Infant mortality of babies born extremely preterm (EPT) is more than 100 times that of babies born at term, and those who survive are at high risk of neurodevelopmental disabilities. These babies have very fragile brain microvasculature and immature cardiovascular reflexes, which renders them highly vulnerable to brain injury, such as intracranial hemorrhage (IVH) or ischemia. Much of the injury is believed to occur during the few minutes of transition from intrauterine to extrauterine life. Common protocol for assisting EPT babies during transition is for obstetricians to clamp the umbilical cord immediately following delivery to permit neonatologists to provide resuscitation measures as required. New evidence suggests that delaying cord clamping (DCC) 30 or more seconds after birth may be beneficial for preterm infants. Nevertheless, most obstetricians have not adopted DCC for all EPT babies, with the concern that some of these high-risk babies will need assistance with breathing, thus requiring cutting of the cord quickly to give the babies access to neonatologists. In fact, most of the previous DCC studies have excluded babies who require resuscitation. Animal studies have shown that assisting breathing while the preterm newborn is attached to the placenta is more important than just the placental transfusion that occurs during DCC. This multicenter trial will compare in babies born extremely preterm, including those requiring resuscitation, 30 sec of delayed cord clamping followed by assisted ventilation (the standard cohort), with delayed cord clamping for 120 sec while ventilation is assisted with the cord intact between 30 and 120 sec (the study cohort). If assisting breathing before umbilical cord clamping is shown to result in improved outcomes (better survival without IVH), this study may lead to new guidelines for immediate stabilization of babies born extremely preterm following birth, and subsequently less mortality and morbidity for this very high risk group of babies.

Public Health Relevance

Babies born extremely preterm have a high rate of death or major complications such as brain hemorrhage or other asphyxial injury that can result in permanent disability. Some of these injuries occur immediately after birth, in the transition from fetal to neonatal circulation. There is evidence that delaying clamping of the umbilical cord can benefit preterm infants, but the current standard for an extremely preterm infant not breathing well after birth is to cut the umbilical cord quickly, to permit moving the baby to a resuscitation table, and then assist breathing. However, laboratory studies have shown that assuring good lung ventilation before cord clamping will stabilize blood flow to the body and brain and may therefore lead to less brain hemorrhage and other organ injuries. This multicenter randomized clinical trial will compare providing breathing assistance before cord clamping after birth versus the current standard practice of cord clamping early for babies who are not breathing well. If this simple change leads to improved chances of survival without brain hemorrhage or other neonatal morbidities, this study may lead to significant changes in resuscitation guidelines and subsequently to less mortality and morbidity for this very high risk group of babies.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
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National Institute of Child Health and Human Development Initial Review Group (CHHD)
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Koso-Thomas, Marion
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University of Virginia
Schools of Medicine
United States
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