NIHR DC Discover

NIHR Signal Delayed umbilical cord clamping reduces hospital mortality for preterm infants

Published on 6 February 2018

doi: 10.3310/signal-000548

Delays to clamping the umbilical cord of about a minute can reduce hospital mortality for preterm infants by around 32%. Delayed clamping also reduced the proportion of infants needing a blood transfusion by 10%.

This review adds more precise data on survival from new trials including a large Australian trial (over 1,600 babies) to a previous Cochrane 2012 review of trails including 738 infants and provides new more precise data on the survival benefit.

These findings are consistent with current guidelines which recommend delayed clamping in preterm infants.

Share your views on the research.

Why was this study needed?

The optimal timing of umbilical cord clamping has been debated. Globally, around 15 million children each year are born before 37 weeks gestation, and of these around one million do not survive.

Early clamping used to be standard practice for preterm infants due to concerns about potential consequences from any delay to resuscitation, including hypothermia, jaundice, and polycythaemia.

Evidence from a Cochrane review (2012) included 15 studies (738 infants) found that a delay may improve blood pressure, reduce blood transfusions, intra-ventricular haemorrhage, necrotising enterocolitis, and infection. However, there was insufficient data to be confident about any difference to infant mortality that could be the result of enhanced placenta to baby transfusion from delayed clamping.

This review aimed to update the evidence to include all trials completed since 2012 and to provide more precise estimates, particularly for survival.

What did this study do?

This systematic review and meta-analysis included 18 randomised controlled trials comparing delayed (30 seconds or more) versus early (less than 30 seconds) clamping in 2,834 infants. Trials were included if they enrolled infants born at less than 37 weeks’ gestation and their mothers and included a recent large Australian trial. Trials which estimated cord milking in more than 20% of infants in any arm were ineligible. Responses were received from 13 authors confirming no cord milking was used in any arm.

The main outcome measure was all-cause mortality at any time before hospital discharge. Subgroup analyses were performed according to gestational age (28 weeks or less compared with 29-37 weeks), duration of cord clamping, and mode of delivery.

Eighteen trials were included (2,834 infants) from high-income countries, including Scotland Israel and US. Twelve trials were considered at a low risk of bias meaning we can be fairly confident in the results.

What did it find?

  • Overall, delayed clamping reduced all-cause hospital mortality before discharge from hospital (relative risk [RR], 0.68; 95% confidence interval [CI] 0.52 to 0.90).
  • In the three trials (996 infants) at 28 weeks gestation or less, delayed clamping also reduced hospital mortality (RR 0.70, 95% CI 0.51 to 0.95).
  • In two trials, delayed clamping increased peak haematocrit by 2.73% (95% CI 1.94 to 3.52%) and there was less need for transfusion.
  • Potential harms of delayed clamping included a 3% increase in the number of babies with excess red blood cells (polycythaemia) and a slight increase in levels of jaundice.
  • Additional analyses showed that mortality did not vary according to the duration of delay in cord clamping, mode of delivery, or timing of resuscitation.

What does current guidance say on this issue?

The World Health Organisation (2012) states delayed cord clamping (performed 1 to 3 minutes after birth) is recommended for all births, preterm and term, while initiating essential neonatal care. Early umbilical cord clamping (less than 1 minute after birth) is not recommended unless the neonate is asphyxiated and needs to be moved immediately for resuscitation.

The Royal College of Obstetrics and Gynaecology (2015) says that in healthy term babies the evidence supports deferring clamping of the umbilical cord, as this appears to improve iron stores in infancy.

What are the implications?

This review supports current clinical guidelines recommending delayed clamping in preterm infants. It adds more precise data on survival from a large Australian trial which adds over 1,600 babies to a previous Cochrane review of 738 infants.

Using delayed instead of early clamping could potentially save between 11,000 to 100,000 babies globally each year, the researchers say.

Benefits may be greater for some subgroups or periods of delayed clamping. For example, the effects of gestational age were limited by missing data, emphasising the need for individual patient data to inform future, more specific research.

Citation and Funding

Fogarty M, Osborn DA, Askie L, et al. Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis. Am J Obstet Gynecol. 2018;218(1):1-18.

This project was funded by Australian National Health and Medical Research Council, and the NHMRC Clinical Trials Centre, University of Sydney.

Bibliography

ACOG. Committee Opinion: Delayed Umbilical Cord Clamping After Birth. Washington: American College of Obstetricians and Gynaecologists; 2017.

NIH. Umbilical cord ‘milking’ improves blood flow in preterm infants. Maryland: National Institutes of Health; 2015.

