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

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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.