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REVIEW ARTICLE

From decidua to brain: Immune pathways linking maternal infections to neurodevelopmental disorders in offspring

Liesl Strydom1,2 ,  Khethelo R. Xulu1 ,  Michael Z. Zulu2,3*
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1 School of Molecular & Cell Biology, Faculty of Science, University of the Witwatersrand, Johannesburg , South Africa
2 Division of Virology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg , South Africa
3 Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town , South Africa
JCTR, 026320084 https://doi.org/10.36922/JCTR026320084
Received: 6 August 2026 | Revised: 24 August 2026 | Accepted: 4 September 2026 | Published online: 8 October 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Background: The decidua, a specialised endometrial tissue formed during pregnancy, balances maternal tolerance to the semi-allogeneic fetus with defence against pathogens; maternal infections disrupt this environment, triggering maternal immune activation, placental dysfunction, and adverse fetal neurodevelopment. Aim: To compare how human immunodeficiency virus (HIV), Zika virus, and cytomegalovirus (CMV) dysregulate the decidual microenvironment and how these disruptions contribute to adverse neurodevelopmental outcomes in offspring. Methods: A narrative review of the published literature was conducted, synthesising evidence on pathogen-specific effects on decidual immune regulation, maternal immune activation, placental dysfunction, epigenetic modifications, and neurodevelopmental outcomes. Results: HIV predominantly induces chronic systemic inflammation and placental insufficiency; Zika virus directly infects decidual and placental cells to breach the maternal–fetal barrier; and CMV exerts combined cytopathic and inflammatory effects. Despite distinct mechanisms, all three pathogens disrupt the decidual microenvironment and converge on epigenetic reprogramming as a shared molecular pathway linking prenatal immune challenge to persistent neurodevelopmental impairment. Conclusion: Comparative evaluation of pathogen-specific mechanisms clarifies how maternal infections influence fetal neurodevelopment and highlights shared and divergent targets for future preventive and therapeutic strategies. Relevance for patients: These findings may support earlier prenatal screening, informed clinical management of at-risk pregnancies, and interventions to reduce long-term neurodevelopmental disorders in exposed children.

Keywords
Decidua
Maternal–fetal interface
Human immunodeficiency virus
Zika virus
Cytomegalovirus
Neurodevelopment
Epigenetics
Funding
M.Z.Z. is supported by the South African Medical Research Council (SAMRC) through its Division of Research Capacity Development under the Research Capacity Development Initiative from funding received from the South African National Treasury. The content and findings reported/illustrated are the sole deduction, view and responsibility of the researcher and do not reflect the official position and sentiments of the SAMRC.
Conflict of interest
The authors declare they have no competing interests.
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Journal of Clinical and Translational Research, Electronic ISSN: 2424-810X Print ISSN: 2382-6533, Published by AccScience Publishing
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