Prenatal exposure to organophosphate ester flame retardants and behavioral outcomes in early childhood in the Environmental influences on Child Health Outcomes (ECHO) cohort

Jiwon Oh¹, Lesliam Quirós-Alcalá², Xuan Li³, Kurunthachalam Kannan⁴, Wenjie Lyu⁵, Lyndsay A Avalos⁶, Emily S Barrett⁷, Theresa M Bastain⁸, Jessie P Buckley⁹, Patricia Cintora¹⁰, Lisa A Croen¹¹, Anne L Dunlop¹², Akhgar Ghassabian¹³, Rima Habre¹⁴, Julie B Herbstman¹⁵, Ixel Hernandez-Castro¹⁶, Irva Hertz-Picciotto¹⁷, Donghai Liang¹⁸, Cindy T McEvoy¹⁹, Thomas G O'Connor²⁰, Sheela Sathyanarayana²¹, Susan L Schantz²², Rebecca J Schmidt²³, Julie B Schweitzer²⁴, Anne P Starling²⁵, Heather E Volk²⁶, Megan L Woodbury²⁷, Tracey J Woodruff²⁸, Qi Zhao²⁹, Yeyi Zhu³⁰, Deborah H Bennett³¹; ECHO Cohort Consortium

Affiliations

¹ Department of Public Health Sciences, University of California Davis, Medical Sciences 1C, Davis, CA 95616, USA. Electronic address: jiwoh@ucdavis.edu.
² Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. Electronic address: lalcala1@jhu.edu.
³ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. Electronic address: xli332@jh.edu.
⁴ Division of Environmental Health Sciences, Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12237, USA; Department of Environmental Health Sciences, University at Albany, State University of New York, 1400 Washington Ave, Albany, NY 12222, USA. Electronic address: kurunthachalam.kannan@health.ny.gov.
⁵ Department of Pediatrics, New York University Grossman School of Medicine, 550 1st Ave., New York, NY 10016, USA; Department of Environmental Medicine, New York University Grossman School of Medicine, 550 1st Ave., New York, NY 10016, USA. Electronic address: wenjie.lyu@nyulangone.org.
⁶ Division of Research, Kaiser Permanente Northern California, 1 Kaiser Plaza, Oakland, CA 94612, USA. Electronic address: Lyndsay.A.Avalos@kp.org.
⁷ Department of Biostatistics and Epidemiology, Rutgers School of Public Health, 683 Hoes Ln W, Piscataway, NJ 08854, USA; Environmental and Occupational Health Sciences Institute, Rutgers, the State University of New Jersey, 170 Frelinghuysen Rd, Piscataway, NJ 08854, USA. Electronic address: esb104@eohsi.rutgers.edu.
⁸ Department of Population and Public Health Sciences, University of Southern California, 1845 N Soto St, Los Angeles, CA 90032, USA. Electronic address: bastain@usc.edu.
⁹ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 135 Dauer Dr, Chapel Hill, NC 27599, USA. Electronic address: Jessie.Buckley@unc.edu.
¹⁰ Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, 405 N Mathews Ave, Urbana, IL 61801, USA. Electronic address: cintora2@illinois.edu.
¹¹ Division of Research, Kaiser Permanente Northern California, 1 Kaiser Plaza, Oakland, CA 94612, USA. Electronic address: Lisa.A.Croen@kp.org.
¹² Department of Gynecology and Obstetrics, Emory University School of Medicine, 1518 Clifton Rd N E, Atlanta, GA 30322, USA. Electronic address: amlang@emory.edu.
¹³ Department of Pediatrics, New York University Grossman School of Medicine, 550 1st Ave., New York, NY 10016, USA; Department of Population Health, New York University Grossman School of Medicine, 550 1st Ave., New York, NY 10016, USA. Electronic address: Akhgar.Ghassabian@nyulangone.org.
¹⁴ Department of Population and Public Health Sciences, University of Southern California, 1845 N Soto St, Los Angeles, CA 90032, USA. Electronic address: habre@usc.edu.
