Exposure to Dioxin-like polychlorinated biphenyls during Pregnancy and fetal thyroid function; A mixture analysis

Despite growing evidence of the endocrine-disrupting effects of dioxin-like polychlorinated biphenyls (DL-PCBs), the specific impact of maternal exposure to these pollutants on fetal thyroid hormone levels remains largely unexplored. This study uniquely investigates the association between prenatal DL-PCB exposure and thyroid hormone levels in umbilical cord blood within a cohort of pregnant women in Shenyang, China, during 2022-2023. A total of 2240 pregnant women were enrolled in the study. Umbilical thyroid hormone levels (free thyroxine (T4), free triiodothyronine (T3), and thyroid-stimulating hormone (TSH)) were measured using electro-chemiluminescence immunoassays. 12 specific congeners of DL-PCB levels in serum samples were assessed. Linear regression models, quantile g-computation (g-comp), generalized weighted quantile sum (g-WQS) regression, and Bayesian Kernel Machine Regression (BKMR) were used to analyze the data and evaluate the effects of DL-PCBs exposure on thyroid hormone levels, adjusting for various confounders. Linear regression analysis revealed significant negative associations between several DL-PCB congeners and umbilical T4 levels, with the strongest effect observed for PCB126. PCB105 was negatively associated with umbilical T3 levels, while multiple congeners (PCB77, PCB81, PCB105, PCB169, and PCB189) were negatively associated with TSH levels. No significant associations were found for the T4/T3 ratio. The g-comp analysis confirmed that mixture exposure to DL-PCBs was significantly associated with decreased umbilical T4 and TSH levels, with reductions seen with each one-quartile increase in exposure. However, no significant associations were observed for T3 levels or the T4/T3 ratio. The gWQS analysis did not find significant associations between DL-PCB exposure and thyroid hormones, suggesting potential sensitivity differences between mixture modeling approaches. BKMR analysis indicated a downward trend in T4 and TSH levels with increasing DL-PCB exposure, especially at lower exposure quartiles, though the wide confidence intervals suggest some uncertainty. Overall, our findings suggest that prenatal exposure to DL-PCBs may disrupt fetal thyroid function, particularly affecting T4 and TSH levels.