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

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.

Keywords: HIV exposure; brain development; immune marker; inflammation; magnetic resonance spectroscopy; maternal immune activation.

Figure 1.. Associations between maternal or child serum markers and child neurometabolite ratios

Scatter plots displaying statistically significant associations between maternal or child serum markers (IL-5, IL-8, IL-13, MMP-9, YKL-40) and child neurometabolite ratios to total creatine (myo-inositol, glutamate, N-acetyl-aspartate) in specific parietal brain regions, as found in adjusted linear regression analyses. Regression lines represent the direction and strength of the associations, with 95% confidence intervals shaded. Data points are colour-coded based on maternal HIV status.