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Author Notes:

Donghai Liang, 1518 Clifton Rd, Atlanta, GA 30322, USA. Email: donghai.liang@emory.edu

Che-Jung Chang: Formal Analysis, Investigation, Writing-Original Draft, Writing-Review&Editing, Visualization. Dana Boyd Barr: Methodology, Validation, Resources, Data Curation, Writing-Review&Editing, Supervision, Funding acquisition. P. Barry Ryan: Methodology, Resources, Data Curation, Writing-Review&Editing, Supervision, Funding acquisition. Parinya Panuwet: Methodology, Resources, Writing-Review&Editing. Melissa M. Smarr: Methodology, Writing-Review&Editing. Ken Liu: Data Curation, Methodology, Writing-Review&Editing. Kurunthachalam Kannan: Data Curation, Methodology, Writing-Review&Editing. Volha Yakimavets: Data Curation, Writing-Review&Editing. Youran Tan: Data Curation, Writing-Review&Editing. ViLinh Ly: Data Curation, Methodology, Writing-Review&Editing. Carmen J. Marsit: Resources, Writing-Review&Editing, Funding acquisition. Dean P. Jones: Methodology, Resources, Writing-Review&Editing, Funding acquisition. Elizabeth J. Corwin: Resources, Data Curation, Writing-Review&Editing, Funding acquisition. Anne L. Dunlop: Investigation, Resources, Data Curation, Writing-Review&Editing, Project administration, Funding acquisition. Donghai Liang: Conceptualization, Methodology, Investigation, Writing-Original Draft, Writing-Review&Editing, Supervision, Funding acquisition.

Additionally, we are grateful for our colleagues –Nathan Mutic, Cierra Johnson, Erin Williams, Priya D’Souza, Estefani Ignacio Gallegos, Nikolay Patrushev, Kristi Maxwell Logue, Castalia Thorne, Shirleta Reid, Cassandra Hall, and the clinical health care providers and staff at the prenatal recruiting sites for helping with data and sample collection and logistics and sample chemical analyses in the laboratory.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Research Funding:

This work was supported by the Environmental Influences on Child Health Outcomes (ECHO) program, Office of the Director, National Institutes of Health [5U2COD023375-05/A03-3824], the National Institute of Health (NIH) research grants [R01NR014800, R01MD009064, R24ES029490, R01MD009746, R21ES032117], NIH Center Grants [P50ES02607, P30ES019776, UH3OD023318, U2CES026560, U2CES026542, U24ES026539], and Environmental Protection Agency (USEPA) center grant [83615301].

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Environmental Sciences
  • Environmental Sciences & Ecology
  • High-resolution metabolomics
  • PFAS
  • Fetal growth
  • Biomarkers
  • FOR-GESTATIONAL-AGE
  • EVIDENCE-BASED MEDICINE
  • HIGH-RESOLUTION METABOLOMICS
  • BILE-ACID LEVELS
  • PERFLUOROALKYL SUBSTANCES
  • URIC-ACID
  • PERFLUOROOCTANOIC ACID
  • INTRAHEPATIC CHOLESTASIS
  • OXIDATIVE STRESS
  • AIR-POLLUTION

Per- and polyfluoroalkyl substance (PFAS) exposure, maternal metabolomic perturbation, and fetal growth in African American women: A meet-in-the-middle approach

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Journal Title:

ENVIRONMENT INTERNATIONAL

Volume:

Volume 158

Publisher:

, Pages 106964-106964

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Background: Prenatal exposures to per- and polyfluoroalkyl substances (PFAS) have been linked to reduced fetal growth. However, the detailed molecular mechanisms remain largely unknown. This study aims to investigate biological pathways and intermediate biomarkers underlying the association between serum PFAS and fetal growth using high-resolution metabolomics in a cohort of pregnant African American women in the Atlanta area, Georgia. Methods: Serum perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) measurements and untargeted serum metabolomics profiling were conducted in 313 pregnant African American women at 8–14 weeks gestation. Multiple linear regression models were applied to assess the associations of PFAS with birth weight and small-for-gestational age (SGA) birth. A high-resolution metabolomics workflow including metabolome-wide association study, pathway enrichment analysis, and chemical annotation and confirmation with a meet-in-the-middle approach was performed to characterize the biological pathways and intermediate biomarkers of the PFAS-fetal growth relationship. Results: Each log2-unit increase in serum PFNA concentration was significantly associated with higher odds of SGA birth (OR = 1.32, 95% CI 1.07, 1.63); similar but borderline significant associations were found in PFOA (OR = 1.20, 95% CI 0.94, 1.49) with SGA. Among 25,516 metabolic features extracted from the serum samples, we successfully annotated and confirmed 10 overlapping metabolites associated with both PFAS and fetal growth endpoints, including glycine, taurine, uric acid, ferulic acid, 2-hexyl-3-phenyl-2-propenal, unsaturated fatty acid C18:1, androgenic hormone conjugate, parent bile acid, and bile acid-glycine conjugate. Also, we identified 21 overlapping metabolic pathways from pathway enrichment analyses. These overlapping metabolites and pathways were closely related to amino acid, lipid and fatty acid, bile acid, and androgenic hormone metabolism perturbations. Conclusion: In this cohort of pregnant African American women, higher serum concentrations of PFOA and PFNA were associated with reduced fetal growth. Perturbations of biological pathways involved in amino acid, lipid and fatty acid, bile acid, and androgenic hormone metabolism were associated with PFAS exposures and reduced fetal growth, and uric acid was shown to be a potential intermediate biomarker. Our results provide opportunities for future studies to develop early detection and intervention for PFAS-induced fetal growth restriction.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
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