Abstract #2256

Maternal immune activation is associated with neuroinflammation in children who are HIV-exposed and uninfected: a South African birth cohort

Cesc Bertran Cobo^1,2, Frances C Robertson^1,3,4, Tusekile S Kangwa^1,2, Jenna Annandale^1,2, Sivenesi Subramoney⁵, Katherine L Narr⁶, Shantanu H Joshi⁶, Nadia Hoffman², Heather J Zar^5,7, Dan J Stein^1,2,8, Kirsten A Donald^1,5, Catherine J Wedderburn^1,5,9, and Petrus J W Naudé^1,2

¹Neuroscience Institute, University of Cape Town, Cape Town, South Africa, ²Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa, ³Department of Human Biology, University of Cape Town, Cape Town, South Africa, ⁴Cape Universities Body Imaging Centre (CUBIC), Cape Town, South Africa, ⁵Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital, University of Cape Town, Cape Town, South Africa, ⁶Departments of Neurology, Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, United States, ⁷SAMRC Unit on Child & Adolescent Health, University of Cape Town, Cape Town, South Africa, ⁸SAMRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa, ⁹Department of Clinical Research, London School of Hygiene and Tropical Medicine, Cape Town, South Africa

Synopsis

Keywords: Neuro, Spectroscopy, Neuroinflammation, Biomarker, Data Analysis

Motivation: Neurodevelopmental risks faced by children who are HIV-exposed and uninfected (CHEU) may be caused by inflammatory intrauterine conditions. The pathways linking maternal immune activation to early brain development remain unclear.

Goal(s): To investigate the effect of maternal HIV on CHEU neurometabolic development and identify immune markers associated with early-life neuroinflammation in a South African birth cohort.

Approach: Maternal and child immune profiles were longitudinally analysed alongside cross-sectional MRS data from parietal brain regions to explore associations with child neurometabolites.

Results: Maternal markers IL-5, IL-8, IL-13, and MMP-9 were associated with neurometabolite ratios indicative of neuroinflammation (myo-inositol) and altered neuronal health (glutamate) in CHEU.

Impact: This study elucidates novel immunological pathways through which maternal HIV infection may influence neurometabolic development in children, underscoring the potential for future research on prognostic tools and early interventions to mitigate neurodevelopmental risks in HIV-exposed uninfected children.

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