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

摘要 严重形式的先天性心脏病，如大动脉转位(TGA)是常见的出生 缺陷。随着正常心血管生理的恢复，TGA的预后显著改善 在新生儿手术后。尽管如此，患有TGA的儿童经历了显著的神经发育(ND) 生命周期中的损伤表明产前和新生儿的生理可能会产生持久的影响 关于ND结果。已知患有TGA的新生儿从子宫开始就有大脑发育延迟，并且 获得性新生儿脑白质损伤(WMI)的风险增加，大多数观察到在 新生儿手术。这些观察和我们的初步数据表明，在 围产期从胎儿到新生儿的过渡可能在出生后WMI的易感性中起着重要作用。 围产期过渡是神经保护性干预的关键时期，例如脐带延迟 夹住，这已被证明为足月和早产儿提供神经保护。在这 建议，我们的目标是填补我们领域的一个重大空白，即如何在心血管和 围产期过渡期脑血流动力学影响TGA患者的脑健康。我们的两个中心 在胎儿和新生儿神经成像和神经监测方面的经验，使我们能够采取独特的 从胎儿时期开始的纵向方法首先确定大脑发育不良和 第二，探讨过渡性生理学对获得性新生儿WMI的影响。我们将测试 假设在子宫中减少脑组织的氧合容易导致大脑不成熟，即 由此导致的不成熟增加了获得性新生儿WMI的易感性，这是由于围产期循环特征 TGA，这可以通过通过延迟脐带改善围产期脑供氧来改善 夹紧。我们的长期目标是使用这项提案的数据来设计神经保护试验，重点是 有可能优化该患者群体ND结局的过渡期。

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.