Abstract :
Keywords Maternal adverse childhood experiences (maternal ACEs); Maternal distress; Infant DNA methylation; Intergenerational trauma; APrON study Highlights * Exposure to maternal adverse childhood experiences (ACEs) increase risk for mental and physical health problems * DNA methylation is an epigenetic mark that guides gene regulatory processes in early development * DNA methylation patterns in offspring have been linked to prenatal and postnatal exposures * We test for possible associations between Maternal ACEs and infant DNA methylation, and a possible in utero connection Abstract Exposure to adverse childhood experiences (ACEs) increases risk for mental and physical health problems. Intergenerationally, mothers' ACEs predict children's health problems including neurodevelopmental and behavioural problems and poorer physical health. Theories of intergenerational trauma suggest that ACEs experienced in one generation negatively affect the health and well-being of future generations, with DNA methylation (DNAm) being one of several potential biological explanations. To begin exploring this hypothesis, we tested whether infant DNA methylation associated with intergenerational trauma. Secondary analysis employed data from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Subsample data were collected from mothers during pregnancy and postpartum on measures of distress, stress and ACEs and from infants at 3 months of age on DNAm from blood (n = 92) and buccal epithelial cells (BECs; n = 124; primarily nonoverlapping individuals between tissues). Blood and BECs were examined in separate analyses. Preliminary associations identified in blood and BECs suggest that infant DNAm patterns may relate to maternal ACEs. For the majority of ACE-related DNAm sites, neither maternal perinatal distress, nor maternal cortisol awakening response (CAR; a measure of hypothalamic-pituitary-adrenocortical axis function), substantially reduced associations between maternal ACEs and infant DNAm. However, accounting for maternal perinatal distress and cortisol substantially changed the effect of ACEs in a greater proportion of blood DNAm sites than BEC DNAm sites in the top ACEs-associated correlated methylated regions (CMRs), as well as across all CMRs and all remaining CpGs (that did not fall into CMRs). Possible DNAm patterns in infants, thus, might capture a signature of maternal intergenerational trauma, and this effect appears to be more dependent on maternal perinatal distress and CAR in blood relative to BECs. Author Affiliation: (a) BC Children's Hospital Research Institute and Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada (b) Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada (c) Department of Pediatrics & Owerko Centre at the Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada (d) Faculty of Nursing, University of Calgary, Calgary, Alberta, Canada (e) Department of Psychiatry and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada * Corresponding author at: Owerko Centre at the Alberta Children's Hospital Research Institute, Child Development Centre, 3rd Floor, 3820 24 Avenue NW, University of Calgary, Calgary T2N 1N4, Alberta, Canada. Article History: Received 7 April 2021; Revised 18 October 2021; Accepted 24 November 2021 Byline: Sarah R. Moore (a), Sarah M. Merrill (a), Bikram Sekhon (b), Julia L. MacIsaac (a), Michael S. Kobor (a), Gerald F. Giesbrecht (b,c), Nicole Letourneau [nicole.letourneau@ucalgary.ca] (b,c,d,e,*)