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PubMed · 41240871

Prenatal organophosphate ester exposure and epigenetic changes at birth: a characterization of the methylome in the ECHO cohort.

Rose Schrott·Jennifer L Ames·Emily S Barrett·Deborah H Bennet·Lisa A Croen·Sarah D Geiger·Kurunthachalam Kannan·Zorimar Rivera-Nunez·Jiwon Oh·Alicia K Peterson·J Richard Pilsner·Rebecca J Schmidt·Anne P Starling·Yeyi Zhu·Christine Ladd-Acosta·ECHO Cohort Consortium
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Abstract

BACKGROUND: Prenatal exposure to organophosphate esters (OPEs) affects multiple child health domains. Alterations to the DNA methylome are a plausible mechanism through which these changes occur. This study characterized DNA methylation signatures at birth associated with prenatal OPE biomarkers. METHODS: We included 736 mother-infant pairs from 7 sites in the Environmental influences on Child Health Outcomes (ECHO) Cohort. Five OPE biomarkers were quantified in maternal urine samples collected during the second and third trimesters and modeled as log2-transformed continuous variables. Using covariate-adjusted linear regression, we tested associations between OPE biomarkers and locus-specific, regional, and global cord blood DNA methylation changes measured by Illumina 450&#xa0;K and EPIC arrays, and gestational epigenetic age measured by the Knight gestational age epigenetic clock generated with measures from the 27&#xa0;K, 450&#xa0;K, and EPIC arrays. When feasible, we examined relationships by sex. FINDINGS: Global hypomethylation at multiple regions was associated with BDCPP concentrations (p&#xa0;=&#xa0;0.003 to 0.02, coef&#xa0;=&#xa0;-0.002). Differentially methylated regions annotated to PCDHGB1 and SLC43A2 were associated with BDCPP and DPHP concentrations, respectively (FDR q&#xa0;<&#xa0;0.05). In sex-specific analyses, global hypomethylation was associated with prenatal BDCPP (p&#xa0;=&#xa0;0.006 to 0.03, coef&#xa0;=&#xa0;-0.0003 to -0.0002) and DBUP_DIBP (p&#xa0;=&#xa0;0.01, coef&#xa0;=&#xa0;-0.0007 to -0.0006) concentrations in females; and global hypermethylation was associated with DBUP_DIBP concentrations in males (p&#xa0;<&#xa0;0.05, coef&#xa0;=&#xa0;0.0004). BCETP concentrations were significantly associated with decelerated epigenetic aging at birth in females (p&#xa0;<&#xa0;0.05, coef&#xa0;=&#xa0;-0.05). INTERPRETATION: Prenatal exposure to OPEs impacts child methylation at birth, suggesting a potential mechanism for the association between prenatal OPE exposure and child health outcomes.

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HumansFemaleDNA MethylationPregnancyMaleEpigenesis, GeneticMaternal ExposureOrganophosphatesAdultPrenatal Exposure Delayed EffectsCohort StudiesEpigenomeEstersInfant, NewbornBiomarkersFetal BloodChild healthDNA methylationGestational ageJournal Article

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Rose Schrott, Jennifer L Ames, Emily S Barrett, Deborah H Bennet, Lisa A Croen, Sarah D Geiger, Kurunthachalam Kannan, Zorimar Rivera-Nunez, Jiwon Oh, Alicia K Peterson, J Richard Pilsner, Rebecca J Schmidt, Anne P Starling, Yeyi Zhu, Christine Ladd-Acosta, ECHO Cohort Consortium. 2025-11-07. Prenatal organophosphate ester exposure and epigenetic changes at birth: a characterization of the methylome in the ECHO cohort.. https://doi.org/10.1016/j.envint.2025.109908

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