Perinatal Solutions for Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) is a congenital condition of unknown aetiology occurring in 1 in 2500 live births. These infants have pulmonary hypoplasia (PH) resulting from both an intrinsic defect in lung development and the lack of space in the thorax which is occupied by the herniating abdominal viscera. Pulmonary hypoplasia manifests as respiratory insufficiency and pulmonary hypertension in the newborn. Up to 35% of neonates die despite in utero referral to a high volume centre offering standardised neonatal care. Survivors undergo diaphragmatic closure in the first few days of life with up to 30% of these requiring a patch to close the defect. Patch closure is associated with higher rates of re-herniation, scoliosis and bowel obstruction. This project aimed to tackle both the prenatal and postnatal challenges represented by the disease. Firstly, I investigated prenatal medical therapies to reverse pulmonary hypoplasia in the animal model of congenital diaphragmatic hernia. I studied multiple possible treatment modalities and routes in the fetal rabbit model of CDH. These have included GLP-1, nano-delivery of VEGF to the fetal airways and the role of a particular microRNA family - miR200b in pulmonary hypoplasia. Secondly, I aimed to develop our growing rabbit model of the postnatal disease by increasing defect size and testing traditional patches against a collagen based alternative. Finally, I undertook a clinical research project in the CDH populations of Barcelona and Leuven, which are unique as selected patients are treated with tracheal occlusion.

Jaar van publicatie:2017