Maternal Thyroid Hormones as Mediators between Phthalate Exposure and Neonatal Birth Weight: A Cross-Sectional Study from the Zunyi Birth Cohort

Abstract

Studies have shown that exposure to phthalates can affect neonatal birth weight. However, epidemiological evidence on the mediating role of maternal thyroid hormones is limited. Therefore, this study, based on the Compliance Birth Cohort, aimed to reveal the potential mediating function of maternal thyroid hormones during pregnancy between phthalic acid ester (PAE) exposure and neonatal birth weight. The study included 1274 mother−infant pairs. Linear regression analysis revealed a negative association between MIBP and neonatal birth weight (β = −62.236; 95% CI: −118.842, −5.631). Bayesian kernel-machine regression (BKMR) indicated a nonlinear negative association between PAE metabolites (PAEs) and birth weight. Linear regression analysis revealed a positive association between neonatal birth weight and FT3 (β = 41.605; 95% CI: 2.631, 80.380). The BKMR model also found a positive association between thyroid hormones and birth weight but in a nonlinear manner. Additionally, linear regression analyses showed that TSH, TT3, TT4, FT3, and FT4 were associated with PAEs. The BKMR model revealed an inverted U-shaped association of PAEs with TT3 and FT3 and a nonlinear association with TSH, TT4, and FT4. Structural equation modeling revealed that MMP, MIBP, MBP, MEHP, MOP, MBZP, and MEOHP contributed to a net reduction in neonatal birth weight of 32 g through the TT3, FT3, TT4, and FT4 pathways. The findings suggest that exposure to PAEs during pregnancy leads to a reduction in neonatal birth weight, possibly due to the involvement of maternal thyroid hormones as mediators. Controlling maternal thyroid hormone levels during pregnancy may be a viable method to reduce the harmful effects of phthalate exposure on the developing fetus.