Mother's childhood adversity is associated with accelerated epigenetic aging in pregnancy and in male newborns.

Background: Adverse childhood experiences (ACEs) are correlated with accelerated epigenetic aging, but it is not clear whether altered epigenetic aging from childhood adversities persists into adulthood and can be transmitted to the next generation. Thus, we tested whether mothers' childhood adversity is associated with accelerated epigenetic aging during pregnancy and in their newborn offspring.

Methods: Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC) sub-study, Accessible Resource for Integrated Epigenomic Studies (ARIES). Women provided retrospective self-reports during pregnancy of ACE exposure. DNA methylation was measured in mothers during pregnancy and cord blood at birth. Estimates of epigenetic age acceleration were calculated using Principal Components of Horvath, Hannum skin & blood, GrimAge, PhenoAge, and DunedinPACE epigenetic clocks for mothers; and the Knight and Bohlin cord blood clocks for newborns. Associations between a cumulative maternal ACE score and epigenetic age acceleration were estimated using linear regression models, adjusting for maternal age at pregnancy, smoking during pregnancy, education, and pre-pregnancy BMI. Models for offspring were stratified by sex and additionally adjusted for gestation age.

Results: Mothers' total ACE score was positively associated with accelerated maternal PhenoAge and GrimAge. In newborn offspring, mothers' total ACE score was positively associated with accelerated epigenetic aging in males using the Bohlin clock, but not in females using either epigenetic clock. We found male offsprings' epigenetic age was accelerated in those born to mothers exposed to neglect using the Knight clock; and parental substance abuse using the Bohlin clock.

Conclusion: Our results show that mothers' ACE exposure is associated with DNAm age acceleration in male offspring, supporting the notion that DNAm age could be a marker of intergenerational biological embedding of mothers' childhood adversity. This is consistent with findings on vulnerability of male fetuses to environmental insults.