Rapid Responses to:

ANALYSIS:
Nicholas M Fisk and Rifat Atun
Public-private partnership in cord blood banking
BMJ 2008; 336: 642-644 [Full text]
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Rapid Responses published:

[Read Rapid Response] Cord clamping and cord blood banking
David JR Hutchon   (22 March 2008)
[Read Rapid Response] Cord Bank Funding - A Third Way
Stephen McEwan   (29 March 2008)

Cord clamping and cord blood banking 22 March 2008
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David JR Hutchon,
Consultant Obstetrician
Darlington Memorial Hospital. DL3 6HX

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Re: Cord clamping and cord blood banking

Fisk and Atun point out that “demand for stem cells from cord blood is greater than supply” (1) This is true. The demand is from the baby but the supply is usually artificially manipulated by the cord clamp. This may have very serious consequences for the newborn baby. The solution in this situation is simple. If the baby is allowed to receive as much blood from the placenta as it requires then the supply will always be sufficient. There are mechanisms which naturally partition a volume of blood in the baby and a volume of blood in the placenta. Once the baby has filled its requirements and closed down the placental circulation, there may be sufficient blood left in the placenta to store or to be given for autologous cord blood transplantation.

Common practice
"Cord blood is usually discarded at birth" While this is common practice, the amount of blood discarded can vary considerably depending on how the birth is managed. A physiological third stage often leaves little residual blood in the cord and placenta. (2) Clamping the cord immediately after birth leaves a much larger residual volume in the placenta and a much smaller volume in the newborn baby than normal(3). Why this “usual” practice is supported by obstetricians, paediatricians and some midwives is a mystery. The only ethical reason for supporting immediate clamping is benefit and/or absence of harm to the baby and/or mother. All the evidence indicates that there is harm to the newborn baby by clamping the cord immediately. (4,5) None of the many randomised controlled trials showed any harm from delayed clamping. (6)

If the justification for immediate cord clamping was to increase the volume of blood for cord blood collection this would be totally unethical and probably illegal.

Establishing trust
Any information given to parents considering donating their baby’s blood for banking must be complete. They must be told that delayed cord clamping may make the volume of residual blood in the placenta too small to be useful. They must be told that immediate cord clamping may increase the risk of intraventricular haemorrhage, infection, anaemia and the need for transfusion in preterm babies. They must be told that immediate cord clamping increases the risk of neonatal anaemia, especially in populations vulnerable to anaemia. They must be told that delayed cord clamping has no effect on the active management of the third stage of labour and postpartum haemorrhage. They must be told what the current hospital practice is, that some hospitals e.g.Darlington Memorial Hospital have a policy for delayed cord clamping and there is current debate and ongoing research about the best practice. There is no RCOG guideline at present.

Weeks (7) recently called for a three minute wait before clamping the cord at birth. The question centres around the normal physiological changes which occur in the baby’s circulation and breathing at birth(8), the risks of neonatal anaemia(9), risk of elevated lead levels (10), the potential for mesenchymal stem cells to repair birth injury (11), and the risk of hypovolaemia at birth (12,13). The need for cord blood pH testing is sometimes put forwards as an argument for immediate cord clamping. The result of the test done at birth is rarely timely enough to be of any value to the health of the baby and is simply for medicolegal purposes to try to protect the obstetrician, midwife or hospital.

How many parents who know these risks are going to ask for immediate cord clamping? I doubt there would be many but until we provide them with the information we will not know. Patrick O'Brien, spokesman for the Royal College of Obstetricians and Gynecologists said: “The latest research [on cord clamping] does suggest parents should be given a choice and it should be discussed routinely in antenatal classes.” (14)

