Study suggests maternal adverse childhood experiences may become biologically embedded

By Pooja Toshniwal PahariaReviewed by Danielle Ellis, B.Sc.Aug 13 2024

In a recent study published in JAMA Network Open, researchers investigated the relationship between maternal traumatic childhood experiences and epigenetic age acceleration throughout pregnancy and among infants. They also determined whether depression mediated these correlations.

Background

Studies associated traumatic experiences during childhood and epigenetic aging in later life, which might be passed down through generations. These events raise the chance of poor mental and physical health during pregnancy, as well as adverse effects on child development, behavior, and health. Accumulation of adverse childhood experiences (ACEs) is associated with higher sadness and worse health outcomes in mothers and babies.

Studies reveal that maternal ACEs cause alterations in neonatal cord blood and children's epigenetic aging. Although epigenetic clocks help us understand biological aging, limited studies have examined them across generations, including during gravidity and among babies.

About the study

The researchers analyzed data provided by the Accessible Resource for Integrated Epigenomic Studies (ARIES) study participants. The ARIES study, a subset of the Avon Longitudinal Study of Parents and Children (ALSPAC) study, included 1,018 mother-child pairs based on their deoxyribonucleic acid (DNA) sample availability in 2014. The parent ALPSAC study recruited 14,541 females delivering babies within the Avon Health region of the United Kingdom from April 1991 to December 1992.

Researchers measured DNA methylation using peripheral blood sampled from mothers during antenatal health visits and cord blood sampled at delivery for offspring. Enrolled mothers submitted ACE self-reports between weeks 18 and 32 of gestation and when their child was approximately three years old through mailed questionnaires. The researchers estimated epigenetic age by DNA methylation epigenetic clocks (such as Hannum, Horvath, PhenoAge, GrimAge, and DunedinPACE) among expecting mothers and the Bohlin and Knight umbilical cord blood-based clocks in their offspring. They analyzed data from October 2022 to November 2023.

The primary study exposure was a composite measurement of maternal adverse childhood experiences in maternal and neonatal models. ACEs included physical abuse, emotional abuse, sexual abuse, physical neglect, emotional neglect, domestic violence, loss of parents due to divorce or death, family members with addictions or mental disorders, and family member incarceration. In a secondary evaluation, researchers measured individual ACEs separately. They used the Edinburgh Postnatal Depression Scale (EPDS) to assess pregnancy depression as a study exposure.

The primary endpoint in maternal study models included epigenetic age accelerations (EAA) during gravidity, while neonatal analyses included epigenetic gestational aging accelerations (GAA) changes. The researchers used linear regressions to evaluate the relationship between maternal adverse childhood experiences and the endpoints. Study covariates included maternal age during pregnancy, parity, number of cigarettes smoked daily in the initial trimester, education, prenatal BMI, sample type, and sample cell-type composition. In addition, neonatal analyses included gestational age at delivery and neonatal sample type as covariates.

Results

In this study of 883 maternal-offspring pairs, the mean age of mothers at childbirth was 30 years, and there were 398 female (45%) and 389 male (44%) offspring. The mean gestational age of offspring at birth was 40 weeks for females and 39 weeks for male offspring. The mean maternal ACE score was 1.3; 93 women (11%) experienced at least three ACEs, of which sexual abuse was most frequent (295).

The mean EPDS score was 6.3, with 159 women (18%) scoring above 10. The mean prenatal BMI was 23. Mothers had a greater epigenetic age compared to chronological age. The mean offspring epigenetic gestational age was normal using the Knight and Bohlin clocks (39 to 40 weeks).

Expecting women with more traumatic childhood experiences showed higher GrimAge clock EAA. However, maternal traumatic childhood experiences were not related to GAA in offspring. Sensitivity analysis, excluding cell-type composition, showed similar associations between maternal ACE scores and GrimAge EAA. In male offspring, maternal exposure to any neglect, especially emotional neglect, was related to higher Knight GAA. In female offspring, the team found maternal exposure to parental domestic violence, divorce, or death associated with lower Knight GAA. The team found associations between depression and higher GrimAge-based EAA among expecting mothers but not among offspring and no influence of depression on the relationship between traumatic childhood experiences and EAA.

Conclusion

The study found that women with adverse childhood experiences had greater GrimAge EAA during pregnancy, which might be related to epigenetic aging in later adulthood. These events affect the growing fetus, underlying organs, and immune cells, influencing both development and long-term health effects. EAA during pregnancy may reflect organ system integrity and functionality, which can contribute to long-term illness vulnerability and the consequences of unfavorable exposures on future generations.