Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial—statistical analysis plan for a multicenter randomized controlled trial
Sten P. Willemsen,
Ronny Knol,
Emma Brouwer,
Thomas van den Akker,
Philip L. J. DeKoninck,
Enrico Lopriore,
Wes Onland,
Willem P. de Boode,
Anton H. van Kaam,
Debbie H. Nuytemans,
Irwin K. M. Reiss,
G. Jeroen Hutten,
Sandra A. Prins,
Estelle E. M. Mulder,
Christian V. Hulzebos,
Sam J. van Sambeeck,
Mayke E. van der Putten,
Inge A. Zonnenberg,
Arjan B. te Pas,
Marijn J. Vermeulen
Affiliations
Sten P. Willemsen
Department of Intensive Care Neonatology and Children, Division of Neonatology, Sophia Children’s Hospital, Erasmus MC University Medical Center
Ronny Knol
Department of Intensive Care Neonatology and Children, Division of Neonatology, Sophia Children’s Hospital, Erasmus MC University Medical Center
Emma Brouwer
Department of Pediatrics, Division of Neonatology, Leiden University Medical Center
Thomas van den Akker
Department of Obstetrics, Leiden University Medical Center
Philip L. J. DeKoninck
Department of Obstetrics and Gynaecology, Erasmus MC University Medical Center
Enrico Lopriore
Department of Pediatrics, Division of Neonatology, Leiden University Medical Center
Wes Onland
Department of Neonatology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam and Vrije Universiteit Amsterdam
Willem P. de Boode
Department of Pediatrics, Division of Neonatology, Radboud University Medical Center, Radboud Institute for Health Sciences, Amalia Children’s Hospital
Anton H. van Kaam
Department of Neonatology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam and Vrije Universiteit Amsterdam
Debbie H. Nuytemans
Department of Neonatology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam and Vrije Universiteit Amsterdam
Irwin K. M. Reiss
Department of Intensive Care Neonatology and Children, Division of Neonatology, Sophia Children’s Hospital, Erasmus MC University Medical Center
G. Jeroen Hutten
Department of Neonatology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam and Vrije Universiteit Amsterdam
Sandra A. Prins
Department of Neonatology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam and Vrije Universiteit Amsterdam
Estelle E. M. Mulder
Department of Neonatology, Isala Women and Children’s Hospital
Christian V. Hulzebos
Department of Pediatrics, Division of Neonatology, Beatrix Children’s Hospital, University Medical Center Groningen
Sam J. van Sambeeck
Department of Pediatrics, Maxima Medical Center
Mayke E. van der Putten
Department of Pediatrics, Maastricht University Medical Center
Inge A. Zonnenberg
Department of Neonatology, Wilhelmina Children’s Hospital, University Medical Center Utrecht
Arjan B. te Pas
Department of Pediatrics, Division of Neonatology, Leiden University Medical Center
Marijn J. Vermeulen
Department of Intensive Care Neonatology and Children, Division of Neonatology, Sophia Children’s Hospital, Erasmus MC University Medical Center
Abstract Background Mortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of umbilical cord clamping affects hemodynamic stability during transition. Standard care is time-based cord clamping (TBCC), with clamping irrespective of lung aeration. It is unknown whether delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) is more beneficial. This document describes the statistical analyses for the ABC3 trial, which aims to assess the efficacy and safety of PBCC, compared to TBCC. Methods The ABC3 trial is a multicenter, randomized trial investigating PBCC (intervention) versus TBCC (control) in very preterm infants. The trial is ethically approved. Preterm infants born before 30 weeks of gestation are randomized after parental informed consent. The primary outcome is intact survival, defined as the composite of survival without major cerebral injury and/or NEC. Secondary short-term outcomes are co-morbidities and adverse events assessed during NICU admission, parental reported outcomes, and long-term neurodevelopmental outcomes assessed at a corrected age of 2 years. To test the hypothesis that PBCC increases intact survival, a logistic regression model will be estimated using generalized estimating equations (accounting for correlation between siblings and observations in the same center) with treatment and gestational age as predictors. This plan is written and submitted without knowledge of the data. Discussion The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management at birth. Trial registration ClinicalTrials.gov NCT03808051. Registered on 17 January 2019.
