The Lancet: Deferred clamping of umbilical cord reduces risk of death in premature babies by at least a third, suggest two studies with the most comprehensive analysis to date

(Press-News.org) Peer-reviewed / Systematic review and meta-analysis / People

The Lancet: Deferred clamping of umbilical cord reduces risk of death in premature babies by at least a third, suggest two studies with the most comprehensive analysis to date

Meta-analysis of 3,292 infants across 21 studies finds premature babies whose umbilical cord is clamped 30 seconds or more after birth are less likely to die before leaving the hospital, compared to those whose cord is clamped immediately after birth. A second companion meta-analysis of 47 trials including 6,094 babies suggests waiting at least two minutes before clamping the cord of a premature baby may reduce the risk of death compared with waiting less to clamp the cord. Researchers say these results can inform a change in clinical practice, leading to teams of midwives and doctors working together to defer clamping the umbilical cord while ensuring the baby is warm, breathing, and cared for. However, they caution that the results might not be generalisable in low-income settings and to babies requiring immediate resuscitation, unless the hospital is able to provide safe initial breathing help with the cord intact, and call for more research in this area. Waiting for two minutes or longer to clamp the umbilical cord of a premature baby likely reduces the risk of death soon after birth, compared with immediately clamping the cord or waiting a shorter time, according to two companion systematic reviews and meta-analyses published in The Lancet.  

Deferring clamping of the umbilical cord allows blood to flow from the placenta to the baby whilst the baby’s lungs fill with air and is thought to potentially ease the transition into breathing and to potentially reduce the risk of iron deficiency in the infant.

It is now recommended routine practice for babies born at full term to have their cords clamped after waiting for a minute or two. However, previous research has been unclear on whether this practice is also beneficial for babies born prematurely, leading to varying recommendations in national and international guidelines. The two new studies provide the most comprehensive analysis of all available evidence.

“Worldwide, almost 13 million babies are born prematurely each year and, sadly, close to 1 million die shortly after birth. Our new findings are the best evidence to date that waiting to clamp the umbilical cord can save the lives of some premature babies. We are already working with international guideline developers to make sure these results are reflected in updated guidelines and clinical practice in the near future”, says first author Dr Anna Lene Seidler at the NHMRC Clinical Trials Centre, University of Sydney, Australia. [1]

The researchers conducted a systematic review to identify studies on umbilical cord management in premature babies. Investigators from over 60 studies including more than 10,000 babies shared their complete raw datasets with the research team in an international collaboration (the iCOMP collaboration), forming one of the largest combined databases in this research field. The authors used these large, combined datasets to firstly conduct a meta-analysis comparing the impact of different cord clamping strategies on premature baby mortality, and a second meta-analysis to compare different timings of cord clamping. 

The first meta-analysis included data from 21 randomised controlled trials from high-income and middle-income countries that compared deferred versus immediate umbilical cord clamping in 3,292 babies altogether. In the deferred clamping groups, the delay ranged from 30 seconds to more than 180 seconds (with some trials encouraging delays of up to five minutes where feasible). For the immediate clamping groups, most trials specified clamping within 10 seconds. Of all infants, 61% (1950/3292) were born by caesarean section.

In total, 6.0% (98/1622) of the babies who received deferred cord clamping died before leaving the hospital compared to 8.2% (134/1641) whose cords were cut immediately. After analysis, this equates to the deferred clamping of the umbilical cord likely reducing the risk of death in premature babies by a third (an odds ratio of 0.68) compared to immediate clamping. 

In a subgroup of premature babies where infants were born before 32 weeks of pregnancy, 44.9% (449/1001) of the babies with immediate cord clamping experienced hypothermia after birth, compared to 51.2% (509/994) of those with deferred clamping. The average difference in temperature between the deferred clamping group and the immediate clamping group was -0.13 °C.

“Our findings highlight that particular care should be taken to keep premature babies warm when deferring umbilical cord clamping. This could be done by drying and wrapping the baby with the cord intact, and then by placing the dry baby directly on the mother’s bare chest under a blanket, or using bedside warming trollies”, says Prof Lisa Askie, senior author of the study at the NHMRC Clinical Trials Centre, University of Sydney. [1].

The second network meta-analysis included 47 trials with a total of 6,094 infants. For this analysis, deferred clamping was split into three groups: ‘short deferral’ (15–45 seconds), ‘medium deferral’ (45–120 seconds), and ‘long deferral’ (120 seconds or more). 

Compared with immediate clamping, waiting at least two minutes before clamping the cord reduced the risk of death in premature babies by two thirds (odds ratio of 0.31). Statistical analysis found that waiting two or more minutes to clamp the cord had a 91% probability of being the best treatment to prevent death shortly after birth in premature babies out of the different timings compared in the study. Immediate clamping had a very low (<1%) probability of being the best treatment for preventing death.

“Until recently, it was standard practice to clamp the umbilical cord immediately after birth for premature babies so they could be dried, wrapped, and if necessary, resuscitated with ease. Our study shows that there is no longer a case for immediate clamping and, instead, presently available evidence suggests that deferring cord clamping for at least two minutes is likely the best cord management strategy to reduce the risk of premature babies dying shortly after birth”, says Dr Sol Libesman, lead statistician for this study and research fellow at the NHMRC Clinical Trials Centre (CTC), University of Sydney. [1]

The authors highlight several factors that are important to consider when implementing these findings into practice, including that the results are not generalisable to babies requiring immediate resuscitation, unless the hospital is able to provide safe initial breathing help with the cord intact (several current trials are investigating this further [2,3]). 

“We need further research into how to best provide immediate care to the sickest premature babies while the cord is intact. Even for healthier premature babies, it may seem counter-intuitive to some doctors to defer cord clamping when the baby requires care, but with appropriate training and equipment, along with a full team approach involving midwives, doctors and parents, it is possible to successfully defer cord clamping whilst ensuring the baby is warm, breathing, and cared for”, says Dr Seidler. [1] 

The authors note some further limitations of their study, including that although several trials were conducted in middle-income countries, all of them were in hospitals with neonatal intensive care units. Therefore, findings may not be generalisable to low-resource settings. Additionally, there was little data on whether the doctors followed the cord management strategy that the baby had been randomised to in the trials. When trial adherence was reported, it was the case that some babies randomised to deferred clamping were administered a different strategy, such as immediate clamping instead, potentially due to doctors clamping the cord earlier to allow for immediate care. 

NOTES TO EDITORS

These studies were funded by the Australian National Health and Medical Research Council. They were conducted by researchers from The University of Sydney, University of Nottingham and the National Childbirth Trust.

[1] Quote direct from author and cannot be found in the text of the Article.
[2] Knol R, Brouwer E, van den Akker T, et al. Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial-study protocol for a multicentre randomised controlled trial. Trials 2022; 23: 838. 
[3] Winter J, Kattwinkel J, Chisholm C, Blackman A, Wilson S, Fairchild K. Ventilation of Preterm Infants during Delayed Cord Clamping (VentFirst): a pilot study of feasibility and safety. Am J Perinatol 2017; 34: 111–16.

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