1/2 CORD-CHD: Clamp OR Delay among neonates with Congenital Heart Disease

项目摘要/摘要 夹住和切断脐带是人类最常见的干预措施，发生在1.4亿人中 每年的出生量。为了最大限度地方便(处理第三产程，启动新生儿复苏)，早期脐带 夹紧(ECC)在交付后约30秒内执行。最近，关于健康益处的证据出现了。 延迟夹住脐带(DCC，夹住前等待~1-2分钟)。在足月新生儿中，多项随机 对照试验(RCT)表明，DCC将血液从胎盘转移到新生儿身上，导致更少的铁- 与ECC相比，缺乏性贫血和改善神经发育(神经运动)的结果持续了4年。 尽管对健康的新生儿有好处，但鉴于他们被排除在以前的随机对照试验之外，最好的方法是 脐带夹闭在高危妊娠中的应用，尤其是合并胎儿诊断为危重先天性的妊娠 心脏病(CCHD)，目前仍不确定。尽管有人可能会认为DCC在低风险新的- 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 患有CCHD的新生儿提示，这一亚组中发生DCC的风险可能不同于没有CCHD的新生儿。 因此，在CCHD新生儿出生时最佳的脐带夹持方法存在治疗难题。这个 拟议的研究题为CORD-CHD(先天性心脏病新生儿的钳夹或延迟)试验将 确定DCC和ECC对出生后和神经发育结局的有效性的首例随机对照试验 对CCHD新生儿的影响。我们的初步数据表明，在CCHD新生儿中，DCC导致总体水平较低 排名得分(GRS)，表明更好的健康结果，比ECC。GRS是一种经过验证的综合衡量标准， 基于心脏手术或导尿术后的最差结果，并反映了复杂血管内注射的必要性。 无微不至的关怀。鉴于缺乏高质量的数据，产妇的结局也将得到确定。我们将利用 网站网络具有必要的基础设施，制定了高遵从率和高待遇的指导方针 忠诚度和协作记录。目的1是检验假设，在CCHD新生儿中，DCC 结果心脏手术或导尿术后较低的GRS(较好的结果)，基于较高的胜算(Win-Obs) 调整为包括平局在内的比率)，而不是与ECC。目标2是测试假设，在患有CCHD的新生儿中， 基于双变量结果的联合测试，DCC将在出生后22-26个月时导致更好的神经运动结果 幼儿第二版运动评分与Hammersmith新生儿的发育评价 神经学检查)而不是ECC。作为次要目标，我们将检验假设，在CCHD中 新生儿在3-4个月时改善神经运动特征(一般运动评估)中介神经功能改善 22-26个月的运动结果。目标3是精确估计产妇产后风险的差异。 DCC和ECC之间的出血以评估分娩CCHD新生儿的母亲的安全性。这 试验将推进对CCHD新生儿的护理，并提供国家和国际要求的证据 这将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 in 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 complex inten- sive 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 neuro- motor outcomes at 22-26mos. Aim 3 is to precisely estimate the difference in the risk of maternal postpartum 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 international organizations, creating a global impact on umbilical cord management among a vulnerable population.