Early Pregnancy Exposure to Per- and Polyfluoroalkyl Substances and Hypertensive Disorders of Pregnancy: A Cohort Study in China.

Maternal exposure to per- and polyfluoroalkyl substances (PFAS) has shown inconsistent associations with hypertensive disorders of pregnancy (HDP). This prospective cohort study examined the associations between early pregnancy serum PFAS concentrations and HDP risk, evaluating potential effect modification by fetal sex among 2,984 pregnant women in Henan Province, China (2018-2021). Sixteen PFAS were measured in early pregnancy serum samples, with nine retained for analysis based on detection rates ≥70%. Multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for confounders. Of the participants, 112 (3.8%) developed gestational hypertension and 137 (4.6%) developed preeclampsia. Doubling of serum PFDoA concentration was nominally associated with increased odds of both gestational hypertension (OR = 1.31; 95% CI: 1.08, 1.60) and preeclampsia (OR = 1.21; 95% CI: 1.01, 1.45). Conversely, doubling of 6:2Cl-PFESA was nominally associated with lower odds of preeclampsia (OR = 0.86; 95% CI: 0.77, 0.97). Quantile g-computation indicated that although the overall PFAS mixture was not significantly associated with HDP risk, PFDoA consistently contributed substantial positive weights to the mixture effects for both outcomes. In exploratory analyses, fetal sex appeared to modify the association between PFDoA and gestational hypertension (P-interaction = 0.035), with elevated odds observed among female fetuses (OR = 1.71; 95% CI: 1.27, 2.35) compared to male fetuses (OR = 1.07; 95% CI: 0.82, 1.39). These findings suggest congener-specific effects and sex-modulated susceptibility, indicating that early pregnancy PFDoA exposure may be associated with elevated HDP risk, warranting further investigation to validate these associations.