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: 9199891
• 负责人: Barbara Laughton
• 金额: $ 53.71万
• 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/9199891
• 关键词: Acoustics; Adopted; Affect; Africa South of the Sahara; Aftercare; 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; 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; 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; Structure; Students; Substance abuse problem; Techniques; Technology; Testing; Thick; Third Pregnancy Trimester; Tissues; Training; Universities; Validation; Vertical Disease Transmission; Visit; World Health Organization; base; brain metabolism; cognitive performance; cognitive testing; cohort; cost effective; experience; falls; feeding; gray matter; improved outcome; in utero; indexing; mental development; morphometry; mortality; myelination; neonatal brain; neonatal magnetic resonance imaging; neonate; neurodevelopment; neuroimaging; neuropsychological; peer; postnatal; prenatal exposure; technique development; 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.

项目总结