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HomeEditor's PickTwo-minute delay in cord clamping helps preterm babies' survival rates, experts find

Two-minute delay in cord clamping helps preterm babies' survival rates, experts find

Recent research shows that if doctors wait at least two minutes after a baby’s birth to clamp the umbilical cord, they significantly improve in-hospital survival rates for premature infants, with experts saying the data are convincing, although it’s not entirely clear why the strategy seems to help.

Delayed cord clamping – an intervention that can be introduced at relatively little cost – is believed to help because it allows umbilical cord blood, which is rich in iron, stem cells and antibodies, to flow back to the baby.

The American College of Obstetricians and Gynaecologists already recommends delaying clamping by 30 to 60 seconds for both full-term and preterm newborns, reports The New York Times.

In preterm infants (born before 37 weeks of gestation), delayed clamping leads to improved circulation, less need for blood transfusions and a lower incidence of serious complications, such as necrotising enterocolitis, or inflammation of the digestive tract.

The evidence about whether the practice is beneficial for them has been inconsistent, according to Dr Anna Lene Seidler, lead author of two new review papers and a senior research fellow at the University of Sydney in Australia.

The recent research also sought to determine the optimal time to wait before clamping. The longest delays that were studied were three minutes after birth.

“We found that the longer we wait, the better, and the more we can reduce mortality,” Seidler said. “We were astounded by how consistent the findings are.”

Two companion papers, published in The Lancet, analysed dozens of studies involving thousands of babies born in hospitals in various countries, including Britain, India, Iran and the United States.

Two-minute postponement seems optimal

One of the reviews compared the effectiveness of three techniques: immediate cord clamping, deferred clamping and milking an intact umbilical cord so that more blood flowed to the newborn.

The paper examined 48 randomised trials and analysed data on 6 367 infants, finding that delayed cord clamping reduced in-hospital deaths of preterm newborns by one-third, compared with immediate cord clamping. There were no statistically significant differences between any other interventions.

A second review and meta-analysis, which included data from 47 trials with 6 094 participants, compared umbilical cord milking with immediate clamping less than 45 seconds after birth, between 45 seconds and up to 120 seconds after birth, and two minutes or more after birth.

The analysis found that the longest deferral of clamping increased survival the most, compared with immediate clamping. But the authors noted that if the newborn required immediate resuscitation, the cord should be kept intact only as long as resuscitation can be provided at the same time.

Why it matters

Worldwide, some 13m premature babies are born every year, and almost 1m of them die within a month of birth. A low-cost, low-tech intervention like delayed cord clamping has the potential to save many lives.

But implementing a change in guidelines to delay clamping the umbilical cord for two minutes or more may be complicated. A delay might mean that the necessary equipment has to be brought into the operating room even though it should be kept in a sterile environment, like a neonatal intensive care unit, said Dr Anup Katheria, director of neonatal research at Sharp Mary Birch Hospital for Women & Newborns in San Diego.

“I don’t think we know the full ramifications a change in guidelines could entail,” Katheria said. “But if it really reduces the risk of death, why would you cut the cord?”

Study 1 details

Short, medium, and long deferral of umbilical cord clamping compared with umbilical cord milking and immediate clamping at preterm birth: a systematic review and network meta-analysis with individual participant data

Anna Lene Seidler, Sol Libesman, Lisa Askie, et al.

Published in The Lancet on 14 November 2023

Summary

Background
Deferred (also known as delayed) cord clamping can improve survival of infants born preterm (before 37 weeks of gestation), but the optimal duration of deferral remains unclear. We conducted a systematic review and individual participant data network meta-analysis with the aim of comparing the effectiveness of umbilical cord clamping strategies with different timings of clamping or with cord milking for preterm infants.

Methods
We searched medical databases and trial registries from inception until Feb 24, 2022 (updated June 6, 2023) for randomised controlled trials comparing cord clamping strategies for preterm infants. Individual participant data were harmonised and assessed for risk of bias and quality. Interventions were grouped into immediate clamping, short deferral (≥15 s to <45 s), medium deferral (≥45 s to <120 s), long deferral (≥120 s), and intact cord milking. The primary outcome was death before hospital discharge. We calculated one-stage, intention-to-treat Bayesian random-effects individual participant data network meta-analysis. This study was registered with PROSPERO, CRD42019136640.

