Placental Transfer of PFAS and Their Sex-Specific Associations With Neonatal Thyroid Hormones in a Chinese Birth Cohort.

Abstract

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent environmental endocrine-disrupting chemicals that can cross the placental barrier and may disrupt fetal thyroid homeostasis; however, the sex-specific thyroid toxicity of PFAS remains poorly characterized. This study recruited 247 mother-infant pairs from a tertiary hospital in Wuhan, China, and measured PFAS concentrations in maternal and cord serum. The results showed that perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorohexane sulfonate (PFHxS) were the predominant PFAS in both maternal and cord serum. Their median concentrations were 5.520, 3.896, and 4.154 ng/mL in maternal serum, respectively, and 7.112, 2.704, and 2.422 ng/mL in cord serum, respectively. Several short-chain PFAS, including perfluoropentanoic acid (PFPeA), perfluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), and perfluoropentane sulfonic acid (PFPeS), exhibited relatively high transplacental transfer efficiency (TTE). PFAS with a cord serum detection rate > 90% were selected for subsequent analyses. Spearman correlation analysis showed strong coexposure patterns among several long-chain PFCAs, with the strongest correlations observed among PFDA, PFNA, and PFUdA (r = 0.81-0.89, p < 0.01). PFAS-thyroid hormone correlations were generally weak; only PFHpS was inversely correlated with TSH (r = -0.16, p < 0.01). In multivariable linear regression models, PFHxS was positively associated with TSH in the overall sample (β = 0.085, p < 0.05), whereas PFHxA was inversely associated with FT4 (β = -0.106, p < 0.01). Among female newborns, GenX was inversely associated with TSH (β = -9.411, p < 0.05), whereas PFHxS was positively associated with TSH (β = 0.109, p < 0.05). Among male newborns, PFDA (β = -0.132, p < 0.05), PFHxA (β = -0.137, p < 0.01), PFNS (β = -0.287, p < 0.01), and PFOS (β = -0.029, p < 0.05) were inversely associated with FT4. No individual PFAS was significantly associated with FT3. Formal interaction analysis showed evidence of sex heterogeneity for the PFNS-FT4 association (P for interaction = 0.008). Qgcomp showed nonsignificant overall mixture effects for FT3, FT4, and TSH. Similarly, BKMR showed no statistically significant overall mixture effects or individual PFAS associations with thyroid hormone levels.