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Author Notes:

Address correspondence to M.-A. Verner, Department of Occupational and Environmental Health, School of Public Health, Université de Montréal, 2375 chemin de la Cote-Sainte-Catherine, Suite 4105, Montréal, Quebec, Canada H3T 1A8. Telephone: (514) 343-6465. E-mail: verner.marcandre@gmail.com

M.A.V. conducted this study as a consultant for the Hamner Institutes for Health Sciences, an independent nonprofit organization.

The following authors received no compensation from DuPont or 3M: N.H.M., R.M., M.M., M.M., R.K., C.M., M.H.C., W.S.H., and M.P.L.

R.M. was employed by Aegis Technologies, Huntsville, Alabama.

All authors certify that their freedom to design, conduct, interpret, and publish research was not compromised by any sponsor.

The authors declare they have no actual or potential competing financial interests.


Research Funding:

This study was supported by grants from DuPont and 3M, and by the Intramural Research Program of the National Institutes of Environmental Health Sciences (NIEHS), the National Institutes of Health (NIH).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Environmental Sciences
  • Public, Environmental & Occupational Health
  • Toxicology
  • Environmental Sciences & Ecology
  • PFOA

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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Journal Title:

Environmental Health Perspectives


Volume 123, Number 12


, Pages 1317-1324

Type of Work:

Article | Final Publisher PDF


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 concentrations 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 2.72 g (95% CI: –3.40, –2.04), and for perfluorooctanoic acid (PFOA) was 7.13 g (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 5.00 g (95% CI: –21.66, –7.78) and 14.72 g (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.

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