Exposure to Bisphenol a Substitutes and Gestational Diabetes Mellitus: A Prospective Cohort Study in China

Background: The association of bisphenol A (BPA) and gestational diabetes mellitus (GDM) has been investigated in only a small number of studies, and research on the associations between BPA substitutes and GDM is scarce. Objective: We aimed to investigate the associations of four bisphenols [bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF)] levels in urine sample with the risk of gestational diabetes mellitus (GDM) and plasma glucose levels. Methods: A total of 1,841 pregnant women from a cohort study were recruited at their first prenatal examination between 2013 and 2015 in Wuhan, China. Concentrations of four bisphenols (BPA, BPS, BPF, BPAF) were measured in first-trimester urine samples using Ultra-high performance liquid chromatography system coupled to a Triple Quadrupole mass spectrometer (UHPLC-TQMS). An oral glucose tolerance test (OGTT) was performed at 24–28 gestational weeks and GDM was diagnosed post hoc using International Association of Diabetes and Pregnancy Study Groups criteria. We used multivariable logistic regression models to examine the associations of urinary bisphenols with the risk of GDM, and multiple linear regression models to determine the associations between bisphenols exposure and plasma glucose levels. Results: Urinary BPAF was associated with increased odds of GDM among women with normal pre-pregnancy BMI [adjusted odds ratio (aOR) = 1.70 (95% CI: 1.08, 2.67) for the highest group compared to the lowest group], and the association remained significant after additional adjustment for other bisphenols [aOR = 1.68 (95% CI: 1.03, 2.72)]. No significant associations were observed for other bisphenols and GDM. Consistent with the result of GDM, women in the highest BPAF category had a mean of 0.05 mmol/L (95% CI: 0.01, 0.09) higher fasting plasma glucose (FPG) levels than women in the lowest category. For BPA and plasma glucose, non-linear associations were observed between urinary BPA and FPG and the sum of the PG z-score among women who were overweight (p for non-linear association < 0.05). We also found that the per-unit increase in natural log transformed specific gravity adjusted BPS [ln (SG-adj BPS)] was associated with a 0.03 mmol/L (95% CI: 0.01, 0.04) increase in FPG levels and the associations might be modified by fetal sex (p for interaction < 0.05). Among women with female fetus, a per-unit increase in ln (SG-adj BPS) was associated with a 0.04 mmol/L (95% CI: 0.02, 0.06) increase in FPG, a 0.11 mmol/L (95% CI: 0.04, 0.17) increase in 1 h-PG and a 0.19 mmol/L (95% CI: 0.08, 0.30) increase in the sum of PG z-score. Conclusions: Our results provide evidence that BPAF and BPS might be potential risk factors of GDM, which require to be studied further.