Royal College of Obstetricians & Gynaecologists. Clamping of the Umbilical Cord and Placental Transfusion. London: Royal College of Obstetricians & Gynaecologists; 2015.

WHO. Guideline: Delayed Umbilical Cord Clamping for improved maternal and infant health and nutrition outcomes. Geneva: World Health Organisation; 2014.

Why was this study needed?

The optimal timing of umbilical cord clamping has been debated. Globally, around 15 million children each year are born before 37 weeks gestation, and of these around one million do not survive.

Early clamping used to be standard practice for preterm infants due to concerns about potential consequences from any delay to resuscitation, including hypothermia, jaundice, and polycythaemia.

Evidence from a Cochrane review (2012) included 15 studies (738 infants) found that a delay may improve blood pressure, reduce blood transfusions, intra-ventricular haemorrhage, necrotising enterocolitis, and infection. However, there was insufficient data to be confident about any difference to infant mortality that could be the result of enhanced placenta to baby transfusion from delayed clamping.

This review aimed to update the evidence to include all trials completed since 2012 and to provide more precise estimates, particularly for survival.

What did this study do?

This systematic review and meta-analysis included 18 randomised controlled trials comparing delayed (30 seconds or more) versus early (less than 30 seconds) clamping in 2,834 infants. Trials were included if they enrolled infants born at less than 37 weeks’ gestation and their mothers and included a recent large Australian trial. Trials which estimated cord milking in more than 20% of infants in any arm were ineligible. Responses were received from 13 authors confirming no cord milking was used in any arm.

The main outcome measure was all-cause mortality at any time before hospital discharge. Subgroup analyses were performed according to gestational age (28 weeks or less compared with 29-37 weeks), duration of cord clamping, and mode of delivery.

Eighteen trials were included (2,834 infants) from high-income countries, including Scotland Israel and US. Twelve trials were considered at a low risk of bias meaning we can be fairly confident in the results.

What did it find?

  • Overall, delayed clamping reduced all-cause hospital mortality before discharge from hospital (relative risk [RR], 0.68; 95% confidence interval [CI] 0.52 to 0.90).
  • In the three trials (996 infants) at 28 weeks gestation or less, delayed clamping also reduced hospital mortality (RR 0.70, 95% CI 0.51 to 0.95).
  • In two trials, delayed clamping increased peak haematocrit by 2.73% (95% CI 1.94 to 3.52%) and there was less need for transfusion.
  • Potential harms of delayed clamping included a 3% increase in the number of babies with excess red blood cells (polycythaemia) and a slight increase in levels of jaundice.
  • Additional analyses showed that mortality did not vary according to the duration of delay in cord clamping, mode of delivery, or timing of resuscitation.

What does current guidance say on this issue?

The World Health Organisation (2012) states delayed cord clamping (performed 1 to 3 minutes after birth) is recommended for all births, preterm and term, while initiating essential neonatal care. Early umbilical cord clamping (less than 1 minute after birth) is not recommended unless the neonate is asphyxiated and needs to be moved immediately for resuscitation.

The Royal College of Obstetrics and Gynaecology (2015) says that in healthy term babies the evidence supports deferring clamping of the umbilical cord, as this appears to improve iron stores in infancy.

What are the implications?

This review supports current clinical guidelines recommending delayed clamping in preterm infants. It adds more precise data on survival from a large Australian trial which adds over 1,600 babies to a previous Cochrane review of 738 infants.

Using delayed instead of early clamping could potentially save between 11,000 to 100,000 babies globally each year, the researchers say.

Benefits may be greater for some subgroups or periods of delayed clamping. For example, the effects of gestational age were limited by missing data, emphasising the need for individual patient data to inform future, more specific research.

Citation and Funding

Fogarty M, Osborn DA, Askie L, et al. Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis. Am J Obstet Gynecol. 2018;218(1):1-18.

This project was funded by Australian National Health and Medical Research Council, and the NHMRC Clinical Trials Centre, University of Sydney.

Bibliography

ACOG. Committee Opinion: Delayed Umbilical Cord Clamping After Birth. Washington: American College of Obstetricians and Gynaecologists; 2017.

NIH. Umbilical cord ‘milking’ improves blood flow in preterm infants. Maryland: National Institutes of Health; 2015.

Royal College of Obstetricians & Gynaecologists. Clamping of the Umbilical Cord and Placental Transfusion. London: Royal College of Obstetricians & Gynaecologists; 2015.

WHO. Guideline: Delayed Umbilical Cord Clamping for improved maternal and infant health and nutrition outcomes. Geneva: World Health Organisation; 2014.

