Background
The effects of delayed cord clamping of the umbilical cord in preterm infants are
unclear.
Objective
We sought to compare the effects of delayed vs early cord clamping on hospital mortality
(primary outcome) and morbidity in preterm infants using Cochrane Collaboration neonatal
review group methodology.
Study Design
We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Chinese
articles, cross-referencing citations, expert informants, and trial registries to
July 31, 2017, for randomized controlled trials 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. Two reviewers independently selected studies, assessed
bias, and extracted data. Relative risk (ie, risk ratio), risk difference, and mean
difference with 95% confidence intervals were assessed by fixed effects models, heterogeneity
by I2 statistics, and the quality of evidence by Grading of Recommendations, Assessment,
Development, and Evaluations.
Results
Eighteen randomized controlled trials compared delayed vs early clamping in 2834 infants.
Most infants allocated to have delayed clamping were assigned a delay of ≥60 seconds.
Delayed clamping reduced hospital mortality (risk ratio, 0.68; 95% confidence interval,
0.52–0.90; risk difference, –0.03; 95% confidence interval, –0.05 to –0.01; P = .005; number needed to benefit, 33; 95% confidence interval, 20–100; Grading of
Recommendations, Assessment, Development, and Evaluations = high, with I2 = 0 indicating no heterogeneity). In 3 trials in 996 infants ≤28 weeks’ gestation,
delayed clamping reduced hospital mortality (risk ratio, 0.70; 95% confidence interval,
0.51–0.95; risk difference, –0.05; 95% confidence interval, –0.09 to –0.01; P = .02, number needed to benefit, 20; 95% confidence interval, 11–100; I2 = 0). In subgroup analyses, delayed clamping reduced the incidence of low Apgar score
at 1 minute, but not at 5 minutes, and did not reduce the incidence of 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 hematocrit by 2.73 percentage points (95% confidence interval, 1.94–3.52; P < .00001) and reduced the proportion of infants having blood transfusion by 10% (95%
confidence interval, 6–13%; P < .00001). Potential harms of delayed clamping included polycythemia and hyperbilirubinemia.
Conclusion
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 randomized controlled
trials will be critically important in reliably evaluating important secondary outcomes.
Key words
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Article info
Publication history
Published online: October 30, 2017
Accepted:
October 26,
2017
Received in revised form:
October 25,
2017
Received:
October 5,
2017
Footnotes
Supported by the Australian National Health and Medical Research Council (NHMRC) (project grant 517309; program grants 1037786 and 512657) and the NHMRC Clinical Trials Center, University of Sydney.
The authors report no conflict of interest.
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