The effect of hypertensive disorders in pregnancy and HIV-infection on maternal, birth and infant outcomes in South Africa

项目摘要 候选人：斯洛格罗夫博士坚定不移地致力于寻找母婴疾病的解决方案 中低收入国家的儿童健康挑战。她最终将自己想象成一个全球范围内的 艾滋病毒暴露未感染(HEU)儿童研究的领导者，并在当地作为农村孕产妇和儿童的领导者 健康研究单位。斯洛格罗夫博士的5年职业发展计划侧重于三个具体领域：1) 在流行病学博士和博士后研究的基础上发展先进的流行病学技能；2) 加强领导能力；3)扩大孕产妇保健专业知识，补充儿科专科医生 培训，全面研究母子动态。这将通过利用 四所合作关系密切的领先机构的优势：斯泰伦博什大学、开普敦大学 小镇、哥伦比亚大学和哈佛大学。斯洛格罗夫博士组建了一支经验丰富的导师团队 将孕产妇和儿童艾滋病毒临床研究方面的专业知识与公共卫生、流行病学和 生物统计学。 研究：这项研究旨在从流行病学角度了解艾滋病毒和抗逆转录病毒疗法(ART)是否 与妊娠期高血压疾病(HDP)相关，以及这是否代表着一条不利的途径 产妇、分娩和HEU婴儿结局。具体目标是确定：1)产妇艾滋病毒和 产前抗逆转录病毒治疗与HDP有关；2)HDP对HIV感染妇女的不利影响 产妇和分娩结果；3)产妇发病率和死亡率以及不良分娩的影响 HEU新生儿和婴儿发病率和死亡率的结果。这项早期职业奖励研究将整合 在NICHD资助的B型阳性研究范围内，全面评估普遍的孕产妇抗逆转录病毒战略 在整个南非西开普省的人口水平上。省级监控通过 统一现有省级电子例行数据来源与哨点现场活动相结合，以 更深入地调查人口趋势。这提供了一个独一无二的机会来询问 在19%的婴儿在子宫内感染艾滋病毒并暴露于抗逆转录病毒治疗的人群中，婴儿易受HEU感染。海流 应用程序利用B阳性电子协调数据平台评估特定目标 西开普省为期两年的整个孕妇队列的人口水平(N≈190,000) 并在两个哨所(N≈17,000)进行更深入的部署。将使用调解分析来了解 与产前抗逆转录病毒治疗相关的不良分娩结局部分是由HDP的增加所调节的，反过来 它们是否在一定程度上调节了新生儿和婴儿的发病率和死亡率。这项研究将很快确定 整个人群是否广泛使用产前抗逆转录病毒疗法与HDP有关，以及这是否 代表了一条导致母婴结局不良的途径，从而导致过高的婴儿发病率和 死亡率。确定孕期抗逆转录病毒治疗的安全性对30%的人来说具有至关重要的公共卫生重要性 感染艾滋病毒的南非孕妇。

Project Summary Candidate: Dr. Slogrove is unwaveringly committed to a career focused on finding solutions to maternal and child health challenges in low-middle income countries (LMIC). She ultimately envisions herself globally as a leader in HIV exposed uninfected (HEU) child research and locally as the leader of a rural maternal and child health research unit. Dr. Slogrove’s 5-year career development plan is focused on three specific areas: 1) to develop advanced epidemiologic skills building on doctoral and post-doctoral studies in epidemiology; 2) to strengthen leadership ability; 3) to expand maternal health expertise complementing pediatric specialist training to comprehensively research the maternal-child dynamic. This will be achieved through drawing on the strengths of four leading institutions with strong collaborative ties, Stellenbosch University, University of Cape Town, Columbia University and Harvard. Dr. Slogrove has assembled a highly experienced mentorship team combining expertise in maternal and child HIV clinical research with public health, epidemiology and biostatistics. Research: This study aims to understand epidemiologically whether HIV and antiretroviral therapy (ART) are associated with hypertensive disorders in pregnancy (HDP) and whether this represents a pathway to adverse maternal, birth and HEU infant outcomes. The specific aims are to determine: 1) whether maternal HIV and antenatal ART are associated with HDP; 2) the contribution of HDP in HIV-infected women to adverse maternal and birth outcomes; 3) the contribution of maternal morbidity and mortality and adverse birth outcomes to HEU neonatal and infant morbidity and mortality. This early career award study will be integrated within the NICHD-funded B-POSITIVE study, comprehensively evaluating the universal maternal ART strategy at a population level in the entire Western Cape Province of South Africa. Provincial surveillance through harmonization of existing provincial electronic routine data sources is combined with sentinel-site activities to investigate population trends in greater depth. This presents a unique opportunity to interrogate pathways of HEU infant vulnerability in a population where 19% of infants are in utero HIV and ART exposed. The current application utilizes the B-POSITIVE electronic harmonized data platform to evaluate the specific aims at a population level in the entire cohort of pregnant women in the Western Cape for a 2-year period (N≈190,000) and in greater depth at two sentinel sites (N≈17,000). Mediation analysis will be used to understand whether the adverse birth outcomes associated with antenatal ART are partly mediated by increased HDP and in turn whether they partly mediate neonatal and infant morbidity and mortality. This study will rapidly determine in an entire population whether widely used antenatal ART regimens are associated with HDP and whether this represents a pathway to adverse maternal and birth outcomes leading to excess HEU infant morbidity and mortality. Establishing the safety of ART during pregnancy is of critical public health importance for the 30% of pregnant South African women who are HIV-infected.