¹⁵ Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, 722 W 168th St, New York, NY 10032, USA. Electronic address: jh2678@cumc.columbia.edu.
¹⁶ Department of Population and Public Health Sciences, University of Southern California, 1845 N Soto St, Los Angeles, CA 90032, USA. Electronic address: ixelhern@usc.edu.
¹⁷ Department of Public Health Sciences, University of California Davis, Medical Sciences 1C, Davis, CA 95616, USA; UC Davis MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, 2825 50th St, Sacramento, CA 95817, USA. Electronic address: iher@ucdavis.edu.
¹⁸ Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Rd N E, Atlanta, GA 30322, USA. Electronic address: donghai.liang@emory.edu.
¹⁹ Department of Pediatrics, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA. Electronic address: mcevoyc@ohsu.edu.
²⁰ Department of Psychiatry, University of Rochester, 500 Joseph C. Wilson Blvd. Rochester, NY 14627, USA. Electronic address: tom_oconnor@urmc.Rochester.edu.
²¹ Department of Pediatrics, University of Washington and Seattle Children's Research Institute, 4800 Sand Point Way NE Seattle, WA 98105, USA. Electronic address: sheela.sathyanarayana@seattlechildrens.org.
²² Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, 405 N Mathews Ave, Urbana, IL 61801, USA. Electronic address: schantz@illinois.edu.
²³ Department of Public Health Sciences, University of California Davis, Medical Sciences 1C, Davis, CA 95616, USA; UC Davis MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, 2825 50th St, Sacramento, CA 95817, USA. Electronic address: rjschmidt@ucdavis.edu.
²⁴ UC Davis MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, 2825 50th St, Sacramento, CA 95817, USA; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California at Davis, 4610 X St, Sacramento, CA 95817, USA. Electronic address: jschweitzer@ucdavis.edu.
²⁵ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 135 Dauer Dr, Chapel Hill, NC 27599, USA; Center for Lifecourse Epidemiology of Adiposity and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: anne.starling@unc.edu.
²⁶ Department of Mental Health, Johns Hopkins University, 615 N Wolfe St, Baltimore, MD 21205, USA. Electronic address: hvolk1@jhu.edu.
²⁷ College of Engineering, Northeastern University, Snell Engineering Center, 360 Huntington Ave, Boston, MA 02115, USA. Electronic address: m.woodbury@northeastern.edu.
²⁸ Program on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, 490 Illinois Street, Floor 10, San Francisco, CA 94143, USA. Electronic address: tracey.woodruff@ucsf.edu.
²⁹ Department of Preventive Medicine, University of Tennessee Health Science Center, 920 Madison Ave, Memphis, TN 38163, USA. Electronic address: qzhao11@uthsc.edu.
³⁰ Division of Research, Kaiser Permanente Northern California, 1 Kaiser Plaza, Oakland, CA 94612, USA. Electronic address: Yeyi.Zhu@kp.org.
³¹ Department of Public Health Sciences, University of California Davis, Medical Sciences 1C, Davis, CA 95616, USA. Electronic address: dhbennett@ucdavis.edu.

PMID: 40628179
PMCID: PMC12498345
DOI: 10.1016/j.envint.2025.109649

Prenatal exposure to organophosphate ester flame retardants and behavioral outcomes in early childhood in the Environmental influences on Child Health Outcomes (ECHO) cohort

Jiwon Oh et al. Environ Int. 2025 Aug.

. 2025 Aug:202:109649.

doi: 10.1016/j.envint.2025.109649. Epub 2025 Jun 28.

