Fetal markers of neurodevelopmental outcomes in congenital heart disease

先天性心脏病神经发育结果的胎儿标志物

• 批准号: 9927690
• 负责人: Shabnam Peyvandi
• 金额: $ 19.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9927690
• 关键词: Acute; Adult; Advisory Committees; Area; Award; Behavioral; Birth; Blood; Brain; Brain Injuries; Brain imaging; Cardiac; Cardiology; Cardiovascular Physiology; Cerebrovascular Circulation; Cerebrum; Child; Childhood; Chronic; Clinical Research; Clinical Trials; Cognitive; Complex; Congenital Abnormality; Consumption; Cross-Sectional Studies; Data; Development; Echocardiography; Educational Activities; Emotional; Environment; Etiology; Exhibits; Faculty; Fetus; Funding; Future; Goals; Heart; Homeostasis; Hyperoxia; Hypoplastic Left Heart Syndrome; Hypoxia; Impairment; Infant Development; Infrastructure; Intervention; Intervention Studies; Lesion; Link; Literature; Longterm Follow-up; Magnetic Resonance Imaging; Measures; Mentors; Mentorship; Metabolism; Methods; Mothers; Motor; Neonatal; Neurodevelopmental Impairment; Neurologic; Neurological outcome; Newborn Infant; Operative Surgical Procedures; Organ; Outcome; Oxygen; Oxygen Therapy Care; Patients; Perfusion; Perioperative; Physiological; Physiology; Population; Pregnancy; Program Development; Prospective cohort study; Protocols documentation; Regulation; Research; Research Personnel; Research Proposals; Resources; Risk; Secondary to; Structure; Techniques; Therapeutic; Third Pregnancy Trimester; Time; Training; Training Programs; Transposition of Great Vessels; Ultrasonography; Vascular resistance; Vasodilation; Work; base; blood oxygen level dependent; brain health; career; career development; cerebral hemodynamics; cerebrovascular; comparative; congenital heart disorder; experience; fetal; high risk population; hypoperfusion; imaging program; imaging study; improved; improved outcome; neonate; operation; postnatal; prenatal; recruit; response; student mentoring; tissue oxygenation; tool; white matter injury

PROJECT SUMMARY This proposal describes a five-year training program for development of a career in clinical research focused on fetal predictors of neurodevelopmental (ND) outcome in critical congenital heart disease (CHD). The candidate has training in pediatric and fetal cardiology. The goals of this award are to rigorously conduct this research proposal, to use the training obtained to develop into a mentor to other trainees and junior faculty and to use this award as a vehicle to become a federally funded independent investigator. To achieve these goals, the applicant has set up a training plan that will include mentoring, course work, hands-on conduct of research and didactic educational activities. This project will be carried out under the mentorship of Patrick McQuillen, MD, a leader in neurodevelopmental outcomes of children with CHD. Complementary mentorship will be provided by Drs. Donna Ferriero and Jim Barkovich, experts in establishing correlations between brain imaging and neurologic outcomes. This mentoring team has successfully mentored students, fellows and junior faculty, including K-level awards. An advisory committee has been assembled to help guide the candidate's career development. This application focuses on understanding the regulation of cerebral blood flow and oxygenation in fetuses with critical CHD as compared to a normal comparative group. Furthermore, the protocol aims to identify the link between fetal cerebral regulation and adaptation with postnatal structural and functional neurologic outcomes in patients with transposition of the great arteries (TGA) and hypoplastic left heart syndrome (HLHS), two common yet physiologically distinct cardiac lesions. Literature demonstrates that these patients have evidence of delayed brain development in late gestation and at birth and are vulnerable to peri- operative white matter injury. The etiology of these findings is likely related to abnormalities in cerebral oxygen delivery as a result of CHD, which may be secondary to decreased cerebral perfusion, decreased blood oxygen content, changes in metabolism or a combination of all. The first part of this proposal focuses on the prenatal time period. We plan to demonstrate differences in regulation of cerebral blood flow (as measured by trans-cranial Doppler) and oxygenation (as measured by T2* MRI) in CHD fetuses as compared to normal fetuses by utilizing brief administration of maternal hyperoxia to acutely alter physiology. To achieve this, we plan to perform a cross-sectional study comparing these measures between CHD and normal fetuses. The second component of this proposal extends to the postnatal time period and aims to understand the relationship between fetal cerebral regulation and postnatal brain structure (MRI at birth) and function (ND outcome at 12 months) in CHD. To achieve this, we plan to conduct a prospective cohort study of fetuses with TGA and HLHS to assess this relationship and to assess differences by cardiac lesion. This proposal will identify fetal physiologic effects on ND outcome in fetuses with CHD, providing critical information to set up future intervention studies with an eventual goal of improving ND outcomes in children with complex CHD.

项目摘要 该建议描述了一项为期五年的培训计划，以开发临床研究职业 关注关键先天性心脏病（CHD）中神经发育（ND）结局的胎儿预测因子。 候选人接受了小儿和胎儿心脏病学培训。 该奖项的目标是严格执行这项研究建议，使用获得的培训 发展成为其他学员和初级教师的导师，并将此奖项用作成为一种工具 联邦资助的独立研究员。为了实现这些目标，申请人制定了一个培训计划， 将包括指导，课程工作，动手进行研究和教学教育活动。这 项目将在神经发育领导者帕特里克·麦奎伦（Patrick McQuillen）的指导下进行 冠心病儿童的结果。补充指导将由Drs提供。 Donna Ferriero和Jim 巴科维奇（Barkovich），在脑成像与神经系统结局之间建立相关性的专家。这 指导团队已成功指导学生，研究员和初级教师，包括K级奖项。一个 咨询委员会已被组成，以帮助指导候选人的职业发展。 该应用的重点是了解对大脑血流和氧合的调节 与正常的比较组相比，具有关键冠心病的胎儿。此外，该协议的目的是 确定胎儿脑调节与适应产后结构和功能之间的联系 大动脉转座（TGA）和左心心脏的患者的神经系统结局 综合征（HLHS），两个常见但生理上不同的心脏病变。文学表明这些 患者有证据表明妊娠晚期和出生时大脑发育延迟，并且很容易受到围裙的影响 手术白质伤害。这些发现的病因可能与脑氧异常有关 由于冠心病的递送，可能是脑灌注降低的继发于血液的降低 氧含量，代谢的变化或所有人的组合。该提案的第一部分着重于 产前时间。我们计划展示大脑血流调节的差异（如 与正常人相比 胎儿利用孕产妇高氧急性生理学的胎儿。为了实现这一目标，我们 计划进行横断面研究，以比较冠心病和正常胎儿之间的这些措施。 该提案的第二个组成部分扩展到产后时间段，旨在了解 胎儿大脑调节与产后大脑结构（出生时MRI）与功能之间的关系（ND 12个月的结果）在冠心病。为了实现这一目标，我们计划对胎儿进行前瞻性队列研究 TGA和HLHS评估这种关系并评估心脏病变的差异。该提议将 确定冠心病的胎儿生理影响对冠心病的胎儿的结局，提供关键信息以设置 未来的干预研究，最终的目标是改善复杂CHD儿童的ND结果。