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Abstract
Accelerated epigenetic aging relative to chronological age has been found to be associated with higher risk of mortality in adults. However, little is known about whether and how in utero exposures might shape child gestational epigenetic age (EA) at birth. We aimed to explore associations between maternal psychosocial risk factors and deviation in child gestational EA at birth (i.e., greater or lower EA relative to chronological age) in a South African birth cohort study—the Drakenstein Child Health Study. Maternal psychosocial risk factors included trauma/stressor exposure; posttraumatic stress disorder (PTSD); depression; psychological distress; and alcohol/tobacco use. Child gestational EA at birth was calculated using an epigenetic clock previously devised for neonates; and gestational EA deviation was calculated as the residuals of the linear model between EA and chronological gestational age. Bivariate linear regression was then used to explore unadjusted associations between maternal/child risk factors and child gestational EA residuals at birth. Thereafter, a multivariable regression method was used to determine adjusted associations. Data from 271 maternal-child dyads were included in the current analysis. In the multivariable regression model, maternal PTSD was significantly and negatively associated with child gestational EA residuals at birth (β = −1.95; p = 0.018), controlling for study site, sex of the child, head circumference at birth, birthweight, mode of delivery, maternal estimated household income, body mass index (BMI) at enrolment, HIV status, anaemia, psychological distress, and prenatal tobacco or alcohol use. Given the novelty of this preliminary finding, and its potential translational relevance, further studies to delineate underlying biological pathways and to explore clinical implications of EA deviation are warranted.
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1 University of Cape Town, Department of Psychiatry and Mental Health, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151); South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, Cape Town, South Africa (GRID:grid.415021.3) (ISNI:0000 0000 9155 0024); University of Cape Town, Neuroscience Institute, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151)
2 University of Manitoba, Children’s Hospital Research Institute of Manitoba, Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, Winnipeg, Canada (GRID:grid.21613.37) (ISNI:0000 0004 1936 9609)
3 University of Cape Town, Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151); University of Cape Town, Division of Epidemiology and Biostatistics, School of Public Health and Family Medicine, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151)
4 University of Cape Town, Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151)
5 University of Cape Town, Neuroscience Institute, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151); University of Cape Town, Division of Developmental Paediatrics, Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151)
6 University of Cape Town, Department of Paediatrics & Child Health and SAMRC Unit on Child and Adolescent Health, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151)
7 University of Cape Town, Department of Psychiatry and Mental Health, Cape Town, South Africa (GRID:grid.7836.a) (ISNI:0000 0004 1937 1151)
8 University of British Columbia, Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830)
9 University of British Columbia, Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute, Vancouver, Canada (GRID:grid.17091.3e) (ISNI:0000 0001 2288 9830); BC Children’s Hospital Research Institute, Vancouver, Canada (GRID:grid.414137.4) (ISNI:0000 0001 0684 7788); Canadian Institute for Advanced Research, Toronto, Canada (GRID:grid.440050.5) (ISNI:0000 0004 0408 2525)
10 Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Massachusetts General Hospital, Psychiatric and Neurodevelopmental Genetics Unit and Department of Psychiatry, Boston, USA (GRID:grid.32224.35) (ISNI:0000 0004 0386 9924)