References
1. Fisk N M and Atun R. Analysis. Public-private partnership in cord blood banking BMJ 2008; 336: 642-644
2. Usher R, Shephard M, Lind J. The blood volume of the newborn infant and placental transfusion. Acta Paediatr Scand. 1963
3. Yao, A.C., M. Moinian, and J. Lind, Distribution of blood between infant and placenta after birth. Lancet, 1969. 2(7626): p. 871-3.
4. Rabe H, Reynolds G, Diaz-Rossello J. Early versus delayed umbilical cord clamping in preterm infants. Cochrane Database Syst Rev 2004;(4):CD003248
5. Hutton EK, Hassan ES. Late vs early clamping of the umbilical cord in full-term neonates: systematic review and meta-analysis of controlled trials. JAMA. 2007 Mar 21;297(11):1241-52.
6. Mercer JS. Current best evidence: a review of the literature on umbilical cord clamping. J Midwifery Women's Health 2001;46:402–14.
7. Weeks A Umbilical cord clamping after birth BMJ, Aug 2007; 335: 312 - 313
8. Mercer J S, & Skovgaard RL. Neonatal Transitional Physiology: A New Paradigm. Journal of Perinatal & Neonatal Nursing. 2002; 15:; 56-75
9. van Rheenen P, Brabin B. Late umbilical cord-clamping as an intervention for reducing iron deficiency anaemia in term infants in developing and industrialised countries: a systematic review. Ann Trop Paediatr 2004;24:3-16
10. CHAPARRO C M, FORNES, R. NEUFELD L M, ALVEZ G T, CEDILLO R E, AND DEWEY K G Early Umbilical Cord Clamping Contributes to Elevated Blood Lead Levels among Infants with Higher Lead Exposure J Pediatr 2007;151:506-12
11. Meier, C., et al., Spastic paresis after perinatal brain damage in rats is reduced by human cord blood mononuclear cells. Pediatr Res, 2006. 59(2): p. 244-9.
12. Linderkamp O. Placental transfusion: determinants and effects. Immediate cord clamping can result in hypotension, hypovolemia and anemia. Clinics in Perinatology 1982;9:559-592
13. Dunn P M. Tight nuchal cord and neonatal hypovolaemiaic shock. Arch Dis Child 1988 63 570-571
14. Johnston L Daily Express Weekend 16th December 2007 p10 Cord clamping danger to babies

Competing interests: None declared
Cord Bank Funding - A Third Way 29 March 2008
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Stephen McEwan,
Chief Executive, Anthony Nolan Trust
The Anthony Nolan Trust, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG

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Re: Cord Bank Funding - A Third Way

Dear Sirs

Fisk and Atun’s balanced critique of the contribution that Virgin Health Bank might make to increased numbers of nationally stored cord blood units is to be welcomed. However, I believe that the role of the Anthony Nolan Trust, an organisation funded by charitable donations, also needs to be taken into account when considering the UK’s future therapeutic use of cord blood and the funding required to increase the country’s cord inventory.

Currently, as the major importer from overseas banks of cord material for UK patients, the Charity is playing a key role in stem cell provision.

In addition, the Charity is undertaking a pilot cord blood collection scheme in collaboration with King’s College Hospital, London, and has recently set up a purpose-built processing and storage facility in Nottingham.

It is planned to increase the number of collection centres over the next few years. Subject to suitable funding, working with centres in ten major hospitals across the UK, the Charity could substantially increase the cord inventory by 20,000 over the next five years.

Our experience so far indicates that NHS staff are supportive of the collection of cord blood for our public bank as our collection model includes providing additional charity-funded personnel to work alongside NHS maternity unit staff.

The Charity’s Cord Blood Programme has two other important elements: material not suitable for banking will be made available for research initiatives aimed at investigating the possible therapeutic use of the stem cells in cord blood in a wide range of diseases and a system of support is being developed to provide assistance to physicians in selecting the most suitable stem cell graft available for a particular clinical situation.

In these ways, the full potential of publically donated cords can hopefully be realised using an alternative funding model not dependent on charging parents which, even with an acceptable collection system, is clearly skewed towards those with the ability to pay.

Yours faithfully Dr Steve McEwan Chief Executive

Competing interests: Chief Executive The Anthony Nolan Trust