Delayed Versus Early Umbilical Cord Clamping for Preterm Infants: A Systematic Review and Meta-Analysis

Published on 4 November 2017

Fogarty, M.,Osborn, D. A.,Askie, L.,Seidler, A. L.,Hunter, K.,Lui, K.,Simes, J.,Tarnow-Mordi, W.

Am J Obstet Gynecol , 2017

OBJECTIVE: To compare the effects of delayed versus early cord clamping on hospital mortality (primary outcome) and morbidity in preterm infants using Cochrane Collaboration Neonatal Review Group methodology. DATA SOURCES: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Chinese articles, cross-referencing citations, expert informants and trial registries to 31 July 2017. STUDY ELIGIBILITY: RCTs of delayed (>/= 30 seconds) vs early (<30 seconds) clamping in infants born <37 weeks gestation. Before searching the literature we specified that trials estimated to have cord milking in >20% of infants in any arm would be ineligible. STUDY APPRAISAL AND SYNTHESIS: Two reviewers independently selected studies, assessed bias and extracted data. Relative risk (i.e. Risk Ratio, RR), risk difference (RD) and mean difference (MD) with 95% confidence intervals (CI) were assessed by fixed effects models, heterogeneity by I2 statistics and the quality of evidence by Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Eighteen RCTs compared delayed vs early clamping in 2834 infants. Most infants allocated to have delayed clamping were assigned a delay of 60 seconds or more. Delayed clamping reduced hospital mortality (RR 0.69, 95% CI 0.52 to 0.91, P=0.009; RD 0.02, 95% CI -0.03 to -0.00, P=0.04; GRADE high, with I2=0 indicating no heterogeneity). In three trials in 996 infants </=28 weeks gestation, delayed clamping reduced hospital mortality (RR 0.70, 95% CI 0.51 to 0.95; RD -0.05, 95% CI -0.09 to -0.01, P=0.02, number needed to benefit 20, 95% CI 11 to 100; I2=0). Subgroup analyses showed no differences between randomized groups in Apgar scores, intubation for resuscitation, admission temperature, mechanical ventilation, intraventricular hemorrhage, brain injury, chronic lung disease, patent ductus arteriosus, necrotizing enterocolitis, late-onset sepsis or retinopathy of prematurity. Delayed clamping increased peak haematocrit by 2.73% (95% CI 1.94 to 3.52; P<0.00001) and reduced the proportion of infants having blood transfusion by 10% (95% CI 6 to 13%, P<0.00001). Potential harms of delayed clamping included polycythemia and hyperbilirubinemia. CONCLUSIONS: This systematic review provides high quality evidence that delayed clamping reduced hospital mortality, which supports current guidelines recommending delayed clamping in preterm infants. This review does not evaluate cord milking, which may also be of benefit. Analyses of individual patient data in these and other RCTs will be critically important in reliably evaluating important secondary outcomes.

Peak haematocrit is the proportion by volume of the blood that consists of red blood cells and is expressed as a percentage. Babies born at term usually have a higher hematocrit, compared to older children and adults. It can also be referred to as the retention of blood cells.

Cord milking is a technique which also is also thought to be of benefit during the delivery of preterm infants delivered by caesarean section. It increases the blood flow from the umbilical cord into the infant’s circulatory system, to improve blood pressure and red blood cell levels. The researchers excluded trials of this to avoid confusing the result.

Expert commentary

Facts overturn strong opinions and received wisdom. Deferred cord clamping is already partially embedded in practice, so we can't expect a one-third reduction in mortality of preterm infants. Reducing other complications of prematurity, such as necrotising enterocolitis will need other approaches. 

Early interventions can do harm, as well as good, even at low gestations. When a baby is well at birth, we now know to defer cord clamping.

Should a “breathe first” cord intact approach to initial stabilisation, be used for babies whose condition is poor? It will be challenging to deliver, and research. But it might be important.

Sam Oddie, Consultant Neonatologist, Bradford Neonatology

Expert commentary

Cheap, quick and effective interventions in medicine are rare, but delayed clamping of the umbilical cord at birth appears to be just that.

A systematic review of 18 trials including almost 3,000 preterm babies confirms that delaying cord clamping by 60 seconds reduces mortality before hospital discharge. It also makes it less likely that babies will need blood transfusions, and there is no apparent increase in morbidity for mother or baby.

On a worldwide scale, given the large number of babies born before 37 weeks of gestation, the potential benefits of waiting patiently for just one minute are huge.

Dr Elaine Boyle, Associate Professor in Neonatal Medicine, University of Leicester; Honorary Consultant Neonatologist, University Hospitals of Leicester NHS Trust