Associations of co-exposure to organophosphate flame retardants and pesticides with maternal thyroid function in early pregnancy: Findings from the Shanghai Birth Cohort

BACKGROUND: Early pregnancy exposure to organophosphate flame retardants (OPFRs) and pesticides (OPPs) may disrupt maternal thyroid function, but mixed effects remain unclear. METHODS: This study examined 403 pregnant women (<16 weeks of gestation) from the Shanghai Birth Cohort, measuring urinary metabolites of eight OPFRs and six OPPs using ultra-performance liquid chromatography-tandem mass spectrometry. Free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPOAb) status were also assessed. Single-exposure effects were analyzed using multiple linear/logistic regressions, and mixture effects with quantile g-computation (Qgcomp) and Bayesian kernel machine regression (BKMR) models. RESULTS: Single-exposure analysis revealed significant associations between specific organophosphate metabolites and maternal thyroid function parameters: O,O-diethyl phosphate with suppressed TSH levels, O,O-diethyl thiophosphate with elevated FT3, and Di-o-tolyl-phosphate with increased risk of TPOAb positivity. Qgcomp analysis indicated non-significant mixture effects, including an overall trend toward TSH suppression, elevated FT3 and FT4 levels, and heightened TPOAb positivity risk. BKMR confirmed the presence of the aforementioned nonlinear correlation in the mixture. Stratified analysis revealed that mixed exposure significantly impacted FT3 and FT4 levels in multiparous women and FT4 levels in pregnant women with female fetuses. CONCLUSION: Early pregnancy exposure to OPFR/OPP mixtures is associated with potential disrupted maternal thyroid homeostasis and increases autoimmune risk.