# 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

## TL;DR

This study finds that maternal and child immune profiles are linked to brain chemistry in HIV-exposed but uninfected children, suggesting early-life neuroinflammation may affect development.

## Contribution

The study identifies novel associations between maternal immune markers and neurometabolite profiles in HIV-exposed uninfected children.

## Key findings

- Maternal IL-5 and IL-8 are associated with myo-inositol ratios in HEU children's brain regions.
- Child MMP-9 at two years correlates with myo-inositol in midline parietal grey matter.
- Maternal IL-13 shows opposite associations with glutamate ratios in HEU and HU children.

## 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.