Neonatal imaging as an early marker of neurodevelopment and predictor of cognitive performance in infants exposed to HIV and ART in utero and perinatally

新生儿成像作为子宫内和围产期接触 HIV 和 ART 的婴儿神经发育的早期标志和认知表现的预测因子

• 批准号: 9352865
• 负责人: Barbara Laughton
• 金额: $ 46.29万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-19 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9352865
• 关键词: Acoustics; Adopted; Advanced Development; Affect; Africa South of the Sahara; Age; Age-Months; Anti-Retroviral Agents; Area; Basal Ganglia; Birth; Body Image; Boston; Brain; Brain Injuries; Brain imaging; Breast Feeding; Caring; Child; Childhood; Choline; Clinic; Clinical; Collaborations; Communities; Community Health Centers; Conceptions; Creatine; Custom; DNA; Data; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Drops; Epidemic; Ethics; Exposure to; Fetal Alcohol Exposure; General Hospitals; Gestational Age; Government; Growth; Guidelines; HIV; HIV antiretroviral; HIV-1; HIV-exposed uninfected infant; Head; Image; Infant; Infant Health; Infection; Inositol; Low Prevalence; Magnetic Resonance; Magnetic Resonance Imaging; Massachusetts; Maternal Health; Measures; Mental Depression; Metabolism; Mother-to-child HIV transmission; Mothers; Motion; N-acetylaspartate; Neonatal; Neurons; Neuropsychology; Newborn Infant; Outcome; Participant; Perinatal; Perinatal Exposure; Perinatal Infection; Pharmaceutical Preparations; Policies; Population; Pregnancy; Pregnant Women; Prevention; Prevention program; Property; Recommendation; Recruitment Activity; Reporting; Research; Research Infrastructure; Resolution; Resources; Risk; Sedation procedure; South Africa; South African; Spectrum Analysis; Standardization; Structure; Students; Substance abuse problem; Techniques; Technology; Testing; Thick; Third Pregnancy Trimester; Tissues; Training; Universities; Validation; Vertical Disease Transmission; Visit; World Health Organization; anatomic imaging; antenatal; base; brain metabolism; cognitive performance; cognitive testing; cohort; cost effective; experience; feeding; gray matter; imaging study; improved outcome; in utero; indexing; mental development; morphometry; mortality; myelination; neonatal brain; neonatal magnetic resonance imaging; neonate; neurodevelopment; neuroimaging; peer; postnatal; prenatal exposure; technique development; tractography; treatment planning; treatment strategy; university student; white matter

Project Summary In 2010, 330,000 infants were born with HIV, predominantly due to mother-to-child transmission (MTCT), and 90% of these infants were born in Sub-Saharan Africa. The number has dropped considerably due to increasingly successful prevention of MTCT using combination (triple) antiretrovirals (ARVs). The HIV epidemic remains substantial in South Africa, with 30% infection in pregnant women presenting at South African antenatal clinics. The Western Cape Government has adopted the WHO recommended “Option B+” treatment plan, which has the potential to reduce HIV MTCT to under 1%, and the MTCT rate has fallen considerably. However, it has been reported that HIV-exposed, uninfected infants experience neurodevelopmental delays relative to their unexposed peers. In this study, we propose to measure the effects of in utero and perinatal exposure to ART and HIV on the developing infant brain, using neuroimaging at 38 to 41 weeks gestational age (GA) and neurodevelopmental assessments at 9 and 19 months of age. We aim to determine whether early clinical indicators, including both infant and maternal health, and neuroimaging of the neonatal brain are predictive of later neurodevelopmental outcomes, whether HIV and ART exposure affect infant neurodevelopment, and whether the duration of in utero ART exposure affects outcomes. We will recruit 210 pregnant women, 140 HIV-infected and 70 uninfected, attending the antenatal clinic at the Michael Mapongwana Community Health Centre in Khayelitsha. Infected mothers and infants are treated according to the “Option B+” guidelines, so that their infants will have been exposed to ARVs in utero either since conception (70 infants) or after 12 weeks (70 infants), postnatally and longer if breast feeding. Infants will be tested with HIV-1 DNA PCR at birth, and every 3 months if breast feeding. At 38 to 41 weeks GA, the infants will undergo neuroimaging at the Cape Universities Body Imaging Centre, including structural imaging for brain morphometry, diffusion for brain connectivity, and spectroscopy for brain metabolism. Participants will be followed every three months, with general examinations and growth assessments of the infants, and maternal health assessments, including depression, feeding practices and ARV compliance. Comprehensive neurodevelopmental testing with the Griffiths Mental Development Scale will be done at 9 and 19 months at the KID-CRU at Stellenbosch University (SUN). Acquisition and analysis techniques will be developed jointly by the University of Cape Town (UCT) and Massachusetts General Hospital (MGH). This project extends a successful collaboration between Dr. Barbara Laughton (SUN), Dr. Ernesta Meintjes (UCT) and Dr. André van der Kouwe (MGH). The project will build leading-edge neonatal brain imaging capacity in Cape Town, with unique imaging sequences and hardware, and infant handling techniques developed locally for ethically imaging neonates without sedation. UCT and SUN students will be involved in developing and applying the imaging, cognitive testing and analysis techniques used in the study.

