Delayed Umbilical Cord Clamping: The Controversy Continues

We’ve heard a lot about delayed umbilical cord clamping in preterm infants over the last several years. I recently began work on an extensive literature review to prepare for a lecture on this topic. I was surprised to see the level of disagreement, reported inconsistency in practice, and continued discussion on this topic.

There were two papers in two 2014 obstetrical journal issues that show the two sides to the story.  McAdams asked why this was not a standard of care for preterm infants in particular, and Tarnow-Mordi et al warn that more evidence is needed before implementation.^{1, 2} First, what is the evidence to support immediate cord clamping? While there was little to no evidence from randomized controlled trials to support this, it reportedly became standard of practice due to concerns about excessive placental transfusion resulting in increased hyperbilirubinemia. In addition, early cord clamping was used for active management of the third stage of labor, to aid in placental separation and prevent hemorrhage.

Many trials have now been performed in preterm infants and demonstrated advantages to delayed cord clamping, such as a need for fewer transfusions, prevention of iron deficiency into childhood, reductions in necrotizing enterocolitis, intraventricular hemorrhage and late onset sepsis. However, Tarnow-Mordi et al argue that, while there are many studies, the overall numbers of included infants was still too small upon which to ensure there were no disadvantages to this practice.² In addition, studies have not consistently evaluated the same method of delayed clamping, so systematic reviews were not helpful. Timing of delayed cord clamping varies: from 30 seconds to 120 seconds, others until the cord stops pulsating (particularly in term infants), and still others study the milking of the cord rather than delayed clamping.

Two pieces of information are important in evaluating cord clamping:

First, if the cord is unclamped until pulsation stops, how much blood is actually provided to the infant or flows back to the placenta?  Polycythemia and resulting hyperbilirubinemia is the concern that has been raised for delayed cord clamping in term infants. Even though studies in this group do not show a significant difference in hyperbilirubinemia high enough to need phototherapy treatment, it remains a concern for providers.  Boere et al studied flow through the umbilical cord of healthy term infants following delivery.³ Even though cord clamping was performed as late as 5 minutes after birth on average with a range up to just over 10 minutes, pulsations continued in some of the cords.  During this time, some cords had bi-directional flow and others had unidirectional flow back to the placenta independent of pulsations in the cord (or at least pulsations could not be felt by the providers).

Second, at what level should the infant be held during the period of time that the cord is still providing a connection to the infant?  Does this affect the amount of blood provided during delayed clamping?  An early study by Yao & Lind led to recommendations that infants should not be held more than 20 cm above or below the introitus.⁴  The Neonatal Resuscitation Program advises that infants should be held at the level of the introitus for vaginal delivery or the mother’s thighs for cesarean section delivery .⁵  Vain et al studied the effect of infant position on amount of placental transfer.⁶   They found no significant effect on infant position and placental transfusion in term infants. If there truly is no effect of infant position on amount of placental transfusion, this may make both the delivery in term, healthy infants and infants who need resuscitation prior to cord clamping easier. Infants could be placed higher for resuscitation or on the mother’s abdomen for bonding while the cord is still attached.

Another interesting finding in the Boere et al study, and others, is that flow through the placenta is affected by the start of spontaneous ventilation or breathing, amongst other factors.³  Cord milking has sometimes been the preferred method for basically getting more blood to the preterm infant in less time. I have witnessed this myself. Both obstetricians and the neonatal team have a hard time waiting even 30 seconds to clamp the cord in a blue, limp infant. Milking of the cord could be done much faster and supposedly provide the same or at least comparable benefit.^{7, 8}  However, this is being questioned as preterm lamb studies have demonstrated that early cord clamping leads to bradycardia and decreased cerebral perfusion unless pulmonary perfusion has been increased prior to cord clamping.⁹ The bradycardia and decreased cerebral perfusion is likely related to a decrease in preload to the heart caused by early cord clamping. Therefore, establishing ventilation prior to clamping the cord, whether spontaneously or through resuscitative efforts, appears to have an advantage. And early cord clamping may result in a need for more resuscitation. However, the practical difficulty in establishing ventilation in a non-breathing infant while still attached to the placenta is great. Babies who need resuscitation often have short cords or nuchal cords that prevent the cord from being long enough to allow the infant to be in a position where sufficient resuscitation can be provided. Even with normal length cords, the amount of equipment and personnel needed presents a challenge given the space available.

So, many questions related to cord clamping remain. Even if we agree that there is benefit to either delayed cord clamping or cord milking, which is best in what situation is not yet clear. Furthermore, we don’t know exactly how to define “delayed” cord clamping. Is it 30 seconds for some, as long as 120 seconds or more for others? When is it more beneficial to cut the cord and start resuscitation for those who need it? Is there benefit to a different approach in term, preterm and extremely preterm infants?

This highlights the overall need for more research in the neonatal population.  Since being in a position to approach parents for consent for clinical neonatal research studies, I have encountered shock and horror on the part of both healthcare providers and parents at the thought of doing research in such a vulnerable population. However, without well-run clinical trials, everything we do is “experimental” and remains without any control or data gathering and evaluation that will help to inform future practice.  Even something as simple and routine as clamping a cord at delivery seems to have a significant impact on not only immediate outcome but also long-term neurodevelopmental outcome. We should really know how to do it right, and the only way that will happen is through additional research.

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Resources:

1. McAdams, R. M. (2014). Time to implement delayed cord clamping. Obstetrics & Gynecology, 123(3), 549-552.

2. Tarnow-Mordi, W. O., Duley, L., Field, D., Marlow, N., Morris, J., Newnham, J., … & Sweet, D. (2014). Timing of cord clamping in very preterm infants: more evidence is needed. American journal of obstetrics and gynecology, 211(2), 118-123.

3. Boere, I., Roest, A. A. W., Wallace, E., Ten Harkel, A. D. J., Haak, M. C., Morley, C. J., … & Te Pas, A. B. (2015). Umbilical blood flow patterns directly after birth before delayed cord clamping. Archives of Disease in Childhood-Fetal and Neonatal Edition, 100(2), F121-F125.

4. Yao, A., & Lind, J. (1969). Effect of gravity on placental transfusion. The Lancet, 294(7619), 505-508.

5. Wyckoff, M. H. (2014, February). Initial resuscitation and stabilization of the periviable neonate: The Golden-Hour approach. In Seminars in perinatology (Vol. 38, No. 1, pp. 12-16). WB Saunders.

6. Vain, N. E., Satragno, D. S., Gorenstein, A. N., Gordillo, J. E., Berazategui, J. P., Alda, M. G., & Prudent, L. M. (2014). Effect of gravity on volume of placental transfusion: a multicentre, randomised, non-inferiority trial. The Lancet, 384(9939), 235-240.

7. Mercer, McGrath, Hensman, Silver, Oh (2003).  Immediate and delayed cord clamping in infants born between 24 and 32 weeks: A pilot randomized controlled trial. Journal of Perinatology.  23:466-472.

8. March, M. I., Hacker, M. R., Parson, A. W., Modest, A. M., & De Veciana, M. (2013). The effects of umbilical cord milking in extremely preterm infants: a randomized controlled trial. Journal of Perinatology, 33(10), 763-767.

9. Bhatt, S., Alison, B. J., Wallace, E. M., Crossley, K. J., Gill, A. W., Kluckow, M., … & Hooper, S. B. (2013). Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs. The Journal of physiology, 591(8), 2113-2126.