Cross-sectional associations between prenatal maternal 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 Cathey; Deborah J Watkins; Rita S Strakovsky; Brad A Ryva; Subramaniam Pennathur; Lixia Zeng; David Weller; June-Soo Park; Sabrina Smith; Erin DeMicco; Amy Padula; Rebecca C Fry; Bhramar Mukherjee; Andrea Aguiar; Sarah Dee Geiger; Shukhan Ng; Gredia Huerta-Montanez; Carmen Vélez-Vega; Zaira Rosario; Jose F Cordero; Emily Zimmerman; Tracey J Woodruff; Rachel Morello-Frosch; Susan L Schantz; John D Meeker; Akram Alshawabkeh; Max T Aung

doi:10.1101/2023.11.03.23297930

Cross-sectional associations between prenatal maternal per- and poly-fluoroalkyl substances and bioactive lipids in three Environmental influences on Child Health Outcomes (ECHO) cohorts

medRxiv [Preprint]. 2023 Nov 7:2023.11.03.23297930. doi: 10.1101/2023.11.03.23297930.

Authors

Himal Suthar¹, Tomás Manea¹, Dominic Pak¹, Megan Woodbury², Stephanie M Eick³, Amber Cathey⁴, Deborah J Watkins⁴, Rita S Strakovsky^{5

6}, Brad A Ryva^{5

7

8}, Subramaniam Pennathur^{9

10}, Lixia Zeng⁹, David Weller¹¹, June-Soo Park¹², Sabrina Smith¹², Erin DeMicco¹³, Amy Padula¹³, Rebecca C Fry¹⁴, Bhramar Mukherjee¹⁵, Andrea Aguiar^{16

17}, Sarah Dee Geiger^{17

18}, Shukhan Ng¹⁷, Gredia Huerta-Montanez², Carmen Vélez-Vega¹⁹, Zaira Rosario²⁰, Jose F Cordero¹⁹, Emily Zimmerman²¹, Tracey J Woodruff¹³, Rachel Morello-Frosch^{13

22}, Susan L Schantz^{16

17}, John D Meeker⁴, Akram Alshawabkeh², Max T Aung¹

Affiliations

¹ Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
² Department of Civil and Environmental Engineering, Northeastern University, Boston, MA, USA.
³ Gangarosa Department of Environmental Health, Emory University Rollins School of Public Health, Atlanta, GA, USA.
⁴ Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, MI, USA.
⁵ Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, USA.
⁶ Department of Food Sciences and Human Nutrition, Michigan State University, East Lansing, MI, USA.
⁷ Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
⁸ College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
⁹ Department of Internal Medicine-Nephrology, University of Michigan, Ann Arbor, MI, USA.
¹⁰ Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
¹¹ NSF International, Ann Arbor, MI, USA.
¹² Environmental Chemistry Laboratory, Department of Toxic Substances Control, California Environmental Protection Agency, Berkeley, CA, USA.
¹³ Program on Reproductive Health and the Environment, University of California, San Francisco, San Francisco, CA, USA.
¹⁴ Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, Gillings School of Global Public Health, Chapel Hill, NC, USA.
¹⁵ Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
¹⁶ Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Illinois, USA.
¹⁷ Department of Comparative Biosciences, University of Illinois Urbana-Champaign, IL, USA.
¹⁸ Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, Illinois, USA.
¹⁹ Department of Epidemiology and Biostatistics, University of Georgia, Athens, Georgia, USA.
²⁰ University of Puerto Rico Graduate School of Public Health, San Juan, PR, USA.
²¹ Department of Communication Sciences and Disorders, Northeastern University, Boston, MA, USA.
²² Department of Environmental Science, Policy and Management and School of Public Health, University of California, Berkeley, Berkeley, CA, USA.

Abstract

Background: Per- and poly-fluoroalkyl substances (PFAS) exposure can occur through ingestion of contaminated food and water, and inhalation of indoor air contaminated with these chemicals from consumer and industrial products. Prenatal PFAS exposures may confer risk for pregnancy-related outcomes such as hypertensive and metabolic disorders, preterm birth, and impaired fetal development through intermediate metabolic and inflammation pathways.

Objective: Estimate associations between maternal pregnancy PFAS exposure (individually and as a mixture) and bioactive lipids.

Methods: Our study included pregnant women in the Environmental influences on Child Health Outcomes Program: Chemicals in our Bodies cohort (CiOB, n=73), Illinois Kids Developmental Study (IKIDS, n=287), and the ECHO-PROTECT cohort (n=54). We measured twelve PFAS in serum and 50 plasma bioactive lipids (parent fatty acids and eicosanoids derived from cytochrome p450, lipoxygenase, and cyclooxygenase) during pregnancy (median 17 gestational weeks). Pairwise associations across cohorts were estimated using linear mixed models and meta-analysis. Associations between the PFAS mixture and individual bioactive lipids were estimated using quantile g-computation.

Results: PFDeA, PFOA, and PFUdA were associated (p<0.05) with changes in bioactive lipid levels in all three enzymatic pathways (cyclooxygenase [n=6 signatures]; cytochrome p450 [n=5 signatures]; lipoxygenase [n=7 signatures]) in at least one combined cohort analysis. The strongest signature indicated that a doubling in PFOA corresponded with a 24.3% increase (95% CI [7.3%, 43.9%]) in PGD2 (cyclooxygenase pathway) in the combined cohort. In the mixtures analysis, we observed nine positive signals across all pathways associated with the PFAS mixture. The strongest signature indicated that a quartile increase in the PFAS mixture was associated with a 34% increase in PGD2 (95% CI [8%, 66%]), with PFOS contributing most to the increase.

Conclusions: Bioactive lipids were revealed as biomarkers of PFAS exposure and could provide mechanistic insights into PFAS' influence on pregnancy outcomes, informing more precise risk estimation and prevention strategies.

Keywords: Bioactive lipids; Eicosanoids; Mixtures; PFAS.

Publication types

Preprint

Abstract

Publication types

Grants and funding