Delayed Cord Clamping in extremely preterm infants – effect on measures of systemic blood flow, cerebral oxygenation and clinical outcomes

Abstract

Background: There is uncertainty regarding optimum timing of umbilical-cord clamping in infants <30 weeks gestation, but trial data suggest benefits from delayed clamping. The mechanism of reported benefit of delayed cord clamping (DCC) is unknown. Aim: To determine the effect of DCC (> 60 sec) on composite outcome of death or major morbidity. To determine whether the effect of DCC is mediated by its effect on systemic blood flow, measured as superior vena cava (SVC) flow by functional cardiac ultrasound or regional cerebral oxygenation measured by near infrared spectroscopy. To determine the interobserver agreement of measures of systemic blood flow and its associations with clinical outcomes. Methods: A multicentre randomised controlled trial (RCT) comparing DCC versus immediate cord clamping (ICC) was conducted in seven countries. A functional cardiac ultrasound substudy (nested RCT) was conducted in five centres to study the effect of DCC on systemic blood flow. A prospective observational study on a subset of infants was performed to study the effect of DCC on cerebral oxygenation. Interobserver agreement for the functional cardiac ultrasound measures were assessed on a subset of infants. A nested observational study of the infants in the substudy was conducted to determine the associations and clinical outcomes of functional cardiac ultrasound measures. Results: Delayed cord clamping as compared to immediate cord clamping did not result in a lower incidence of the primary composite outcome of death or major morbidity at 36 weeks of gestation. The mortaility was significantly lower in the DCC group as compared to ICC group (6.4% vs. 9.0%) in an unadjusted analysis. In the functional cardiac ultrasound substudy, DCC had no effect on mean lowest SVC flow in the first 24 hours. A sensitivity analysis revealed DCC ≥30 s was associated with improved cerebral oxygenation measures in the first 24 hours. The interobserver variability for SVC flow is consistent with those reported before. The nested observational study revealed infants with low SVC flow had no significant difference in mortality and major morbidity. Conclusion: Fewer infants in the DCC group than in the ICC group died by 36 weeks. DCC had no effect on systemic blood flow and may improve cerebral oxygenation. The interobserver variability of SVC flow was consistent with previously reported and low SVC flow was not associated with important neonatal morbidities.