TY - JOUR
T1 - Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts
AU - on behalf of Program Collaborators for Environmental Influences on Child Health Outcomes
AU - Suthar, Himal
AU - Manea, Tomás
AU - Pak, Dominic
AU - Woodbury, Megan
AU - Eick, Stephanie M.
AU - Cathey, Amber
AU - Watkins, Deborah J.
AU - Strakovsky, Rita S.
AU - Ryva, Brad A.
AU - Pennathur, Subramaniam
AU - Zeng, Lixia
AU - Weller, David
AU - Park, June Soo
AU - Smith, Sabrina
AU - DeMicco, Erin
AU - Padula, Amy
AU - Fry, Rebecca C.
AU - Mukherjee, Bhramar
AU - Aguiar, Andrea
AU - Geiger, Sarah Dee
AU - Ng, Shukhan
AU - Huerta-Montanez, Gredia
AU - Vélez-Vega, Carmen
AU - Rosario, Zaira
AU - Cordero, Jose F.
AU - Zimmerman, Emily
AU - Woodruff, Tracey J.
AU - Morello-Frosch, Rachel
AU - Schantz, Susan L.
AU - Meeker, John D.
AU - Alshawabkeh, Akram N.
AU - Aung, Max T.
N1 - Research reported in this publication was supported by the Environmental Influences on Child Health Outcomes (ECHO) Program, Office of the Director, National Institutes of Health (NIH), under award numbers U2COD023375 (Coordinating Center), U24OD023382 (Data Analysis Center), U24OD023319 with co-funding from the Office of Behavioral and Social Science Research (Pro-Core), U2COD023375 (Opportunities and Infrastructure Fund), UH3OD023251 (Alshawabkeh), UH3OD023272 (Schantz and Woodruff). This work was additionally supported by the Children\u2019s Environmental Health and Disease Prevention Research Center (grant numbers ES022848 and RD83543401), the Molecular Phenotyping and Metabolomics Core, Michigan Nutrition and Obesity Center (5P30DK089503), US Environmental Protection Agency (grant number RD83543301), National Institute of Environmental Health Sciences (NIEHS; grant numbers P42ES017198, P50ES026049, P01ES022841, P30ES019776, P30ES030284, and P30ES007048). M.T.A. and S.M.E. were also supported in part by the JPB Foundation Environmental Health Fellows Program. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
PY - 2024/5/14
Y1 - 2024/5/14
N2 - 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.
AB - 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.
KW - bioactive lipids
KW - eicosanoids
KW - inflammatory pathways
KW - metabolic pathways
KW - mixtures
KW - PFAS
KW - pregnancy outcomes
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U2 - 10.1021/acs.est.4c00094
DO - 10.1021/acs.est.4c00094
M3 - Article
C2 - 38691655
AN - SCOPUS:85192274195
SN - 0013-936X
VL - 58
SP - 8264
EP - 8277
JO - Environmental Science and Technology
JF - Environmental Science and Technology
IS - 19
ER -