Exposure to contaminants of emerging concern and gestational diabetes mellitus subtypes: An exploratory nested case-control study

The association of combined exposure to contaminants of emerging concern (CECs), including ultraviolet stabilizers (UVs), with gestational diabetes mellitus (GDM) remains unreported. To address this gap, the present study quantified plasma concentrations of 99 CECs, aiming to estimate associations of early pregnancy CEC exposure with GDM and its subtypes, and identify key contributors. This nested case-control study enrolled 120 participants from the Zhoushan cohort: 90 GDM cases (30 each of isolated fasting hyperglycemia [IFH], isolated postprandial hyperglycemia [IPH], combined hyperglycemia [CH]) and 30 normal glucose tolerance (NGT) controls. Conditional logistic regression evaluated single-pollutant effects on GDM. Combined exposure was assessed via adaptive elastic net (AENET), Bayesian kernel machine regression (BKMR), and quantile g-computation (qgcomp). Among valid detected chemicals, 12 CECs showed significantly higher levels in GDM (UV-P [2.66 vs. 1.40 ng/mL in NGT controls]). Conditional logistic regression showed positive associations of PAHs, PAEs, UVs, synthetic antioxidants with GDM. Three statistical approaches identified positive correlations between combined CEC exposure and risks of GDM, IFH, CH. qgcomp showed combined exposure associated with GDM [1.39 (95 %CI=1.15-1.67)], IFH [1.94 (95 %CI=1.39-2.70)], CH [1.96 (95 %CI=1.32-2.89)]. BKMR identified UV-P and DEP as key contributors. These findings warrant validation in large prospective studies with mechanistic evidence.