Per- and polyfluoroalkyl substances in drinking water and hypertensive disorders of pregnancy in the United States during 2013-2015

Background: Per- and polyfluoroalkyl substances (PFAS) widely exist in the environment and human bodies. Contaminated drinking water is one of the major exposure pathways for humans. Previous studies found weak or moderate associations between PFAS and hypertensive disorders of pregnancy (HDP). Methods: We obtained the number of births and counts of HDP cases for singleton births multiply stratified by county, maternal age, race, education, smoking status, and parity from CDC WONDER, and PFAS water concentrations from EPA UCMR3 data in the United States during 2013-2015. We used binomial regression on the multiply stratified HDP data to produce equal effect estimates and standard errors to those that would be derived from using individual-level data on binary HDP status and demographic covariates in logistic regression. Results: After adjusting for demographic covariates, we found small but statistically significant positive associations between HDP and population-weighted average water concentrations (ng/L) of all four PFAS: Odds ratio (OR) = 1.009, 95% CI = (1.001, 1.016) per IQR increase in perfluorooctanoic acid (PFOA); 1.030, 95% CI = (1.021, 1.040) per IQR increase in perfluorooctane sulfonate (PFOS); 1.008, 95% CI = (1.005, 1.011) per IQR increase in perfluoroheptanoic acid (PFHpA); 1.007, 95% CI = (1.004, 1.010) per IQR increase in perfluorohexane sulfonic acid (PFHxS), and 1.032, 95% CI = (1.022, 1.042) per IQR increase in the sum of four PFAS. Further adjustment for coexposures reversed the effect of PFOA from positive to inverse, and attenuated the effects of PFOS and PFHxS toward the null. After drinking water to serum concentration conversions, our effect estimates for PFOA, PFOS, and PFHxS are similar to previous studies. Conclusions: We found a weak positive association between the PFAS mixture and HDP, although the generalizability is subject to inherent limitations of the public-available datasets.