Maternal adverse childhood experiences (ACEs) and DNA methylation of newborns in cord blood

Abstract

Background Adverse childhood experiences (ACEs) increase the risk of poor health outcomes later in life. Psychosocial stressors may also have intergenerational health effects by which parental ACEs are associated with mental and physical health of children. Epigenetic programming may be one mechanism linking parental ACEs to child health. This study aimed to investigate epigenome-wide associations of maternal preconception ACEs with DNA methylation patterns of children. In the Center for the Health Assessment of Mothers and Children of Salinas study, cord blood DNA methylation was measured using the Illumina HumanMethylation450 BeadChip. Preconception ACEs, which occurred during the mothers’ childhoods, were collected using a standard ACE questionnaire including 10 ACE indicators. Maternal ACE exposures were defined in this study as (1) the total number of ACEs; (2) the total number of ACEs categorized as 0, 1–3, and > 4; and (3) individual ACEs. Associations of ACE exposures with differential methylated positions, regions, and CpG modules determined using weighted gene co-expression network analysis were evaluated adjusting for covariates. Results Data on maternal ACEs and cord blood DNA methylation were available for 196 mother/newborn pairs. One differential methylated position was associated with maternal experience of emotional abuse (cg05486260/FAM135B gene; q value < 0.05). Five differential methylated regions were significantly associated with the total number of ACEs, and 36 unique differential methylated regions were associated with individual ACEs (Šidák p value < 0.05). Fifteen CpG modules were significantly correlated with the total number of ACEs or individual ACEs, of which 8 remained significant in fully adjusted models (p value < 0.05). Significant modules were enriched for pathways related to neurological and immune development and function. Conclusions Maternal ACEs prior to conception were associated with cord blood DNA methylation of offspring at birth. Although there was limited overlap between differential methylated regions and CpGs in modules associated with ACE exposures, statistically significant regions and networks were related to genes involved in neurological and immune function. Findings may provide insights to pathways linking psychosocial stressors to health. Further research is needed to understand the relationship between changes in DNA methylation and child health.

Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence

“…We must also acknowledge limitations of our study. First, we did not measure certain factors that have been associated with methylation of specific loci in cord blood cells and, therefore, could potentially influence our results, such as maternal exposure to environmental endocrine disruptors [ 68 ] and green space [ 40 ] during pregnancy or maternal adverse childhood experiences [ 69 ]. We excluded women with clinical depression, but attention should be also paid to maternal depressed mood during pregnancy [ 39 ].…”

Impact of sex, race, and social determinants of health on neonatal outcomes

“…In one report, mothers exposed to 4 or more ACEs had a 3.74 times risk for low birth weight (0.050 vs. 0.187) and a 1.74 times greater risk for prematurity (0.085 vs. 0.148) than those whose mothers reported no ACE exposure ( 216 ). The biological basis for adverse early childhood events leading to adverse maternal and fetal outcomes later in life may be explained by epigenetic changes and DNA methylation ( 217 ). Social inclusion and non-discrimination …”

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

“…19,20 Multiple studies have reported that ACEs are associated with advanced epigenetic aging. [21][22][23][24][25][26] In previous studies, investigators found that maternal ACEs were associated with epigenome-wide changes in DNA methylation in newborn cord blood 27,28 and in epigenetic aging changes in children. 29 Evidence suggests that altered epigenetic aging can be programmed early in development, 30 even in utero, increasing disease risk over a person's lifespan.…”