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This editorial (18) raises a lot of very interesting and controversial questions. They start by raising the importance of our understanding of pathophysiology, and I fully agree. However I am at a loss in understanding why we continue to distort teaching and understanding of the physiology of respiratory and circulatory transition at birth. Virtually every textbook of physiology,(1,2,3) paediatrics,(3,4,5) and cardiology (6) describes the cord clamp as part of the physiological process. This is reflected in the teaching of highly respected authorities who probably do not realise themselves the subconscious prejudice about the cord clamp.(7) Gray’s Anatomy (8) is the only text book to describe a process which is natural.
Preterm labour and birth is not natural but it is not a license to administer an intervention no matter how much we may assume that the intervention should be helpful. The fact that immediate or early cord clamping is also carried out routinely at term birth is also no reason to incorporate it into preterm birth. It should be said that immediate or early cord clamping at term birth is of no advantage to the mother and is harmful to the baby. (9,10,11) Some people may think the continued practice of immediate or early cord clamping is surprising given the recommendation of influential organisations such as WHO. We need to thoroughly review what is our understanding of the physiology during transition at birth and ensure that this is taught correctly in textbooks and medical schools. This will remove the fundamental and institutionalised misunderstanding (12) that exists today.
The rational of giving a tocolytic is to allow time for the antenatal corticosteroids to stimulate the production of surfactant by the lungs and reduce the severity of RDS and other complications of prematurity. At about the same time that Liggins was working on antenatal steroids in Auckland(13), Dunn was working on delayed cord clamping (or a physiological transition) in Bristol (14) and found an improved survival similar to that reported by Liggins. It is a sad fact that it is a lot easier to give medication than to do something like DCC, and a randomised trial was never attempted and the approach largely ignored. Many years later Kinmond (15) showed in a RCT a considerable reduction in anaemia after delayed cord clamping and a reduction in the severity of RDS at a time when the use of antenatal steroids were not universal. The subsequent Cochrane review of delayed cord clamping confirmed the reduced anaemia and also a reduction in IVH and NEC. (16) The results for IVH (Outcome 13 in the timing of cord clamping review and outcome 17 in the Calcium channel blocker review) are almost identical for both reviews. Neither review showed any effect for severe IVH but this may have been due to the small number involved. Improved outcomes for NEC were also similar between the two reviews. Mercer et al (17) has also shown improved morbidity in very preterm babies managed with delayed cord clamping at birth. As Carlin et al (18) point out the diagnosis of preterm labour is imprecise and many patients will get treated unnecessarily with both steroid and tocolytic. Allowing a physiological transition by delayed cord clamping can be targeted to those who actually deliver prematurely.
9. A. Lalonde a,*, B.A. Daviss b,1, A. Acosta c,2, K. Herschderfer MATERNAL AND NEWBORN CARE Postpartum hemorrhage today: ICM/FIGO initiative 2004—2006 International Journal of Gynecology and Obstetrics (2006) 94, 243—253
10. WHO Technical Consultation on Prevention of Postpartum Haemorrhage Château de Penthes, Geneva, Switzerland 18–20 October 2006
11. Beyond Survival. Pan American Health Organization Chaparro C et al Essemtial delvery care practices for maternal and newborn health and nutrition.
12. Hutchon DJR NICE is encouraging artificial intervention. BMJ 2007;334:651
13. Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972;50:515-25.
14. Dunn P M, Caesarean Section and the prevention of respiratory distress syndrome of the newborn. In: Bossart, H et al (eds) Perinatal Medicine. 3rd Europ. Congr. Perinatal Medicine, Lausanne, 1972,135-45. Bern, Hans Huber
15. Kinmond S, Aitchison T C, Holland B M, Jones J G, Turner T L, Wardrop C A J. Umbilical cord clamping and preterm infants: a randomised trial. BMJ (1993) vol 306 p172 – 175
16. Rabe H, Reynolds G, Diaz-Rossello J. Early versus delayed umbilical cord clamping in preterm infants. Cochrane Database Syst Rev 2004;(4):CD003248
17. Mercer J S, Vohr B R, McGrath M M, Padbury J F, Wallach M, Oh W. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular haemorrhage and late onset sepsis: A randomised controlled trial. Pediatrics 2006 117 1235 – 1242
18. Carlin A, Norman J, Cole S, Smith R. Tocolytics and preterm labour. Editorials BMJ 2009;338:b195
19. Crowley P. Prophylactic corticosteroids for preterm birth. Cochrane Database Syst Rev 2000;(2):CD000065.
20. Roberts D, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004454. DOI: 10.1002/14651858.CD004454.pub2.
21. Dalziel SR, Walker NK, Parag V, Mantell C, Rea HH, Rodgers A et al. Cardiovascular risk factors after exposure to antenatal betamethasone: 30-year follow-up of a randomised controlled trial. Lancet 2005;365:1856-62.
22. Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A et al. Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in a randomised controlled trial. BMJ 2005;331:665-8.
Physiology and neonatal transition
This editorial (18) raises a lot of very interesting and controversial questions. They start by raising the importance of our understanding of pathophysiology, and I fully agree. However I am at a loss in understanding why we continue to distort teaching and understanding of the physiology of respiratory and circulatory transition at birth. Virtually every textbook of physiology,(1,2,3) paediatrics,(3,4,5) and cardiology (6) describes the cord clamp as part of the physiological process. This is reflected in the teaching of highly respected authorities who probably do not realise themselves the subconscious prejudice about the cord clamp.(7) Gray’s Anatomy (8) is the only text book to describe a process which is natural.
Preterm labour and birth is not natural but it is not a license to administer an intervention no matter how much we may assume that the intervention should be helpful. The fact that immediate or early cord clamping is also carried out routinely at term birth is also no reason to incorporate it into preterm birth. It should be said that immediate or early cord clamping at term birth is of no advantage to the mother and is harmful to the baby. (9,10,11) Some people may think the continued practice of immediate or early cord clamping is surprising given the recommendation of influential organisations such as WHO. We need to thoroughly review what is our understanding of the physiology during transition at birth and ensure that this is taught correctly in textbooks and medical schools. This will remove the fundamental and institutionalised misunderstanding (12) that exists today.
The rational of giving a tocolytic is to allow time for the antenatal corticosteroids to stimulate the production of surfactant by the lungs and reduce the severity of RDS and other complications of prematurity. At about the same time that Liggins was working on antenatal steroids in Auckland(13), Dunn was working on delayed cord clamping (or a physiological transition) in Bristol (14) and found an improved survival similar to that reported by Liggins. It is a sad fact that it is a lot easier to give medication than to do something like DCC, and a randomised trial was never attempted and the approach largely ignored. Many years later Kinmond (15) showed in a RCT a considerable reduction in anaemia after delayed cord clamping and a reduction in the severity of RDS at a time when the use of antenatal steroids were not universal. The subsequent Cochrane review of delayed cord clamping confirmed the reduced anaemia and also a reduction in IVH and NEC. (16) The results for IVH (Outcome 13 in the timing of cord clamping review and outcome 17 in the Calcium channel blocker review) are almost identical for both reviews. Neither review showed any effect for severe IVH but this may have been due to the small number involved. Improved outcomes for NEC were also similar between the two reviews. Mercer et al (17) has also shown improved morbidity in very preterm babies managed with delayed cord clamping at birth. As Carlin et al (18) point out the diagnosis of preterm labour is imprecise and many patients will get treated unnecessarily with both steroid and tocolytic. Allowing a physiological transition by delayed cord clamping can be targeted to those who actually deliver prematurely.
It should be pointed out that the Cochrane review referenced in this editorial (19) has actually been withdrawn and replaced by an updated version (20) with corrected figures.
