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 majordeterminant of postnatal survival in infants with acongenital diaphragmatic hernia (CDH). The current careduring the perinatal stabilisation period in these infantsmight contribute to the development of pulmonaryhypertension after birth—in particular umbilical cordclamping before lung aeration. An ovine model ofdiaphragmatic hernia demonstrated that cord clampingafter lung aeration, called physiological-based cordclamping (PBCC), avoided the initial high pressures in thelung vasculature while maintaining adequate blood flow,thereby avoiding vascular remodelling and aggravationof pulmonary hypertension. We aim to investigate if theimplementation of PBCC in the perinatal stabilisation periodof infants born with a CDH could reduce the incidence ofpulmonary hypertension in the first 24 hours after birth.Methods and analysis We will perform a multicentre,randomised controlled trial in infants with an isolatedleft-sided CDH, born at ≥35.0 weeks. Before birth, infantswill be randomised to either PBCC or immediate cordclamping, stratified by treatment centre and severity ofpulmonary hypoplasia on antenatal ultrasound. PBCCwill be performed using a purpose- built resuscitationtrolley. Cord clamping will be performed when the infantis considered respiratory stable, defined as a heartrate >100 bpm, preductal oxygen saturation >85%,while using a fraction of inspired oxygen of <0.5. Theprimary outcome is pulmonary hypertension diagnosedin the first 24 hours after birth, based on clinical andechocardiographic parameters. Secondary outcomesinclude neonatal as well as maternal outcomes.Ethics and dissemination Central ethical approvalwas obtained from the Medical Ethical Committee ofthe Erasmus MC, Rotterdam, The Netherlands (METC2019-0414). Local ethical approval will be obtained bysubmitting the protocol to the regulatory bodies and localinstitutional review boards

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 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