Prenatal exposures to organophosphate ester metabolites and early motor development in the MADRES cohort

Ixel Hernandez-Castro; Sandrah P Eckel; Xinci Chen; Tingyu Yang; Mario J Vigil; Helen B Foley; Kurunthachalam Kannan; Morgan Robinson; Brendan Grubbs; Deborah Lerner; Nathana Lurvey; Laila Al-Marayati; Rima Habre; Genevieve F Dunton; Shohreh F Farzan; Max T Aung; Carrie V Breton; Theresa M Bastain

doi:10.1016/j.envpol.2023.123131

Prenatal exposures to organophosphate ester metabolites and early motor development in the MADRES cohort

Environ Pollut. 2024 Feb 1:342:123131. doi: 10.1016/j.envpol.2023.123131. Epub 2023 Dec 11.

Authors

Ixel Hernandez-Castro¹, Sandrah P Eckel¹, Xinci Chen¹, Tingyu Yang¹, Mario J Vigil¹, Helen B Foley¹, Kurunthachalam Kannan², Morgan Robinson², Brendan Grubbs³, Deborah Lerner⁴, Nathana Lurvey⁴, Laila Al-Marayati³, Rima Habre¹, Genevieve F Dunton⁵, Shohreh F Farzan¹, Max T Aung¹, Carrie V Breton¹, Theresa M Bastain⁶

Affiliations

¹ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
² Wadsworth Center, New York State Department of Health, Albany, NY, USA.
³ Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
⁴ Eisner Health, Los Angeles, CA, USA.
⁵ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Department of Psychology, University of Southern California, Los Angeles, CA, USA.
⁶ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: bastain@usc.edu.

PMID: 38092343
PMCID: PMC10872268 (available on 2025-02-01)
DOI: 10.1016/j.envpol.2023.123131

Abstract

Organophosphate esters (OPEs) are increasingly considered neurotoxicants which may impact gross and fine motor development. We evaluated associations between prenatal OPE exposures and infant motor development. Third trimester urinary concentrations of nine OPE metabolites were measured in 329 mother-infant dyads participating in the Maternal And Developmental Risks from Environmental and Social Stressors (MADRES) cohort. Child gross and fine motor development at 6, 9, 12, and 18-months were assessed with the Ages and Stages Questionnaire-3 (ASQ-3) and operationalized in models using dichotomous instrument-specific cutoffs for typical motor development. Five OPE metabolites with >60% detection were specific-gravity-adjusted, natural log-transformed, and modeled continuously, while four metabolites with <60% detection were modeled dichotomously (detected/not-detected). We fit mixed effects logistic regression between OPE metabolites and fine/gross motor development and assessed sex-specific effects using a statistical interaction term and sex-stratified models. Among children, 31% and 23% had gross and fine motor scores, respectively, below the ASQ-3 at-risk cutoffs at least once across infancy. A doubling in prenatal diphenyl phosphate (DPHP) exposure was associated with 26% increased odds of potential fine motor delays (OR_fine = 1.26, 95% CI: 1.02, 1.57, p = 0.04). We also observed significant interactions by infant sex for associations of detected dipropyl phosphate (DPRP) with gross motor development (p_interaction = 0.048) and detected bis(1-chloro-2-propyl) phosphate (BCIPP) with fine motor development (p_interaction = 0.02). Females had greater odds of potential motor delays for both detected DPRP (females vs males OR_gross (95% CI) = 1.48 (0.71, 3.09), p = 0.30 vs 0.27 (0.06, 1.29), p = 0.10) and detected BCIPP (females vs males OR_fine (95% CI) = 2.72 (1.27, 5.85), p = 0.01 vs 0.76 (0.31, 1.90), p = 0.56). There were no other significant associations between other metabolites and motor development, despite similar patterns. We found evidence of adverse effects of prenatal OPE exposures on infant motor development with greater adverse effects among female infants with some OPE metabolites.

Keywords: Motor development; Neurodevelopment; OPEs; Prenatal exposures.

MeSH terms

Child
Esters / urine
Female
Flame Retardants* / metabolism
Humans
Infant
Male
Organophosphates / metabolism
Phosphates
Pregnancy
Prenatal Exposure Delayed Effects*

Substances

bis(1-chloro-2-propyl)phosphate
Esters
Organophosphates
Phosphates
Flame Retardants

Abstract

MeSH terms

Substances

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