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.

项目摘要 2010年，有330,000名婴儿出生于艾滋病毒，主要是由于母亲到孩子传播（MTCT）， 这些婴儿中有90％出生在撒哈拉以南非洲。由于 使用组合（三重）抗逆转录病毒（ARV）越来越成功地预防MTCT。艾滋病毒流行 南非仍然很大，在南非出现的孕妇感染30％ 产前诊所。西开普政府采用了WHO推荐的“选项B+”治疗 计划有可能将HIV MTCT降低到1％以下，并且MTCT率谨慎下降。 但是，据报道，艾滋病毒暴露，未感染的婴儿经历神经发育延迟 相对于他们意外的同龄人。在这项研究中，我们建议测量子宫内和围产期的影响 使用38至41周的神经影像在发育中的婴儿大脑上接触ART和HIV 在9个月大的年龄（GA）和神经发育评估。我们旨在确定是否 早期的临床指标，包括婴儿和孕妇健康，以及新生儿大脑的神经影像学 预测后来的神经发育结果，HIV和ART暴露是否影响婴儿 神经发育以及子宫艺术暴露的持续时间是否会影响结果。 我们将招募210名孕妇，140名HIV感染和70个未感染的孕妇 Khayelitsha的Michael Mapongwana社区健康中心。受感染的母亲和婴儿接受治疗 根据“选项B+”指南 由于概念（70个婴儿）或12周后（70个婴儿），如果母乳喂养，则在产后且更长。婴儿会 出生时用HIV-1 DNA PCR进行测试，如果母乳喂养，则每3个月进行一次测试。在38至41周GA时 婴儿将在开普敦大学身体成像中心进行神经影像学，包括结构成像 用于脑形态计量学，大脑连通性的扩散以及脑代谢的光谱法。参与者会 每三个月进行一次，对婴儿进行一般检查和增长评估，以及 孕产妇的健康评估，包括抑郁症，喂养实践和ARV依从性。综合的 Griffiths心理发展量表的神经发育测试将在9个月和19个月中进行 Stellenbosch University（Sun）的Kid-Cru。获取和分析技术将共同开发 开普敦大学（UCT）和马萨诸塞州综合医院（MGH）。 该项目扩展了Barbara Laughton博士（Sun），Ernesta Meintjes博士之间的成功合作。 （UCT）和AndréVander Kouwe博士（MGH）。该项目将建立前沿的新生儿大脑成像 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 在不镇静的情况下，在当地开发了在道德上成像的新生儿。 UCT和太阳学生将参与 研究中使用的成像，认知测试和分析技术。