Maternal Exposure to Childhood Adversity and Infant Epigenetic Age Acceleration: Moderation by Mother’s Restless Sleep

• In Event: Parent and Child Sleep in the Context of Family Adversity

Abstract

Extant evidence supports the notion that offspring are affected by parental exposure to adversity and trauma occurring before birth, and possibly even prior to conception (Yehuda & Lehner, 2018). Indeed, maternal exposure to adverse childhood experiences (ACEs) has been linked to pregnancy complications and poorer infant health (Racine et al., 2018). Epigenetic alterations are one potential mechanism through which maternal psychosocial stressors may influence phenotypic variation in health and developmental outcomes in infants. Epigenetic age acceleration, which reflects the difference between chronological age and biological age, has been linked to maternal stress exposure and may serve as a biomarker of altered development (Appleton et al., 2022). However, it remains unclear which factors exacerbate the association between maternal stress and infant biological aging, and whether this accelerated aging is harmful in infancy (McEwen et al., 2019). Sleep is one factor that, during pregnancy, influences fetal outcomes (Lu et al., 2021), though its association with epigenetic aging remains unknown. The goal of this study was to examine whether mother’s self-reported restless sleep during pregnancy moderates the association between exposure to childhood adversity and infant epigenetic age acceleration.

Data were obtained from a prospective cohort study of pregnant women and their infants. Mothers (n = 338; Mage at delivery = 29.8; 40% Black; 25% Hispanic ethnicity) self-reported their exposure to childhood adversity and restless sleep during pregnancy during the 2nd trimester. Adverse childhood experiences were assessed using the 10-item measure from the CDC-Kaiser ACE Study. Restless sleep was assessed from a single item from the Center for Epidemiologic Studies Depression Scale, reflecting sleep in the past week. DNA methylation data were obtained from human umbilical vein endothelial cells and processed on the Illumina EPIC array. Four epigenetic clocks were created: PedBE (McEwen et al., 2019), Bohlin (Bohlin et al., 2016), Knight (Knight et al., 2016), and EPIC (Haftorn et al., 2021). Multivariate linear regression was used to test the study hypothesis with each clock, adjusting for study cohort, maternal race, ethnicity, body mass index, and tobacco use during pregnancy (four total models).

There was evidence to suggest restless sleep moderates the association between maternal exposure to childhood adversity and infant epigenetic age acceleration, measured using the EPIC clock (p = 0.04; Figure 1). Specifically, infants of mothers reporting neither childhood adversity nor restless sleep had faster epigenetic age acceleration compared to infants of mothers reporting no adversity but restless sleep. Similarly, infants of mothers reporting adversity and restless sleep had faster epigenetic age acceleration compared to infants of mothers reporting adversity and no restless sleep. There was no evidence to suggest main effects or interactions of ACEs or restless sleep in the other models.

Findings highlight possible trans/intergenerational impact of adversity and sleep; however, epigenetic age acceleration may not always be harmful in infancy. That is, our results may reflect an example of the integration between the differential susceptibility and developmental mismatch hypotheses (Hoogland & Ploeger, 2022), whereby age acceleration due to an environmental match (positive or negative) may reflect adaptive changes.

Authors

• David W Sosnowski, Johns Hopkins University
  Presenting Author

• Gang Peng

• Cathrine Hoyo

• Susan K Murphy

• Joan Kaufman

• Sara B Johnson