Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts
Himal Suthar, Tomás Manea, Dominic Pak, Megan Woodbury, Stephanie M. Eick, Amber L. Cathey, Deborah J. Watkins, Rita S. Strakovsky, Brad A. Ryva, Subramaniam Pennathur, Lixia Zeng, David M. Weller, June-Soo Park, Sabrina Smith, Erin DeMicco, Amy Padula, Rebecca C. Fry, Bhramar Mukherjee, Andréa Aguiar, Sarah Dee Geiger, Shukhan Ng, Gredia Huerta-Montañez, Carmen M. Vélez-Vega, Zaira Rosario, José F. Cordero, Emily Zimmerman, Tracey J. Woodruff, Rachel Morello‐Frosch, Susan L. Schantz, John D. Meeker, Akram N. Alshawabkeh, Max T. Aung, on behalf of Program Collaborators for Environmental Influences on Child Health Outcomes
Abstract
High Resolution Image Download MS PowerPoint Slide Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks’ gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA ( p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA ( q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3–43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8–66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS’ influence on pregnancy outcomes.