Systematic review and network meta-analysis with individual participant data on cord management at preterm birth (iCOMP): study protocol
Anna Lene Seidler, Lelia Duley, Anup Katheria, Catalina De Paco Matallana, Eugene Dempsey, Heike Rabe, John Kattwinkel, Judith Mercer, Justin Josephsen, Karen D. Fairchild, Ola Andersson, Shigeharu Hosono, Venkataseshan Sundaram, Vikram Datta, Walid El‐Naggar, William Tarnow-Mordi, Thomas P. A. Debray, Stuart B. Hooper, Martin Kluckow, Graeme R. Polglase, Peter G. Davis, Alan Montgomery, Kylie E Hunter, Angie Barba, John Simes, Lisa Askie
Abstract
INTRODUCTION: Timing of cord clamping and other cord management strategies may improve outcomes at preterm birth. However, it is unclear whether benefits apply to all preterm subgroups. Previous and current trials compare various policies, including time-based or physiology-based deferred cord clamping, and cord milking. Individual participant data (IPD) enable exploration of different strategies within subgroups. Network meta-analysis (NMA) enables comparison and ranking of all available interventions using a combination of direct and indirect comparisons. OBJECTIVES: (1) To evaluate the effectiveness of cord management strategies for preterm infants on neonatal mortality and morbidity overall and for different participant characteristics using IPD meta-analysis. (2) To evaluate and rank the effect of different cord management strategies for preterm births on mortality and other key outcomes using NMA. METHODS AND ANALYSIS: Systematic searches of Medline, Embase, clinical trial registries, and other sources for all ongoing and completed randomised controlled trials comparing cord management strategies at preterm birth (before 37 weeks' gestation) have been completed up to 13 February 2019, but will be updated regularly to include additional trials. IPD will be sought for all trials; aggregate summary data will be included where IPD are unavailable. First, deferred clamping and cord milking will be compared with immediate clamping in pairwise IPD meta-analyses. The primary outcome will be death prior to hospital discharge. Effect differences will be explored for prespecified participant subgroups. Second, all identified cord management strategies will be compared and ranked in an IPD NMA for the primary outcome and the key secondary outcomes. Treatment effect differences by participant characteristics will be identified. Inconsistency and heterogeneity will be explored. ETHICS AND DISSEMINATION: Ethics approval for this project has been granted by the University of Sydney Human Research Ethics Committee (2018/886). Results will be relevant to clinicians, guideline developers and policy-makers, and will be disseminated via publications, presentations and media releases. REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR) (ACTRN12619001305112) and International Prospective Register of Systematic Reviews (PROSPERO, CRD42019136640).