Physiological-based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia (PinC): study protocol for a multicentre, randomised controlled trial

Introduction Pulmonary hypertension is a major determinant of postnatal survival in infants with a congenital diaphragmatic hernia (CDH). The current care during the perinatal stabilisation period in these infants might contribute to the development of pulmonary hypertension after birth—in particula...

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Main Authors: Arjan B te Pas, Neysan Rafat, Thomas Schaible, Stuart B Hooper, René M H Wijnen, Kelly J Crossley, Philip L J DeKoninck, Ronny Knol, Irwin K M Reiss, Marijn J Vermeulen, Florian Kipfmueller, Berndt Urlesberger, Anne Debeer, Emily J J Horn-Oudshoorn, Suzan C M Cochius-den Otter, Calum T Roberts, Willem P de Boode
Format: Article
Language:English
Published: BMJ Publishing Group 2022-03-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/12/3/e054808.full
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author Arjan B te Pas
Neysan Rafat
Thomas Schaible
Stuart B Hooper
René M H Wijnen
Kelly J Crossley
Philip L J DeKoninck
Ronny Knol
Irwin K M Reiss
Marijn J Vermeulen
Florian Kipfmueller
Berndt Urlesberger
Anne Debeer
Emily J J Horn-Oudshoorn
Suzan C M Cochius-den Otter
Calum T Roberts
Willem P de Boode
author_facet Arjan B te Pas
Neysan Rafat
Thomas Schaible
Stuart B Hooper
René M H Wijnen
Kelly J Crossley
Philip L J DeKoninck
Ronny Knol
Irwin K M Reiss
Marijn J Vermeulen
Florian Kipfmueller
Berndt Urlesberger
Anne Debeer
Emily J J Horn-Oudshoorn
Suzan C M Cochius-den Otter
Calum T Roberts
Willem P de Boode
author_sort Arjan B te Pas
collection DOAJ
description Introduction Pulmonary hypertension is a major determinant of postnatal survival in infants with a congenital diaphragmatic hernia (CDH). The current care during the perinatal stabilisation period in these infants might contribute to the development of pulmonary hypertension after birth—in particular umbilical cord clamping before lung aeration. An ovine model of diaphragmatic hernia demonstrated that cord clamping after lung aeration, called physiological-based cord clamping (PBCC), avoided the initial high pressures in the lung vasculature while maintaining adequate blood flow, thereby avoiding vascular remodelling and aggravation of pulmonary hypertension. We aim to investigate if the implementation of PBCC in the perinatal stabilisation period of infants born with a CDH could reduce the incidence of pulmonary hypertension in the first 24 hours after birth.Methods and analysis We will perform a multicentre, randomised controlled trial in infants with an isolated left-sided CDH, born at ≥35.0 weeks. Before birth, infants will be randomised to either PBCC or immediate cord clamping, stratified by treatment centre and severity of pulmonary hypoplasia on antenatal ultrasound. PBCC will be performed using a purpose-built resuscitation trolley. Cord clamping will be performed when the infant is considered respiratory stable, defined as a heart rate >100 bpm, preductal oxygen saturation >85%, while using a fraction of inspired oxygen of <0.5. The primary outcome is pulmonary hypertension diagnosed in the first 24 hours after birth, based on clinical and echocardiographic parameters. Secondary outcomes include neonatal as well as maternal outcomes.Ethics and dissemination Central ethical approval was obtained from the Medical Ethical Committee of the Erasmus MC, Rotterdam, The Netherlands (METC 2019-0414). Local ethical approval will be obtained by submitting the protocol to the regulatory bodies and local institutional review boards.Trial registration number NCT04373902.
