Association between maternal perceived stress during pregnancy and offspring DNA methylation changes in HPA axis genes at birth in the ECHO Consortium
Year: 2025
Type: article
Abstract: Evidence has linked maternal exposure to stress during pregnancy with poor offspring health and neurodevelopmental outcomes. However, the precise mechanism by which this may occur has not been fully elucidated. In this study, we examined whether maternal perceived stress during pregnancy was associated with newborn blood DNA methylation (DNAm) in hypothalamic–pituitary–adrenal axis-related genes (NR3C1, FKBP5, and HSD11B2) in single CpG site and gene-based analyses. We analysed a subset of 661 mother–child pairs from the Environmental Influences on Child Health Outcomes cohort study that met our analytic inclusion criteria. Maternal perceived stress was measured during pregnancy using the perceived stress scale, and newborn DNAm was measured using the Illumina 450K and EPIC Beadchips in cord blood and dried blood spots. Single-site associations were evaluated using linear regression models, and gene-based associations were evaluated using mean burden and variance component tests, adjusted for sociodemographic and lifestyle covariates. Sex-stratified models were used to evaluate sex differential effects. Prenatal perceived stress was statistically significantly associated with newborn DNAm in one CpG site (cg06613263) in NR3C1 and with aggregate DNAm in NR3C1 and FKBP5. Aggregate DNAm in FKBP5 was more strongly associated with prenatal perceived stress in female infants. These results may have important implications for improving offspring health and well-being by providing molecular targets that can be used to identify high-risk individuals and as a basis for developing and evaluating effective behaviour and pharmaceutical interventions.
Source: Current Zoology
DOI: 10.1093/eep/dvaf024
Institutions: Johns Hopkins University, Northwell Health, Cohen Children's Medical Center, Kaiser Permanente Northern California, University of Washington, Seattle Children's Research Institute, University of California, San Francisco, University of California, Irvine, Humboldt-Universität zu Berlin, Deutsches Zentrum für Psychische Gesundheit, Charité - Universitätsmedizin Berlin, University of Pittsburgh, Purdue University West Lafayette, Oregon Health & Science University, Colorado School of Public Health, University of Colorado Anschutz, California State University, Dominguez Hills
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Awards: G1869699344, G1974852530, G1988135985, G2190254635, G2516051815, Early Life Stress and the Environmental Origins of Disease: a Population-based Prospective Longitudinal Study of Children in Rural Poverty (ECHO), ECHO in Agricultural Washington and Rural Environments (ECHO AWARE), ECHO Renewal for the INSPIRE Study Cohort, Early Life Determinants of Child Health: A New Denver-Based Cohort, G5869702591, G833303656, Preconception and Prenatal Health Impacting Factors and Child Health, G9000027450, G9000027494, G9000027636, G9000030369, G9000031755, G9000035545, G9000037579, G9000043298, G9000045817, G9000052929, G9000054878, G9000056855, G9000063312, G9000072616, G9000085602, G9000089160, G9000095024, G9000107045, G9000134580, G9000143578, G9000145361, G9000175423, G9000182430, G9000190789, G9000202576, G9000213019, G9000217873, G9000247545, G9000277210, G9000289244, G9000326798, Atlanta ECHO Pediatric Cohort, Environmental influences on Child Health Outcomes (ECHO) Coordinating Center, Human Health Exposure Analysis Resource Core: Untargeted Analysis, ECHO DAC (Environmental Influences on Child Health Outcomes Data Analysis Center), Duke Environmental Analysis Laboratory
OpenAlex ID: W4413106148