Association of Umbilical Cord Management Strategies With Outcomes of Preterm Infants: A Systematic Review and Network Meta-analysis

Abstract

Importance: It is unclear which umbilical cord management strategy is the best for preventing mortality and morbidities in preterm infants.

Objective: To systematically review and conduct a network meta-analysis comparing 4 umbilical cord management strategies for preterm infants: immediate umbilical cord clamping (ICC), delayed umbilical cord clamping (DCC), umbilical cord milking (UCM), and UCM and DCC.

Data sources: PubMed, Embase, CINAHL, and Cochrane CENTRAL databases were searched from inception until September 11, 2020.

Study selection: Randomized clinical trials comparing different umbilical cord management strategies for preterm infants were included.

Data extraction and synthesis: Data were extracted for bayesian random-effects meta-analysis to estimate the relative treatment effects (odds ratios [OR] and 95% credible intervals [CrI]) and surface under the cumulative ranking curve values.

Main outcomes and measures: The primary outcome was predischarge mortality. The secondary outcomes were intraventricular hemorrhage, severe intraventricular hemorrhage, need for packed red blood cell transfusion, and other neonatal morbidities. Confidence in network meta-analysis software was used to assess the quality of evidence and grade outcomes.

Results: Fifty-six studies enrolled 6852 preterm infants. Compared with ICC, DCC was associated with lower odds of mortality (22 trials, 3083 participants; 7.6% vs 5.0%; OR, 0.64; 95% CrI, 0.39-0.99), intraventricular hemorrhage (25 trials, 3316 participants; 17.8% vs 15.4%; OR, 0.73; 95% CrI, 0.54-0.97), and need for packed red blood cell transfusion (18 trials, 2904 participants; 46.9% vs 38.3%; OR, 0.48; 95% CrI, 0.32-0.66). Compared with ICC, UCM was associated with lower odds of intraventricular hemorrhage (10 trials, 645 participants; 22.5% vs 16.2%; OR, 0.58; 95% CrI, 0.38-0.84) and need for packed red blood cell transfusion (9 trials, 688 participants; 47.3% vs 32.3%; OR, 0.36; 95% CrI, 0.23-0.53), with no significant differences for other secondary outcomes. There was no significant difference between UCM and DCC for any outcome.

Conclusions and relevance: Compared with ICC, DCC was associated with the lower odds of mortality in preterm infants. Compared with ICC, DCC and UCM were associated with reductions in intraventricular hemorrhage and need for packed red cell transfusion. There was no significant difference between UCM and DCC for any outcome. Further studies directly comparing DCC and UCM are needed.

Figure 1.. Summary of Study Selection Process

RCT indicates randomized clinical trial.

Figure 2.. Network Plots for Mortality and Severe Intraventricular Hemorrhage Across Study Population and Subgroups

Each node indicates an umbilical cord management modality and is sized proportionally to the number of infants who received the modality. Each line connecting 2 nodes indicates a direct comparison between 2 modalities, and the thickness of each is proportional to the number of trials directly comparing the 2 modalities. DCC indicates delayed umbilical cord clamping; ICC, immediate umbilical cord clamping; UCM, umbilical cord milking; UCM+DCC, combination of umbilical cord milking followed by delayed cord clamping.

Figure 3.. Treatment Effects on Outcomes of Predischarge Mortality, Intraventricular Hemorrhage, and Severe Intraventricular Hemorrhage (Preterm Infants <37 Weeks’ Gestation)

CrI indicates credible interval; DCC, delayed umbilical cord clamping; ICC, immediate umbilical cord clamping; NA, not available; OR, odds ratio; UCM, umbilical cord milking. ^aActual values are 1.01 × 10⁻⁹ (1.21 × 10⁻²⁹; 0.07). ^bActual values are 3.6 × 10⁻¹¹ (2.0 × 10⁻³⁶; 0.11).

Figure 4.. Treatment Effects on Outcomes of Need for Packed Red Cell Transfusion, Late-Onset Sepsis, and Bronchopulmonary Dysplasia (Preterm Infants <37 Weeks’ Gestation)

CrI indicates credible interval; DCC, delayed umbilical cord clamping; ICC, immediate umbilical cord clamping; NA, not available; OR, odds ratio; UCM, umbilical cord milking. ^aActual values are 2.4 × 10⁻⁹ (2.8 × 10⁻³²; 0.10). ^bActual values are 3.6 × 10⁻¹⁰ (7.1 × 10⁻²⁸; 0.22).