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.

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.

FUNDING

Australian National Health and Medical Research Council.

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests iCOMP trial representatives comprised principal investigators of studies included in this meta-analysis. Trial representatives did not input on study eligibility, data integrity assessments, data extraction, or risk of bias assessments for their own studies. Trial representatives did not make final decisions on certainty of evidence ratings. ALS reports Australian National Health and Medical Research Council (NHMRC) project and Investigator grants (funds paid directly to the University of Sydney). JXS reports travel grants and scholarships from the Association of Interdisciplinary Meta-science and Open-Science, Pediatric Academic Societies, and the Perinatal Society of Australia and New Zealand. KEH reports NHMRC funding paid directly to the University of Sydney. All other authors declare no competing interests. The full list of iCOMP Collaborators and their declaration of interests are noted in the appendix (pp 318–21).