Introduction

Over 1 million children are born to mothers living with HIV every year, and in some countries, more than 1 in 5 children have HIV exposure. Thanks to antiretroviral medications there have been huge successes in preventing transmission of HIV, meaning that most of these children will remain HIV-free. However, although these children do not get HIV infection, being exposed to HIV in pregnancy may still increase the risk of poorer health, growth, and developmental outcomes. Evidence suggests more children with HIV exposure have delays in early language and motor function than children without HIV exposure. Brain development underpins cognitive function and advances in neuroimaging now allow us to study how HIV exposure may impact brain development. This research provides new insights into the potential effects of HIV exposure on child brain and language development. 

What inspired this study and why is it important?

Early neurodevelopment is critical to later health and societal outcomes. Worldwide, over 250 million children under five are at-risk of not reaching their developmental potential, with the highest numbers in sub-Saharan Africa. The reasons for this are varied, and include factors like infectious diseases. Given many children in this region are exposed to HIV in pregnancy, it is crucial that we study how HIV exposure affects child brain development. Understanding the effects of HIV exposure on the brain may help guide interventions that ensure children not only remain HIV-free, but also thrive, reaching their full developmental potential.

What makes this study unique?

Neuroimaging of young children is extremely challenging because it requires them to stay still for long periods of time to capture high quality clear images. Across Africa there are also very few magnetic resonance imaging (MRI) scanners and access to imaging is therefore limited. This is the first study to examine the components of cortical brain structure in children with HIV exposure in pregnancy. 

What did this study do?

The Drakenstein Child Health Study is a population-based birth cohort in the Western Cape of South Africa. In this study, we conducted MRI in natural sleep in children with HIV exposure and compared their brain structure to those without HIV exposure, and how it corresponded to language development outcomes.

What did the study show?

Children who were exposed to HIV in pregnancy showed differences in brain structure compared to children not exposed to HIV. Specifically, their brain cortex, particularly in the medial orbitofrontal region, was on average thicker than in children without HIV exposure. Secondly, children with HIV exposure had lower mean language scores compared to HIV-unexposed children, and the brain differences were linked to the lower language scores, Overall, the study found that differences in cortical brain structure in specific brain regions may partly explain the connection between HIV exposure and poor language outcomes.

The main takeaway from this study is that HIV exposure in utero may impact early brain development and language function for some children. With over 16 million children worldwide who are HIV-exposed and uninfected, these findings may inform monitoring and intervention strategies to improve outcomes. Another recent study has shown that better maternal HIV care improves the child brain outcomes, which suggests ways to optimise neurodevelopment in the future. Finally, the study also highlights how brain development relates to language skills in all children.

References:

Gilmore JH, Knickmeyer RC, Gao W. Imaging structural and functional brain development in early childhood. Nat Rev Neurosci. 2018;19(3):123–37. DOI: 10.1038/nrn.2018.1

UNAIDS. AIDSinfo. Available from: http://aidsinfo.unaids.org

Wedderburn CJ, Subramoney S, Yeung S, Fouche JP, Joshi SH, Narr KL, et al. Neuroimaging young children and associations with neurocognitive development in a South African birth cohort study. Neuroimage. 2020;219:116846. DOI: 10.1016/j.neuroimage.2020.116846

Wedderburn CJ, Weldon E, Bertran-Cobo C, Rehman AM, Stein DJ, Gibb DM, et al. Early neurodevelopment of HIV-exposed uninfected children in the era of antiretroviral therapy: a systematic review and meta-analysis. Lancet Child Adolesc Health. 2022;6(6):393–408. DOI: 10.1016/S2352-4642(22)00071-2

Zar HJ, Barnett W, Myer L, Stein DJ, Nicol MP. Investigating the early-life determinants of illness in Africa: the Drakenstein Child Health Study. Thorax. 2015;70(6):592-4. DOI: 10.1136/thoraxjnl-2014-206242