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.