Neural correlates of in utero HIV and ART exposure: early childhood follow-up of a prospectively recruited cohort

子宫内 HIV 和 ART 暴露的神经相关性：前瞻性招募队列的儿童早期随访

• 批准号: 10751757
• 负责人: Barbara Laughton
• 金额: $ 65.22万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-22 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751757
• 关键词: 2 year old; Africa South of the Sahara; Age; Algorithms; Behavior assessment; Birth; Brain; Brain imaging; Cessation of life; Child; Childhood; Clinic; Clinical assessments; Cognition; Collaborations; Communities; Conceptions; Data; Development; Diffusion Magnetic Resonance Imaging; Drug Combinations; Enrollment; Ensure; Environment; Environmental Risk Factor; Exhibits; Exposure to; Face; Faculty; Fetal Development; Functional disorder; General Hospitals; Gestational Age; Growth; HIV; HIV Infections; HIV Seropositivity; HIV-1; Health; High Prevalence; Home; Human; Human Milk; Image; Imaging technology; Impaired cognition; Infant; Infant Development; Infection; Infrastructure; Intervention; Investments; Life; Link; Magnetic Resonance; Magnetic Resonance Imaging; Massachusetts; Maternal Health; Mediating; Metabolic; Metabolism; Milk; Monitor; Morbidity - disease rate; Mothers; Nutritional; Oligosaccharides; Outcome; Performance; Personal Satisfaction; Population; Postdoctoral Fellow; Pregnancy; Pregnant Women; Prevention Guidelines; Public Health; Readiness; Regimen; Reporting; Research Personnel; Resource-limited setting; Risk; Role; Sampling Studies; Schools; Site; South Africa; Spectrum Analysis; System; Tenofovir; Testing; Toxic effect; Training; United States National Institutes of Health; Universities; Vertical Transmission; Woman; antenatal; brain health; cognitive performance; cognitive testing; cohort; comparative; computing resources; cost; early childhood; efavirenz; emtricitabine; eye hand coordination; fetal; follow-up; graduate student; gray matter; high risk; in utero; inclusion criteria; infancy; infant nutrition; longitudinal analysis; maternal wellbeing; mental development; microbial; microbiome; morphometry; mortality; multimodal neuroimaging; multimodality; neonate; neural; neural correlate; neurodevelopment; neuroimaging; peer; perinatal HIV; postnatal; prenatal; prevent; programs; prospective; recruit; social; socioeconomics; success; three-arm study; tool; white matter

Project Summary Programs to prevent vertical transmission of HIV have been extremely effective. As a result, there is an increasing population of HIV-exposed and uninfected children (CHEU). Currently, at least one in every five children (approximately 4.1 million children) in South Africa is HEU. These children face higher risks even though they are not infected, exhibiting reduced growth, neurodevelopmental delays and increased risk of severe infections and even death before age two years. In 2017, we started recruiting a cohort of pregnant women living with HIV who had either commenced triple-regimen ART prior to conception or during pregnancy immediately upon testing positive for HIV infection, along with uninfected women. We thus established a cohort of infants in three study arms viz. unexposed, exposed with ART throughout fetal development, and exposed with ART started later in pregnancy. In R01 HD085813, we imaged the children at 39-45 weeks equivalent gestational age with MRI to assess brain development, and we performed cognitive and clinical assessments at regular intervals. We observed structural, functional and metabolic differences in deep gray and white matter in CHEU, and poorer cognitive performance at 10 and 20 months. In R01 HD093578, we additionally studied the relationship between neuroimaging in infancy and between one and two years of age, and microbiome markers of infant development, including infant nutrition and breastmilk, to establish the relationship between gut microbial diversity, milk oligosaccharide composition and the brain. This study is ongoing. There is an urgent need to understand how and why children exposed to HIV are not thriving as well as their unexposed peers. Early life factors around birth may have consequences throughout life. In this study we will follow this well-characterized cohort established before birth to examine the effects of pre- and perinatal HIV/ART exposure on neurodevelopment around ages 6 and 8 years, using multimodality neuroimaging (morphometry, spectroscopy and connectivity) and clinical and cognitive assessments. This period is important as the children start school at 7 years. We expect to enroll 150 children from the original infant cohort. Our data will enable a longitudinal assessment of HIV/ART exposure on neurodevelopmental out-comes, and potential moderation by environmental factors, infant nutrition and maternal well-being and health. We will continue to sustain the capacity for pediatric neuroimaging and cognitive assessment built up over more than a decade of NIH-supported collaboration between Drs. Meintjes (University of Cape Town), Laughton (Stellenbosch University) and van der Kouwe (Massachusetts General Hospital). We will build new capacity for brain imaging in resource-limited settings by imaging our cohort with a low-field mobile MRI scanner alongside the high-field scanner. With these comparative images we will develop longitudinal morphometric analysis tools to discriminate between healthy and atypical neurodevelopment, making these algorithms cloud-ready so that they are accessible to users with limited computing resources.

项目摘要 防止艾滋病毒垂直传播的程序非常有效。结果，有一个 艾滋病毒暴露和未感染的儿童（CHEU）增加。目前，每五个中至少有一个 南非的儿童（约410万儿童）是HEU。这些孩子甚至面临更高的风险 尽管它们没有被感染，但表现出降低的生长，神经发育延迟和增加的风险 严重的感染，甚至在两岁之前死亡。 2017年，我们开始招募一系列怀孕 患有艾滋病毒的妇女要么在受孕之前或怀孕期间开始三重型艺术 与未感染的妇女一起测试HIV感染阳性的阳性。因此，我们建立了一个队列 三个研究臂中的婴儿。在整个胎儿发育中暴露，暴露在艺术中，并暴露 随着艺术在怀孕后期开始。在R01 HD085813中，我们在39-45周相当地成像了孩子 MRI胎龄评估大脑发育，我们进行了认知和临床评估 定期间隔。我们观察到深灰色和白质的结构，功能和代谢差异 在Cheu和10个月时的认知表现较差。在R01 HD093578中，我们还研究了 婴儿期和一到两岁之间的神经影像学之间的关系，微生物组 婴儿发育的标志物，包括婴儿营养和母乳，以建立 肠道微生物多样性，牛奶寡糖组成和大脑。这项研究正在进行中。 迫切需要了解如何以及为什么接触艾滋病毒的孩子不像 他们未暴露的同龄人。生命的早期因素在生命中可能会产生后果。在这项研究中，我们 将遵循在出生前建立的这个良好特征的队列，以检查前和围产期的影响 艾滋病毒/艺术暴露于6岁和8岁左右的神经发育，使用多模仿性神经成像 （形态计量学，光谱和连通性）以及临床和认知评估。这个时期很重要 随着孩子们在7岁开始上学。我们预计将从原始婴儿队列中注册150名儿童。我们的数据 将对神经发育外的艾滋病毒/艺术暴露进行纵向评估，并进行潜在 环境因素，婴儿营养以及孕产妇的健康和健康。 我们将继续维持儿科神经影像学和认知评估的能力 在DRS之间，多达十多年来的NIH支持的合作。 Meintjes（开普敦大学）， Laughton（Stellenbosch University）和Van der Kouwe（马萨诸塞州综合医院）。我们将建立新的 通过低场移动MRI对我们的队列进行成像，在资源有限的设置中进行大脑成像的能力 扫描仪与高场扫描仪一起。使用这些比较图像，我们将发展纵向 形态计量分析工具以区分健康和非典型神经发育，使其 算法云准备就绪，因此有限的计算资源的用户可以访问它们。