Findings
We included individual participant data from 47 trials with 6094 participants. Of all interventions, long deferral reduced death before discharge the most (compared with immediate clamping; odds ratio 0·31 [95% credibility interval] 0·11–0·80; moderate certainty). The risk of bias was low for 10 (33%) of 30 trials, 14 (47%) had some concerns, and 6 (20%) were rated as having a high risk of bias. Heterogeneity was low, with no indication of inconsistency.

Interpretation
This study found that long deferral of clamping leads to reduced odds of death before discharge in preterm infants. In infants assessed as requiring immediate resuscitation, this finding might only be generalisable if there are provisions for such care with the cord intact. These results are based on thoroughly cleaned and checked individual participant data and can inform future guidelines and practice.

Study 2 details

Deferred cord clamping, cord milking, and immediate cord clamping at preterm birth: a systematic review and individual participant data meta-analysis

Anna Lene Seidler, Mason Aberoumand, Lisa Askie, et al.

Published in The Lancet on 14 November 2023

Summary

Background
Umbilical cord clamping strategies at preterm birth have the potential to affect important health outcomes. The aim of this study was to compare the effectiveness of deferred cord clamping, umbilical cord milking, and immediate cord clamping in reducing neonatal mortality and morbidity at preterm birth.

Methods
We conducted a systematic review and individual participant data meta-analysis. We searched medical databases and trial registries (from database inception until Feb 24, 2022; updated June 6, 2023) for randomised controlled trials comparing deferred (also known as delayed) cord clamping, cord milking, and immediate cord clamping for preterm births (<37 weeks' gestation). Quasi-randomised or cluster-randomised trials were excluded. Authors of eligible studies were invited to join the iCOMP collaboration and share individual participant data. All data were checked, harmonised, re-coded, and assessed for risk of bias following prespecified criteria. The primary outcome was death before hospital discharge. We performed intention-to-treat one-stage individual participant data meta-analyses accounting for heterogeneity to examine treatment effects overall and in prespecified subgroup analyses. Certainty of evidence was assessed with Grading of Recommendations Assessment, Development, and Evaluation.

Findings
We identified 2 369 records, of which 48 randomised trials provided individual participant data and were eligible for our primary analysis. We included individual participant data on 6367 infants (3303 [55%] male, 2667 [45%] female, two intersex, and 395 missing data). Deferred cord clamping, compared with immediate cord clamping, reduced death before discharge (odds ratio [OR] 0·68 [95% CI 0·51–0·91], high-certainty evidence, 20 studies, n=3260, 232 deaths). For umbilical cord milking compared with immediate cord clamping, no clear evidence was found of a difference in death before discharge (OR 0·73 [0·44–1·20], low certainty, 18 studies, n=1561, 74 deaths). Similarly, for umbilical cord milking compared with deferred cord clamping, no clear evidence was found of a difference in death before discharge (0·95 [0·59–1·53], low certainty, 12 studies, n=1303, 93 deaths). We found no evidence of subgroup differences for the primary outcome, including by gestational age, type of delivery, multiple birth, study year, and perinatal mortality.

Interpretation
This study provides high-certainty evidence that deferred cord clamping, compared with immediate cord clamping, reduces death before discharge in preterm infants. This effect appears to be consistent across several participant-level and trial-level subgroups. These results will inform international treatment recommendations.

 

The Lancet article – Short, medium, and long deferral of umbilical cord clamping compared with umbilical cord milking and immediate clamping at preterm birth: a systematic review and network meta-analysis with individual participant data (Open access)

 

The Lancet article – Deferred cord clamping, cord milking, and immediate cord clamping at preterm birth: a systematic review and individual participant data meta-analysis (Open access)

 

The New York Times article – A simply way to save premature babies (Restricted access)

 

See more from MedicalBrief archives:

 

A 60 second delay in cord-clamping cuts relative mortality by 30%

 

Preterm birth a strong predictor of ill health throughout childhood — 1m-child NHS study

 

Bonding effect of skin-to-skin contact in preterm infants

 

 

 

 

 

 

 

 

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