LCAH:母亲抗逆转录病毒治疗对未感染HIV的儿童早期神经发育的影响

2022-07-31 从医路漫漫 MedSci原创

HIV

据估计,全世界有1540万未感染艾滋病毒(HEU)的儿童,占一些艾滋病毒负担高的国家每年新生儿的20%以上。

背景:怀孕大大减少了艾滋病毒的垂直传播,这意味着大多数艾滋病毒携带者母亲所生的孩子都接触过艾滋病毒,但没有感染。据估计,全世界有1540万未感染艾滋病毒(HEU)的儿童,占一些艾滋病毒负担高的国家每年新生儿的20%以上。HEU儿童和未接触艾滋病毒(HU)的儿童在早期死亡率和发病率方面存在明显差异,人们对艾滋病毒和ART暴露对神经发育的影响表示关注。儿童早期发展是未来学术成就和社会经济成果的基础。可持续发展目标认识到儿童神经发展的重要性,因为早期阶段是大脑发育的基础。重要的是了解发育受损的各种风险因素,以便为增强儿童神经发展潜力的干预战略提供信息。然而,在年轻时很难衡量神经发育,这使得解释单一研究的结果具有挑战性。

现有文献表明,与HU儿童相比,HEU儿童可能存在认知、语言和运动障碍的不良风险。虽然已经进行了两次荟萃分析,但都仅限于使用贝利婴幼儿发育量表的研究,其中一些研究有偏颇的风险。在一次荟萃分析中,所有来自美国以外的研究都被归类为低质量研究,因为潜在的混淆和样本量小,从而限制了对艾滋病毒高流行地区HEU儿童结局的了解。

在怀孕和哺乳期间接受抗逆转录病毒药物治疗的机会已经扩大,从而提高了产妇存活率和母乳喂养率,这可能会影响神经发育。在推出抗逆转录病毒药物后进行的几项研究报告称,高尿酸血症儿童仍然面临神经发育迟缓的风险;然而,其他研究发现与HU儿童没有区别。分别地,宫内暴露于抗逆转录病毒药物与不良神经发育相关。

目的:。我们的第一个目的是通过对HEU儿童和HU儿童的比较来研究宫内HIV暴露对儿童神经发育的影响,第二个目的是研究宫内ART暴露对HEU儿童神经发育的影响。

方法 在这个系统回顾和荟萃分析中,我们搜索了MEDLINE、Embase、PubMed、Africa-Wide Information、PsycInfo和Global Health数据库,从开始到2020年5月27日,寻找过去20年报告0-5岁HEU儿童与HIV未暴露(HU)儿童的神经发育的研究(目标1),以及不同孕产妇抗逆转录病毒治疗方案对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,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,以获得加权的效应大小估计值。本研究已在PROSPERO注册,CRD42018075910。

研究结果 我们筛选了35 527条记录,纳入了31项研究的45篇文章。总的来说,21项研究中的12项(57%)比较了高考儿童和大学儿童,发现高考儿童的神经发育至少在一个领域比较差。研究设计和方法学质量是可变的,在不同人群中具有异质性。荟萃分析包括8项高质量的研究,在12-24个月时将1856名HEU儿童与3067名HU儿童进行比较;在有数据的HEU儿童中,1732人中有1709人(99%)接触过ART。与HU儿童相比,HEU儿童的语言表达能力(效果大小为-0-17 [95% CI -0-27 to -0-07], p=0-0013)和粗大运动功能(-0-13 [-0-20 to -0-07], p<0-0001)较差,但认知发展(-0-06 [-0-19 to 0-06], p=0-34)、接受性语言发展(-0-10 [-0-23 to 0-03], p=0-14)和精细运动能力(-0-05 [-0-15 to 0-06], p=0-36)相似。结果表明,几乎没有证据表明特定的母亲抗逆转录病毒疗法对神经发育的影响;研究的异质性妨碍了荟萃分析。

图1 HEU儿童和HU儿童的神经发育比较,Cd=认知发展。LD=语言发展。MD=运动发育。AB=适应性行为。SEB=社交-情绪行为。HEU=接触艾滋病毒但未感染的人。HU=HIV-未暴露。ADBB=警报窘迫婴儿等级。贝利婴儿神经发育筛查器。BSID-II=贝利婴幼儿发展量表第二版。BSID-III=贝利婴幼儿发展量表第三版。CDI=麦克阿瑟-贝茨传播发展清单。DDST-II=丹佛发育筛查测验第二版。发展里程碑核对表。FSDQ=全面发展商。GMDS=Griffiths智力发展量表。KABC-II=考夫曼儿童评估电池,第二版。MDAT=马拉维发展评估工具。MSEL=马伦早期学习量表。皮博迪发育运动量表。RITLS=Rossetti幼儿语言量表。SDQ=优点和困难问卷。Snijders-Oomen非语言智力测试。VABs=Vinland适应性行为量表。Beery-VMI=Beery Buktenica视觉运动整合测试。*如果域之间的数字不同,则列出最高的数字。†的语言和运动发展综合得分或BSID-II智力发展指数被用来反映认知和语言发展;另外,在适用的情况下,认知发展使用MSEL认知综合得分、MDAT总分或GMDS总商进行评估。‡未调整的分析结果,以P<0.05的统计学意义或通过95%的CI在组内比较平均或比较延迟(如适用)来定义。§如果评估的中位年龄在这一时间点的1个月内,则将年龄定为12个月(附录,第19-20页)。;在平均分分析上,Le Roux和同事10报告的平均分数没有显著的组间差异;韦德伯恩和同事32报告说,在未经调整和经过调整的分析中,HEU儿童的接受性和表现性语言得分低于HU儿童,而在未经调整的分析中,认知得分更低。|BSID-II仅在6个月和18个月有差异,DDST在6个月有差异。**在不良结果分析上,在未经调整和调整的分析中,HEU儿童的语言不良结果显著高于HU儿童。††研究纳入年龄范围内的中位数年龄

图2 在荟萃分析中,HEU=未感染HIV的HEU儿童与HU儿童的神经发育结果的比较。HU=HIV-未暴露。

图3 母亲ART对感染艾滋病毒的未感染儿童的神经发育差异

表1:HEU儿童与HU儿童的头围和神经影像结果比较(目标1)

结论:HEU儿童在2岁前有可能出现语言表达和粗大运动发育方面的细微障碍。我们发现,尽管证据不多,但母亲的抗逆转录病毒治疗方案没有一致的影响。我们强调有必要进行大规模的高质量的纵向研究,以评估HEU儿童的神经发育轨迹,并研究潜在的机制,为干预策略提供依据。

原文出处:Wedderburn CJ,  Weldon E,  Bertran-Cobo C, 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 06;6(6)

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    2022-10-28 mjldent
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    2022-08-05 hxj0117
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    2022-07-29 neurowu
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Pediatrics:性活跃青少年的年度性传播感染检测

鉴于青少年中STI的高发病率、感染的严重后果(包括盆腔炎和不孕症), 以及衣原体筛查的成本效益,美国妇产科学院建议对青少年和年轻成年人进行某种程度的性传播感染筛查。

JAMA Netw Open:美国新诊断为HIV感染者中脑膜炎球菌疫苗接种率

感染艾滋病毒的人患脑膜炎球菌病的风险增加4.5%到12.9倍。