Prenatal exposure to organophosphate ester flame retardants and child cognition: Findings from the environmental influences on child Health Outcomes cohort

Akhgar Ghassabian; Taylor Etzel; Jennifer L Ames; Thomas G O'Connor; Jessie P Buckley; Sarvenaz Shahin; Julie B Herbstman; Emily S Barrett; Donghai Liang; Lisa A Croen; Rebecca J Schmidt; Lesliam Quirós-Alcalá; Susan L Schantz; Kristen Lyall; Giehae Choi; Courtney C Carignan; Tracey J Woodruff; Rachel Morello-Frosch; Hyeong-Moo Shin; Claudia Buss; Zhongmin Li; Kurunthachalam Kannan; Deborah H Bennett; ECHO Cohort Consortium

doi:10.1016/j.envpol.2025.127446

Prenatal exposure to organophosphate ester flame retardants and child cognition: Findings from the environmental influences on child Health Outcomes cohort

Environ Pollut. 2026 Feb 1:390:127446. doi: 10.1016/j.envpol.2025.127446. Epub 2025 Nov 28.

Authors

Akhgar Ghassabian¹, Taylor Etzel², Jennifer L Ames³, Thomas G O'Connor⁴, Jessie P Buckley⁵, Sarvenaz Shahin⁶, Julie B Herbstman⁷, Emily S Barrett⁸, Donghai Liang⁹, Lisa A Croen³, Rebecca J Schmidt¹⁰, Lesliam Quirós-Alcalá¹¹, Susan L Schantz¹², Kristen Lyall¹³, Giehae Choi¹¹, Courtney C Carignan¹⁴, Tracey J Woodruff¹⁵, Rachel Morello-Frosch¹⁶, Hyeong-Moo Shin¹⁷, Claudia Buss¹⁸, Zhongmin Li¹⁹, Kurunthachalam Kannan²⁰, Deborah H Bennett²¹; ECHO Cohort Consortium

Affiliations

¹ Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA; Department of Population Health, New York University Grossman School of Medicine, New York, NY, USA. Electronic address: Akhgar.ghassabian@nyulangone.org.
² Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
³ Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, USA.
⁴ Departments of Psychiatry, Psychology, Neuroscience, and Obstetrics and Gynecology, University of Rochester, Rochester, NY, USA.
⁵ Department Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁶ Department of Pediatrics, New York University Grossman School of Medicine, New York, NY, USA.
⁷ Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA.
⁸ Department of Biostatistics and Epidemiology, Rutgers School of Public Health; Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, NJ, USA.
⁹ Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
¹⁰ Department of Public Health Sciences, University of California Davis School of Medicine, Sacramento, CA, USA; Medical Investigations of Neurodevelopmental Disorders Institute, University of California Davis, Sacramento, CA, USA.
¹¹ Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹² Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL, USA.
¹³ Department of Epidemiology and Biostatistics, Drexel University, Philadelphia, PA, USA.
¹⁴ Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI, USA.
¹⁵ Program on Reproductive Health and the Environment, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, San Francisco, CA, USA.
¹⁶ Department of Environmental Science, Policy, & Management, School of Public Health, University of California Berkeley, Berkeley, CA, USA.
¹⁷ Department of Environmental Science, Baylor University, Waco, TX, USA.
¹⁸ Department of Medical Psychology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany; Department of Pediatrics, University of California Irvine School of Medicine, Irvine, CA, USA.
¹⁹ Wadsworth Center, Division of Environmental Health Sciences, New York State Department of Health, Albany, NY, USA.
²⁰ Wadsworth Center, Division of Environmental Health Sciences, New York State Department of Health, Albany, NY, USA; Department of Environmental Health Sciences, University at Albany, State University of New York, Albany, NY, USA.
²¹ Department of Public Health Sciences, University of California Davis School of Medicine, Sacramento, CA, USA.

Abstract

Experimental evidence shows that organophosphate esters (OPEs), common flame retardants and plasticizers, can cause developmental neurotoxicity. We investigated the extent to which prenatal OPE exposure was associated with child cognition. Participants were 831 mother-child pairs from 3 sites in the Environmental influences on Child Health Outcomes (ECHO) Cohort with data on urinary levels of 9 OPE analytes during gestation (2009-2019) and child cognition. Based on detection frequencies, analytes were modeled continuously (adjusted for urinary dilution and log2-transformed), categorically (high/low/non-detect), or dichotomously (detect/non-detect). Children's cognition was measured using the Wechsler Preschool and Primary Scale of Intelligence or Wechsler Intelligence Scale for Children at mean age 5.7 years (SD = 0.7). We examined associations of OPE analyte with age- and sex-standardized cognition scores using linear regression with generalized estimating equations to account for clustering within sites. We also tested for effect measure modification by sex. The analyte with the highest detection frequency (96.4 %) was diphenyl phosphate (DPHP), a primary metabolite of triphenyl phosphate (TPHP). Higher concentrations of DPHP were associated with lower cognition scores (βˆ per doubling of concentrations = -0.46, 95 %CI: -0.90, -0.02). Bis(butoxyethyl) phosphate (BBOEP), bis(1-chloro-2-propyl) phosphate (BCPP), and bis(2-methylphenyl) phosphate (BMPP) above the detection limit (vs. below) were associated with higher cognition scores mainly in boys; but, sex interaction with BMPP was not significant. Prenatal exposure to DPHP, a widely detected OPE, was associated with lower cognitive functioning, though the effect size was small. Given widespread exposure, findings related to this and other OPEs should be further examined in mechanistic studies.

Keywords: Developmental neurotoxicity; Diphenyl phosphate (DPHP); Flame retardants; Organophosphate esters (OPEs).

MeSH terms

Adult
Child
Child Health
Child, Preschool
Cognition* / drug effects
Cohort Studies
Environmental Pollutants*
Esters
Female
Flame Retardants*
Humans
Male
Maternal Exposure* / statistics & numerical data
Organophosphates*
Pregnancy
Prenatal Exposure Delayed Effects* / epidemiology

Substances

Flame Retardants
Organophosphates
Esters
Environmental Pollutants

Abstract

MeSH terms

Substances

Grants and funding