Mothers with a history of adverse childhood experiences and their emotional states during pregnancy: study of epigenetic components as potential mediators

Adverse childhood experiences (ACEs) have detrimental intergenerational health consequences; however, mechanisms require elucidation. We test the associations among mothers’ ACEs, mothers’ prenatal anxiety and depression symptoms, and DNA methylation (DNAm) in maternal prenatal blood and infant umbilical cord blood. Maternal ACE score was associated with higher prenatal depression (β= 0.84, p=0.004) and anxiety (β = 1.36, p=0.02) symptoms and lower rates of secure attachment at 3 months (OR= 0.52 p=0.003). Prenatal depression (OR= 0.92, p=0.194) and anxiety (OR= 0.94, p= 0.072) were not correlated with infant attachment. Results from the regression of epigenetic age acceleration in maternal prenatal blood on maternal ACE score were: β =0.49, p= 0.09. Regressing epigenetic age in cord blood on prenatal depression yielded: β = -0.10, p=0.07 and on anxiety yielded β =-0.05, p=0.07. No CMR was associated with maternal ACE score at the FDR-corrected p<.05 level. ACE-associated DNAm variation was enriched for genes related to nervous and reproductive systems development. ACEs may affect the next generation through maternal mental health, infant attachment, and DNAm. Data were analyzed from 67 women in Buenos Aires, Argentina and a subsample of 24 for DNAm data. DNAm was analyzed using Illumina EPIC microarray. Regression analyses were used to assess the associations between maternal ACEs and infant attachment, prenatal depression and anxiety, and DNAm age. ANCOVA assessed differential methylation in co-methylated regions (CMRs) between ACE+ and ACE- dyads. Genes associated with CMRs with unadjusted p-values below 0.05 were used for gene set enrichment analysis and functional annotation using ShinyGO.