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Associations of Organophosphate Ester Flame Retardant Exposures during Pregnancy with Gestational Duration and Fetal Growth: The Environmental influences on Child Health Outcomes (ECHO) Program

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Last modified
  • 02/05/2026
Type of Material
Authors
    Jiwon Oh, University of California DavisJessie P. Buckley, Johns Hopkins UniversityXuan Li, Johns Hopkins UniversityKennedy K. Gachigi, Johns Hopkins UniversityKurunthachalam Kannan, University of AlbanyWenjie Lyu, New York UniversityJennifer L. Ames, Kaiser Permanente Northern CaliforniaEmily S. Barrett, Rutgers UniversityTheresa M. Bastain, University of Southern CaliforniaCarrie V. Breton, University of Southern CaliforniaClaudia Buss, Universitätsmedizin BerlinLisa A. Croen, Kaiser Permanente Northern CaliforniaAnne L. Dunlop, Emory UniversityAssiamira Ferrar, Kaiser Permanente Northern CaliforniaAkhgar Ghassabian, New York UniversityJulie B. Herbstman, Columbia UniversityIxel Hernandez-Castro, University of Southern CaliforniaIrva Hertz-Picciotto, University of California DavisLinda G. Kahn, New York UniversityMargaret R. Karagas, Dartmouth CollegeJordan R. Kuiper, Johns Hopkins UniversityCindy T. McEvoy, Oregon Health and Science UniversityJohn D. Meeker, University of MichiganRachel Morello-Frosch, University of California BerkeleyAmy M. Padula, University of California San FranciscoMegan E. Romano, Dartmouth CollegeSheela Sathyanarayana, University of Washington, SeattleSusan Schantz, University of Illinois Urbana-ChampaignRebecca J. Schmidt, University of California DavisHyagriv Simhan, University of PittsburghAnne P. Starling, University of North Carolina Chapel HillFrances A. Tylavsky, University of Tennessee Health Science CenterHeather E. Volk, Johns Hopkins UniversityTracey J. Woodruff, University of California San FranciscoYeyi Zhu, Kaiser Permanente Northern CaliforniaDeborah H. Bennett, University of California Davis
Language
  • English
Date
  • 2024-01-24
Publisher
  • NIH
Publication Version
Copyright Statement
  • EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 132
Issue
  • 1
Start Page
  • 017004
Grant/Funding Agency
  • National Institutes of Health
  • Office of Behavioral and Social Science Research
  • ECHO Program
Grant/Funding Information
  • Research reported in this publication was supported by the ECHO Program, Office of The Director, National Institutes of Health (NIH), under award nos. U2COD023375 (Coordinating Center), U24OD023382 (Data Analysis Center), U24OD023319, with co-funding from the Office of Behavioral and Social Science Research (PRO Core), U2CES026542 (K. Kannan), UH3OD023286, UH3OD023318, R01NR014800, R24ESO29490, P50ESO2607, EPA 83615301 (A.L. Dunlop), UH3OD023271 (C. Karr, S. Sathyanarayana, F.A. Tylavsky), P01ES022841, RD83543301, R01ES027051 (T.J. Woodruff), UH3OD023272 (R. Morello-Frosch, S. Schantz, T.J. Woodruff), UH3OD023342 (H.E. Volk), UH3OD023290 (J.B. Herbstman), UH3OD023248 (D. Dabelea, A.P. Starling), P30ES007048, P50ES026086, EPA 83615801, P50MD01570, UH3OD023287 (C.V. Breton, T.M. Bastain), UH30D023342 (K. Lyall, R.J. Schmidt), UH3OD023365 (D.H. Bennett, I. Hertz-Picciotto, J. Oh), UH3OD023275, NIGMS P20GM104416 (M.R. Karagas, M.E. Romano), UH3OD023305 (L. Trasande, A. Ghassabian), UH3OD023289 (A. Ferrara, L.A. Croen), UH3OD023349, R01HD083369, P30 ES005022 (T. O’Connor, E.S. Barrett), UH3OD023288 (C.T. McEvoy).
