Exposure to Organophosphate Ester Flame Retardants and Plasticizers during Pregnancy and Autism-Related Outcomes in the ECHO Cohort
Year: 2025
Type: article
Study design: Observational Study
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.
DOI: 10.1021/ehp.6c00247
Authors: Jennifer L. Ames, Assiamira Ferrara, Juanran Feng, Stacey Alexeeff, Lyndsay A. Avalos, Emily S. Barrett, Theresa M. Bastain, Deborah H. Bennett, Jessie P. Buckley, Courtney C. Carignan, Patricia Cintora, Akhgar Ghassabian, Monique M. Hedderson, Ixel Hernandez-Castro, Kurunthachalam Kannan, Margaret R. Karagas, Catherine J. Karr, Jordan R. Kuiper, Donghai Liang, Kristen Lyall, Cindy T. McEvoy, Rachel Morello-Frosch, Thomas G. O’Connor, Jiwon Oh, Alicia K. Peterson, Lesliam Quiros-Alcala, Sheela Sathyanarayana, Susan Schantz, Rebecca J. Schmidt, Anne P. Starling, Tracey J. Woodruff, Heather E. Volk, Yeyi Zhu, Lisa A. Croen, ECHO Cohort Consortium
Institutions: Kaiser Permanente, Kaiser Permanente Northern California, Rutgers, The State University of New Jersey, Environmental and Occupational Health Sciences Institute, University of Southern California, University of California, Davis, University of North Carolina at Chapel Hill, Michigan State University, University of Illinois Urbana-Champaign, New York University, New York State Department of Health, State University of New York, Wadsworth Center, University at Albany, State University of New York, Dartmouth College, University of Washington, George Washington University, Emory University, Drexel University, Oregon Health & Science University, University of California System, University of California, Berkeley, University of Rochester Medicine, University of Rochester, Johns Hopkins University, Seattle Children's Research Institute, University of California, San Francisco
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $4,500
Funders: New York State Department of Health, University of Southern California, Kaiser Permanente, Emory University, George Washington University, Michigan State University, University of Washington, University of Rochester, Drexel University, Dartmouth College, York University, National Institutes of Health, University of Illinois at Urbana-Champaign, College of Engineering, Michigan State University, University of California, Davis, University of North Carolina at Chapel Hill, University at Albany, Milken Institute School of Public Health, George Washington University, NYU Grossman School of Medicine, NIH Office of the Director, National Institute of Environmental Health Sciences
Awards: G117716216, G1233299452, G1265279961, G1402355829, G1420069246, G1535368911, G1577859456, BUILDS MARBLES: Biorepository Upkeep and Infrastructure for Longitudinal Data Sharing for MARBLES, G1809484252, G2383750895, G2582047383, Prenatal and Early Childhood Pathways To Health: An Integrated Model of Chemical and Social Exposures, Biological Mechanisms, and Sex-Specific Effects on Neurodevelopment and Respiratory Outcomes, Minnesota HHEAR Targeted Analysis Laboratory, G2734434967, G2802474135, G2874253020, G2902226377, G2923296027, Wadsworth Center's Human Health and Exposure Analysis Resource (WC-HHEAR), G331487048, G3454750618, G3552459294, G357450107, G3613858386, G3708975527, ECHO in Agricultural Washington and Rural Environments (ECHO AWARE), G3992137979, G4210819941, G431454446, G4314815125, G4496374262, G4536280156, Prenatal Environment And Child Health (PEACH) in ECHO, G5169424388, G5190275236, G5266077834, G5464503000, G5632655246, G5674308206, G591223016, G5925771568, G5974885013, G6174129243, G6255386742, G6268627264, G6319612048, Prenatal and Early Childhood Pathways To Health: An Integrated Model of Chemical and Social Exposures, Biological Mechanisms, and Sex-Specific Effects on Neurodevelopment and Respiratory Outcomes, G6388429347, Revisiting ReCHARGE: ECHO Follow up on Middle Childhood and Adolescence, G6637261855, G6643551124, G669826900, G6732704575, G678761164, G7137783347, G7832061188, G7952817345, G807183906, G8127973462, G8180517946, G824227816, G827152050, G8400686185, G8652783348, G8758770919, G8782537771, G8824569650, G8935306782, G8949028958, Early Life Exposure to Endocrine Disrupting Chemicals and Child Growth, Adiposity, and Neurodevelopment, Early Life Determinants of Child Health: A New Denver-Based Cohort, Prenatal Environment And Child Health (PEACH) in ECHO, Mount Sinai HHEAR Network Untargeted Lab Hub, Human Health Exposure Analysis Resource Core: Untargeted Analysis, Revisiting ReCHARGE: ECHO Follow up on Middle Childhood and Adolescence, ECHO Yakima Valley, Human Health Exposure Analysis Resource (HHEAR): Coordinating Center, Mount Sinai HHEAR Network Targeted Lab Hub, BUILDS MARBLES: Biorepository Upkeep and Infrastructure for Longitudinal Data Sharing for MARBLES, Human Health Exposure Analysis Resource (HHEAR) Data Center, Duke Environmental Analysis Laboratory
OpenAlex ID: W4411200409