The association of maternal psychological distress with child neurodevelopment and mental health: an epigenetic perspective

van der Westhuizen, Mia

The association of maternal psychological distress with child neurodevelopment and mental health: an epigenetic perspective

Thesis / Dissertation

2026

Publisher

University of Cape Town

Department

Department of Psychiatry and Mental Health

Faculty

Faculty of Health Sciences

Abstract

Background Maternal psychological distress during the perinatal period has been associated with adverse child neurodevelopmental and mental health outcomes. However, evidence from low- and middle-income countries (LMICs), including South Africa, remains limited. DNA methylation (DNAm) has been proposed as a biological mechanism through which maternal distress may influence child outcomes. This thesis aimed to investigate these associations through: (1) a systematic review, and (2) secondary analyses of data from the Drakenstein Child Health Study (DCHS), an ongoing South African birth cohort. Methods The systematic review, registered on PROSPERO (CRD42024512131), followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Within the DCHS, prenatal maternal psychological distress was assessed using the Self-Reporting Questionnaire (SRQ-20). Newborn DNAm was profiled using either the Illumina Infinium MethylationEPIC BeadChip (n = 143) or the HumanMethylation450 BeadChip (n = 102). Child neurodevelopment (cognitive, language, and motor domains) was assessed at ages 24 and 42 months using the Bayley Scales of Infant and Toddler Development (3rd edition), and mental health at 42 months using the Child Behavior Checklist. Associations between maternal psychological distress and DNAm were examined in an epigenome-wide association study (EWAS) of 245 mother-child dyads, followed by mediation analyses to explore potential associations with child outcomes. Analyses were adjusted for relevant covariates, with Bonferroni correction applied for multiple testing. Results The systematic review of seven studies suggested that maternal psychological distress is associated with differential DNAm in genes related to stress regulation, immunity, metabolism, and neurogenesis. These DNAm changes were also associated with subsequent adverse child mental health outcomes. In the DCHS, the EWAS identified nine differentially methylated CpG sites and two differentially methylated regions, annotating to genes previously implicated in nervous system development, immunity, DNA repair, and mood disorders. Although maternal psychological distress was associated with poor language development at 24 months, DNAm at the identified CpG sites did not mediate this relationship. Maternal distress was not associated with child mental health outcomes, precluding further mediation analyses. Conclusion While these findings suggest that maternal psychological distress may alter DNAm in children, further research is needed to clarify biological mechanisms, identify mediating pathways, and explore long-term developmental implications.