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.