Timing of Umbilical Cord Clamping at Birth in Full-term Infants

Delayed clamping of the umbilical cord at birth results in placental transfusion. The amount of blood transfusion depends on several factors, including timing of cord clamping, initiation of first breath and cry, gravity, mode of delivery, and intensity of uterine contractions at the end of the second stage of labor. It has been estimated that in a vaginally born full-term infant, delaying cord clamping by 2 to 3 minutes results in an increase in neonatal blood volume of approximately 20 to 30 mL per kilogram of body weight.¹ Cesarean delivery has the same effect but to a lesser extent.²

This acute increase in blood volume necessitates physiologic adaptation with transudation of fluid from intravascular to extravascular (primarily interstitial) compartments, including the lung. Transudation of fluid to the interstitial lung tissue results in a lower lung compliance and accounts for the transient increase in respiratory rate observed in these infants during the first few hours of life.³ The additional red blood cells given to the infant, as well as increased iron stores, also result in some demonstrable consequences. On the positive side is the lower incidence of iron deficiency anemia during infancy,⁴ which is particularly relevant in countries where this condition is of high prevalence.⁵ On the negative side is the increased risk for hyperbilirubinemia,⁶ polycythemia, and hyperviscosity.⁷

Because of uncertainty about the beneficial and potential harmful effects of placental transfusion, the clinical timing of cord clamping has been highly variable worldwide. In the western hemisphere, the umbilical cord tends to be clamped soon after birth, presumably to facilitate resuscitation and stabilization of infants and bonding of infants with mothers and because of concerns regarding the adverse effects of placental transfusion. Surveys examining the practice of physicians⁸ and nurse midwives⁹ confirm this. In developing countries the practice is much more variable, and there is a trend toward delayed cord clamping (with the resulting increase in blood and iron received by the infant at birth) to counter the higher incidence of anemia during infancy in these countries.

In view of the controversy, and as reported in this issue of JAMA, Hutton and Hassan¹⁰ performed a thorough and careful meta-analysis involving 1912 infants enrolled in 15 controlled trials to examine the benefits and harmful effects of delayed cord clamping in full-term neonates. The authors concluded that there is adequate evidence that delaying cord clamping for a minimum of 2 minutes following birth is of significant benefit to the neonate, extending into infancy and causing little harm to the health of full-term infants. This conclusion was based on the authors' analysis that showed a significantly lower incidence of anemia at age 2 to 3 months and an insignificant difference in the incidence of transient tachypnea, jaundice, and polycythemia in term infants with delayed cord clamping.

When considering the strength of evidence in formulating evidence-based medical practice, meta-analysis is second in hierarchy to a properly performed, large, randomized controlled trial.¹¹ The level of credibility of a meta-analysis depends on the quality of data analyzed as well as the care and methods used by the authors who performed the analysis.¹² The quality of the meta-analysis by Hutton and Hassan is sufficiently high to warrant consideration by clinicians regarding timing of cord clamping in term infants. However, a stronger and universal endorsement of delayed clamping will require a well-designed and preferably multicenter (to factor in center effects) randomized controlled trial with a sample size that is powered to address both benefits and potential adverse effects of this intervention.

For some clinicians who may consider the evidence provided by meta-analysis strong enough to modify their practice by delaying cord clamping of term infants at birth, several issues deserve consideration. First, in the event of fetal distress and neonatal depression, immediate resuscitation should take priority over placental transfusion; immediate clamping of the cord may be necessary so the infant can be resuscitated. Second, to facilitate placental transfer of blood, the infant should be held approximately 10 inches below the introitus to allow gravity to aid the transfusion.¹³ Third, the review by Hutton and Hassan¹⁰ did not address the effects of uterine contraction resulting from administration of oxytocin; thus, the current practice of administering oxytocin at the end of labor should not be altered. Fourth, delayed cord clamping should not preclude the practice of nutritional anticipatory guidance and iron supplementation to reduce the incidence of iron deficiency anemia in infancy. And fifth, clinicians who are charged with the subsequent care of the newborn should be informed about the delayed cord clamping. This information will increase the awareness of pediatricians, neonatologists, and others who care for the newborn about the need for subsequent observation and management of potential adverse effects such as transient tachypnea, hyperbilirubinemia, and polycythemia.

The practice of timing the clamping of the umbilical cord is variable worldwide. The review by Hutton and Hassan provides evidence that favors delaying clamping for at least 2 minutes after birth of a full-term infant. Randomized controlled trials with sample sizes that are adequately powered for beneficial and potential adverse effects are needed before the practice of delayed clamping can be strongly endorsed.