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

• 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
• 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

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.

项目摘要 撒哈拉以南非洲接触艾滋病毒但未受感染的儿童在头两年的健康结果较差 与未感染艾滋病毒的儿童相比， 生长和认知发育受损。然而，目前尚不确定这些差距是否会持续下去， 儿童进入学校，以及在早期生活中的根本原因是什么。健康、成长和 神经发育可能是多因素的，包括艾滋病毒特异性风险因素，如暴露于 产妇病毒血症和抗逆转录病毒药物，以及普遍的风险因素，如贫困、出生体重低和 母亲抑郁症这项建议利用了津巴布韦农村现有的高浓缩铀和高浓缩铀儿童群体， 她们从怀孕早期到2岁都有很好的特征，现在已经7岁了。的 该提案的目标是，首先，了解健康差异是否在学龄期持续存在， 对高浓缩铀和高浓缩铀的生长、身体和认知功能进行全面评估 其次，通过以下方式确定早期生活的根本原因网络 利用早孕至2岁之间“麻烦”测量的丰富数据集。 在该补助金的第一阶段（R61），一组900名儿童，以前在纵向跟踪， 津巴布韦农村地区的卫生保健婴儿营养功效（SHINE）试验将由一个网络确定， 村卫生工作者（VHW），并在7岁时重新注册。所有参加SHINE的HEU儿童 将从整个农村地区确定（N=300），对于每个登记的HEU儿童，2个HUU儿童匹配 将选择年龄、性别和群集（N=600）。艾滋病毒暴露和感染状况、社会环境， 将更新母子对的主要逆境和病史，每个孩子将与 关于从怀孕到2岁的生物、社会和环境接触的现有元数据。一 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，队列将开始每月由VHW进行前瞻性健康监测，以确定急性疾病， 实时的门诊就诊和住院情况。在R61阶段结束时， HEU和HUU儿童之间的生长、身体和认知功能将被表征， 与这些差异相关的早期生活因素。在第二阶段（R33）， VHW将继续进行健康监测，并每年评估生长，身体和认知功能 (with生物标本的储存），以查明高浓缩铀和 HUU儿童在9岁，10岁和11岁，以及与这些结果相关的早期生活暴露。一 300名儿童（150名HEU和150名HUU）的亚组将接受认知功能、精神和行为的深度表型分析。 健康，身体组成，代谢健康，炎症和慢性合并症，使用一系列切割- 边缘技术，以提供详细的见解高浓缩铀儿童在童年中期的功能能力。