Authors

Affiliations

¹ Department of Public Health Sciences, University of California Davis, Medical Sciences 1C, Davis, CA 95616, USA. Electronic address: jiwoh@ucdavis.edu.
² Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. Electronic address: lalcala1@jhu.edu.
³ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Baltimore, MD 21205, USA. Electronic address: xli332@jh.edu.
⁴ Division of Environmental Health Sciences, Wadsworth Center, New York State Department of Health, Empire State Plaza, Albany, NY 12237, USA; Department of Environmental Health Sciences, University at Albany, State University of New York, 1400 Washington Ave, Albany, NY 12222, USA. Electronic address: kurunthachalam.kannan@health.ny.gov.
⁵ Department of Pediatrics, New York University Grossman School of Medicine, 550 1st Ave., New York, NY 10016, USA; Department of Environmental Medicine, New York University Grossman School of Medicine, 550 1st Ave., New York, NY 10016, USA. Electronic address: wenjie.lyu@nyulangone.org.
⁶ Division of Research, Kaiser Permanente Northern California, 1 Kaiser Plaza, Oakland, CA 94612, USA. Electronic address: Lyndsay.A.Avalos@kp.org.
⁷ Department of Biostatistics and Epidemiology, Rutgers School of Public Health, 683 Hoes Ln W, Piscataway, NJ 08854, USA; Environmental and Occupational Health Sciences Institute, Rutgers, the State University of New Jersey, 170 Frelinghuysen Rd, Piscataway, NJ 08854, USA. Electronic address: esb104@eohsi.rutgers.edu.
⁸ Department of Population and Public Health Sciences, University of Southern California, 1845 N Soto St, Los Angeles, CA 90032, USA. Electronic address: bastain@usc.edu.
⁹ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 135 Dauer Dr, Chapel Hill, NC 27599, USA. Electronic address: Jessie.Buckley@unc.edu.
¹⁰ Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, 405 N Mathews Ave, Urbana, IL 61801, USA. Electronic address: cintora2@illinois.edu.
¹¹ Division of Research, Kaiser Permanente Northern California, 1 Kaiser Plaza, Oakland, CA 94612, USA. Electronic address: Lisa.A.Croen@kp.org.
¹² Department of Gynecology and Obstetrics, Emory University School of Medicine, 1518 Clifton Rd N E, Atlanta, GA 30322, USA. Electronic address: amlang@emory.edu.
¹³ Department of Pediatrics, New York University Grossman School of Medicine, 550 1st Ave., New York, NY 10016, USA; Department of Population Health, New York University Grossman School of Medicine, 550 1st Ave., New York, NY 10016, USA. Electronic address: Akhgar.Ghassabian@nyulangone.org.
¹⁴ Department of Population and Public Health Sciences, University of Southern California, 1845 N Soto St, Los Angeles, CA 90032, USA. Electronic address: habre@usc.edu.
¹⁵ Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, 722 W 168th St, New York, NY 10032, USA. Electronic address: jh2678@cumc.columbia.edu.
¹⁶ Department of Population and Public Health Sciences, University of Southern California, 1845 N Soto St, Los Angeles, CA 90032, USA. Electronic address: ixelhern@usc.edu.
¹⁷ Department of Public Health Sciences, University of California Davis, Medical Sciences 1C, Davis, CA 95616, USA; UC Davis MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, 2825 50th St, Sacramento, CA 95817, USA. Electronic address: iher@ucdavis.edu.
¹⁸ Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, 1518 Clifton Rd N E, Atlanta, GA 30322, USA. Electronic address: donghai.liang@emory.edu.
¹⁹ Department of Pediatrics, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA. Electronic address: mcevoyc@ohsu.edu.
²⁰ Department of Psychiatry, University of Rochester, 500 Joseph C. Wilson Blvd. Rochester, NY 14627, USA. Electronic address: tom_oconnor@urmc.Rochester.edu.
²¹ Department of Pediatrics, University of Washington and Seattle Children's Research Institute, 4800 Sand Point Way NE Seattle, WA 98105, USA. Electronic address: sheela.sathyanarayana@seattlechildrens.org.
²² Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, 405 N Mathews Ave, Urbana, IL 61801, USA. Electronic address: schantz@illinois.edu.
²³ Department of Public Health Sciences, University of California Davis, Medical Sciences 1C, Davis, CA 95616, USA; UC Davis MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, 2825 50th St, Sacramento, CA 95817, USA. Electronic address: rjschmidt@ucdavis.edu.
²⁴ UC Davis MIND (Medical Investigations of Neurodevelopmental Disorders) Institute, 2825 50th St, Sacramento, CA 95817, USA; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California at Davis, 4610 X St, Sacramento, CA 95817, USA. Electronic address: jschweitzer@ucdavis.edu.
²⁵ Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 135 Dauer Dr, Chapel Hill, NC 27599, USA; Center for Lifecourse Epidemiology of Adiposity and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: anne.starling@unc.edu.
²⁶ Department of Mental Health, Johns Hopkins University, 615 N Wolfe St, Baltimore, MD 21205, USA. Electronic address: hvolk1@jhu.edu.
²⁷ College of Engineering, Northeastern University, Snell Engineering Center, 360 Huntington Ave, Boston, MA 02115, USA. Electronic address: m.woodbury@northeastern.edu.
²⁸ Program on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, 490 Illinois Street, Floor 10, San Francisco, CA 94143, USA. Electronic address: tracey.woodruff@ucsf.edu.
²⁹ Department of Preventive Medicine, University of Tennessee Health Science Center, 920 Madison Ave, Memphis, TN 38163, USA. Electronic address: qzhao11@uthsc.edu.
³⁰ Division of Research, Kaiser Permanente Northern California, 1 Kaiser Plaza, Oakland, CA 94612, USA. Electronic address: Yeyi.Zhu@kp.org.
³¹ Department of Public Health Sciences, University of California Davis, Medical Sciences 1C, Davis, CA 95616, USA. Electronic address: dhbennett@ucdavis.edu.

