PMID- 38346483 OWN - NLM STAT- Publisher LR - 20240316 IS - 1096-0953 (Electronic) IS - 0013-9351 (Linking) VI - 250 DP - 2024 Feb 10 TI - Associations of per- and polyfluoroalkyl substances with maternal metabolic and inflammatory biomarkers in early-to-mid-pregnancy. PG - 118434 LID - S0013-9351(24)00338-4 [pii] LID - 10.1016/j.envres.2024.118434 [doi] AB - BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) can disrupt metabolism. Early-to-mid pregnancy is characterized by amplified metabolic processes and inflammation to support maternal adaptations and fetal growth. Thus, we cross-sectionally evaluated whether PFAS are individually and jointly associated with these processes in early-to-mid pregnancy. METHODS: Pregnant Illinois women (n = 452) provided fasted blood samples at median 17 weeks gestation. We quantified serum perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid (Me-PFOSA-AcOH), perfluorohexanesulfonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid. Key outcomes were plasma glucose, insulin, C-peptide, insulin-like growth factor 1 (IGF-1), adiponectin, leptin, triglycerides, free fatty acids, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein, tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6. We calculated homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL). We evaluated associations of PFAS with each metabolic/inflammatory biomarker individually using covariate-adjusted linear regression and jointly using quantile-based g-computation. RESULTS: In linear regression, all PFAS (except Me-PFOSA-AcOH) were negatively associated with insulin, HOMA-IR, and leptin, whereas all PFAS were positively associated with HDL cholesterol. We also observed negative associations of some PFAS with TNF-alpha and MCP-1; positive associations with adiponectin and total cholesterol also emerged. Additionally, PFOS was positively, whereas Me-PFOSA-AcOH was negatively, associated with triglycerides and VLDL. Each 25% increase in the PFAS mixture was associated with -31.3% lower insulin (95%CI: -45.8, -12.9), -31.9% lower HOMA-IR (95%CI: -46.4, -13.4), and -9.4% lower leptin (95%CI: -17.3, -0.8), but 7.4% higher HDL cholesterol (95%CI: 4.6, 10.3). For most outcomes, the major contributors to the PFAS mixture often differed compared to single-PFAS analyses. IMPLICATIONS: Individual and joint PFAS exposures were associated with markers of maternal metabolism and inflammation in pregnancy. Further investigation is needed to elucidate possible mechanisms and consequences of these findings. CI - Copyright (c) 2024 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Cinzori, Maria E AU - Cinzori ME AD - Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, 48824, USA; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824, USA; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, 48824, USA. FAU - Pacyga, Diana C AU - Pacyga DC AD - Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, 48824, USA; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824, USA. FAU - Rosas, Libeth AU - Rosas L AD - The Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, IL, 61801, USA. FAU - Whalen, Jason AU - Whalen J AD - Michigan Diabetes Research Center Chemistry Laboratory, University of Michigan, Ann Arbor, MI, 48109, USA. FAU - Smith, Sabrina AU - Smith S AD - Environmental Chemistry Laboratory, Department of Toxic Substances Control, California Environmental Protection Agency, Berkeley, CA, 94710, USA. FAU - Park, June-Soo AU - Park JS AD - Environmental Chemistry Laboratory, Department of Toxic Substances Control, California Environmental Protection Agency, Berkeley, CA, 94710, USA; Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA 94158, USA. FAU - Geiger, Sarah D AU - Geiger SD AD - The Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, IL, 61801, USA; Department of Kinesiology and Community Health, University of Illinois, Urbana-Champaign, IL 61801, USA. FAU - Gardiner, Joseph C AU - Gardiner JC AD - Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, 48824, USA. FAU - Braun, Joseph M AU - Braun JM AD - Department of Epidemiology, Brown University, Providence, RI, 02912, USA. FAU - Schantz, Susan L AU - Schantz SL AD - The Beckman Institute for Advanced Science and Technology, University of Illinois, Urbana-Champaign, IL, 61801, USA; Department of Comparative Biosciences, University of Illinois, Urbana-Champaign, IL 61802, USA. FAU - Strakovsky, Rita S AU - Strakovsky RS AD - Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, 48824, USA; Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824, USA. Electronic address: strakovs@msu.edu. LA - eng GR - UG3 OD023272/OD/NIH HHS/United States GR - UH3 OD023272/OD/NIH HHS/United States PT - Journal Article DEP - 20240210 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 SB - IM OTO - NOTNLM OT - Inflammation OT - Metabolism OT - Mixtures OT - PFAS OT - Pregnancy COIS- Declaration of competing interest 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. EDAT- 2024/02/13 00:42 MHDA- 2024/02/13 00:42 CRDT- 2024/02/12 19:12 PHST- 2023/11/16 00:00 [received] PHST- 2024/02/02 00:00 [revised] PHST- 2024/02/04 00:00 [accepted] PHST- 2024/02/13 00:42 [pubmed] PHST- 2024/02/13 00:42 [medline] PHST- 2024/02/12 19:12 [entrez] AID - S0013-9351(24)00338-4 [pii] AID - 10.1016/j.envres.2024.118434 [doi] PST - aheadofprint SO - Environ Res. 2024 Feb 10;250:118434. doi: 10.1016/j.envres.2024.118434.