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

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.