Premature Infants Receiving Cord Milking Or Delayed Cord Clamping

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BACKGROUND: Preterm brain injury from intraventricular hemorrhage (IVH) is a pressing worldwide public health problem. Over 12,000 premature newborns develop IVH every year in the US alone. Delaying clamping the umbilical cord at birth for 30-60 seconds provides the newborn with a significant autologous transfusion of blood from the placenta and has been shown to reduce IVH. Delayed cord clamping (DCC) has been shown to reduce overall IVH (mainly lower grades 1 and 2) by 50 percent, but has not reduced the incidence of severe IVH or death. This may reflect inadequate placental transfusion for newborns delivered by Cesarean section (C/S), the most common mode of delivery for very preterm infants. In 3 DCC trials an increased placental transfusion was evident in infants born by vaginal delivery (V/D), but no or minimal transfusion in infants delivered by C/S. We evaluated a technique – umbilical cord milking (UCM) – which provides a placental transfusion by grasping the unclamped umbilical cord and pushing blood towards the newborn several times before the cord is clamped. Our Phase 1 pilot trial (PREMOD) compared UCM to DCC in premature newborns delivered by C/S and V/D. Results were equivalent for V/D. UCM improved blood flow and organ perfusion in C/S infants. SPECIFIC AIMS: The specific aims of this trial are: Aim 1. To compare the incidence of severe IVH and/or death in premature newborns <32 weeks GA delivered by C/S receiving UCM to those receiving DCC. Aim 2. To compare the safety and efficacy profiles of premature newborns <32 weeks GA delivered by C/S receiving UCM vs. DCC during their hospitalization and at 24 months corrected age. Aim 3. To compare the outcomes of premature newborns <32 weeks GA delivered by C/S (from Aims 1 and 2) with those born by V/D receiving UCM or DCC. DESIGN: This trial has a 2-tiered approach that will first demonstrate that the incidence of severe IVH and/or death in premature newborns <32 weeks delivered by C/S with UCM is equivalent to DCC (non-inferiority), and then test whether there is a decreased incidence of severe IVH and/or death with UCM (superiority). This approach is being used in other neonatal trials, is endorsed by the FDA, and can be done within the scope and sample of the proposed trial. DCC: The obstetrician will wait at least 60 seconds to clamp the cord. UCM: The obstetrician will milk about 20 cm of umbilical cord four times over 2 seconds each. Brain oxygenation will be recorded for the first 72 hours of life. Outcomes will include resuscitation interventions and neurodevelopmental follow-up at 2 years. UCM is simple and allows resuscitation of the most critical infants without delay, which justifies its use, even if UCM is equivalent to DCC. Optimal umbilical cord management in premature newborns is an area that urgently needs scientific evidence to establish clear guidelines worldwide.