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

dc.contributor.advisorKoen, Nastassja
dc.contributor.advisorStein, Dan
dc.contributor.advisorWingo, Aliza
dc.contributor.authorChalumbila, Tsaone
dc.date.accessioned2026-07-03T10:04:03Z
dc.date.available2026-07-03T10:04:03Z
dc.date.issued2026
dc.date.updated2026-07-03T09:57:45Z
dc.description.abstractIntroduction: 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.
dc.identifier.apacitationChalumbila, T. (2026). <i>Investigating adverse intergenerational effects of prenatal maternal psychological distress through infant gene expression profiles</i>. (). Unversity of Cape Town ,Faculty of Health Sciences ,Department of Psychiatry and Mental Health. Retrieved from http://hdl.handle.net/11427/43463en_ZA
dc.identifier.chicagocitationChalumbila, Tsaone. <i>"Investigating adverse intergenerational effects of prenatal maternal psychological distress through infant gene expression profiles."</i> ., Unversity of Cape Town ,Faculty of Health Sciences ,Department of Psychiatry and Mental Health, 2026. http://hdl.handle.net/11427/43463en_ZA
dc.identifier.citationChalumbila, T. 2026. Investigating adverse intergenerational effects of prenatal maternal psychological distress through infant gene expression profiles. . Unversity of Cape Town ,Faculty of Health Sciences ,Department of Psychiatry and Mental Health. http://hdl.handle.net/11427/43463en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Chalumbila, Tsaone AB - 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. DA - 2026 DB - OpenUCT DP - University of Cape Town KW - maternal psychological distress LK - https://open.uct.ac.za PB - Unversity of Cape Town PY - 2026 T1 - Investigating adverse intergenerational effects of prenatal maternal psychological distress through infant gene expression profiles TI - Investigating adverse intergenerational effects of prenatal maternal psychological distress through infant gene expression profiles UR - http://hdl.handle.net/11427/43463 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/43463
dc.identifier.vancouvercitationChalumbila T. Investigating adverse intergenerational effects of prenatal maternal psychological distress through infant gene expression profiles. []. Unversity of Cape Town ,Faculty of Health Sciences ,Department of Psychiatry and Mental Health, 2026 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/43463en_ZA
dc.language.isoen
dc.language.rfc3066eng
dc.publisher.departmentDepartment of Psychiatry and Mental Health
dc.publisher.facultyFaculty of Health Sciences
dc.publisher.institutionUnversity of Cape Town
dc.subjectmaternal psychological distress
dc.titleInvestigating adverse intergenerational effects of prenatal maternal psychological distress through infant gene expression profiles
dc.typeThesis / Dissertation
dc.type.qualificationlevelDoctoral
dc.type.qualificationlevelPhD
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