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Associations of Perfluoroalkyl Substances (PFAS) with Lower Birth Weight : An Evaluation of Potential Confounding by Glomerular Filtration Rate Using a Physiologically Based Pharmacokinetic Model (PBPK)

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Title: Associations of Perfluoroalkyl Substances (PFAS) with Lower Birth Weight : An Evaluation of Potential Confounding by Glomerular Filtration Rate Using a Physiologically Based Pharmacokinetic Model (PBPK)
Authors: Verner, Marc-André Browse this author
Loccisano, Anne E. Browse this author
Morken, Nils-Halvdan Browse this author
Yoon, Miyoung Browse this author
Wu, Huali Browse this author
McDougall, Robin Browse this author
Maisonet, Mildred Browse this author
Marcus, Michele Browse this author
Kishi, Reiko Browse this author →KAKEN DB
Miyashita, Chihiro Browse this author →KAKEN DB
Chen, Mei-Huei Browse this author
Hsieh, Wu-Shiun Browse this author
Andersen, Melvin E. Browse this author
Clewell, Harvey J. Browse this author
Longnecker, Matthew P. Browse this author
Issue Date: 1-Dec-2015
Journal Title: Environmental Health Perspectives
Volume: 123
Issue: 12
Start Page: 1317
End Page: 1324
Publisher DOI: 10.1289/ehp.1408837
Abstract: Background: Prenatal exposure to perfluoroalkyl substances (PFAS) has been associated with lower birth weight in epidemiologic studies. This association could be attributable to glomerular filtration rate (GFR), which is related to PFAS concentration and birth weight.oBjectives: We used a physiologically based pharmacokinetic (PBPK) model of pregnancy to assess how much of the PFAS–birth weight association observed in epidemiologic studies might be attributable to GFR.Methods: We modified a PBPK model to reflect the association of GFR with birth weight (estimated from three studies of GFR and birth weight) and used it to simulate PFAS concentra-tions in maternal and cord plasma. The model was run 250,000 times, with variation in parameters,to simulate a population. Simulated data were analyzed to evaluate the association between PFAS levels and birth weight due to GFR. We compared simulated estimates with those from a meta-analysis of epidemiologic data.results: The reduction in birth weight for each 1-ng/mL increase in simulated cord plasma for perfluorooctane sulfonate (PFOS) was 2.72g (95%CI: –3.40,–2.04), and for perfluorooctanoic acid (PFOA) was 7.13g (95%CI: –8.46,–5.80); results based on maternal plasma at term were similar. Results were sensitive to variations in PFAS level distributions and the strength of the GFR–birth weight association. In comparison, our meta-analysis of epidemiologic studies suggested that each 1-ng/mL increase in prenatal PFOS and PFOA levels was associated with 5.00g (95%CI:–21.66,–7.78) and 14.72g (95%CI: –8.92,–1.09) reductions in birth weight, respectively.conclusion: Results of our simulations suggest that a substantial proportion of the association between prenatal PFAS and birth weight may be attributable to confounding by GFR and that confounding by GFR may be more important in studies with sample collection later in pregnancy.
Type: article
URI: http://hdl.handle.net/2115/84597
Appears in Collections:環境健康科学研究教育センター (Center for Environmental and Health Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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