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: 10345355
• 负责人: Shabnam Peyvandi
• 金额: $ 58.21万
• 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/10345355
• 关键词: Adult; Affect; Aorta; Biological Markers; Birth; Brain; Brain Injuries; 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; Face; Fetal Growth; Fetal Hemoglobin; Fetus; Future; Goals; Heart; Hematocrit procedure; Hour; Intervention; Life; 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; Term Birth; Testing; Third Pregnancy Trimester; Time; Tissues; Transposition of Great Vessels; base; brain health; brain magnetic resonance imaging; brain tissue; brain volume; cerebral hemodynamics; cerebral oxygenation; congenital heart disorder; d-transposition of the great arteries; design; experience; fetal; improved; in utero; motor impairment; neonatal magnetic resonance imaging; neonate; neuroimaging; neuroprotection; operation; patient population; postnatal; premature; prenatal; preterm newborn; primary outcome; programs; rate of change; restoration; 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形式，例如大动脉转置（TGA）是普通的出生 缺陷。随着正常心血管生理的恢复，TGA的结果显着改善 新生儿手术后。尽管如此，患有TGA的儿童经历了重要的神经发育（ND） 整个生命周期的障碍表明产前和新生儿生理可能会产生持久的影响 以nd结果。众所周知，患有TGA的新生儿从子宫开始延迟大脑发育，是 在获得新生儿白质损伤（WMI）的风险增加的情况下，大多数在 新生儿操作。这些观察结果和我们的初步数据表明，电路调整 从胎儿到新生儿生活的围产期过渡可能在出生后对WMI的敏感性中起重要作用。 围产期过渡是一个关键时间段，具有神经保护干预措施的潜力，例如延迟绳 夹紧，已证明可以为术语和早产新生儿提供神经保护作用。在这个 提案，我们旨在填补与心血管和心血管的生理变化如何变化有关的领域的重大空白 围产期过渡期间的脑血液动力学会影响TGA患者的脑健康。我们的两个中心 具有胎儿和新生儿神经影像和神经监测的经验，使我们独特地定位 纵向方法始于胎儿生活，首先识别出脑部成熟不良的产前生物标志物 其次检查过渡生理学对获得的新生儿WMI的影响。我们将测试 假设降低子宫内脑组织氧合的假设倾向于脑的不成熟， 由于围产期电路特征，导致的不成熟会增加对获得新生儿WMI的敏感性 TGA，可以通过通过延迟绳索改善围产期脑氧递送来修改这 夹紧。我们的长期目标是使用该建议中的数据来设计针对的神经保护试验 过渡时间有可能优化该患者人群的ND结局。