Associations of maternal neighborhood and trauma-related stressors with mitochondrial DNA copy number and telomere length in maternal and cord blood

Neighborhood and individual-level trauma-related stressors during pregnancy can increase oxidative stress, potentially altering cellular disease pathway biomarkers such as mitochondrial DNA copy number (mtDNAcn) and telomere length (TL). However, the biological mechanisms linking early-life stressors to long-term health outcomes remain understudied. In a subset of Project Viva participants (n = 415-917), we evaluated associations of neighborhood and individual-level stressors with mean relative mtDNAcn and TL measured in first trimester maternal blood and cord blood. Neighborhood stressors during pregnancy were assessed using the Child Opportunity Index (COI) and Social Vulnerability Index (SVI). Trauma-related stressors were measured using the Personal Safety Questionnaire (PSQ), administered mid-pregnancy, and maternal Adverse Childhood Experiences (ACEs), reported during a mid-life follow-up. In multivariable linear regression analysis, residence in a very high versus very low opportunity neighborhood was associated with lower maternal mtDNAcn ([Formula: see text]= - 0.09, 95% confidence interval (CI) - 0.17, - 0.02), while residence in a very high versus very low vulnerability area was associated with higher maternal mtDNAcn ([Formula: see text]= 0.06, 95% CI 0.01, 0.12). Additionally, residence in moderate versus very low opportunity neighborhoods was associated with longer cord blood TL ([Formula: see text]= 0.39, 95% CI 0.0002, 0.78), but associations were attenuated after cell-type adjustment. Our findings suggest that prenatal neighborhood stressors are associated with increased maternal mtDNAcn and neighborhood opportunity is associated with longer fetal TL, indicating possible links to biological pathways related to oxidative stress and cellular aging.