项目概要 2010年，有33万名婴儿出生时就携带艾滋病毒，主要是由于母婴传播（MTCT）， 其中 90% 的婴儿出生在撒哈拉以南非洲地区。数量大幅下降是因为 使用联合（三联）抗逆转录病毒药物（ARV）预防母婴传播越来越成功。艾滋病毒流行 南非的感染率仍然很高，在南非就诊的孕妇中有 30% 感染 产前诊所。西开普省政府已采用世界卫生组织推荐的“B+方案”治疗 该计划有可能将艾滋病毒母婴传播减少到 1% 以下，而且母婴传播率已大幅下降。 然而，据报道，暴露于艾滋病毒、未感染的婴儿会出现神经发育迟缓 相对于未接触过的同龄人。在这项研究中，我们建议测量子宫内和围产期的影响 使用妊娠 38 至 41 周时的神经影像学研究暴露于 ART 和 HIV 对发育中婴儿大脑的影响 9 个月和 19 个月时的年龄 (GA) 和神经发育评估。我们的目标是确定是否 早期临床指标，包括婴儿和孕产妇健康以及新生儿大脑的神经影像学 预测后期神经发育结果，HIV 和 ART 暴露是否影响婴儿 神经发育，以及子宫内 ART 暴露的持续时间是否会影响结果。 我们将招募 210 名孕妇，其中 140 名艾滋病毒感染者和 70 名未感染者，前往位于 Khayelitsha 的 Michael Mapongwana 社区卫生中心。受感染的母亲和婴儿接受治疗 根据“选项 B+”指南，这样他们的婴儿就会在子宫内暴露于抗逆转录病毒药物 自受孕后（70 名婴儿）或 12 周后（70 名婴儿）、产后，如果母乳喂养则更长。婴儿会 出生时接受 HIV-1 DNA PCR 检测，如果母乳喂养，则每 3 个月接受一次检测。在 GA 38 至 41 周时， 婴儿将在开普大学身体成像中心接受神经影像检查，包括结构成像 用于大脑形态测量、用于大脑连接的扩散以及用于大脑代谢的光谱学。参与者将 每三个月进行一次随访，对婴儿进行一般检查和生长评估，以及 孕产妇健康评估，包括抑郁症、喂养方式和抗逆转录病毒药物依从性。综合的 格里菲斯心理发展量表的神经发育测试将在第 9 个月和第 19 个月时进行 斯泰伦博斯大学 (SUN) 的 KID-CRU。将共同开发采集和分析技术 由开普敦大学 (UCT) 和麻省总医院 (MGH) 提供。 该项目延续了 Barbara Laughton 博士（SUN）和 Ernesta Meintjes 博士之间的成功合作 （UCT）和 André van der Kouwe 博士（MGH）。该项目将打造领先的新生儿脑成像技术 开普敦的能力，具有独特的成像序列和硬件以及婴儿处理技术 本地开发用于在不使用镇静剂的情况下对新生儿进行合乎道德的成像。 UCT和SUN的学生将参与 开发和应用研究中使用的成像、认知测试和分析技术。