Several “Forever” Chemicals Are Associated With Increased Risk of Late-onset Preeclampsia

Perfluoroalkyl substances (PFAS), a set of widely used synthetic chemicals, don’t degrade in the environment and are sometimes called “forever” chemicals. They’re commonly detected in humans around the world, and exposure has been linked to a wide variety of adverse health outcomes, including preeclampsia.

David E. Cantonwine, PhD, MPH, a perinatal environmental epidemiologist in the Division of Maternal–Fetal Medicine at Brigham and Women’s Hospital, and colleagues recently conducted the first study of PFAS and preeclampsia that distinguished between early- and late-onset preeclampsia, which have different risk factors, severities and pathophysiologies.

In Environmental Health Perspectives they report PFAS was strongly associated only with late-onset preeclampsia (≥34 weeks gestation).


This case–control study was nested within LIFECODES, an ongoing prospective study of pregnant women at the Brigham that began in 2006. Plasma samples are collected at enrollment and at three additional study visits.

The 150 participants included in this analysis (75 with preeclampsia, 75 without) were recruited between 2006 and 2008. The cases and controls were matched on gestational age at the time of the first study visit.

Maternal plasma concentrations of nine legacy PFAS were measured in samples collected at the first study visit (median, 10 weeks of gestation). A legacy PFAS is one that’s being phased out of production, but the concentrations measured are presumably still relevant to ongoing risk. Eight of the legacy PFAS were detected in ≥80% of the participants and were carried into further analyses.

Any Preeclampsia

Most PFAS were associated with an elevated risk of preeclampsia, but the increase was statistically significant only for perfluorodecanoic acid, a fluorosurfactant once used in industry as a flame retardant (adjusted OR, 1.41; 95% CI 1.00, 2.00).

Preeclampsia Subtypes

When subtypes of preeclampsia were examined separately, late-onset preeclampsia (52 cases) was significantly associated with:

  • Perfluorodecanoic acid (aOR, 1.64; 95% CI 1.08, 2.47)
  • Perfluorooctane sulfonic acid (aOR, 1.60; 95% CI 1.06, 2.43)

Perfluorooctane sulfonic acid was the key ingredient in a consumer product called Scotchguard and other stain repellants.

Associations between PFAS and early-onset preeclampsia (19 cases) were primarily below the null, although the findings were imprecise because of the small number of cases.

Angiogenic Biomarkers

Toxicology studies have demonstrated that PFAS can influence angiogenesis in the placenta. The researchers, therefore, examined two indicators of angiogenesis: soluble fms-like tyrosine kinase-1 (sFLT-1, anti-angiogenic) and placental growth factor (PlGF, pro-angiogenic). The balance of these factors within the placenta has been shown to predict preeclampsia.

The team measured circulating sFLT-1 and PlGF in the plasma samples collected at each study visit. After adjustment for potential confounders, few associations were noted between PFAS concentrations and angiogenic biomarkers, and point estimates were consistently below the null.


Given this weak evidence of any effect of PFAS on angiogenic biomarkers, PFAS probably influences preeclampsia via other mechanisms, such as maternal inflammatory or metabolic dysregulation.

Preeclampsia is typically investigated as a single disorder, and this study exemplifies the value of considering its heterogeneity. Moreover, different populations may have different distributions of preeclampsia subtypes.