Cord plasma metabolomic signatures of prenatal per- and polyfluoroalkyl substance (PFAS) exposures in the Boston Birth Cohort

Zeyu Li; Mingyu Zhang; Xiumei Hong; Guoying Wang; Giehae Choi; Kari C. Nadeau; Jessie P. Buckley; Xiaobin Wang

Environment International (Dec 2024)

Cord plasma metabolomic signatures of prenatal per- and polyfluoroalkyl substance (PFAS) exposures in the Boston Birth Cohort

Zeyu Li,
Mingyu Zhang,
Xiumei Hong,
Guoying Wang,
Giehae Choi,
Kari C. Nadeau,
Jessie P. Buckley,
Xiaobin Wang

Affiliations

Zeyu Li: Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Mingyu Zhang: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Xiumei Hong: Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Guoying Wang: Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Giehae Choi: Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
Kari C. Nadeau: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Jessie P. Buckley: Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Corresponding authors at: Department of Epidemiology, University of North Carolina at Chapel Hill, McGavran-Greenberg Hall CB#7435, 2106-B, Chapel Hill, NC 27599, USA.
Xiaobin Wang: Center on the Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, USA; Corresponding authors at: Center on the Early Life Origins of Disease, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, E4132, Baltimore, MD 21205, USA.

Journal volume & issue: Vol. 194
p. 109144

Abstract

Read online

Background: Prenatal per- and polyfluoroalkyl substance (PFAS) exposures are associated with adverse offspring health outcomes, yet the underlying pathological mechanisms are unclear. Cord blood metabolomics can identify potentially important pathways associated with prenatal PFAS exposures, providing mechanistic insights that may help explain PFAS' long-term health effects. Methods: The study included 590 mother-infant dyads from the Boston Birth Cohort. We measured PFAS in maternal plasma samples collected 24–72 h after delivery and metabolites in cord plasma samples. We used metabolome-wide association studies and pathway enrichment analyses to identify metabolites and pathways associated with individual PFAS, and quantile-based g-computation models to examine associations of metabolites with the PFAS mixture. We used False Discovery Rate to account for multiple comparisons. Results: We found that 331 metabolites and 18 pathways were associated with ≥ 1 PFAS, and 38 metabolites were associated with the PFAS mixture, predominantly amino acids and lipids. Amino acids such as alanine and lysine and their pathways, crucial to energy generation, biosynthesis, and bone health, were associated with PFAS and may explain PFAS’ effects on fetal growth restriction. Carnitines and carnitine shuttle pathway, associated with 7 PFAS and the PFAS mixture, are involved in mitochondrial fatty acid β-oxidation, which may predispose higher risks of fetal and child growth restriction and cardiovascular diseases. Lipids, such as glycerophospholipids and their related pathway, can contribute to insulin resistance and diabetes by modulating transporters on cell membranes, participating in β-cell signaling pathways, and inducing oxidative damage. Neurotransmission-related metabolites and pathways associated with PFAS, including cofactors, precursors, and neurotransmitters, may explain the PFAS’ effects on child neurodevelopment. We observed stronger associations between prenatal PFAS exposures and metabolites in males. Conclusions: This prospective birth cohort study contributes to the limited literature on potential metabolomic perturbations for prenatal PFAS exposures. Future studies are needed to replicate our findings and link prenatal PFAS associated metabolomic perturbations to long-term child health outcomes.

Published in Environment International

ISSN: 0160-4120 (Print)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/environment-international

About the journal

Abstract

Keywords