PMID: 40628179
PMCID: PMC12498345
DOI: 10.1016/j.envint.2025.109649

Abstract

Background: Prenatal exposure to organophosphate esters (OPEs) has been linked to neurotoxic effects in children; however, epidemiological evidence remains inconclusive. We investigated associations of prenatal OPE exposure with child behaviors.

Methods: We analyzed data of 2948 mother-child dyads from 12 prospective cohorts of the Environmental influences on Child Health Outcomes (ECHO) Cohort. Nine OPE biomarkers quantified in prenatal maternal urine were modeled based on detection frequency. Child behaviors were assessed using the Child Behavior Checklist for Ages 1½-5. We used linear mixed effects models to examine associations between each OPE biomarker and composite T-scores. We evaluated child sex and social vulnerability as potential effect modifiers.

Results: Low bis(butoxyethyl) phosphate exposure, versus non-detect, was associated with higher T-scores for all composite scales (β_{internalizing} = 1.06, 95% confidence interval [CI]: 0.14, 1.98; β_{externalizing} = 1.06, 95% CI: 0.18, 1.95; β_total = 1.19, 95% CI: 0.28, 2.11). Low and high bis(1-chloro-2-propyl) phosphate (BCPP) exposure, versus non-detect, were associated with higher T-scores for externalizing problems (β_{externalizing} = 1.18, 95% CI: 0.29, 2.07; β_{externalizing} = 1.12, 95% CI: 0.21, 2.04). Conversely, detectable dipropyl phosphate (25% detection) was associated with lower externalizing T-scores (β_{externalizing} = -0.89, 95% CI: -1.74, -0.04). Associations between high BCPP exposure and higher externalizing and total problem T-scores were stronger among children from highly vulnerable neighborhoods compared to those from less vulnerable neighborhoods (p-interaction < 0.1). Child sex modified associations for bis(1,3-dichloro-2-propyl) phosphate and high BCPP exposure, with males exhibiting greater adverse behaviors for all associations.

Discussion: Gestational exposure to several OPEs may be adversely associated with early behavioral development.

