Maternal levels of perfluoroalkyl substances (PFAS) during early pregnancy in relation to preeclampsia subtypes

Abstract

BACKGROUND AND AIM: Prenatal exposure to perfluoroalkyl substances (PFAS) has been previously associated with preeclampsia, although findings are mixed. However, no studies have examined associations between PFAS and preeclampsia subtypes, which may have distinct etiologies. Thus, we examined associations between PFAS and individual preeclampsia subtypes (i.e. early- and late-onset) using both single- and multi-pollutant approaches. METHODS: This case-control study (n = 75 cases, n = 75 controls) was sampled from the prospective LIFECODES birth cohort. Within the sample of preeclampsia cases, 21 were defined as early-onset ( 34 weeks gestation) and 54 were defined as late-onset (≥ 34 weeks). Nine legacy PFAS were quantified in maternal plasma from early pregnancy (median 10 weeks). As a single-pollutant approach, we used logistic regression to estimate the odds ratios (OR) and 95% confidence intervals (95% CI) of the association between an interquartile range (IQR)-increase in PFAS and preeclampsia subtypes. As a multi-pollutant approach, we used quantile g-computation to estimate the joint association of PFAS with preeclampsia subtypes. RESULTS:After adjusting for potential confounders, both perfluorodecanoic acid (PFDA; OR: 1.76, 95% CI: 1.07, 2.91) and perfluorooctane sulfonic acid (PFOS; OR: 2.29, 95% CI: 1.21, 4.35) were associated with higher odds of late-onset preeclampsia. Using quantile g-computation, a simultaneous one-quartile increase in all PFAS was also associated with higher odds of late-onset preeclampsia (OR: 2.28, 95% CI: 1.12, 4.64). Individual and joint associations between PFAS and early-onset preeclampsia were null, as were associations with overall preeclampsia diagnosis. CONCLUSIONS:Maternal PFAS concentrations were associated with odds of late-onset preeclampsia, though associations were null for early-onset preeclampsia. These findings suggest that PFAS exposure may be more closely associated with late-onset preeclampsia and warrant further study. In addition, heterogeneity of preeclampsia should be considered in future studies as populations may have different distributions of disease subtypes. KEYWORDS: PFAS, Pregnancy outcomes, Mixtures