Associations between environmental phthalates exposure and maternal thyroid hormone levels during pregnancy

Phthalates (PAEs) are well-recognized endocrine-disrupting compounds. Despite their established status as such, the association between maternal exposure to PAEs during pregnancy and the levels of maternal thyroid hormones remains a subject of considerable debate. To shed light on this contentious issue, we conducted an investigation involving 1,156 pregnant women from the Zunyi birth cohort. The aim was to elucidate the relationship between urinary metabolites of PAEs and serum thyroid hormones during the gestational period. In this study, we employed a linear mixed-effects model (LMM) to assess the correlation between PAE metabolites and thyroid hormones. Additionally, restricted cubic spline (RCS) analysis was utilized to explore the dose-response relationship between these PAE metabolites and thyroid hormones. Furthermore, Bayesian kernel machine regression (BKMR) was applied to determine the potential overall effects and to uncover any non-linear relationships that might exist. Our results revealed that several PAE metabolites, namely, monomethyl phthalate (MMP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-isobutyl phthalate (MIBP), mono(2-ethyl-5-oxohexyl) phthalate (MOP), and monobenzyl phthalate (MBZP), were associated with correlations involving total thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4). Subsequently, the restricted cubic spline (RCS) analyses demonstrated a clear dose-response relationship between the PAE metabolites and maternal thyroid hormones, with MEHP, MBZP, MIBP, and MBZP emerging as the major contributors to this relationship. Finally, the BKMR model indicated a non-linear relationship, specifically an inverted U-shaped relationship, between maternal exposure to PAEs during pregnancy and the levels of TT4, FT3, and FT4. Collectively, our findings strongly suggest that exposure to PAEs during pregnancy has a detrimental impact on the secretion of maternal thyroid hormones. To safeguard the health of both the mother and the fetus, it is advisable to minimize exposure to phthalates during pregnancy and to monitor any alterations in thyroid hormone levels closely.