Reducing the risk of pulmonary hypertension in infants with a congenital diaphragmatic hernia.

This project focuses on congenital diaphragmatic hernia (CDH), a birth defect characterised by a failed closure of the diaphragm, creating a continuity between the thoracic and abdominal cavities. As a result, there is displacement of abdominal organs into the chest and this limits the space for the lungs to develop in the fetus. This leads to small lungs with abnormal airways and vessels, a condition called lung hypoplasia . Whilst in utero, lung hypoplasia is not a problem as the fetus receives oxygen via the placenta, but immediately after birth is potentially lethal. It often results in respiratory insufficiency requiring respiratory support with invasive mechanical ventilation and is complicated by persistent pulmonary hypertension of the newborn (PPHN). The latter is caused by a smaller cross-sectional area of the lung vasculature combined with raised vascular tone due to increased muscularisation of the vessels. Overall, postnatal mortality of CDH is high (30-40%) and is significantly worse when complicated with severe PPHN (up to 56%). There is an urgent need to mitigate the effects of PPHN and improve outcomes for infants born with CDH. We believe that by optimising the transition period immediately after birth we could significantly reduce the risk of pulmonary hypertension. We propose further pre-clinical studies that will answer fundamental questions about the management of the transition period for these challenging infants.