Exposure to organophosphate ester flame retardants and plasticizers during pregnancy and autism-related outcomes in the ECHO Cohort

Jennifer L Ames¹, Assiamira Ferrara¹, Juanran Feng¹, Stacey Alexeeff¹, Lyndsay A Avalos¹, Emily S Barrett², Theresa M Bastain³, Deborah H Bennett⁴, Jessie P Buckley⁵, Courtney C Carignan⁶, Patricia Cintora⁷, Akhgar Ghassabian⁸, Monique M Hedderson¹, Ixel Hernandez-Castro³, Kurunthachalam Kannan^{9

10}, Margaret R Karagas¹¹, Catherine J Karr¹², Jordan R Kuiper¹³, Donghai Liang¹⁴, Kristen Lyall¹⁵, Cindy T McEvoy¹⁶, Rachel Morello-Frosch¹⁷, Thomas G O'Connor¹⁸, Jiwon Oh⁴, Alicia K Peterson¹, Lesliam Quiros-Alcala¹⁹, Sheela Sathyanarayana²⁰, Susan Schantz⁷, Rebecca J Schmidt^{4

21}, Anne P Starling²², Tracey J Woodruff²³, Heather E Volk²⁴, Yeyi Zhu¹, Lisa A Croen¹; ECHO Cohort Consortium

Affiliations

¹ Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, USA.
² Department of Biostatistics and Epidemiology, Rutgers School of Public Health, and the Environmental and Occupational Health Sciences Institute, Piscataway, NJ, USA.
³ Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
⁴ Department of Public Health Sciences, University of California, Davis, Davis, CA, USA.
⁵ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁶ Department of Food Science and Human Nutrition, Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
⁷ University of Illinois Urbana-Champaign, Urbana, IL, USA.
⁸ Departments of Pediatrics and Population Health, New York University Grossman School of Medicine,New York, NY, USA.
⁹ Wadsworth Center, Division of Environmental Health Sciences, New York State Department of Health, Albany, New York, USA.
¹⁰ Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, New York, USA.
¹¹ Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
¹² Department of Pediatrics and Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
¹³ Department of Environmental and Occupational Health, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
¹⁴ Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
¹⁵ A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA, USA.
¹⁶ Department of Pediatrics, Pape Pediatric Research Institute, Oregon Health and Science University, Portland, OR, USA.
¹⁷ School of Public Health and Department of Environmental Science, Policy and Management, University of California, Berkeley, CA, USA.
¹⁸ Departments of Psychiatry, Neuroscience, and Obstetrics and Gynecology, University of Rochester, Rochester, NY, USA.
¹⁹ Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
²⁰ University of Washington Department of Pediatrics, Epidemiology, Environmental and Occupational Health Sciences, and Center for Child Health, Behavior, and Development, Seattle Children's Research Institute,Seattle, WA, USA.
²¹ The MIND Institute, University of California Davis, Sacramento, CA, USA.
²² Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
²³ Program on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA.
²⁴ Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

PMID: 40499048
DOI: 10.1289/EHP16177

Free article

Exposure to organophosphate ester flame retardants and plasticizers during pregnancy and autism-related outcomes in the ECHO Cohort

Jennifer L Ames et al. Environ Health Perspect. 2025.

Free article

. 2025 Jun 11.

doi: 10.1289/EHP16177. Online ahead of print.