Supplemental Material (URL)
Abstract
  • Background: Widespread exposure to organophosphate ester (OPE) flame retardants with potential reproductive toxicity raises concern regarding the impacts of gestational exposure on birth outcomes. Previous studies of prenatal OPE exposure and birth outcomes had limited sample sizes, with inconclusive results. Objectives: We conducted a collaborative analysis of associations between gestational OPE exposures and adverse birth outcomes and tested whether associations were modified by sex. Methods: We included 6,646 pregnant participants from 16 cohorts in the Environmental influences on Child Health Outcomes (ECHO) Program. Nine OPE biomarkers were quantified in maternal urine samples collected primarily during the second and third trimester and modeled as log2-transformed continuous, categorized (high/low/nondetect), or dichotomous (detect/nondetect) variables depending on detection frequency. We used covariate-adjusted linear, logistic, and multinomial regression with generalized estimating equations, accounting for cohort-level clustering, to estimate associations of OPE biomarkers with gestational length and birth weight outcomes. Secondarily, we assessed effect modification by sex. Results: Three OPE biomarkers [diphenyl phosphate (DPHP), a composite of dibutyl phosphate and di-isobutyl phosphate (DBUP/DIBP), and bis(1,3-dichloro-2-propyl) phosphate] were detected in >85% of participants. In adjusted models, DBUP/DIBP [odds ratio (OR) per doubling=1.07; 95% confidence interval (CI): 1.02, 1.12] and bis(butoxyethyl) phosphate (OR for high vs. nondetect=1.25; 95% CI: 1.06, 1.46), but not other OPE biomarkers, were associated with higher odds of preterm birth. We observed effect modification by sex for associations of DPHP and high bis(2-chloroethyl) phosphate with completed gestational weeks and odds of preterm birth, with adverse associations among females. In addition, newborns of mothers with detectable bis(1-chloro-2-propyl) phosphate, bis(2-methylphenyl) phosphate, and dipropyl phosphate had higher birth weight-for-gestational-age 𝑧-scores (β for detect vs. nondetect=0.04–0.07); other chemicals showed null associations. Discussion: In the largest study to date, we find gestational exposures to several OPEs are associated with earlier timing of birth, especially among female neonates, or with greater fetal growth. https://doi.org/10.1289/EHP13182
Author Notes
  • Acknowledgements: We acknowledge the contribution of the following ECHO Program collaborators: ECHO Components—Coordinating Center: Duke Clinical Research Institute, Durham, North Carolina: P.B. Smith, L.K. Newby; Data Analysis Center: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland: L.P. Jacobson; Research Triangle Institute, Durham, North Carolina: D.J. Catellier; Person-Reported Outcomes Core: Northwestern University, Evanston, Illinois: R. Gershon, D. Cella. ECHO Awardees and Cohorts—Emory University, Atlanta, Georgia: A.L. Dunlop; University of Washington, Department of Environmental and Occupational Health Sciences, Seattle, Washington: C. Karr; University of California, San Francisco, San Francisco, California: T.J. Woodruff; EARLI; Columbia University Medical Center, New York, New York: J.B. Herbstman; University of Colorado Denver, Denver, Colorado: D. Dabelea; University of Illinois, Beckman Institute, Urbana, Illinois: S. Schantz; University of Southern California, Los Angeles, California: C.V. Breton; University of Rochester Medical Center, Rochester, New York: T. O’Connor; University of California, Davis, Davis, California: R.J. Schmidt; Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire: M.R. Karagas; New York University Grossman School of Medicine, New York, New York: L. Trasande; Kaiser Permanente Northern California Division of Research, Oakland, California: A. Ferrara; Oregon Health and Science University, Portland, Oregon: C.T. McEvoy. We thank our Environmental influences on Child Health Outcomes (ECHO) Program colleagues; the medical, nursing, and program staff; as well as the children and families participating in the ECHO cohorts.
  • Correspondence: Deborah H. Bennett, One Shields Ave., Davis, CA 95616 USA. Telephone: (530) 754-8282. Email: dhbennett@ucdavis.edu
Keywords
Subject - Topics
  • Reproductive health
  • Environmental health

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