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)
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.
1Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA; 2Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 3Center for Human Health Assessment, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, USA; 4Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; 5Department of Obstetrics and Gynecology, Haukeland University Hospital, Bergen, Norway; 6Aegis Technologies, Huntsville, Alabama, USA; 7Biostatistics and Epidemiology Department, College of Public Health, East Tennessee State University, Johnson City, Tennessee, USA; 8Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA; 9Center for Environmental and Health Sciences, Hokkaido University, Sapporo, Japan; 10Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 11Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA
Recommended Citation:
Marc-,ré Verner,1,et al. 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)[J]. Environmental Health Perspectives,2015-01-01,Volume 123(Issue 12):1317