Study 3: Impact of perinatal HIV exposure on neuroimmune development from birth to 6–7 years: associations with neurodevelopment in a South African birth cohort

This third study will test how perinatal HIV exposure shapes neuroimmune development from early infancy to school entry, and whether longitudinal neurometabolite measurements in the developing brain associate with school readiness in the Drakenstein Child Health Study cohort. Using repeated parietal MR spectroscopy assessments at 6–10 weeks, 2–3 years, and 6–7 years, we will model child-specific neurometabolite trajectories of glutamate, myo-inositol, choline, and N-acetyl-aspartate ratios to creatine, and examine whether these trajectories predict school readiness scores at 6–7 years, with effect modification by maternal HIV status. We will also evaluate whether maternal immune marker levels in pregnancy and child immune marker trajectories from 6 weeks to 5 years predict neurometabolite trajectories and mediate pathways linking maternal HIV status, neurometabolite development, and school readiness. Finally, we will assess whether child hospitalisations are associated with neurometabolite trajectories and modify key neuroimmune–neurodevelopment relationships.