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

项目摘要 2010年，33万名婴儿出生时就感染了艾滋病毒，主要是由于母婴传播， 其中90%的婴儿出生在撒哈拉以南非洲地区。由于以下原因，这一数字大幅下降 使用联合(三重)抗逆转录病毒药物(ARV)预防母婴传播日益成功。艾滋病毒的流行 在南非仍然很大，30%的孕妇在南非就诊 产前诊所。西开普省政府已采用世卫组织建议的“B+”治疗方案。 该计划有可能将艾滋病毒母婴传播降低到1%以下，母婴传播率已大幅下降。 然而，据报道，接触艾滋病毒的未受感染的婴儿会出现神经发育迟缓。 相对于他们未暴露的同龄人。在这项研究中，我们建议测量宫内和围产期的影响 孕期38-41周的婴儿大脑发育中暴露于抗逆转录病毒治疗和艾滋病毒的神经成像研究 在9个月和19个月龄时进行年龄(GA)和神经发育评估。我们的目标是确定是否 早期临床指标，包括婴儿和产妇的健康，以及新生儿大脑的神经成像 预测以后的神经发育结果，是否艾滋病毒和抗逆转录病毒治疗会影响婴儿 神经发育，以及宫内ART暴露的持续时间是否影响结果。 我们将招募210名孕妇到产前诊所就诊，其中140人感染艾滋病毒，70人未感染。 Khayelitsha的Michael Mapongwana社区卫生中心。受感染的母亲和婴儿得到治疗 根据“方案B+”的指导方针，因此他们的婴儿在子宫内也会接触到抗逆转录病毒药物。 从受孕开始(70名婴儿)或12周后(70名婴儿)，出生后更长时间如果是母乳喂养。婴儿会 在出生时进行HIV-1DNA聚合酶链式反应检测，如果是母乳喂养，每隔3个月进行一次检测。在38至41周出生时， 婴儿将在开普敦大学身体成像中心接受神经成像，包括结构成像 用于脑形态测量，用于脑连接的扩散，以及用于脑代谢的光谱。参与者将 每三个月跟踪一次，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、喂养做法和抗逆转录病毒药物依从性。全面 使用Griffiths智力发育量表进行神经发育测试将在9个月和19个月时进行 斯泰伦博什大学(SUN)的Kid-CRU。采集和分析技术将共同开发 由开普敦大学(UCT)和马萨诸塞州综合医院(MGH)提供。 该项目扩展了Barbara Laughton博士(SUN)、Ernesta Meintjes博士之间的成功合作 和Andrévan der Kouwe博士(MGH)。该项目将建立前沿的新生儿脑成像 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 在当地开发，用于对没有镇静的新生儿进行伦理成像。UCT和SUN的学生将参与到 开发和应用研究中使用的成像、认知测试和分析技术。

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.