Keywords: Externalizing behavior; Flame retardants; Internalizing behavior; Organophosphate esters; Plasticizers; Pregnancy.

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Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rebecca J. Schmidt consults for Beasley Law, Inc. Rebecca J. Schmidt received travel support to present at the 35th Annual Meeting of the Organization of Teratology Information Specialists (OTIS). Rebecca J. Schmidt and Deborah H. Bennett consult for Linus Biotechnology, Inc. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

**Fig. 1.**
Adjusted differences and respective 95% confidence intervals in CBCL/1½–5 T-scores for internalizing, externalizing, and total problems in association with prenatal maternal OPE biomarker concentrations in the overall sample and stratified by child sex across 12 ECHO cohorts. Point estimates represent regression coefficients, and error bars represent 95% confidence intervals. The null value for regression coefficients is 0, as indicated by the dashed line. Numeric data regarding regression coefficients and 95% confidence intervals for main effects and interaction terms between child sex and OPE biomarkers are presented in Table S5. Linear mixed effects models were adjusted for maternal race/ethnicity, maternal age at delivery, maternal education, maternal marital status, maternal pre-pregnancy body mass index, maternal smoking during pregnancy, parity, season of birth, and child sex and age at behavior assessment. Abbreviations: BBOEP, bis(butoxyethyl) phosphate; BCETP, bis(2-chloroethyl) phosphate; BCPP, bis(1-chloro-2-propyl) phosphate; BDCPP, bis(1,3-dichloro-2-propyl) phosphate; BEHP, bis(2-ethylhexyl) phosphate; BMPP, bis(2-methylphenyl) phosphate; CBCL/1½–5, Child Behavior Checklist for Ages 1½–5; CI, confidence interval; DBUP/DIBP, composite of dibutyl phosphate and di-isobutyl phosphate; DPHP, diphenyl phosphate; DPRP, dipropyl phosphate; ECHO, Environmental influences on Child Health Outcomes; ND, non-detect; OPE, organophosphate ester.

**Fig. 2.**
Adjusted differences and respective 95% confidence intervals in CBCL/1½–5 T-scores for internalizing, externalizing, and total problems in association with prenatal maternal OPE biomarker concentrations stratified by social vulnerability index across 12 ECHO cohorts (n = 1946). Point estimates represent regression coefficients, and error bars represent 95% confidence intervals. The null value for regression coefficients is 0, as indicated by the dashed line. Numeric data regarding regression coefficients and 95% confidence intervals for main effects and interaction terms between SVI and OPE biomarkers are presented in Table S7. Linear mixed effects models were adjusted for maternal race/ethnicity, maternal age at delivery, maternal education, maternal marital status, maternal pre-pregnancy body mass index, maternal smoking during pregnancy, parity, season of birth, and child sex and age at behavior assessment. Abbreviations; BBOEP, bis(butoxyethyl) phosphate; BCETP, bis(2-chloroethyl) phosphate; BCPP, bis(1-chloro-2-propyl) phosphate; BDCPP, bis(1,3-dichloro-2-propyl) phosphate; BEHP, bis(2-ethylhexyl) phosphate; BMPP, bis(2-methylphenyl) phosphate; CBCL/1½–5, Child Behavior Checklist for Ages 1½–5; CI, confidence interval; DBUP/DIBP, composite of dibutyl phosphate and di-isobutyl phosphate; DPHP, diphenyl phosphate; DPRP, dipropyl phosphate; ECHO, Environmental influences on Child Health Outcomes; ND, non-detect; OPE, organophosphate ester; SVI, social vulnerability index.

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Prenatal exposure to organophosphate ester flame retardants and behavioral outcomes in early childhood in the Environmental influences on Child Health Outcomes (ECHO) cohort

Affiliations

Prenatal exposure to organophosphate ester flame retardants and behavioral outcomes in early childhood in the Environmental influences on Child Health Outcomes (ECHO) cohort

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

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Grants and funding

LinkOut - more resources

Full Text Sources

Medical

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