Association of perfluoroalkyl substances with gestational hypertension and preeclampsia in the MIREC study

Abstract

Background: Perfluoroalkyl substances (PFAS) have been linked with a number of developmental, reproductive, hepatic, and cardiovascular health outcomes. However, the evidence for an association between PFAS and hypertensive disorders of pregnancy (including gestational hypertension and preeclampsia) is equivocal and warrants further investigation.

Objectives: To examine the relationship between background levels of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulfonate (PFHxS) and the development of gestational hypertension or preeclampsia in a Canadian pregnancy cohort. We also explored the potential for effect modification according to fetal sex.

Methods: Maternal plasma samples were collected in the first trimester from participants in the MIREC study and were analyzed for PFOA, PFOS, and PFHxS. Blood pressure was measured during each trimester. Gestational hypertension and preeclampsia were defined using the Society of Obstetricians and Gynaecologists of Canada guidelines. Logistic regression models were used to derive adjusted odds ratios (OR) and 95% confidence intervals (CI) for associations between PFAS concentrations (per doubling of concentration as well as according to tertiles) and gestational hypertension or preeclampsia. Linear mixed models were used to examine the association between PFAS concentrations and changes in blood pressure throughout pregnancy.

Results: Data from 1739 participants were analyzed. 90% of women were normotensive throughout pregnancy, 7% developed gestational hypertension without preeclampsia, and 3% developed preeclampsia. In the full analyses, neither PFOA nor PFOS were associated with gestational hypertension or preeclampsia. However, each doubling of PFHxS plasma concentration was associated with higher odds of developing preeclampsia (OR = 1.32; 95% CI: 1.03, 1.70). In addition, participants in the highest PFHxS tertile (1.4-40.0 μg/L) had higher odds of developing preeclampsia relative to those in the lowest tertile (OR = 3.06; 95% CI: 1.27, 7.39). In stratified analyses, this effect was only apparent among women carrying a female fetus (OR = 4.90; 95% CI: 1.02, 22.3). However, among women carrying a male fetus, both PFOS and PFHxS were associated with gestational hypertension, but not preeclampsia. Higher plasma concentrations of all three PFAS were associated with increases in diastolic blood pressure throughout pregnancy, and PFOA and PFHxS were also associated with systolic blood pressure. Discrepant findings were similarly revealed in analyses stratified by fetal sex.

Conclusions: Higher levels of PFHxS were associated with the development of preeclampsia, but not gestational hypertension. Neither PFOA nor PFOS were associated with either outcome. However, we show, for the first time, that fetal sex may modify these associations, a finding which warrants replication and further study.

Keywords: Environmental chemicals; Perfluoronated compounds; Preeclampsia; Pregnancy; Sex differences.