Neurodevelopment of HIV-exposed uninfected children in Cape Town, South Africa

Abstract

Background Evidence shows that antiretroviral (ART) exposure is associated with neurodevelopmental delays in human immunodeficiency virus (HIV)-exposed uninfected (HEU) children. However, there are few insights into modifiable maternal and child factors that may play a role in improving neurodevelopment in HEU children. We used a parent-centric neurodevelopment tool, Ages & Stages Questionnaire (ASQ) to examined neurodevelopment in HEU children at 12–24 months of age, and associations with maternal and child factors. Methods 505 HIV-infected women (initiated ART pre- or during pregnancy) with live singleton births attending primary health care were enrolled; 355 of their HEU children were assessed for neurodevelopment (gross motor, fine motor, communication, problem solving and personal-social domains) at 12–24 months using age-specific ASQ administered by a trained fieldworker. Associations with maternal and child factors were examined using logistic regression models. Results Among mothers (median age 30 years, IQR, 26–34), 52% initiated ART during pregnancy; the median CD4 count was 436 cells/μl (IQR, 305–604). Most delayed neurodevelopment in HEU children was in gross (9%) and fine motor (5%) functions. In adjusted models, maternal socio-economic status (aOR 0.42, 95% CI 0.24–0.76) was associated with reduced odds of delayed gross-fine motor neurodevelopment. Maternal age ≥35 years (aOR 0.22, 95% CI 0.05–0.89) and maternal body mass index (BMI) <18.5 (aOR 6.76, 95% CI 1.06–43.13) were associated with delayed communication-problem-solving-personal-social neurodevelopment. There were no differences in odds for either domain by maternal ART initiation timing. Conclusions Delayed neurodevelopment was detected in both gross and fine motor functions in this cohort of HEU children, with strong maternal predictors that may be explored as potentially modifiable factors associated with neurodevelopment at one to two years of age.

The association of breastfeeding with cognitive development and educational achievement in sub-Saharan Africa: A systematic review

“…There was high variability in sample sizes, ranging from 54 to 6573. The studies were conducted across ten sub-Saharan African countries, but most were done in South Africa [ 23 , 27 , 29 , 30 , 31 , 34 , 36 ]. Three studies were multicentred, pooling data from Uganda and Burkina Faso [ 39 ], Uganda and Malawi [ 24 ], and Ghana and Malawi [ 33 ].…”

“…Of the 17 studies on cognitive development, 12 were prospective cohort studies [23][24][25][26][27][28][29][30][31][32][33][34], four were cross-sectional studies [35][36][37][38], and one was a cluster RCT [39] (Table 1 and Table S3 in the Online Supplementary Document). These studies were published between 2013 and 2021, with the majority (88%) published in the last five years.…”

“…11 of the cognitive development studies did not adjust for any confounders [24][25][26][27][28][29][33][34][35][36][37], and two studies adjusted for some confounders but not maternal education or family socioeconomic status [31,32] (Table S3 and S4 Table in the Online Supplementary Document). Only four studies controlled for maternal education or measures of family socioeconomic status [23,30,38,39], with one of these adjusting for maternal intelligence [23].…”

Maternal ART throughout gestation prevents caudate volume reductions in neonates who are HIV exposed but uninfected

“…Specifically in Southern Africa, three studies, one each from South Africa ( Wedderburn et al, 2019b ), Botswana ( Chaudhury et al, 2017 ) and Zimbabwe ( Ntozini et al, 2020 ), reported language delay in HEU infants and children; two studies, one in South Africa ( Le Roux et al, 2018 ) and one in Zimbabwe ( Ntozini et al, 2020 ), poorer motor development; and one study ( Springer et al, 2012 ) poorer adaptive behavior. Another study performed in South Africa found delayed gross and fine motor development (that was independent of ART initiation timing) in a higher proportion of HEU infants at age 12–24 months than typically seen in unexposed infants from similar communities ( Madlala et al, 2020 ).…”

Cardiovascular effects of intrauterine exposure to maternal HIV and antiretroviral therapy in Ethiopian infants followed from fetal life

“…However, investigations of these effects are often hampered by the lack of representative HIV-unexposed controls. In addition to negative associations with survival [8], growth [7] and cognitive development [9], several observational studies have described cardiac changes from early life stages in HEU children [10,11]. We have previously reported structural and functional cardiac changes in utero of Spanish HEU infants, mainly related to maternal zidovudine-containing ART regimens [12,13].…”