Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa; The Neuroscience Institute, University of Cape Town, Cape Town, South Africa; Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; MRC Clinical Trials Unit, University College London, London, UK.
Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, University of Cape Town, Cape Town, South Africa.
Lancet Child Adolesc Health. 2022 Jun;6(6):393-408. doi: 10.1016/S2352-4642(22)00071-2. Epub 2022 Apr 26.
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.
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.
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.
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.
Wellcome Trust and Medical Research Council.
全世界有 1540 万艾滋病毒暴露但未感染的儿童。早期儿童发育对以后的学业和社会经济因素至关重要。然而，在接受抗逆转录病毒疗法（ART）的母亲时代，艾滋病毒暴露但未感染（HEU）儿童的神经发育结果仍不清楚。我们旨在研究宫内接触艾滋病毒和 ART 对儿童神经发育的影响。
本系统评价和荟萃分析检索了 MEDLINE、Embase、PubMed、Africa-Wide Information、PsycInfo 和全球健康数据库，以获取过去二十年中报告 0-5 岁 HEU 儿童与未感染 HIV 的儿童（目标 1）神经发育情况的研究，以及不同的母亲 ART 方案对 HEU 儿童神经发育的影响（目标 2）。我们对这两个目标进行了叙述性综合分析，并对比较 HEU 儿童和 HU 儿童的高质量研究进行了随机效应荟萃分析，以获得效应大小的加权汇总估计值。本研究已在 PROSPERO 上注册，CRD42018075910。
我们筛选了 35527 条记录，从 31 项研究中纳入了 45 篇文章。总的来说，在比较 HEU 儿童和 HU 儿童的 21 项研究中，有 12 项（57%）研究发现 HEU 儿童在至少一个领域的神经发育较差。研究设计和方法学质量各不相同，人群之间存在异质性。荟萃分析包括 8 项高质量研究，比较了 1856 名 HEU 儿童和 3067 名 HU 儿童在 12-24 个月时的情况；在有可用数据的 HEU 儿童中，1732 名（99%）接受了 ART 治疗。与 HU 儿童相比，HEU 儿童的表达性语言（效应大小-0.17 [95%CI-0.27 至-0.07]，p=0.0013）和粗大运动功能（-0.13 [-0.20 至-0.07]，p<0.0001）较差，但认知发育（-0.06 [-0.19 至 0.06]，p=0.34）、接受性语言发育（-0.10 [-0.23 至 0.03]，p=0.14）和精细运动技能（-0.05 [-0.15 至 0.06]，p=0.36）相似。结果表明，特定的母亲 ART 方案对神经发育的影响很小或没有；研究的异质性妨碍了荟萃分析。
HEU 儿童在 2 岁时就存在表达性语言和粗大运动发育受损的风险。我们没有发现母亲 ART 方案的一致影响，但证据很少。我们强调需要进行大量高质量的纵向研究，以评估 HEU 儿童的神经发育轨迹，并研究潜在的机制，为干预策略提供信息。
惠康信托基金和医学研究委员会。
