eprintid: 10147495
rev_number: 9
eprint_status: archive
userid: 699
dir: disk0/10/14/74/95
datestamp: 2022-04-28 13:25:33
lastmod: 2022-04-28 13:26:10
status_changed: 2022-04-28 13:25:33
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Wedderburn, Catherine J
creators_name: Weldon, Ella
creators_name: Bertran-Cobo, Cesc
creators_name: Rehman, Andrea M
creators_name: Stein, Dan J
creators_name: Gibb, Diana M
creators_name: Yeung, Shunmay
creators_name: Prendergast, Andrew J
creators_name: Donald, Kirsten A
title: Early neurodevelopment of HIV-exposed uninfected children in the era of antiretroviral therapy: a systematic review and meta-analysis
ispublished: inpress
divisions: UCL
divisions: J38
divisions: D65
divisions: B02
note: © 2022 The Author(s). Published by Elsevier Ltd under a Creative Commons license (https://creativecommons.org/licenses/by/4.0/).
abstract: BACKGROUND: There are 15·4 million children who are HIV-exposed and uninfected worldwide. Early child development crucially influences later academic and socioeconomic factors. However, the neurodevelopmental outcomes of HIV-exposed uninfected (HEU) children in the era of maternal antiretroviral therapy (ART) remain unclear. We aimed to examine the effects of in-utero exposure to HIV and ART on child neurodevelopment. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, Africa-Wide Information, PsycInfo, and Global Health databases from inception to May 27, 2020, for studies from the past two decades reporting neurodevelopment of HEU children aged 0–5 years compared with HIV-unexposed (HU) children (aim 1), and effects of different maternal ART regimens on neurodevelopment of HEU children (aim 2). We did narrative syntheses for both aims, and a random-effects meta-analysis of high-quality studies comparing HEU children and HU children, to obtain weighted pooled estimates of effect sizes. This study was registered with PROSPERO, CRD42018075910. FINDINGS: We screened 35 527 records and included 45 articles from 31 studies. Overall, 12 (57%) of 21 studies comparing HEU children and HU children found worse neurodevelopment in HEU children in at least one domain. Study design and methodological quality were variable, with heterogeneity across populations. Meta-analysis included eight high-quality studies comparing 1856 HEU children with 3067 HU children at ages 12–24 months; among HEU children with available data, 1709 (99%) of 1732 were exposed to ART. HEU children had poorer expressive language (effect size –0·17 [95% CI –0·27 to –0·07], p=0·0013) and gross motor function (–0·13 [–0·20 to –0·07], p<0·0001) than HU children, but similar cognitive development (–0·06 [–0·19 to 0·06], p=0·34), receptive language development (–0·10 [–0·23 to 0·03], p=0·14), and fine motor skills (–0·05 [–0·15 to 0·06], p=0·36). Results suggested little or no evidence of an effect of specific maternal ART regimens on neurodevelopment; study heterogeneity prevented meta-analysis. INTERPRETATION: HEU children are at risk of subtle impairments in expressive language and gross motor development by age 2 years. We found no consistent effect of maternal ART regimens analysed, although evidence was scarce. We highlight the need for large high-quality longitudinal studies to assess the neurodevelopmental trajectories of HEU children and to investigate underlying mechanisms to inform intervention strategies. FUNDING: Wellcome Trust and Medical Research Council.
date: 2022-04-26
date_type: published
publisher: Elsevier BV
official_url: https://doi.org/10.1016/S2352-4642(22)00071-2
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1951035
doi: 10.1016/s2352-4642(22)00071-2
lyricists_name: Gibb, Diana
lyricists_id: MGIBB48
actors_name: Gibb, Diana
actors_name: Payne, Roxanne
actors_id: MGIBB48
actors_id: RPAYN74
actors_role: owner
actors_role: impersonator
full_text_status: public
publication: The Lancet Child & Adolescent Health
citation:        Wedderburn, Catherine J;    Weldon, Ella;    Bertran-Cobo, Cesc;    Rehman, Andrea M;    Stein, Dan J;    Gibb, Diana M;    Yeung, Shunmay;         ... Donald, Kirsten A; + view all <#>        Wedderburn, Catherine J;  Weldon, Ella;  Bertran-Cobo, Cesc;  Rehman, Andrea M;  Stein, Dan J;  Gibb, Diana M;  Yeung, Shunmay;  Prendergast, Andrew J;  Donald, Kirsten A;   - view fewer <#>    (2022)    Early neurodevelopment of HIV-exposed uninfected children in the era of antiretroviral therapy: a systematic review and meta-analysis.                   The Lancet Child & Adolescent Health        10.1016/s2352-4642(22)00071-2 <https://doi.org/10.1016/s2352-4642%2822%2900071-2>.    (In press).    Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10147495/1/1-s2.0-S2352464222000712-main.pdf