Physiological-based cord clamping trial aims to reduce pulmonary hypertension in infants with congenital diaphragmatic hernia

For infants born with a congenital diaphragmatic hernia (CDH), pulmonary hypertension is a critical determinant of postnatal survival. Current perinatal stabilization practices, particularly immediate umbilical cord clamping before lung aeration, are hypothesized to exacerbate the development of this severe complication. This conventional approach can lead to abrupt increases in lung vascular pressure, potentially contributing to vascular remodeling and worsening pulmonary hypertension. An ovine model of CDH has previously demonstrated that delaying cord clamping until after lung aeration, termed physiological-based cord clamping (PBCC), effectively avoids these initial high pulmonary vascular pressures while maintaining adequate blood flow, thereby preventing detrimental vascular remodeling.

Investigators are conducting a multicentre, randomized controlled trial involving infants with an isolated congenital diaphragmatic hernia (CDH). Before birth, participants are randomized to receive either physiological-based cord clamping (PBCC) or immediate cord clamping. Randomization is stratified by treatment center and the severity of pulmonary hypoplasia, as determined by antenatal ultrasound. For the PBCC arm, a purpose-designed resuscitation module, the Concord Birth Trolley, will be utilized to facilitate the delayed clamping procedure. The study aims to enroll an estimated 500 infants to evaluate the intervention's impact.

This ongoing trial's primary objective is to investigate whether the implementation of physiological-based cord clamping (PBCC) during the perinatal stabilization period can significantly reduce the incidence of pulmonary hypertension in infants with congenital diaphragmatic hernia (CDH) within the first 24 hours after birth. The hypothesis, supported by preclinical data, is that by allowing lung aeration to occur before cord clamping, the abrupt increase in pulmonary vascular resistance typically seen with immediate clamping will be mitigated. This mechanism is expected to prevent the initial high pressures in the lung vasculature, thereby avoiding the subsequent vascular remodeling and aggravation of pulmonary hypertension that contributes to poor outcomes in CDH infants.

The study specifically targets the reduction of pulmonary hypertension incidence as its primary endpoint, aiming to establish a new standard of care for these vulnerable neonates.