Abstract
HIV-exposed uninfected (HEU) children may have altered immune regulation and poorer neurodevelopment outcomes compared to their HIV-unexposed (HU) counterparts. However, studies investigating the association of maternal and infant inflammation with neurodevelopment in HEU children are limited and longitudinal data are lacking. This study investigated serum inflammatory markers in women living with HIV vs. HIV-uninfected women during pregnancy and in their children, as well as associations with neurodevelopmental outcomes at two years of age in an African birth cohort study. A sub-group of mother–child dyads from the Drakenstein Child Health Study had serum inflammatory markers measured at ≈26 week’s gestation (n = 77 HIV-infected mothers; n = 190 HIV-uninfected mothers), at 6–10 weeks (n = 63 HEU infants and n = 159 HU infants) and at 24–28 months (n = 77 HEU children and n = 190 HU children). Serum inflammatory markers [granulocyte–macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ), interleukin IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor-α (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL) and metalloproteinase-9 (MMP-9)] were analyzed with a multiplex bead array and ELISA assays. The Bayley Scales of Infant and Toddler Development, third edition, was used to assess neurodevelopment at 24–28 months. After correcting for multiple comparisons, HIV infection during pregnancy was associated with lower serum levels of inflammatory markers in mothers at 26 weeks gestation (GM-CSF and MMP-9, p < 0.05) and HEU children at 6–10 weeks (IFN-γ and IL-1β, p < 0.01), and at 24–28 months (IFN-γ, IL-1β, IL-2 and IL-4, p < 0.05) compared to HIV-uninfected mothers and HU children. In HEU infants at 6–10 weeks, inflammatory markers (GM-CSF, IFN-γ, IL-10, IL-12p70, IL-1β, IL-2, IL-4, IL-6 and NGAL, all p < 0.05) were associated with poorer motor function at two years of age. This is the first study to evaluate the associations of follow-up immune markers in HEU children with neurodevelopment. These findings suggest that maternal HIV infection is associated with immune dysregulation in mothers and their children through two years of age. An altered immune system in HEU infants is associated with poorer follow-up motor neurodevelopment. These data highlight the important role of the immune system in early neurodevelopment and provide a foundation for future research.
Highlights
Maternal Human Immunodeficiency Virus (HIV) infection affects maternal physiology and may have far-reaching consequences for the development of the exposed fetus and child
There were significantly more women living with HIV from Mbekweni compared to TC Newman clinic (p < 0.001) as well as more mothers living with HIV with moderate-severe alcohol exposure compared to HIV-uninfected mothers (p = 0.032)
Key findings were that maternal HIV infection was associated with decreased levels of inflammatory markers in pregnant women and in their children at 6–10 weeks and 24–28 months; there was a significant association between inflammatory markers in HIV-exposed uninfected (HEU) infants at 6–10 weeks and poorer motor development at 24–28 months
Summary
Maternal Human Immunodeficiency Virus (HIV) infection affects maternal physiology and may have far-reaching consequences for the development of the exposed fetus and child. With wider access to antiretroviral therapy (ART) to prevent transmission of HIV from mother to child, the number of HIV-exposed uninfected (HEU) children is increasing. This is relevant in South Africa, where the mother-to-child transmission rate dropped to < 5% in 2018, resulting in a current HEU child population of 3 500 000 (UNAIDS, 2019). Previous reports suggest that HIV impacts the maternal immune system by creating a pro-inflammatory environment, which is characterized predominantly by increased levels of certain cytokines, such as interleukin (IL-1, IL-6) and tumor necrosis factor-α (TNF-α) (Faye et al, 2007; Richardson and Weinberg, 2011; Sachdeva et al, 2008). Results on HEU children inflammatory profiles are inconsistent, with evidence for both increased levels (Dirajlal-Fargo et al, 2019; Miyamoto et al, 2017; Prendergast et al, 2017) as well as reduced levels of cytokines in HEU children (Borges-Almeida et al, 2011; Chougnet et al, 2000)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
