Physiological-based cord clamping for infants with congenital diaphragmatic hernia: a multicentre randomised controlled trial

Congenital diaphragmatic hernia is the result of a developmental defect in the
diaphragm, enabling abdominal organs to migrate to the thoracic cavity thereby
interfering with pulmonary development. This result in pulmonary hypoplasia.
Immediately after birth, the lungs are stiff and small and vessels are
underdeveloped, causing persistent pulmonary hypertension of the newborn
(PPHN). The treatment of PPHN remains difficult and may not be successful.
After umbilical cord clamping, changes in the cardiovascular system appear,
especially the bloodflow towards the lungs is increased since the lungs need to
take over oxygenation from the placenta. In most newborns, the transition from
fetus to neonate happens quickly and without problemens. However, the lungs of
children with pulmonary hypoplasia need a longer period of time to be aerated,
leading to an instable circulation with low blood pressures and lower
oxygenation rates.
Studies in preterm infants have revealed that the timing of cord clamping can
make a difference, since delaying cord clamping until after lung aeration would
be beneficial. Furthermore, ovine studies have revealed in CDH lambs, PPHN
occurs less after delayed cord clamping in contrast to immediate cord clamping.

Primary Objective: To evaluate whether PBCC results in a reduced incidence of
pulmonary hypertension in infants with CDH 24hrs after birth.
Secondary Objectives: To measure and monitor physiological parameters during
transition to provide information that improves our further understanding of
the physiological changes occurring during transition for CDH infants.

This is a multicenter, non-blinded, randomized controlled trial in fetuses with
an isolated CDH. The study will be initiated and coordinated by Sophia
Children*s Hospital, Rotterdam. Additional participating centers that have
agreed to collaborate and will join the trial after agreement of the local METC
are: UMC Nijmegen. Patients will be randomized (1:1) between immediate cord
clamping versus PBCC. The infants will be managed using a consensus based
postnatal management protocol after clamping of the cord.

Physiological-based cord clamping (PBCC). For PBCC a new specially designed
resuscitation table (the Concord) will be used. The table is fully equipped to
perform everything that is needed for stabilisation of infants with CDH. All
equipment needed for stabilisation that is attached to the table as well as the
Concord are CE approved medical devices.

In this study, we explore the benefit of PBCC for infants with CDH. Delayed
cord clamping has been incorporated in international guidelines for all
infants, because of the proven beneficial effects. CDH infants need extensive
support immediately after birth and we speculate that optimizing the timing of
cord clamping provides an even greater benefit for these vulnerable infants.

In recent years, there have been several studies evaluating the use of
commercially available resuscitation tables. So far, stabilisation with an
intact cord has been considered a safe approach, both with vaginal delivery as
well as during caesarean section. In addition, a recent feasibility study in
CDH infants did not reveal any safety concerns.

The Concord is fully equipped for stabilisation and resuscitation and our
feasibility study in preterm infants did not show any additional risks for the
mother or the infant. Secondary outcomes include *safety parameters* for the
mother and the infant. While the mother will benefit for having her baby close
to her and able to touch her baby, there is a risk that it will cause anxiety
as interventions take place close to the parents. We will minimize this by
communicating to the parents antenatally what to expect and during the
stabilisation the nurse will communicate what happens during the stabilisation.

The degree of respiratory insufficiency and pulmonary hypertension immediately
after birth is specific for infants with CDH. Any intervention to improve
outcomes in this patient group therefore needs to be studied in this specific
population.