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• Delayed cord clamping saves lives – why does it not affect major complications?
  Judith S Mercer, Heike Rabe
  Published on: 27 June 2024

• Published on: 27 June 2024

  Delayed cord clamping saves lives – why does it not affect major complications?

  • Judith S Mercer, Professor Emerita in Midwifery University of Rhode Island
  • Other Contributors:
    • Heike Rabe, Professor of Perinatal Medicine

  We thank Pettinger et al for their excellent editorial and for offering an intriguing question – why does delayed cord clamping (DCC) not appear to affect major complications? (Pettinger 2024) We offer three answers. First, many of the surviving infants may have died without DCC. Second, we don’t wait for the neonate to obtain enough of its own blood to survive and thrive. Third, during the 30-60 seconds, practices we use stress the infant which may impede the placental transfusion.
  First, many of the surviving infants may have died without a brief delay in cord clamping (30-60 seconds). They may have received enough additional blood to survive, but not to thrive. The survivors will have co-morbidities of prematurity. Cord blood contains many stem cells, red blood cells with fetal hemoglobin, plasma, progesterone, and other messengers as well as providing enhanced perfusion. Enhanced prefusion delivers mechanical stimuli which causes electrochemical signaling to stimulate the endothelial cells (ECs) to secrete tissue specific angiocrine/paracrine growth factors essential for normal function, maturation, maintenance, and repair of all organs [1,2]. ICC and ECC reduce potential blood volume (equivalent to a class 2 or 3 hemorrhage in adults) to the infant thereby contributing to loss of organ specific vascular competence in the GI tract, brain, kidneys, and other organs potentially exacerbating the common problems seen in the NICU.[3]
  At birth, we don’t know ho...

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  We thank Pettinger et al for their excellent editorial and for offering an intriguing question – why does delayed cord clamping (DCC) not appear to affect major complications? (Pettinger 2024) We offer three answers. First, many of the surviving infants may have died without DCC. Second, we don’t wait for the neonate to obtain enough of its own blood to survive and thrive. Third, during the 30-60 seconds, practices we use stress the infant which may impede the placental transfusion.
  First, many of the surviving infants may have died without a brief delay in cord clamping (30-60 seconds). They may have received enough additional blood to survive, but not to thrive. The survivors will have co-morbidities of prematurity. Cord blood contains many stem cells, red blood cells with fetal hemoglobin, plasma, progesterone, and other messengers as well as providing enhanced perfusion. Enhanced prefusion delivers mechanical stimuli which causes electrochemical signaling to stimulate the endothelial cells (ECs) to secrete tissue specific angiocrine/paracrine growth factors essential for normal function, maturation, maintenance, and repair of all organs [1,2]. ICC and ECC reduce potential blood volume (equivalent to a class 2 or 3 hemorrhage in adults) to the infant thereby contributing to loss of organ specific vascular competence in the GI tract, brain, kidneys, and other organs potentially exacerbating the common problems seen in the NICU.[3]
  At birth, we don’t know how much of each baby’s blood is in the placenta and how much is in its body. Benefits from placental transfusion are likely related to the auto-transfusion of the infant’s fresh whole blood and being primed by high progesterone levels to receive it.[4] The fetus has been using all of this fetal/placental blood volume to grow and development normally - circulating the entire volume, 110 -115 ml/kg body weight, throughout the placenta and its body. About ~1/3 (term) to ½ (preterm) of the blood is circulating in the placenta at any point in time. The placenta has served as exteriorized lungs, gastrointestinal, immune, endocrine and other systems but now all organs must function independently from it. There is no “extra” blood in the fetal system. Immediate (ICC) or early (ECC) clamping (<30 seconds) causes much loss of this blood volume to the infant.
  Even with a delay of 30 to 60 seconds, handling of the infant can cause stress activating the infant’s sympathetic nervous system causing vasoconstriction which may hinder the placenta transfusion. We often stress the infant by placing them on their backs, into a plastic bag, and placing a mask on their faces before assessing breathing. Signs of stress (many startles, splaying of fingers) might indicate that the infant’s sympathetic nervous system is activated causing constriction of blood vessels in the visceral organs to redirect blood flow to the muscles so it can “flee or fight.” Secretion of epinephrine and norepinephrine is stimulated, panic and fear ensue, blood pressure is raised, pupils dilate, and gut motility and immune response are inhibited. This is metabolically expensive and likely disrupts a newborn’s homeostasis. Most importantly, it is unlikely that the infant is assimilating much of its placental transfusion in this highly SNS activated state. In contrast, the Mercer trial (2006) found significantly less IVH and culture-positive late onset sepsis in a group of 72 preterm infants (24 to 31 weeks gestation) after DCC of 30 to 45 seconds in which infants were held by the obstetricians wrapped in a warm blanket (nesting position) at or below the perineum.[5] It never occurred to us until recently that the gentleness alone may have benefited the baby as well as the delay in cord clamping. We encourage the international community to fine tune the optimal cord management with implementing a stress free approach to handling the preterm infant.

  [1] Lorenz L, Axnick J, Buschmann T, Henning C, Urner S, Fang S, et al. Mechanosensing by β1 integrin induces angiocrine signals for liver growth and survival. Nature 2018;562:128–32. https://doi.org/10.1038/s41586-018-0522-3.
  [2] Mercer JS, Erickson-Owens DA, Rabe H. Placental transfusion: may the “force” be with the baby. J Perinatol Off J Calif Perinat Assoc 2021;41:1495–504. https://doi.org/10.1038/s41372-021-01055-0.
  [3] Lodha A, Shah PS, Soraisham AS, Rabi Y, Abou Mehrem A, Singhal N, et al. Association of Deferred vs Immediate Cord Clamping With Severe Neurological Injury and Survival in Extremely Low-Gestational-Age Neonates. JAMA Netw Open 2019;2:e191286. https://doi.org/10.1001/jamanetworkopen.2019.1286.
  [4] González-Orozco JC, Camacho-Arroyo I. Progesterone Actions During Central Nervous System Development. Front Neurosci 2019;13:503. https://doi.org/10.3389/fnins.2019.00503.
  [5] Mercer JS, Vohr BR, McGrath MM, Padbury JF, Wallach M, Oh W. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial. Pediatrics 2006;117:1235–42. https://doi.org/10.1542/peds.2005-1706.

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  Conflict of Interest:
  None declared.

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