Birth Outcomes in Relation to Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Stress in the Environmental Influences on Child Health Outcomes (ECHO) Program

Amy M. Padula, Program for Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA.
Xuejuan Ning, Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA.
Shivani Bakre, Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA.
Emily S. Barrett, Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey, USA.
Tracy Bastain, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Deborah H. Bennett, Department of Public Health Sciences, University of California, Davis, Davis, California, USA.
Michael S. Bloom, Department of Global and Community Health, George Mason University, Fairfax, Virginia, USA.
Carrie V. Breton, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Anne L. Dunlop, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia, USA.
Stephanie M. Eick, Program for Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA.
Assiamira Ferrara, Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
Abby Fleisch, Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Portland, Maine, USA.
Sarah Geiger, Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Champaign, Illinois, USA.
Dana E. Goin, Program for Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA.
Kurunthachalam Kannan, Department of Pediatrics and Department of Environmental Medicine, New York University Grossman School of Medicine, New York, New York, USA.
Margaret R. Karagas, Department of Epidemiology, Dartmouth Geisel School of Medicine, Lebanon, New Hampshire, USA.
Susan Korrick, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
John D. Meeker, Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA.
Rachel Morello-Frosch, School of Public Health and Department of Environmental Science, Policy and Management, University of California, Berkeley, Berkeley, California, USA.
Thomas G. O'Connor, Department of Psychiatry, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Emily Oken, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA.
Morgan Robinson, Department of Pediatrics and Department of Environmental Medicine, New York University Grossman School of Medicine, New York, New York, USA.
Megan E. Romano, Department of Epidemiology, Dartmouth Geisel School of Medicine, Lebanon, New Hampshire, USA.
Susan L. Schantz, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Champaign, Illinois, USA.
Rebecca J. Schmidt, Department of Public Health Sciences, University of California, Davis, Davis, California, USA.
Anne P. Starling, Center for Lifecourse Epidemiology of Adiposity and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Yeyi Zhu, Division of Research, Kaiser Permanente Northern California, Oakland, California, USA.
Ghassan B. Hamra, Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA.
Tracey J. Woodruff, Program for Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, California, USA.

Abstract

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals associated with risk of adverse birth outcomes. Results of previous studies have been inconsistent. Associations between PFAS and birth outcomes may be affected by psychosocial stress. OBJECTIVES: We estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships. METHODS: We included 3,339 participants from 11 prospective prenatal cohorts in the Environmental influences on the Child Health Outcomes (ECHO) program to estimate the associations of five PFAS and birth outcomes. We stratified by perceived stress scale scores to examine effect modification and used Bayesian Weighted Sums to estimate mixtures of PFAS. RESULTS: We observed reduced birth size with increased concentrations of all PFAS. For a 1-unit higher log-normalized exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), we observed lower birthweight-for-gestational-age z-scores of [95% confidence interval (CI): , ], (95% CI: , ), (95% CI: , ), (95% CI: , 0.06), and (95% CI: , ), respectively. We observed a lower odds ratio (OR) for large-for-gestational-age: (95% CI: 0.38, 0.83), (95% CI: 0.35, 0.77). For a 1-unit increase in log-normalized concentration of summed PFAS, we observed a lower birthweight-for-gestational-age z-score [; 95% highest posterior density (HPD): , ] and decreased odds of large-for-gestational-age (; 95% HPD: 0.29, 0.82). Perfluorodecanoic acid (PFDA) explained the highest percentage (40%) of the summed effect in both models. Associations were not modified by maternal perceived stress. DISCUSSION: Our large, multi-cohort study of PFAS and adverse birth outcomes found a negative association between prenatal PFAS and birthweight-for-gestational-age, and the associations were not different in groups with high vs. low perceived stress. This study can help inform policy to reduce exposures in the environment and humans. https://doi.org/10.1289/EHP10723.