Perfluoroalkyl Substances in Pregnancy and the Risk of Preeclampsia

Perfluoroalkyl substances (PFASs) are persistent, ubiquitous environmental contaminants and may be related to preeclampsia, a common pregnancy complication. Previous studies have found serum concentrations of PFASs to be positively associated with serum cholesterol in non-pregnant individuals, and also associated with pregnancy-induced hypertension, including preeclampsia. Using data from the large, population-based Norwegian Mother and Child Cohort (MoBa) Study, we estimated associations between PFAS concentrations measured during pregnancy and an independently validated diagnosis of preeclampsia. Additionally, we estimated associations between mid-pregnancy PFAS concentrations and plasma lipid concentrations in order to evaluate one possible mechanism of association between PFASs and preeclampsia. A case-cohort study was conducted to estimate associations between mid-pregnancy plasma PFAS concentrations and preeclampsia. In proportional hazards models adjusted for maternal age, pre-pregnancy body mass index, education and smoking, we observed no positive associations between PFASs and preeclampsia. However, we found an inverse association between perfluoroundecanoic acid (PFUnDA) and preeclampsia, with a hazard ratio of 0.8 (95% confidence interval [CI]=0.7, 0.9) per natural-log unit increase in PFUnDA. In a separate cross-sectional analysis, we found positive associations between mid-pregnancy plasma concentrations of seven PFASs and high-density lipoprotein cholesterol (HDL). The greatest change in HDL per natural-log unit of exposure was associated with PFUnDA. HDL increased 3.7 mg/dL per interquartile shift in PFUnDA (95% CI=2.5, 4.9). A multi-pollutant model for HDL including seven PFAS exposures also showed the strongest association with PFUnDA compared with the other six PFASs. Additionally, perfluorooctane sulfonate (PFOS) was positively associated with plasma total cholesterol. Total cholesterol increased 4.2 mg/dL per interquartile shift in PFOS (95% CI=0.8, 7.7) in adjusted models. We found positive associations between certain PFASs and plasma lipid parameters, and we observed that different PFASs may have different strengths of association with lipid parameters during pregnancy. We did not observe any positive associations between mid-pregnancy plasma PFAS concentrations and a validated diagnosis of preeclampsia. The plasma concentrations of PFOA in this study, while within the range of previous studies of non-occupationally exposed populations, are substantially lower than exposure levels in the previous study that found associations between PFOA and preeclampsia.