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. 2024 Aug 1;7(8):e2427063.
doi: 10.1001/jamanetworkopen.2024.27063.

Maternal Adverse Childhood Experiences and Biological Aging During Pregnancy and in Newborns

Christian K Dye  1 , Daniel M Alschuler  2 , Haotian Wu  1 , Cristiane Duarte  3 , Catherine Monk  2   3   4 , Daniel W Belsky  5 , Seonjoo Lee  2   6 , Kieran O'Donnell  7 , Andrea A Baccarelli  1 , Pamela Scorza  4
Affiliations

Maternal Adverse Childhood Experiences and Biological Aging During Pregnancy and in Newborns

Christian K Dye et al. JAMA Netw Open. .

Abstract

Importance: Adverse childhood experiences (ACEs), potentially traumatic experiences occurring before the age of 18 years, are associated with epigenetic aging later in life and may be transmitted across generations.

Objective: To test evidence of the transmission of biological embedding of life experience across generations by analyzing maternal ACEs and epigenetic clocks measured in mothers during pregnancy and in their children at birth.

Design, setting, and participants: For this cross-sectional study, data from the Accessible Resource for Integrated Epigenomic Studies (ARIES) substudy of the Avon Longitudinal Study of Parents and Children (ALSPAC) were analyzed. The ALSPAC study recruited 14 541 women who gave birth in the Avon Health District in the UK between April 1, 1991, and December 31, 1992. The ARIES substudy comprised 1018 mother-offspring dyads based on the availability of DNA samples profiled in 2014. Epigenetic age was estimated using DNA methylation-based epigenetic clocks (including Horvath, Hannum, GrimAge, PhenoAge, and DunedinPACE) in mothers during pregnancy and the Knight and Bohlin cord blood epigenetic clocks in newborns. Analyses were performed between October 1, 2022, and November 30, 2023.

Exposures: A composite measure of maternal ACEs was the primary exposure in both maternal and offspring models; as a secondary analysis, individual ACEs were measured separately. The Edinburgh Postnatal Depression Scale (EPDS) was used to investigate depression during pregnancy as an exposure.

Main outcomes and measures: Changes in epigenetic age acceleration (EAA) were investigated as the primary outcome in maternal models during pregnancy. Changes in epigenetic gestational age acceleration (GAA) were the primary outcome in offspring analyses. Linear regression analyses were used to determine the association between maternal ACEs and both outcomes.

Results: This study included 883 mother-child dyads. The mean (SD) maternal age at delivery was 29.8 (4.3) years. Pregnant women with higher ACE scores exhibited higher GrimAge EAA (β, 0.22 [95% CI, 0.12 to 0.33] years; P < .001). Maternal ACEs were not associated with GAA in newborns using P < .05 as a cutoff to determine statistical significance. Depression was associated with higher GrimAge EAA (β, 0.06 [95% CI, 0.02 to 0.10] years; P = .01) in mothers during pregnancy, but not in newborns, and did not mediate the association between ACEs and EAA.

Conclusions and relevance: The findings of this study suggest that maternal ACEs may be associated with epigenetic aging later in life, including during pregnancy, supporting a role for maternal ACEs in offspring development and health later in life.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Belsky reported receiving consulting fees from BellSant and personal fees from Hooke outside the submitted work. Dr Belsky also reported holding a patent for the DunedinPACE epigenetic clock, which is licensed by Duke University and the University of Otago to the company TruDiagnostic, and receiving royalties from TruDiagnostic. Dr Duarte reported receiving grants from the National Institutes of Health during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association Between Maternal Adverse Childhood Experiences and Epigenetic Age Acceleration (EAA) in Pregnant Women
Effect size estimates (in years [95% CIs]) for change in epigenetic age in prenatal blood from pregnant women, calculated using 5 DNA methylation clocks: Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE. Results are adjusted for maternal sample type (white blood cell, whole blood), maternal age during pregnancy, parity, number of cigarettes smoked during the first trimester, maternal education, prenatal body mass index (calculated as weight in kilograms divided by height in meters squared), and maternal sample cell-type composition (CD4+ T cells, CD8+ T cells, natural killer cells, B cells, monocytes, and neutrophils). aP < .01. bP < .001. cP < .05.
Figure 2.
Figure 2.. Association Between Maternal Adverse Childhood Experiences and Epigenetic Gestational Age Acceleration (GAA) in Newborns
Effect sizes (in weeks [95% CIs]) for the change in epigenetic gestational age in cord blood collected from newborns, calculated using 2 clocks: Knight (left) and Bohlin (right). Results are adjusted for maternal age during pregnancy, parity, number of cigarettes smoked during the first trimester, maternal education, prenatal body mass index (calculated as weight in kilograms divided by height in meters squared), gestational age at birth, and newborn sample type (white blood cells, blood spot). Color schemes represent statistical significance (P < .05).
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