Antecedents of Impaired Brain Development in Fetuses with Heart Disease

患有心脏病的胎儿大脑发育受损的前因

• 批准号: 8692015
• 负责人: Catherine Limperopoulos
• 金额: $ 75.52万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8692015
• 关键词: Address; Age-Months; Biological Markers; Blood Circulation; Brain; Brain Injuries; Cardiac Surgery procedures; Cerebral cortex; Cerebrovascular Circulation; Cerebrum; Complication; Cross-Sectional Studies; Data; Development; Developmental Disabilities; Doppler Echocardiography; Environment; Failure; Fetus; Functional disorder; Future; Goals; Growth; Growth and Development function; Health; Heart Diseases; Hypoplastic Left Heart Syndrome; Imaging Techniques; Impairment; Individual; Infant; Intervention; Life; Literature; Longevity; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Metabolism; Methods; Morbidity - disease rate; N-acetylaspartate; Neonatal; Neurologic; Neurologic Dysfunctions; Neurons; Newborn Infant; Operative Surgical Procedures; Outcome; Oxygen; Perfusion; Placenta; Population; Pre-Eclampsia; Procedures; Protons; Quality of life; Research Proposals; Risk; Risk Marker; Role; Second Pregnancy Trimester; Subgroup; Survivors; Therapeutic Intervention; Third Pregnancy Trimester; Time; Vascular resistance; Work; aortic arch; brain metabolism; brain size; congenital heart disorder; falls; fetal; hazard; hemodynamics; high risk; imaging modality; in vivo; infancy; insight; mortality; neurodevelopment; neuroprotection; postnatal; prenatal; prevent; public health relevance; repaired; therapy development

DESCRIPTION (provided by applicant): .In the management of congenital heart disease (CHD) has markedly reduced mortality. However, brain injury remains a major impediment to high quality of life in survivors. A growing body of literature suggests that a substantial component of this neurologic morbidity may be prenatal in origin. Our studies in CHD fetuses showed for the first time that impaired brain development occurs predominantly in the third trimester and is associated with evidence of impaired brain perfusion and anaerobic metabolism. The mechanism by which CHD disrupts fetal brain development remains unclear. We have developed and validated methods to safely and reliably quantify brain development and metabolism in the living fetus, and newborn using advanced magnetic resonance imaging (MRI) techniques. In the current proposal, we plan to apply echocardiographic measures of the fetal circulation (as well as quantitative MRI methods) to identify the earliest biomarkers for impaired brain development in the fetus with CHD. We will accomplish this by addressing the following specific aims: 1) to determine whether abnormalities in cortical development and brain metabolism (by quantitative MRI and Magnetic Resonance Spectroscopy) are an early marker for risk of impaired volumetric brain growth in the fetus with CHD compared to control fetuses, 2) to determine whether systemic and cerebral hemodynamic perfusion abnormalities (by echocardiography/Doppler US) predict impaired brain growth and/or elevated cerebral lactate in the fetus with CHD versus controls, and 3) to examine the early and long-term neurodevelopmental significance of fetal biomarkers for impaired brain development identified in aims 1 and 2. Our goal is to develop the capacity to reliably and non-invasively identify fetuses with CHD at risk for early brain injury. This, in turn, will begin to open windows for the development of therapeutic interventions aimed at preventing or limiting impaired brain development in these high-risk fetuses.

描述（申请人提供）：在先天性心脏病（CHD）的管理中，死亡率明显降低。然而，脑损伤仍然是幸存者高质量生活的主要障碍。越来越多的文献表明，这种神经系统疾病的一个重要组成部分可能是产前起源。我们在CHD胎儿中的研究首次表明，脑发育受损主要发生在妊娠晚期，并与脑灌注和无氧代谢受损的证据相关。CHD破坏胎儿大脑发育的机制尚不清楚。我们已经开发并验证了使用先进的磁共振成像（MRI）技术安全可靠地量化活体胎儿和新生儿大脑发育和代谢的方法。在目前的建议中，我们计划应用超声心动图测量胎儿循环（以及定量MRI方法），以确定CHD胎儿大脑发育受损的最早生物标志物。我们将通过实现以下具体目标来实现这一目标：1）确定是否异常皮质发育和脑代谢（通过定量MRI和磁共振波谱）是CHD胎儿与对照胎儿相比脑体积生长受损风险的早期标志物，2）判断全身和脑血流动力学灌注是否异常（通过超声心动图/多普勒超声）预测CHD胎儿与对照组相比脑生长受损和/或脑乳酸升高，和3）检查目标1和2中鉴定的胎儿脑发育受损的生物标志物的早期和长期神经发育意义。我们的目标是发展可靠和非侵入性地识别CHD胎儿早期脑损伤风险的能力。反过来，这将开始为开发旨在预防或限制这些高危胎儿大脑发育受损的治疗干预打开窗口。