Gestational Exposure to Endocrine-Disrupting Chemicals of Emerging Concern and the Risk of Developing Gestational Diabetes Mellitus: A Comprehensive Investigation of Sex-Specific and Trimester-Specific Associations

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