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 预防艾滋病毒垂直传播的计划非常有效。因此，有一个 暴露于艾滋病毒的儿童和未感染的儿童(CHU)的人口不断增加。目前，至少每五个人中就有一个 南非的儿童(大约410万名儿童)是HEU。这些孩子甚至面临更高的风险 虽然他们没有被感染，但表现出生长减慢、神经发育迟缓和患病风险增加 严重感染，甚至在两岁前死亡。2017年，我们开始招募一批孕妇 艾滋病毒携带者在怀孕前或怀孕期间开始三联疗法的妇女 一旦检测出艾滋病毒感染呈阳性，立即与未感染的妇女一起。因此，我们建立了一个队列 在三个研究组中的婴儿。未暴露，在整个胎儿发育过程中暴露于ART，并暴露 ART是在怀孕后期开始的。在R01 HD085813中，我们对39-45周的儿童进行了成像 通过核磁共振检查评估大脑发育情况，并进行认知和临床评估 每隔一段时间。我们观察到深部灰质和白质在结构、功能和代谢方面的差异 在10个月和20个月时，认知表现较差。在R01 HD093578中，我们还研究了 婴儿期及1~2岁儿童神经影像与微生物群的关系 婴儿发育指标，包括婴儿营养和母乳，以建立两者之间的关系 肠道微生物多样性、牛奶低聚糖组成和大脑。这项研究正在进行中。 迫切需要了解接触艾滋病毒的儿童如何以及为什么不能像 他们未暴露的同龄人。出生前后的早期生活因素可能会对一生产生影响。在这项研究中，我们 将遵循这个在出生前建立的特征良好的队列来检查产前和围产期的影响 使用多模式神经成像技术研究HIV/ART暴露对6岁和8岁左右儿童神经发育的影响 (形态测量、光谱和连通性)以及临床和认知评估。这段时间很重要 因为孩子们从7岁开始上学。我们预计将从最初的婴儿队列中招募150名儿童。我们的数据 将能够对HIV/ART暴露于神经发育结果的纵向评估，以及潜在的 受环境因素、婴儿营养以及产妇福祉和健康的影响。 我们将继续保持儿科神经成像和认知评估的能力 十多年来，在NIH的支持下，Meintjes博士(开普敦大学) Laughton(StellenBosch大学)和van der Kouwe(马萨诸塞州综合医院)。我们将建造新的 在资源有限的情况下，通过使用低场移动MRI对我们的队列进行成像，获得脑成像的能力 高场扫描仪旁边的扫描仪。有了这些对比图像，我们将进行纵向开发 形态计量分析工具可以区分健康和不典型的神经发育，使这些 算法支持云，因此计算资源有限的用户可以访问它们。