Authors

Affiliations

¹ Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, USA.
² Department of Biostatistics and Epidemiology, Rutgers School of Public Health, and the Environmental and Occupational Health Sciences Institute, Piscataway, NJ, USA.
³ Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
⁴ Department of Public Health Sciences, University of California, Davis, Davis, CA, USA.
⁵ Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
⁶ Department of Food Science and Human Nutrition, Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
⁷ University of Illinois Urbana-Champaign, Urbana, IL, USA.
⁸ Departments of Pediatrics and Population Health, New York University Grossman School of Medicine,New York, NY, USA.
⁹ Wadsworth Center, Division of Environmental Health Sciences, New York State Department of Health, Albany, New York, USA.
¹⁰ Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, New York, USA.
¹¹ Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
¹² Department of Pediatrics and Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
¹³ Department of Environmental and Occupational Health, Milken Institute School of Public Health, The George Washington University, Washington, DC, USA.
¹⁴ Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
¹⁵ A.J. Drexel Autism Institute, Drexel University, Philadelphia, PA, USA.
¹⁶ Department of Pediatrics, Pape Pediatric Research Institute, Oregon Health and Science University, Portland, OR, USA.
¹⁷ School of Public Health and Department of Environmental Science, Policy and Management, University of California, Berkeley, CA, USA.
¹⁸ Departments of Psychiatry, Neuroscience, and Obstetrics and Gynecology, University of Rochester, Rochester, NY, USA.
¹⁹ Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
²⁰ University of Washington Department of Pediatrics, Epidemiology, Environmental and Occupational Health Sciences, and Center for Child Health, Behavior, and Development, Seattle Children's Research Institute,Seattle, WA, USA.
²¹ The MIND Institute, University of California Davis, Sacramento, CA, USA.
²² Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
²³ Program on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, CA, USA.
²⁴ Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

PMID: 40499048
DOI: 10.1289/EHP16177

Abstract

Background: Organophosphate ester flame retardants and plasticizers (OPEs) have myriad uses in industry and consumer products. Increasing human exposure to OPEs has raised concerns about their potential effects on child neurodevelopment during pregnancy.

Objective: We investigated whether OPE urinary concentrations during pregnancy were associated with child autism-related outcomes.

Methods: We included 4159 mother-child pairs from 15 cohorts in the NIH Environmental influences on Child Health Outcomes (ECHO) Consortium, with children born from 2006-2020 (median age [interquartile range]: 6 [4,10] years). Nine OPE biomarkers were measured in urine samples collected mid- to late pregnancy. Dilution-adjusted biomarkers were modeled continuously, categorically (high [> median], moderate [≤ median], non-detect), or as detect/non-detect depending on their detection frequency. We assessed child autism-related traits via a) parent report on the Social Responsiveness Scale (SRS) and b) clinical autism diagnosis. We examined associations of OPEs with child outcomes, including modification by child sex, using generalized estimating equations to account for clustering by ECHO cohort.

Results: Compared with non-detectable concentrations, high exposure to bis(butoxyethyl) phosphate (BBOEP) was associated with higher autistic trait scores (adj-β 0.97, 95% confidence interval [CI]: 0.42, 1.52) and greater odds of autism diagnosis (adjusted odds ratio [adj-OR]: 1.27, 95% CI: 1.07, 1.50). Bis(1-chloro-2-propyl) phosphate (BCPP) showed associations with autistic trait scores (BCPP adj-β for high exposure vs. non-detect: 0.34, 95% CI: -0.46, 1.13; BCPP adj-β for moderate exposure vs. non-detect: 0.72, 95% CI: 0.24, 1.20). High exposure to bis(2-chloroethyl) phosphate (BCETP) was associated with lower odds of autism diagnosis (adj-OR: 0.76, 95% CI: 0.60, 0.95). Other OPEs showed no associations in adjusted models. Associations between BBOEP and higher autistic trait scores were stronger in males than females.

Discussion: Prenatal exposure to OPEs, specifically BCPP and BBOEP, may be associated with higher risk of autism diagnosis and related traits in childhood. https://doi.org/10.1289/EHP16177.

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Exposure to organophosphate ester flame retardants and plasticizers during pregnancy and autism-related outcomes in the ECHO Cohort

Affiliations

Exposure to organophosphate ester flame retardants and plasticizers during pregnancy and autism-related outcomes in the ECHO Cohort

Authors

Affiliations

Abstract

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Miscellaneous