Investigating adverse intergenerational effects of prenatal maternal psychological distress through infant gene expression profiles

Chalumbila, Tsaone

Investigating adverse intergenerational effects of prenatal maternal psychological distress through infant gene expression profiles

Thesis / Dissertation

2026

Publisher

Unversity of Cape Town

Department

Department of Psychiatry and Mental Health

Faculty

Faculty of Health Sciences

Abstract

Introduction: Maternal psychological distress is prevalent during pregnancy and may contribute to adverse child developmental outcomes. However, the molecular mechanisms underlying these intergenerational effects have not been fully elucidated. This project aimed to investigate these intergenerational mechanisms through newborn messenger RNA (mRNA) and microRNA expression profiles, utilising data from the Drakenstein Child Health Study (DCHS), a South African birth cohort study. Methods: Two systematic reviews and three empirical aims (nested within the DCHS) were undertaken. The systematic reviews investigated the associations between prenatal maternal psychological distress and (a) child developmental outcomes and (b) newborn transcriptomic signatures, respectively. In the DCHS, the Self-Reporting Questionnaire 20 (SRQ-20) was used to assess prenatal maternal psychological distress, and the Bayley Scales of Infant and Toddler Development (Third Edition) to evaluate toddler development at age 24 months. Total RNA sequencing profiles were generated from cord blood of the index newborns; and the Limma Voom R-package was used to identify differentially expressed genes and microRNAs between newborns exposed to prenatal maternal psychological distress versus unexposed newborns. A gene set enrichment analysis was undertaken to identify significantly enriched pathways. Regression analyses were then used to investigate associations between differentially expressed RNAs and child developmental outcomes. All analyses were controlled for potential confounding variables and multiple testing correction was applied. Results. Findings from the two systematic reviews suggest that prenatal maternal psychological distress may be associated with altered expression of genes associated with glucocorticoid and serotonin signalling, placental growth and immune response; and adverse motor, adaptive and social-emotional development in the index children, respectively. In the DCHS, prenatal maternal psychological distress was not significantly associated with differential gene or microRNA expression in the exposed versus unexposed newborns. However, prenatal maternal psychological distress was associated with transcriptomic differences in gene set pathways - associated with cell cycle progression, immune response and haem metabolism in the cord blood of exposed versus unexposed newborns. Conclusion. This project yielded novel, albeit preliminary findings that child transcriptomic pathways may constitute one of the molecular mechanisms underlying the adverse intergenerational effects of prenatal maternal psychological distress in a South African birth cohort.

Keywords

maternal psychological distress

Reference:

Collections

PhD / Doctoral

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