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spelling doaj-art-ef4b32ffdcf04350902c0dc96af0af5d2025-08-20T01:48:11ZengBMJ Publishing GroupBMJ Open2044-60552022-03-0112310.1136/bmjopen-2021-054808Physiological-based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia (PinC): study protocol for a multicentre, randomised controlled trialArjan B te Pas0Neysan Rafat1Thomas Schaible2Stuart B Hooper3René M H Wijnen4Kelly J Crossley5Philip L J DeKoninck6Ronny Knol7Irwin K M Reiss8Marijn J Vermeulen9Florian Kipfmueller10Berndt Urlesberger11Anne Debeer12Emily J J Horn-Oudshoorn13Suzan C M Cochius-den Otter14Calum T Roberts15Willem P de Boode16Division of Neonatology, Department of Paediatrics, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Neonatology, University Medical Centre Mannheim, Mannheim, GermanyDepartment of Neonatology, University Medical Centre Mannheim, Mannheim, Germany5 The Ritchie Centre at Hudson Institute of Medical Research, Clayton, Victoria, AustraliaDepartment of Paediatric Surgery and Intensive Care, Erasmus MC University Medical Center, Rotterdam, The Netherlands3 The Ritchie Centre at Hudson Institute of Medical Research, Clayton, Victoria, AustraliaThe Ritchie Centre, Hudson Institute for Medical Research, Monash University, Melbourne, Victoria, AustraliaDivision of Neonatology, Department of Paediatrics, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDivision of Neonatology, Department of Paediatrics, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDivision of Neonatology, Department of Paediatrics, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Neonatology and Paediatric Intensive Care Medicine, University of Bonn Children`s Hospital, Bonn, GermanyprofessorDepartment of Neonatology, University Hospitals Leuven, Leuven, BelgiumDivision of Neonatology, Department of Paediatrics, Erasmus MC University Medical Center, Rotterdam, The NetherlandsDepartment of Paediatric Surgery and Intensive Care, Erasmus MC University Medical Center, Rotterdam, The Netherlands3 The Ritchie Centre at Hudson Institute of Medical Research, Clayton, Victoria, AustraliaDivision of Neonatology, Department of Paediatrics, Radboudumc University Medical Center, Nijmegen, The NetherlandsIntroduction Pulmonary hypertension is a major determinant of postnatal survival in infants with a congenital diaphragmatic hernia (CDH). The current care during the perinatal stabilisation period in these infants might contribute to the development of pulmonary hypertension after birth—in particular umbilical cord clamping before lung aeration. An ovine model of diaphragmatic hernia demonstrated that cord clamping after lung aeration, called physiological-based cord clamping (PBCC), avoided the initial high pressures in the lung vasculature while maintaining adequate blood flow, thereby avoiding vascular remodelling and aggravation of pulmonary hypertension. We aim to investigate if the implementation of PBCC in the perinatal stabilisation period of infants born with a CDH could reduce the incidence of pulmonary hypertension in the first 24 hours after birth.Methods and analysis We will perform a multicentre, randomised controlled trial in infants with an isolated left-sided CDH, born at ≥35.0 weeks. Before birth, infants will be randomised to either PBCC or immediate cord clamping, stratified by treatment centre and severity of pulmonary hypoplasia on antenatal ultrasound. PBCC will be performed using a purpose-built resuscitation trolley. Cord clamping will be performed when the infant is considered respiratory stable, defined as a heart rate >100 bpm, preductal oxygen saturation >85%, while using a fraction of inspired oxygen of <0.5. The primary outcome is pulmonary hypertension diagnosed in the first 24 hours after birth, based on clinical and echocardiographic parameters. Secondary outcomes include neonatal as well as maternal outcomes.Ethics and dissemination Central ethical approval was obtained from the Medical Ethical Committee of the Erasmus MC, Rotterdam, The Netherlands (METC 2019-0414). Local ethical approval will be obtained by submitting the protocol to the regulatory bodies and local institutional review boards.Trial registration number NCT04373902.https://bmjopen.bmj.com/content/12/3/e054808.full
spellingShingle Arjan B te Pas
Neysan Rafat
Thomas Schaible
Stuart B Hooper
René M H Wijnen
Kelly J Crossley
Philip L J DeKoninck
Ronny Knol
Irwin K M Reiss
Marijn J Vermeulen
Florian Kipfmueller
Berndt Urlesberger
Anne Debeer
Emily J J Horn-Oudshoorn
Suzan C M Cochius-den Otter
Calum T Roberts
Willem P de Boode
Physiological-based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia (PinC): study protocol for a multicentre, randomised controlled trial
BMJ Open
title Physiological-based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia (PinC): study protocol for a multicentre, randomised controlled trial
title_full Physiological-based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia (PinC): study protocol for a multicentre, randomised controlled trial
title_fullStr Physiological-based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia (PinC): study protocol for a multicentre, randomised controlled trial
title_full_unstemmed Physiological-based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia (PinC): study protocol for a multicentre, randomised controlled trial
title_short Physiological-based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia (PinC): study protocol for a multicentre, randomised controlled trial
title_sort physiological based cord clamping versus immediate cord clamping for infants born with a congenital diaphragmatic hernia pinc study protocol for a multicentre randomised controlled trial
url https://bmjopen.bmj.com/content/12/3/e054808.full
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