCS), benzophenone-type\nUV filters, and neonicotinoids (NEOs) affects the odds of GDM. Quantile-based\ng-computation and Bayesian kernel machine regression showed a significant\ninverse relationship between EDC mixtures and the reduced risk of\nGDM (OR = 0.34, 95% CI: 0.13–0.87), which was mainly explained\nby bisphenol (OR = 0.49, 95% CI: 0.29–0.80) and paraben (OR\n= 0.60, 95% CI: 0.40–0.91) exposure. Bisphenol S (BPS), bisphenol\nZ (BPZ), ethylparaben (EtP), propylparaben (PrP), and butylparaben\n(BuP) were identified as key contributors to the joint effect. In\naddition, subgroup analyses suggested that the bisphenols-GDM association\nwas more pronounced in younger/normal-weight participants. The sex-specific\nimpact of exposure to bisphenols on the development of GDM was observed,\nwhereas the second trimester represented a critical window for EDC\nexposure. Continued research efforts, focusing on causal pathways\nand nonmonotonic relationships, will be crucial to elucidate the complex\ninfluence of EDC exposure on the development of GDM.