Considering environmental exposures to per- and polyfluoroalkyl substances (PFAS) as risk factors for hypertensive disorders of pregnancy

Hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension, lead to significant maternal morbidity and in some cases, maternal mortality. Environmental toxicants, especially those that disrupt normal placental and endothelial function, are emerging as potential risk factors for HDP. Per- and polyfluoroalkyl substances (PFAS) are a large group of ubiquitous chemicals found in consumer products, the environment, and increasingly in drinking water. PFAS have been associated with a multitude of adverse health effects, including dyslipidemia, hypertension, and more recently, HDP. In this review, we present epidemiological and mechanistic evidence for the link between PFAS and HDP and recommend next steps for research and prevention efforts. To date, epidemiological studies have assessed associations between only ten of the thousands of PFAS and HDP. Positive associations between six PFAS (PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonic acid; PFHxS, perfluorohexane sulfonic acid; PFHpA, perfluoroheptanoic acid; PFBS, perfluorobutanesulfonic acid; and PFNA, perfluoronanoic acid) and risk for HDP have been reported in some, but not all, studies. PFAS disrupt placental and immune function, cause oxidative stress, and disrupt lipid metabolism. These physiological disruptions may be mechanisms through which PFAS can lead to HDP. Overall, limited epidemiological evidence and plausible mechanisms support PFAS as risk factors for HDP. More research is needed in diverse, well-powered cohorts that assess exposures to as many PFAS as possible. Such research should consider not only individual PFAS but also the totality of exposures to PFAS and other environmental chemicals. Pregnant women may be a group that is vulnerable to PFAS exposure, and as such HDP risk should be considered by policymakers setting PFAS exposure limits. In the interim, medical and public health professionals in regions with PFAS contamination could provide short-term solutions in the form of patient-level prevention, increased monitoring, and early intervention for HDP.