Tocolytics and preterm labourBMJ 2009; 338 doi: https://doi.org/10.1136/bmj.b195 (Published 06 March 2009) Cite this as: BMJ 2009;338:b195
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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.
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)
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Competing interests: No competing interests