Associations between prenatal per- and polyfluoroalkyl substances (PFAS) and repeated measures of bioactive lipids during pregnancy in the LIFECODES cohort.

INTRODUCTION

Per- and polyfluoroalkyl substances (PFAS) are a group of synthetic chemicals used in consumer products and industrial applications. Higher prenatal PFAS levels have been linked to adverse pregnancy outcomes, yet underlying biological mechanisms are not well understood, although disruptions in inflammatory processes are suspected.

OBJECTIVES

Examine associations between prenatal PFAS exposure and maternal bioactive lipid concentrations during pregnancy.

METHODS

We included 436 participants from the racially and socioeconomically diverse LIFECODES cohort in Boston, Massachusetts. Maternal plasma samples collected in early pregnancy [median gestation = 10 weeks] were analyzed for nine PFAS, while a panel of 55 bioactive lipids, including polyunsaturated fatty acid precursors and their oxylipin derivatives, were assessed in samples collected at up to two gestational time points (median gestation = 9.6 and 26 weeks). We examined associations between individual PFAS and repeated measures of bioactive lipids using generalized estimating equation models, adjusting for maternal demographic, socioeconomic, and study-related factors. We additionally conducted study visit- and fetal sex-stratified analyses.

RESULTS

Higher concentrations of certain PFAS were associated with significant changes in bioactive lipid levels, with direction and magnitude varying by specific PFAS, bioactive lipid, and gestational timing. Several PFAS were inversely associated with prostaglandins (PGs), hydroxyeicosatetraenoic acids (HETEs), and oxoeicosatetraenoic acids (oxoETEs) across multiple enzymatic pathways. In contrast, we observed positive associations of several PFAS with leukotriene B4 (LTB4), with an interquartile range (IQR) increase in perfluorooctanoic acid (PFOA) leading to a 14.35% (95% CI: 5.03, 24.5) increase in LTB4 levels. Stratified analysis showed generally stronger associations at the earlier gestational time point than at the later time point, while trends by fetal sex were inconsistent.

CONCLUSIONS

Prenatal PFAS exposure was associated with alterations in maternal bioactive lipid levels, particularly derivatives of arachidonic acid. These shifts suggest that disruption of arachidonic acid metabolism may be an important pathway through which PFAS may exert their biological effects, warranting further mechanistic investigation.