1. Children less than 8 years old infected with HIV and children who were HIV exposed-but-uninfected had poorer neurodevelopmental outcomes compared to unexposed children.
2. Those children who were either HIV-infected or exposed-but-uninfected who also had anti-retroviral exposure may have lower neuropsychological function than those without anti-retroviral exposure.
Evidence Rating Level: 2 (Good)
Study Rundown: HIV infection is known to result in worse neurodevelopmental outcomes in children born to HIV-infected mothers. However, less is known about the outcomes of children who are HIV exposed-but-uninfected (HEU), as well as the impact of anti-retroviral (ARV) exposure on neurodevelopment. In this study, authors conducted a systematic review and meta-analysis of literature pertaining to neurodevelopmental outcomes of children born to HIV-infected mothers. They reviewed 45 studies, 11 of which were used for meta-analysis. Neurodevelopmental outcomes were measured using a standardized neuropsychological assessment tool, the Bayley Scales of Infant and Toddler Development (BSID). HIV infected (HIV+) children and HEU children showed worse cognitive and motor outcomes compared with uninfected (HUU) children, and HEU children showed better outcomes compared to HIV+ children. Furthermore, ARV exposure may also be associated with poorer developmental outcomes, but further data in this area is necessary. Overall, this meta-analysis is a comprehensive, standardized comparison of neurodevelopmental outcomes in these 3 groups of children; however, results were limited by study heterogeneity, and confounders such as location were not controlled for. Overall, this study provides the first, quantitative analysis of neurodevelopment outcomes in HIV-exposed children. This study points to the necessity for more data regarding ARV exposure in the perinatal period. Findings also provide a baseline for efforts to improve neurodevelopmental outcomes in a vulnerable population.
In-Depth [systematic review and meta-analysis]: This meta-analysis reviewed 45 studies, 11 of which were included in a network meta-analysis that met the authors’ criteria. Studies were included based on the use of a standardized neuropsychological assessment (BSID), an age cutoff of 8 years old for subjects, and lack of significant confounding factors. HUU children were used as the statistical reference group. Systematic heterogeneity was assessed with subgroup analysis and meta-regression, and studies were analyzed for their quality, with sub-analyses based on quality ratings. Adjusted meta regression results of both measurements of the Mental Developmental Index (MDI), as well as the Psychomotor Developmental Index (PDI) from within the BSID showed HIV+ children having poorer outcomes than HUU children on both scales (MDI: -16.3 points, 95% CI: [-26.2, -7.1]; PDI: -17.62 points, 95% CI: [-27.3, -7.6]). HEU children showed lower outcomes to a lesser extent (MDI: -6.61 points, 95% CI: [-15.5, 2.54]; PDI: -4.25 points, 95% CI: [-13.71, 5.12]). Measuring the effect of ARV exposure on BSID scores for HIV+ and HEU children suggested a possible effect of ARVs: exposed children had lower mean scores than those unexposed to ARVs in both subdomains of the BSID examined, compared to HUU children (MDI: [HEU: -10.0 vs. 0.95, HIV+: -20.3 vs -7.8]); (PDI: [HEU: -5.5 vs. -1.2, HIV+: -19.4 vs -12.7]).
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