Clinical outcomes of HIV-exposed uninfected children during mid-childhood in rural Zimbabwe

津巴布韦农村地区童年中期暴露于艾滋病毒的未感染儿童的临床结果

基本信息

批准号：
10064192
负责人：
Andrew Prendergast
金额：
$ 32.39万
依托单位：
ZVITAMBO INSTITUTE FOR MATERNAL AND CHILD HEALTH RESEARCH
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-21 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10064192
关键词：
12 year old 2 year old 7 year old Activities of Daily Living Acute Africa South of the Sahara Age Anti-Retroviral Agents Assessment tool Biological Biological Markers Birth Body Composition Child Childhood Chronic Chronic Disease Clinic Visits Clinical Cognition Data Set Disease Enrollment Environmental Exposure Event Exposure to Fatty acid glycerol esters Functional disorder Goals Grant Growth Growth and Development function HIV Health Hospitalization Hygiene Impaired cognition Impairment Infection Inflammation Inflammatory Intervention Life Life Cycle Stages Link Low Birth Weight Infant Measurement Medical History Mental Health Metabolic Metadata Mothers Neuropsychology Organ Outcome Pharmaceutical Preparations Phase Phase Transition Phenotype Physical Function Poverty Pregnancy Prevention Prevention therapy Process Risk Factors Rural Sanitation School-Age Population Schools Sentinel Specimen Subgroup Techniques Thinness Time Update Vertical Disease Transmission Village Health Workers Viremia Vulnerable Populations Zimbabwe antiretroviral therapy cluster trial co-infection cognitive development cognitive function cohort comorbidity data warehouse early life exposure early pregnancy efficacy trial follow-up health difference health disparity human capital improved infant nutrition insight maternal depression mortality neurodevelopment physical conditioning prospective recruit sex social

项目摘要

Project summary HIV-exposed uninfected (HEU) children in sub-Saharan Africa have poorer health outcomes in the first 2 years of life than HIV-unexposed uninfected (HUU) children, with higher mortality, more illness episodes, poorer growth and impaired cognitive development. However, it remains uncertain whether these disparities persist as children enter school, and what the underlying causes are in early life. Impairments in health, growth and neurodevelopment are likely multifactorial, including both HIV-specific risk factors such as exposure to maternal viremia and antiretroviral drugs, and universal risk factors such as poverty, low birth weight and maternal depression. This proposal leverages an existing cohort of HEU and HUU children in rural Zimbabwe, who were well characterized from early pregnancy to 2 years of age, and are now turning 7 years old. The goal of this proposal is, first, to understand whether health differences persist at school-age, by undertaking holistic assessments of the growth, physical and cognitive function of HEU and HUU children in mid-childhood and, second, to identify the network of underlying causes in early life, by leveraging the rich dataset of `exposome' measurements between early pregnancy and 2 years of age. In the first phase of this grant (R61), a cohort of 900 children, previously followed longitudinally in the Sanitation Hygiene Infant Nutrition Efficacy (SHINE) trial in rural Zimbabwe, will be identified by a network of Village Health Workers (VHW) and re-enrolled at 7 years of age. All HEU children who participated in SHINE from an entire rural district will be identified (N=300), and for each enrolled HEU child, 2 HUU children matched on age, sex and cluster will be selected (N=600). HIV exposure and infection status, social circumstances, major adversities and medical history of mother-child pairs will be updated, and each child will be linked to existing meta-data on biological, social and environmental exposures from pregnancy to 2 years of age. A holistic baseline assessment will compare growth, physical and cognitive function between HEU and HUU children, and the cohort will begin monthly prospective health surveillance by VHW to identify acute illness, clinic visits and hospitalization episodes in real-time. At the end of the R61 phase, disparities in school-age growth, physical and cognitive function between HEU and HUU children will have been characterized, and the early-life factors associated with these differences identified. In the second phase (R33), monthly prospective health surveillance by VHW will continue, and an annual assessment of growth, physical and cognitive function (with storage of biological specimens) will be undertaken, to identify longitudinal disparities between HEU and HUU children at ages 9, 10 and 11 years, and the early-life exposures associated with these outcomes. A subgroup of 300 children (150 HEU and 150 HUU) will undergo deep phenotyping of cognitive function, mental health, body composition, metabolic health, inflammation and chronic comorbidities using a range of cutting- edge techniques, to provide detailed insights into the functional capacity of HEU children in mid-childhood.

项目概要撒哈拉以南非洲地区暴露于艾滋病毒的未感染 (HEU) 儿童在头两年内健康状况较差与未接触 HIV 的未感染 (HUU) 儿童相比，死亡率更高、发病次数更多、贫困程度更高生长和认知发展受损。然而，这些差异是否持续存在仍不确定孩子进入学校，以及早年的根本原因是什么。健康、生长和发育受损神经发育可能是多因素的，包括艾滋病毒特异性危险因素，例如接触孕产妇病毒血症和抗逆转录病毒药物，以及贫困、低出生体重和产妇抑郁症。该提案利用了津巴布韦农村地区现有的 HEU 和 HUU 儿童群体，他们从怀孕初期到2岁时都有很好的特征，现在已经7岁了。这该提案的目标首先是了解学龄期间健康差异是否持续存在，方法是对 HEU 和 HUU 的生长、身体和认知功能进行全面评估其次，确定生命早期的根本原因网络，方法是：利用怀孕早期和两岁之间“暴露组”测量的丰富数据集。在这项资助的第一阶段 (R61)，一组 900 名儿童，之前在津巴布韦农村地区的环境卫生婴儿营养功效 (SHINE) 试验将由以下网络进行确定：乡村卫生工作者 (VHW) 并在 7 岁时重新加入。所有参加SHINE的HEU孩子将确定来自整个农村地区的 (N=300)，并且对于每个注册的 HEU 儿童，匹配 2 个 HUU 儿童将选择年龄、性别和聚类（N=600）。 HIV暴露和感染状况、社会环境、母子对的重大不幸经历和病史将被更新，每个孩子都会被链接到关于从怀孕到两岁的生物、社会和环境暴露的现有元数据。一个整体基线评估将比较 HEU 和 HUU 之间的生长、身体和认知功能儿童，该队列将开始由 VHW 每月进行前瞻性健康监测，以识别急性疾病，实时就诊和住院情况。 R61 阶段结束时，学龄差异 HEU 和 HUU 儿童之间的生长、身体和认知功能将得到表征，并且与这些差异相关的早期生活因素已被确定。第二阶段（R33），每月展望 VHW 将继续进行健康监测，并对生长、身体和认知功能进行年度评估（与生物样本的储存）将进行，以确定高浓缩铀和 9、10 和 11 岁的 HUU 儿童，以及与这些结果相关的早期暴露。一个 300 名儿童（150 HEU 和 150 HUU）组成的亚组将接受认知功能、心理功能的深度表型分析使用一系列切割方法来评估健康、身体成分、代谢健康、炎症和慢性合并症边缘技术，为 HEU 儿童在童年中期的功能能力提供详细的见解。