“ Cochrane Database of Systematic Reviews, Issue 1, 2009 (Status in this issue: Withdrawn, commented) Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. DOI:10.1002/14651858.CD000065.pub2 ”
Dalziel et al has carried out a long term follow-up of the Auckland trial. (21,22) They showed no adverse outcomes for the treated group however, they also pointed out that there was similar morbidity and similar mortality between the two groups. From this work, if safety is accepted then effectiveness must be questioned. From the results of other trials, if effectiveness is accepted, safety is still an issue. We cannot have it both ways. As the ORACLE II trial showed that reducing infection did not have the expected long term benefit, reducing the severity of RDS may not be without long term risks. Physiology cannot be ignored. Nature does nothing uselessly. (23) Murphy et al have shown that too much corticosteroid medication may be harmful.(24)
References
1. Berne RM and Levy MN (1996) Principles of Physiology 2nd Edition. Mosby, St Louis p 349
2. Lindsay DT (1996) Functional Human Anatomy Mosby, St Louis p 447
3. Samson Wright’s Applied Physiology 12th Edition Revised by Keel C A and Neil E. Oxford University Press 1971
3. Mc Millan JA (1999) Osaki’s Pediatrics. 3rd Edition Lippincott Williams and Wilkins, Philadelphia p 286
4. Behrman RE, Klieghman RM, Jenson HB. (2004) Nelson’s Textbook of Pediatrics 17th Edition Saunders, Philadelphia. p 1479
5. Campbell AGM and McIntosh N (1998), Forfar and Arneil’s Textbook of Pediatrics 5th Edition Churchill Livingstone New York, Edinburgh. pp 106-107
6. Braunwald E, Zipes DP, Libby P. (2001) Heart Disease, A Textbook of Cardiovascular Medicine 6th edition Saunders Philadelphia p 1512
7. Gardiner H M. Response of the heart to changes in load: from hyperplasia to heart failure. Heart 2005;91:871-873
8. Standring S (2005) Gray’s Anatomy, 39th Edition. Elsevier Churchill Livinstone Edinburgh pp 1052-4
9. A. Lalonde a,*, B.A. Daviss b,1, A. Acosta c,2, K. Herschderfer MATERNAL AND NEWBORN CARE Postpartum hemorrhage today: ICM/FIGO initiative 2004—2006 International Journal of Gynecology and Obstetrics (2006) 94, 243—253
10. WHO Technical Consultation on Prevention of Postpartum Haemorrhage Château de Penthes, Geneva, Switzerland 18–20 October 2006
11. Beyond Survival. Pan American Health Organization Chaparro C et al Essemtial delvery care practices for maternal and newborn health and nutrition.
12. Hutchon DJR NICE is encouraging artificial intervention. BMJ 2007;334:651
13. Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972;50:515-25.
14. Dunn P M, Caesarean Section and the prevention of respiratory distress syndrome of the newborn. In: Bossart, H et al (eds) Perinatal Medicine. 3rd Europ. Congr. Perinatal Medicine, Lausanne, 1972,135-45. Bern, Hans Huber
15. Kinmond S, Aitchison T C, Holland B M, Jones J G, Turner T L, Wardrop C A J. Umbilical cord clamping and preterm infants: a randomised trial. BMJ (1993) vol 306 p172 – 175
16. Rabe H, Reynolds G, Diaz-Rossello J. Early versus delayed umbilical cord clamping in preterm infants. Cochrane Database Syst Rev 2004;(4):CD003248
17. Mercer J S, Vohr B R, McGrath M M, Padbury J F, Wallach M, Oh W. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular haemorrhage and late onset sepsis: A randomised controlled trial. Pediatrics 2006 117 1235 – 1242
18. Carlin A, Norman J, Cole S, Smith R. Tocolytics and preterm labour. Editorials BMJ 2009;338:b195
19. Crowley P. Prophylactic corticosteroids for preterm birth. Cochrane Database Syst Rev 2000;(2):CD000065.
20. Roberts D, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD004454. DOI: 10.1002/14651858.CD004454.pub2.
21. Dalziel SR, Walker NK, Parag V, Mantell C, Rea HH, Rodgers A et al. Cardiovascular risk factors after exposure to antenatal betamethasone: 30-year follow-up of a randomised controlled trial. Lancet 2005;365:1856-62.
22. Dalziel SR, Lim VK, Lambert A, McCarthy D, Parag V, Rodgers A et al. Antenatal exposure to betamethasone: psychological functioning and health related quality of life 31 years after inclusion in a randomised controlled trial. BMJ 2005;331:665-8.
23. Aristotle, Politics, Greek critic, philosopher, physicist, & zoologist (384 BC - 322 BC)
24. Murphy, K E; Hannah, M E; Willan, A R; Hewson, S A; Ohlsson, A; Kelly, E N; Matthews, S G; Saigal, S; Asztalos, E; Rossi, S; Delisle, M F; Amankwah, K; Guselle, P; Gafni, A; Lee, S K; Armson, B A; MACS Collaborative Group, (2008). Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial. Lancet, 372(9656):2143-2151.
Competing interests: No competing interests