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

摘要 严重的先天性心脏病，如大动脉转位（TGA）是常见的出生 缺陷TGA的结局随着正常心血管生理学的恢复而显著改善 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） 在整个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， ND的结果。已知患有TGA的新生儿在子宫内开始的大脑发育延迟， 获得性新生儿白色损伤（白质损伤）的风险增加，大多数在 新生儿手术这些观察结果和我们的初步数据表明， 从胎儿到新生儿的围产期过渡可能在出生后易患早产儿中起重要作用。 围产期过渡期是一个关键的时间段，有可能进行神经保护干预，如延迟脐带 钳夹，这已被证明可以为足月和早产新生儿提供神经保护。在这 我们的目标是填补我们领域的一个重大空白，即心血管和心血管疾病的生理变化， 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 胎儿和新生儿神经成像和神经监测的经验，使我们能够采取独特的 - 从胎儿生命开始的纵向方法，以首先鉴定大脑成熟不良的产前生物标志物， 第二，检查过渡生理学对获得性新生儿腹泻的影响。我们将测试 假设子宫内脑组织氧合减少易导致脑不成熟， 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，这可以通过改善围产期脑氧输送通过延迟脐带来修改 夹紧。我们的长期目标是利用该提案的数据设计神经保护试验，重点是 过渡期有可能优化该患者人群的ND结局。

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.