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

作者：Che-Jung Chang, Dana Boyd Barr, Peter Barry Ryan, Parinya Panuwet, Melissa M. Smarr, Ken Liu, Kurunthachalam Kannan, Volha Yakimavets, Youran Tan, ViLinh Thi Ly, Carmen J. Marsit, Dean P. Jones, Elizabeth J. Corwin, Anne Lang Dunlop, Donghai Liang · 发表于：Environment International · 年份：2021 · DOI：10.1016/j.envint.2021.106964 · 被引用次数：165 · 研究领域：Per- and polyfluoroalkyl substances research、Fluorine in Organic Chemistry、Fluoride Effects and Removal

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: -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 sampl...