Journal Article Preprint Epublish
PubMed: 40166324 DOI: 10.1101/2025.03.17.643628
Maternal and child immune profiles are associated with neurometabolite measures of early-life neuroinflammation in children who are HIV-exposed and uninfected: a South African birth cohort.
bioRxiv
Authors: Cesc Bertran-Cobo, Frances C Robertson, Tusekile Sarah Kangwa, Jenna Annandale, Sivenesi Subramoney, Katherine L Narr, Shantanu H Joshi, Nadia Hoffman, Heather J Zar, Dan J Stein, Kirsten A Donald, Catherine J Wedderburn, Petrus J W Naudé
Affiliations
- Department of Psychiatry and Mental Health, University of Cape Town, Cape Town, South Africa.
- Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
- Department of Human Biology, University of Cape Town, Cape Town, South Africa.
- Cape Universities Body Imaging Centre (CUBIC), Cape Town, South Africa.
- Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
- Departments of Neurology, Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, United States.
- SAMRC Unit on Child & Adolescent Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
- SAMRC Unit on Risk and Resilience in Mental Disorders, University of Cape Town, Cape Town, South Africa.
- Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Abstract
Children who are HIV-exposed and uninfected (HEU) are at risk of neurodevelopmental delays, which may be partially due to maternal immune dysregulation during pregnancy. This study investigates associations between maternal and child immune profiles and early neurometabolite profiles in HEU and HIV-unexposed (HU) children from a South African birth cohort. A subgroup of 156 children (66 HEU, 90 HU) from the Drakenstein Child Health Study underwent magnetic resonance spectroscopy at age 2-3 years, and maternal and child serum markers were measured at multiple timepoints via immunoassays. In HEU children, serum concentrations of maternal pro-inflammatory cytokines IL-5 (β=0.79, p=0.005) and IL-8 (β=0.64, p=0.02) were associated with myo-inositol ratios in parietal grey and white matter regions, respectively, while child serum MMP-9 at two years was associated with myo-inositol ratios in the midline parietal grey matter (β=1.30, p=0.03). The association of maternal anti-inflammatory cytokine IL-13 with glutamate ratios in the midline parietal grey matter was negative in HEU (β=-0.41, p=0.038) and positive in HU children (β=0.42, p<0.0001). These findings suggest maternal immune activation may affect neurometabolite profiles in HEU children.
MeSH
Cytokines, Gray Matter, Serum, Parturition, Inositol, Hiv, Child