2/2 CORD-CHD: Clamp OR Delay among neonates with Congenital Heart Disease

项目总结/摘要 夹紧和切断脐带是人类最常见的干预措施，发生在1.4亿人中。 每年出生。为了最大限度地方便（管理第三产程，开始新生儿复苏）， 夹紧（ECC）在输送后约30秒内进行。最近，有证据表明， 延迟脐带夹紧（DCC，夹紧前等待约1-2分钟）。在足月新生儿中， 对照试验（RCT）表明，DCC将血液从胎盘转移到新生儿，导致铁减少， 与ECC相比，在4年内，缺乏性贫血和改善神经发育（神经运动）结果。 尽管对健康新生儿有优势，但鉴于他们被排除在先前的RCT之外， 在高危妊娠中进行脐带钳夹，特别是那些胎儿诊断为严重先天性 心脏病（CCHD），仍然不确定。虽然人们可能会认为DCC在低风险新- 出生人口将简单地转化为CCHD新生儿，独特的解剖和生理差异， CCHD的新生儿提示此亚组中DCC的风险可能不同于无CCHD的新生儿。 因此，在CCHD新生儿中，出生时最佳脐带夹紧实践存在治疗困境。的 拟定研究，标题为CORD-CHD（先天性心脏病新生儿钳夹或延迟）试验 将是第一个确定DCC与ECC对出生后和神经发育的有效性的RCT CCHD新生儿的结局。我们的初步数据表明，在CCHD新生儿中，DCC导致 较低的全球排名评分（GRS），表明健康结果优于ECC。GRS是一种经过验证的复合材料 根据心脏手术或导管插入术后的最差结果，并反映了对com-cardiac- 复杂的重症监护。由于缺乏高质量的数据，还将确定产妇的结局。我们将 利用具有必要基础设施的站点网络、具有高遵守率的既定准则， 治疗保真度和合作记录。目的1是检验假设，在CCHD新生儿中， DCC导致心脏手术或导管插入术后较低的GRS（更好的结局），基于更高的获胜几率 （胜率调整为包括平局），而不是与ECC。目的2是检验以下假设： 基于双变量联合检验，CCHD、DCC在生后22- 26个月时将导致更好的神经运动结局， 结果（幼儿发展评估第二版运动评分和哈默史密斯 新生儿神经系统检查）。作为第二个目标，我们将测试假设， CCHD新生儿在3- 4个月时改善神经运动特征（一般运动评估）中度改善 22- 26个月时的神经运动结局。目的3是精确估计产妇产后风险的差异， DCC和ECC之间的出血量，以评估母亲生下CCHD新生儿的安全性。 这项试验将促进CCHD新生儿的护理，并提供国家和国际标准所要求的证据。 国际组织，对弱势群体的脐带管理产生全球影响。

PROJECT SUMMARY/ABSTRACT Clamping and cutting the umbilical cord is the most common intervention in humans, occurring in 140 million annual births. To maximize expediency (manage 3rd stage of labor, initiate neonatal resuscitation), early cord clamping (ECC) is performed within ~30 sec of delivery. Recently, evidence has emerged on the health benefits of delayed cord clamping (DCC, waiting ~1-2 min before clamping). Among term neonates, multiple randomized controlled trials (RCTs) have shown that DCC transfers blood from placentas to newborns, resulting in less iron- deficiency anemia and improved neurodevelopmental (neuromotor) outcomes through 4 years, than with ECC. Despite advantages for healthy newborns, in view of their exclusion from previous RCTs, the best approach to cord clamping in higher-risk pregnancies, notably those complicated by a fetal diagnosis of critical congenital heart disease (CCHD), remains uncertain. Although one might assume that the benefits of DCC in low-risk new- born populations would translate simply to CCHD neonates, unique anatomic and physiologic differences in neonates with CCHD suggest that risks of DCC in this subgroup may differ from risks in neonates without CCHD. Thus, a treatment dilemma exists on the optimal cord clamping practice at birth among CCHD neonates. The proposed study, entitled CORD-CHD (Clamp OR Delay among neonates with Congenital Heart Disease) trial will be the first RCT to determine the effectiveness of DCC vs. ECC on postnatal and neurodevelopmental outcomes of CCHD neonates. Our preliminary data demonstrate that, among CCHD neonates, DCC results in lower global rank scores (GRS), indicative of better health outcomes, than ECC. GRS is a validated composite measure, based upon the worst outcome post-cardiac surgery or catheterization and reflects the need for com- plex intensive care. Given the absence of high-quality data, maternal outcomes will also be determined. We will leverage a network of sites with requisite infrastructures, established guidelines with high adherence rates and treatment fidelity, and track records of collaboration. Aim 1 is to test the hypothesis that, among CCHD neonates, DCC results in lower GRS (better outcomes) post-cardiac surgery or catheterization, based on a higher win-odds (win-ratio adapted to include ties), than with ECC. Aim 2 is to test the hypothesis that, among neonates with CCHD, DCC will result in better neuromotor outcomes at 22-26mos postnatal, based on a joint test of a bivariate outcome (Developmental Assessment of Young Children Second Edition motor score and the Hammersmith Neonate Neurological Exam) than with ECC. As a secondary objective, we will test the hypothesis that among CCHD neonates improved neuromotor profiles (General Movement Assessment) at 3-4mos mediate improved neuromotor outcomes at 22-26mos. Aim 3 is to precisely estimate the difference in the risk of maternal postpar- tum hemorrhage between DCC and ECC to evaluate safety among mothers who give birth to CCHD neonates. This trial will advance the care of CCHD neonates and provide the evidence called for by national and interna- tional organizations, creating a global impact on umbilical cord management among a vulnerable population.