Predicting neurodevelopmental risk in children born to mothers living with HIV in Kenya

预测肯尼亚艾滋病毒感染者母亲所生儿童的神经发育风险

基本信息

批准号：
10390434
负责人：
Megan Song McHenry
金额：
$ 66.91万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-09 至 2026-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10390434
关键词：
2 year old Acquired Immunodeficiency Syndrome Affect Africa South of the Sahara African Age-Months Anti-Retroviral Agents Assessment tool Biological Biological Factors Biological Markers Birth Birth History Breast Feeding Cations Child Child Behavior Checklist Clinical Cognition Cohort Studies Communicable Diseases Country Data Databases Development Diarrhea Education Enrollment Epidemiology Etiology Exposure to Face Fetal Alcohol Exposure Future Goals HIV HIV antiretroviral Health Home environment Human Infant Inflammatory Institutes International Intervention Iron deficiency anemia Kenya Knowledge Language Lead levels Life Longitudinal Studies Longitudinal cohort Malaria Malnutrition Measles Measures Meningitis Mental Health Mission Modeling Monitor Morbidity - disease rate Mothers Newborn Infant Outcome Outcome Study Participant Perinatal Pharmaceutical Preparations Pneumonia Population Poverty Predictive Factor Pregnancy Pregnant Women Provider Psychosocial Factor Punishment Quality of life Recording of previous events Research Risk Risk Assessment Risk Factors Sanitation Stress Surveillance Program Toddler Tuberculosis United States National Institutes of Health Water Woman Work antiretroviral therapy cohort disability evidence base health care availability improved motor behavior neurodevelopment peer pharmacovigilance postnatal predictive tools prevention service prospective psychosocial social social factors sociodemographic factors sociodemographics success tool transmission process violence exposure

项目摘要

PROJECT SUMMARY Children who are HIV-exposed but uninfected (HEU) may have worse neurodevelopmental outcomes compared to their HIV-unexposed and uninfected (HUU) peers. However, the etiology of this potential association is unclear. With a growing population of children who are HIV-exposed, making up over 15% of children in some countries, there is a critical need to identify evidence-based risk factors associated with poor neurodevelopment to appropriately target interventions. The specific objectives of this application are: (1): to evaluate potential risk factors longitudinally over the first 2 years of life in children who are HEU and HUU and define those associated with worse neurodevelopmental outcomes at 24 months, and (2) to create a risk assessment tool to predict which children will have worse neurodevelopmental outcomes. The central hypothesis is that children who are HEU and HUU will have different neurodevelopmental outcomes; and that we can use risk factors to predict which children are at risk for worse outcomes before 2 years of age. The rationale for developing this tool is to identify children at risk for worse neurodevelopmental outcomes earlier to allow for targeted intervention. In Aim 1, we will evaluate the potential risk factors for poor neurodevelopment in young children. In Aim 2, we will compare neurodevelopmental outcomes between 24-month-old children who are HEU and those who are HUU in Kenya. In Aim 3, we will create a risk assessment tool to predict which children are at risk for worse neurodevelopmental outcomes at 24 months of age. This study will leverage an existing cohort to prospectively enroll 500 children who are HEU and 500 who are HUU and longitudinally follow them from birth to 24 months of age. Within the first aim, the following factors will be measured every 6 months: infectious morbidity, biological risk factors, and social risk factors (both sociodemographic and psychosocial). We will then compare these factors between children who are HEU and HUU. Within the second aim, we will measure neurodevelopment (cognition, language, motor, and behavior) in children at 24 months of age using the Child Behavior Checklist and the Bayley Scales of Infant and Toddler Development, 3rd edition, which our team has culturally-adapted and internally validated for use in Kenya. We will then compare neurodevelopmental outcomes between children who are HEU and HUU, providing well-powered data to determine whether differences truly exist between the groups. Finally, within the third aim, we will use generalized linear mixed modeling to quantify associations among multiple factors on child neurodevelopment and create a risk assessment tool for use in children <24 months. The proposed study is significant, as we will determine interconnected factors associated with worse neurodevelopmental outcomes in children who are HEU and HUU in Kenya. The resulting risk assessment tool will allow clinical providers to institute interventions for children at risk for worse neurodevelopmental outcomes earlier. This work will also create a longitudinal cohort of children exposed to antiretroviral therapy and HIV that may be monitored for future studies.

项目概要暴露于艾滋病毒但未感染的儿童 (HEU) 可能有更差的神经发育结果与未接触和未感染 HIV（HUU）的同龄人相比。然而，这种潜在的病因关联性尚不明确。随着感染艾滋病病毒的儿童数量不断增加，占儿童总数的 15% 以上在一些国家的儿童中，迫切需要确定与贫困相关的基于证据的风险因素神经发育以适当地针对干预措施。本申请的具体目标是： (1)：纵向评估 HEU 和 HUU 儿童生命前 2 年的潜在危险因素定义那些与 24 个月时神经发育结果较差相关的因素，以及 (2) 创建风险评估工具来预测哪些孩子的神经发育结果会更差。中央假设 HEU 和 HUU 儿童的神经发育结果不同；还有那个我们可以利用风险因素来预测哪些儿童在 2 岁之前面临更糟糕结果的风险。这开发该工具的理由是尽早识别面临神经发育不良风险的儿童允许有针对性的干预。在目标 1 中，我们将评估神经发育不良的潜在风险因素年幼的孩子。在目标 2 中，我们将比较 24 个月大儿童的神经发育结果是肯尼亚的 HEU 和 HUU。在目标 3 中，我们将创建一个风险评估工具来预测哪些风险 24 个月大的儿童面临神经发育结果恶化的风险。这项研究将利用现有队列前瞻性地招募 500 名 HEU 儿童和 500 名 HUU 儿童并纵向招募跟踪他们从出生到 24 个月大。在第一个目标中，将每 6 次测量以下因素月：传染病发病率、生物风险因素和社会风险因素（社会人口统计学和社会风险因素）心理社会）。然后我们将比较 HEU 和 HUU 儿童之间的这些因素。内第二个目标，我们将测量 24 岁儿童的神经发育（认知、语言、运动和行为）使用儿童行为检查表和贝利婴幼儿发展量表，第三版，我们的团队已针对文化进行了调整并进行了内部验证，适合在肯尼亚使用。我们随后将比较 HEU 和 HUU 儿童之间的神经发育结果，提供强有力的证据数据来确定组之间是否确实存在差异。最后，在第三个目标中，我们将使用广义线性混合模型量化儿童神经发育的多个因素之间的关联并创建一个用于 24 个月以下儿童的风险评估工具。拟议的研究意义重大，因为我们将确定与以下儿童神经发育结果较差相关的相互关联因素肯尼亚的 HEU 和 HUU。由此产生的风险评估工具将允许临床提供者采取干预措施针对较早面临神经发育不良风险的儿童。这项工作还将创建一个纵向接受抗逆转录病毒治疗和艾滋病毒治疗的儿童群体，可能会受到监测以用于未来的研究。