The Risk of Acquired Neonatal Significant brain Injury during perinatal Transition in Congenital Heart Disease: TRANSIT CHD study

先天性心脏病围产期过渡期间新生儿获得性严重脑损伤的风险：TRANSIT CHD 研究

• 批准号: 10611960
• 负责人: Shabnam Peyvandi
• 金额: $ 56.67万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611960
• 关键词: Adult; Affect; Aorta; Biological Markers; Birth; Brain; Brain Injuries; Brain region; CHD7 gene; Cardiac Surgery procedures; Cardiovascular Physiology; Cardiovascular system; Cerebrovascular Circulation; Cerebrovascular Physiology; Cerebrum; Child; Closure by clamp; Congenital Abnormality; Congenital Heart Defects; Coupled; Data; Development; Drops; Echocardiography; Fetal Hemoglobin; Fetus; Future; Goals; Growth; Heart; Hematocrit procedure; Hour; Intervention; Life; Live Birth; Longevity; Lung; Magnetic Resonance Imaging; Measures; Medical; Methods; Near-Infrared Spectroscopy; Neonatal; Neurodevelopmental Impairment; Newborn Infant; Observational Study; Operative Surgical Procedures; Outcome; Output; Oxygen; Participant; Patients; Perinatal; Physiological; Physiology; Placenta; Play; Population; Positioning Attribute; Predisposition; Pregnancy; Pulmonary Vascular Resistance; Research; Risk; Role; Site; Survivors; Testing; Third Pregnancy Trimester; Time; Tissues; Transposition of Great Vessels; brain health; brain magnetic resonance imaging; brain tissue; brain volume; cerebral hemodynamics; cerebral oxygenation; comparison control; congenital heart disorder; d-transposition of the great arteries; design; experience; fetal; improved; in utero; infancy; motor impairment; neonatal magnetic resonance imaging; neonate; neuroimaging; neuroprotection; operation; patient population; postnatal; premature; prenatal; preterm newborn; primary outcome; programs; rate of change; restoration; risk mitigation; standard of care; tissue oxygenation; tool; ventilation; white matter injury

ABSTRACT Severe forms of congenital heart disease such as transposition of the great arteries (TGA) are common birth defects. Outcomes for TGA have significantly improved with restoration of normal cardiovascular physiology after the newborn operation. Despite this, children with TGA experience significant neurodevelopmental (ND) impairments across the lifespan suggesting that prenatal and neonatal physiology may have a lasting impact on ND outcome. Newborns with TGA are known to have delayed brain development beginning in utero and are at increased risk for acquired neonatal white matter injury (WMI) with the majority observed before the neonatal operation. These observations and our preliminary data suggest that circulatory adjustments during perinatal transition from fetal to neonatal life may play a significant role in the susceptibility to WMI after birth. Perinatal transition is a key time period with potential for neuroprotective interventions such as delayed cord clamping, which has been demonstrated to provide neuroprotection to term and preterm newborns. In this proposal, we aim to fill a significant gap in our field related to how physiologic changes in cardiovascular and cerebral hemodynamics during perinatal transition affect brain health in patients with TGA. Our two centers’ experience with fetal and neonatal neuroimaging and neuromonitoring, uniquely positions us to take a longitudinal approach beginning in fetal life to first identify a prenatal biomarker of poor brain maturation and second to examine the impact of transitional physiology on acquired neonatal WMI. We will test the hypotheses that decreased cerebral tissue oxygenation in utero predisposes to brain immaturity, that the resulting immaturity increases susceptibility to acquired neonatal WMI due to perinatal circulatory features of TGA, and that this could be modified by improving perinatal cerebral oxygen delivery through delayed cord clamping. Our long term goals are to use data from this proposal to design neuroprotective trials focused on the transitional time period that have the potential to optimize ND outcomes in this patient population.

抽象的 严重的先天性心脏病（例如大动脉转位 (TGA)）很常见 缺陷。随着正常心血管生理机能的恢复，TGA 的结果显着改善 新生儿手术后。尽管如此，患有 TGA 的儿童仍会经历显着的神经发育 (ND) 整个生命周期的损伤表明产前和新生儿生理可能会产生持久的影响 关于 ND 结果。已知患有 TGA 的新生儿从子宫内开始就会延迟大脑发育，并且 获得性新生儿白质损伤 (WMI) 的风险增加，大多数在出生前观察到 新生儿手术。这些观察结果和我们的初步数据表明，在 从胎儿到新生儿的围产期过渡可能在出生后对 WMI 的易感性中发挥重要作用。 围产期过渡是一个关键时期，有可能进行神经保护干预，例如脐带延迟 钳夹已被证明可以为足月和早产新生儿提供神经保护。在这个 提案，我们的目标是填补我们领域中与心血管和生理变化如何相关的重大空白。 围产期过渡期间的脑血流动力学影响 TGA 患者的大脑健康。我们的两个中心 胎儿和新生儿神经影像学和神经监测方面的经验使我们能够独特地采取 从胎儿生命开始的纵向方法首先确定大脑成熟度不佳的产前生物标志物 其次检查过渡生理学对获得性新生儿 WMI 的影响。我们将测试 子宫内脑组织氧合减少容易导致大脑不成熟的假设 由于围产期循环特征，导致的不成熟增加了获得性新生儿 WMI 的易感性 TGA，这可以通过延迟脐带改善围产期脑氧输送来改变 夹紧。我们的长期目标是利用该提案中的数据来设计侧重于以下方面的神经保护试验： 有可能优化该患者群体 ND 结果的过渡时间段。