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

项目总结 感染艾滋病毒但未感染(HEU)的儿童的神经发育结果可能更差 与未接触艾滋病毒和未感染(HUU)的同龄人相比。然而，这种可能性的病因 目前还不清楚是否存在关联。随着接触艾滋病毒的儿童人数不断增加，占全球儿童总数的15%以上 在一些国家，迫切需要确定与贫困有关的循证风险因素 神经发展以适当的干预措施为目标。本申请的具体目标是：(1)： 纵向评估HEU和HUU儿童出生后头两年的潜在危险因素 定义那些与24个月后神经发育结果较差有关的因素，以及(2)产生风险 一种评估工具，用于预测哪些儿童的神经发育结果会更差。中环 假设是HEU和HUU的儿童会有不同的神经发育结果； 我们可以使用风险因素来预测哪些儿童在2岁之前有可能出现更糟糕的结果。这个 开发这一工具的基本原理是及早识别神经发育结果较差的儿童 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危险因素。 年幼的孩子。在目标2中，我们将比较24个月大的儿童和 是HEU和那些在肯尼亚的HUU。在目标3中，我们将创建一个风险评估工具来预测 儿童在24个月大的时候有神经发育不良的风险。这项研究将利用 现有队列，预期招收500名HEU儿童和500名HUU儿童和纵向儿童 从出生一直跟踪到24个月大。在第一个目标内，将每隔6天测量以下因素 月份：传染病发病率、生物风险因素和社会风险因素(社会人口学和 心理社会)。然后，我们将比较HEU和HUU儿童的这些因素。在 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，我们的团队根据文化进行了调整，并在肯尼亚进行了内部验证。到时候我们会的 比较HEU和HUU儿童的神经发育结果，提供更好的动力 数据，以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 用广义线性混合模型量化多因素对儿童神经发育的影响 并创建一种风险评估工具，供24个月的儿童使用。这项拟议的研究意义重大，正如我们将 确定与以下儿童的神经发育不良结果相关的相互关联的因素 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制定干预措施 对于较早出现神经发育不良风险的儿童。这项工作还将创造一个纵向的 接受抗逆转录病毒治疗和艾滋病毒感染的儿童队列，可能会为未来的研究进行监测。

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.