The Role of Iron Deficiency in the Neurodevelopment of Children Perinatally Exposed to HIV

摘要 随着抗逆转录病毒疗法（ART）在撒哈拉以南非洲的怀孕和儿童中越来越多 在人类免疫缺陷病毒（艾滋病毒）最流行的国家， 感染艾滋病毒（HI）但已成年的儿童人数和接触艾滋病毒但未感染艾滋病毒的儿童人数 (HEU)正在增加，将后ART研究议程转向改善儿童的生活质量 围产期接触艾滋病病毒接受抗逆转录病毒治疗的HI儿童和高浓缩铀儿童都有持续的 在整体认知、执行功能、运动发育方面的神经行为（NB）缺陷，但 这种延迟的机制尚不清楚。缺铁症（ID）困扰着30%的59个月以下的儿童， 撒哈拉以南非洲，是儿童大脑发育受损的一个既定原因，但迄今为止，还没有研究表明， 研究了在围产期暴露于HIV的儿童中描述的NB损伤中ID的潜在关联。 基于现有的合作和大量的多学科专业知识，我们将描述铁的地位， 并确定HI（n=70）、HEU（n=70）和HIV未暴露、未感染队列中ID的患病率 (HUU)参加乌干达坎帕拉联合研究中心的儿童（n=70）（目标1），我们将 建立ID和一系列NB测试（目标2）的分数之间的关系，这些测试共同评估 整体认知、运动发育、执行功能和行为。值得注意的是，我们的研究将是第一个 应用行为评定量表，一种测试社交情绪行为缺陷的方法， 在HIV背景下，缺铁大脑中多巴胺能信号的改变。我们假设高浓缩铀和 HI儿童ID（可溶性转铁蛋白受体> 8.3mg/L）患病率高，NB试验差 在每个组中，ID儿童的得分比HUU儿童的得分更差。然而，在这方面， 这种差异在HEU和HI中比在HUU儿童中更大。这项试点和可行性研究将 证明HI和HEU儿童的儿童ID和NB缺陷之间是否存在关联， 同时还建立能力和知识基础设施，以便在JCRC进行NB评估， 未来的纵向研究，可以建立铁缺乏的时间性和其他因素，可能导致 在围产期暴露于艾滋病毒的相当大的和不断增长的儿童群体中，

ABSTRACT With antiretroviral therapy (ART) increasingly available in pregnancy and childhood in sub-Saharan African countries where human immunodeficiency virus (HIV) is most prevalent, both the number of children who are HIV-infected (HI) but reaching adulthood and the number of children exposed to HIV but uninfected themselves (HEU) are increasing, shifting the post-ART research agenda to improving the quality of life in children perinatally exposed to HIV. Both HI children established on ART and HEU children have persistent neurobehavioral (NB) deficits in the areas of global cognition, executive functioning, motor development, but the mechanism of this delay is unclear. Iron deficiency (ID) afflicts 30% of children younger than 59 months in sub-Saharan Africa and is an established cause of impaired child brain development, but to date, no study has examined a potential association for ID in the NB impairments described in children perinatally exposed to HIV. Building on existing collaboration and substantial multidisciplinary expertise, we will characterize iron status and determine the prevalence of ID in a cohort of HI (n=70), HEU (n=70), and HIV-unexposed, uninfected (HUU) children (n=70) (Aim 1) who attend the Joint Research Centre in Kampala, Uganda, and we will establish the relationship between ID and scores from a range of NB tests (Aim 2) that collectively assess global cognition, motor development, executive function, and behavior. Notably, our study will be the first to apply the Behavior Rating Scales, a test for deficits in socioemotional behavior that are secondary to the altered dopaminergic signaling in an iron-deficient brain, in the context of HIV. We hypothesize that HEU and HI children will have a higher prevalence of ID (soluble transferrin receptor > 8.3 mg/L) and poorer NB test scores than HUU children and that within each group, scores will be poorer in ID vs. non-ID children. However, this difference will be greater in HEU and HI than in HUU children. This pilot and feasibility study will demonstrate whether there is an association between childhood ID and NB deficits in HI and HEU children, while also establishing the capacity and intellectual infrastructure to carry out NB assessments at JCRC for future longitudinal studies that can establish the temporality of iron deficiency and other factors that may lead to NB deficits in the sizeable and growing group of children perinatally exposed to HIV.