Effects of per- and polyfluoroalkyl substances on maternal thyroid function: a stratified analysis by maternal iodine status and thyroid autoantibody status

Per- and polyfluoroalkyl substances (PFASs) are persistent environmental pollutants with bioaccumulative properties. Emerging evidence indicates that PFAS disrupts thyroid hormone homeostasis, potentially leading to thyroid dysfunction and impairing physiological functions. However, the associations between PFAS exposure, iodine status, and thyroid function during pregnancy remain insufficiently understood. A total of 911 pregnant women from a birth cohort in Zhejiang Province were included. Serum concentrations of 13 PFASs and thyroid function parameters were measured during the first antenatal visit. Linear regression, quantile regression, and restricted cubic spline models were used to explore associations between individual PFAS and thyroid hormones. Quantile g-computation was conducted to evaluate the overall effects of PFAS mixtures, while Bayesian kernel machine regression was applied to capture potential nonlinear and interactive effects. Stratified analyses were further conducted to examine potential effect modification by iodine status and thyroid autoantibody status. PFOS, PFDA, PFNA, PFUnDA, and PFHpS were negatively associated with FT 3 and positively associated with the FT 4 /FT 3 ratio (all P < 0.05). The novel PFMOAA showed positive associations with TSH ( β = 0.162; 95% CI: 0.069, 0.255) and the TSH/FT 4 ratio ( β = 0.006; 95% CI: 0.0002, 0.011). When all 13 PFASs were modeled as a mixture, higher PFAS concentrations were associated with lower FT 3 levels. Similar inverse associations with FT 3 were observed for the mixture of PFASs selected by Least absolute shrinkage and selection operator. Meanwhile, the mixture composed of PFASs identified as significant in single-pollutant models was additionally associated with higher TSH and an increased FT 4 /FT 3 ratio. Iodine status and thyroid autoantibody status appeared to modify these associations. Prenatal exposure to both legacy PFASs (PFOS, PFDA, PFNA, PFDoDA, PFUnDA, and PFHpS) and novel PFAS (6:2 Cl-PFESA) was associated with lower FT 3 levels, while PFMOAA was positively associated with TSH levels. The effects of PFAS mixtures on thyroid function varied according to their specific composition. Thyroid autoantibody status and iodine status may act as effect modifiers of the associations between PFAS exposure and thyroid hormone levels.