Deferred cord clamping and cord milking: Certainty and quality of the evidence in meta-analyses, and systematic reviews of randomized control trials, guidelines, and implementation studies

Deferred1 cord clamping (DCC) saves lives, so why is it not implemented more routinely? Despite neonatal benefits, DCC is under-utilized, particularly in preterm births. Umbilical cord milking (UCM) also improves some outcomes for preterm infants such as decreasing the need for transfusions. At term, DCC and UCM improve hematological indices.The objective of this chapter is to examine the quality of evidence for both preterm and term DCC (and UCM), clinical practice guidelines and implementation issues.Key evidence, primarily from network meta-analyses, meta-analyses and systematic reviews on both preterm and term DCC (and UCM) from randomized clinical trials, clinical practice guidelines and implementation studies, are summarized through a lens of the certainty and quality of the evidence. Regarding the certainty of evidence, for network meta-analysis the Confidence in Network Meta-analysis tool was used, and for meta-analyses the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) were used. Guideline quality was appraised with two tools: Appraisal of Guidelines for REsearch & Evaluation II (AGREE II) and AGREE-Recommendation EXcellence (AGREE-REX). Implementation study quality was evaluated using The Mixed Method Appraisal tool.In a network meta-analysis of 56 RCTs of cord management strategies, DCC reduced the odds of mortality in preterm infants by 30% compared to immediate cord clamping (ICC), including in the subgroup of infants born before 33 weeks', both with a moderate confidence assessment using the Confidence in Network Meta-analysis tool. DCC reduced the odds of any intraventricular hemorrhage (IVH) by 30%, and the odds of red blood cell transfusion by more than 50%, both with high ratings on the Confidence in Network Meta-analysis. Umbilical Cord Milking (UCM) did not reduce mortality compared to ICC. In contrast to the benefits shown in preterm birth with DCC, a systematic review showed that at term, there were no mortality benefits and few benefits at all except for improved hematological indices. A systematic review of clinical practice guidelines demonstrated that all of them endorsed DCC for uncompromised preterm infants, and 11 more cautiously noted that cord milking might be considered when DCC was not feasible. However, only half (49%) of the recommendations in the guidelines on the optimal duration of DCC were supported by high-quality evidence per AGREE-II and AGREE-REX. Fewer than one in 10 statements (8%) cited a mortality benefit with DCC for preterm infants. Regarding the uptake of DCC, a systematic review of 18 studies on facilitators and barriers to implementation found that almost all (12 of the 14 studies) focused on strategies such as protocols, policy, or toolkits; additionally, 8 of 14 studies used didactic teaching sessions. Only 8 of 18 studies scored high on all four domains of the Mixed Method Appraisal tool.Compared to ICC, DCC in preterm infants conferred significant benefits for mortality, IVH and red blood cell transfusion, with confidence ratings of moderate (mortality) or high. Although guidelines worldwide encouraged preterm (and term) DCC, the quality of the clinical practice guidelines had room for improvement; only half of the recommendations on the optimal duration of preterm DCC were supported by high-quality evidence. Most guidelines did not mention a mortality benefit with preterm DCC and lacked details on practical aspects of implementation. Among implementation studies, which have focused mainly on protocols, policies, toolkits or didactic teaching, quality also demonstrated an opportunity for improvement.