Prenatal exposure to per- and polyfluoroalkyl substances: Association with child behavior in the environmental influences on child health outcomes (ECHO) Cohort

Catherine M Bulka; Lesliam Quiros-Alcala; Xiaoshuang Xun; T Michael O'Shea; Joseph M Braun; Jennifer L Ames; Alison E Hipwell; Vaia Lida Chatzi; Amy M Padula; Dana Dabelea; Anne Starling; Anne L Dunlop; Donghai Liang; Susan Schantz; Hyeong-Moo Shin; Jiwon Oh; Rebecca J Schmidt; Kun Lu; Thomas G O'Connor; Rebecca C Fry; ECHO Cohort Consortium

doi:10.1016/j.envint.2025.109760

Prenatal exposure to per- and polyfluoroalkyl substances: Association with child behavior in the environmental influences on child health outcomes (ECHO) Cohort

Environ Int. 2025 Sep:203:109760. doi: 10.1016/j.envint.2025.109760. Epub 2025 Aug 30.

Authors

Catherine M Bulka¹, Lesliam Quiros-Alcala², Xiaoshuang Xun³, T Michael O'Shea⁴, Joseph M Braun⁵, Jennifer L Ames⁶, Alison E Hipwell⁷, Vaia Lida Chatzi⁸, Amy M Padula⁹, Dana Dabelea¹⁰, Anne Starling¹¹, Anne L Dunlop¹², Donghai Liang¹³, Susan Schantz¹⁴, Hyeong-Moo Shin¹⁵, Jiwon Oh¹⁶, Rebecca J Schmidt¹⁶, Kun Lu¹⁷, Thomas G O'Connor¹⁸, Rebecca C Fry¹⁹; ECHO Cohort Consortium

Affiliations

¹ College of Public Health, University of South Florida, Tampa, FL, USA.
² Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
³ Environmental influences on Child Health Outcomes Data Analysis Center, Johns Hopkins University, Baltimore, MD, USA.
⁴ Department of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
⁵ Department of Epidemiology, Brown University, Providence, RI, USA; Center for Children's Environmental Health, Brown University, Providence, RI, USA.
⁶ Kaiser Permanente Division of Research, Oakland, CA, USA.
⁷ Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA.
⁸ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁹ Program on Reproductive Health and the Environment, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, USA.
¹⁰ Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
¹¹ Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
¹² Department of Gynecology & Obstetrics, School of Medicine, Emory University, Atlanta, GA, USA.
¹³ Department of Environmental Health, Rollins School of Public Health, Emory University Atlanta, GA, USA; Department of Epidemiology, Rollins School of Public Health, Emory University Atlanta, GA, USA.
¹⁴ Department of Psychology, College of Liberal Arts & Sciences, University of Illinois Urbana-Champaign, Champaign, IL, USA.
¹⁵ Department of Environmental Science, College of Arts & Sciences, Baylor University, Waco, TX, USA.
¹⁶ Department of Public Health Sciences, University of California Davis, Davis, CA, USA.
¹⁷ Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina, Chapel Hill, NC, USA.
¹⁸ Department of Psychiatry, University of Rochester Medical Center, Rochester, NY, USA.
¹⁹ Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina, Chapel Hill, NC, USA; Institute for Environmental Health Solutions, Gillings School of Global Public Health, The University of North Carolina, Chapel Hill, NC, USA. Electronic address: rfry@unc.edu.

PMID: 40914105
DOI: 10.1016/j.envint.2025.109760

Abstract

Background: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may adversely impact child neurodevelopment; however, epidemiologic findings remain inconclusive because of small sample sizes, limited exposure variability, and differing neurodevelopmental measures. We aimed to investigate the relationship between prenatal PFAS exposure and child behavior.

Methods: We pooled data from nine study sites in the nationwide Environmental influences on Child Health Outcomes (ECHO) Cohort. PFAS were quantified in maternal serum samples collected between 2 and 42 weeks' gestation. Behavioral and emotional problems were assessed via the Child Behavior Checklist (CBCL) in preschool-age (n = 1,723) and school-age (n = 627) children. We used age-stratified, covariate-adjusted linear mixed-effects models to estimate differences in CBCL scores by PFAS quartile, focusing on analytes detected at >75 %. We also fit quantile g-computation models to examine associations for PFAS mixtures and tested for effect modification by child sex.

Findings: Perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA) were the most frequently detected analytes in maternal prenatal serum, although concentrations were generally low (<5 ng/mL). Associations between PFAS concentrations and CBCL scores were mostly null, except for some suggestive findings for PFHxS in the preschool-age subset. No consistent sex differences were observed, and associations for PFAS mixtures were statistically insignificant.

Interpretation: We found little evidence of associations between prenatal PFAS exposures and child behavioral problems in the ECHO Cohort. Future studies should consider PFAS exposure during the postnatal period, which may be a more sensitive window.

Keywords: Behavior; Child development; PFAS; Pregnancy.

MeSH terms

Adult
Alkanesulfonic Acids
Caprylates
Child
Child Behavior* / drug effects
Child Health
Child, Preschool
Cohort Studies
Environmental Pollutants* / blood
Female
Fluorocarbons* / blood
Humans
Male
Maternal Exposure* / statistics & numerical data
Pregnancy
Prenatal Exposure Delayed Effects* / epidemiology

Substances

Fluorocarbons
Environmental Pollutants
Alkanesulfonic Acids
Caprylates
perfluorooctanoic acid