Association between head circumference and monocyte function in neonates born to mothers with and without HIV at Kalafong Provincial Tertiary Hospital

Abstract

Current data show that an increasing number of women of reproductive age are living with the human immunodeficiency virus (HIV), particularly in Southern Africa. While antiretroviral therapy (ART) reduces the risk of perinatal transmission of HIV from a mother to her child, this in turn leads to more babies being born exposed to HIV and ART. This presents a stark problem as research suggests that mere exposure to HIV, even if the baby is HIV negative, may be linked to increased rates of suboptimal development, as well as increased morbidity and mortality. For these reasons, it is imperative that our understanding of the subsequent development of children born with exposure to HIV and ART is improved. Research suggests that children living with HIV, when compared to children not living with HIV, tend to underperform on general cognitive tests, processing speed, and visual-spatial tasks and also tend to show increased risk of developing psychiatric and mental health-related issues. This is a cause for concern as these children approach school-going age and will be expected to successfully integrate into an education environment. This is a particular concern in South Africa, where up to 30% of children born are HIV-exposed-uninfected (HEU). The role of monocytes and macrophages in the early development of the human brain is an ever-growing field of research. Classically activated macrophages, derived from circulating monocytes, are known to exert neurotoxic effects and, as such, an imbalance of presenting macrophage phenotypes has been associated with a variety of inflammatory conditions. This balance is essential as microglia, in the standard context, contribute to tissue remodelling, repair, and neurogenesis. Less is known about monocyte function and the effect different functional phenotypes might have on the developing brain. The aim of this study was therefore to assess the association between monocyte function and early-life brain development, as reflected by the head circumference (HC). The results of this study were generated and assessed through two main methods: anthropometric measures and cytokine levels before and after whole blood stimulation (WBS). No differences were observed for HC. However, for the other anthropometric measurements, although no statistically significant differences were observed at birth, notable differences emerged at the 6-month and 12-month time-points. HEU infants were significantly smaller at 12 months of age, showing less optimal growth progression than that of the HIV-unexposed-uninfected (HUU) group at this point. These findings indicate stunting in growth linked to HIV exposure in the HEU infants. When the cytokine data were considered, the HEU group were more likely to over-express pro-inflammatory cytokines before and after WBS and, notably, under-express anti-inflammatory cytokines. This observation could be as a result of their pre-birth exposure to an inflammatory intra-uterine environment. Significant positive correlations were observed between HC and the monocyte growth factor, granulocyte monocyte colony stimulating factor (GM-CSF) after stimulation with lipopolysaccharide at birth, as well as tumour necrosis factor-alpha (TNF-α) after stimulation with Polyinosinic:polycytidylic acid at birth. Monocytes are the most important source of TNF-α in humans. Although not providing direct evidence, the positive correlation between these factors and HC indirectly supports the hypothesis that monocytes are important players in brain development.