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: 10245275
• 负责人: Andrew Prendergast
• 金额: $ 29.05万
• 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 2025-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10245275
• 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 repository; 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 撒哈拉以南非洲的未感染艾滋病毒的未感染（HEU）儿童在头两年中的健康状况较差 与艾滋病毒未感染的（HUU）儿童相比，死亡率更高，疾病发作，较差的儿童 成长和认知发展受损。但是，这些差异是否持续为 儿童进入学校，以及早期的基本原因是什么。健康，增长和 神经发育可能是多因素的，包括两个HIV特异性危险因素，例如暴露 母体病毒血症和抗逆转录病毒药物以及普遍的危险因素，例如贫困，低出生体重和 孕产妇抑郁症。该提议利用了津巴布韦农村的HEU和HUU儿童的现有队列， 从怀孕早期到2岁，他们的特征很好，现在已经7岁了。这 该提议的目标是首先要了解健康差异是否持续到学龄 对HEU和HUU的增长，身体和认知功能进行整体评估 儿童中期的儿童，其次是通过 利用早期至2岁之间的“杂物组”测量的丰富数据集。 在这笔赠款的第一阶段（R61），一组900名儿童，以前在 津巴布韦农村地区的卫生卫生婴儿营养效能（Shine）试验将由一个网络确定 乡村卫生工作者（VHW）并在7岁时重新注册。所有参加Shine的HEU孩子 将确定整个农村地区（n = 300），对于每个注册的HEU孩子，有2个Huu儿童匹配 在年龄上，将选择性别和群集（n = 600）。艾滋病毒暴露和感染状况，社会环境， 将更新母子双子的主要逆境和病史，每个孩子都将与 现有关于从怀孕到2岁的生物，社会和环境暴露的元数据。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，该队列将通过VHW每月开始预期的健康监视，以识别急性疾病， 实时诊所就诊和住院发作。在R61阶段结束时，学龄的差异 HEU和HUU儿童之间的生长，身体和认知功能将被表征，并且 与这些差异相关的早期生活因素已确定。在第二阶段（R33），每月预期 VHW的健康监视将继续，并对增长，身体和认知功能进行年度评估 （使用生物标本的存储）将进行，以确定HEU和 Huu 9、10和11岁的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）的亚组将接受认知功能的深层表型，精神 健康，身体成分，代谢健康，炎症和慢性合并症，使用一系列剪裁 边缘技术，以详细的见解，以了解中后期HEU儿童的功能能力。

项目成果

The Sanitation Hygiene Infant Nutrition Efficacy (SHINE) Trial: Protocol for school-age follow-up.

• DOI: 10.12688/wellcomeopenres.19463.1
• 发表时间: 2023
• 期刊: Wellcome open research

Characterising school-age health and function in rural Zimbabwe using the SAHARAN toolbox.

• DOI: 10.1371/journal.pone.0285570
• 发表时间: 2023
• 期刊: PLOS ONE
• 影响因子: 3.7
• 作者: Piper, Joe;Mazhanga, Clever;Mapako, Gloria;Mapurisa, Idah;Mashedze, Tsitsi;Munyama, Eunice J.;Mwapaura, Marian C.;Chidhanguro, Dzivaidzo F.;Mpofu, Eddington V.;Mutasa, Batsirai;Gladstone, Melissa J.;Wells, Jonathan;Langhaug, Lisa;Tavengwa, Naume;Ntozini, Robert;Prendergast, Andrew
• 通讯作者: Prendergast, Andrew

Impact of COVID-19 on schooling in rural Zimbabwe.

• DOI: 10.1111/cch.12955
• 发表时间: 2022-11
• 期刊: CHILD CARE HEALTH AND DEVELOPMENT
• 影响因子: 1.9
• 作者: Piper, Joe D.;Mazhanga, Clever;Chidhanguro, Dzivaidzo;Prendergast, Andrew J.
• 通讯作者: Prendergast, Andrew J.