Pulmonary hypoplasia is a significant cause of perinatal death and occurs with an incidence of 15%. A common (1:2500 newborns) malformation resulting in hypoplastic lungs is congenital diaphragmatic hernia (CDH). Affected lungs have reduced and functionally altered airways and vessels, leading to respiratory deficiency and pulmonary hypertension in the neonatal period. Nowadays, prenatal fetoscopic endoluminal tracheal occlusion (FETO) can be offered in selected cases to prevent excess of pulmonary fluid and thus triggering lung growth. However, the procedure remains invasive with the main risk of premature rupture of the membranes and still 40% of affected neonates succumb, the majority due to persistent hypoplasia. Therefore, pharmacological agents, including vitamins, hyperoncotic agents and growth factors, have been proposed as an additional prenatal treatment approach to further improve postnatal outcome. Experimental section:
We aim to investigate the potential of two important growth factors, VEGF and IGF-1, to stimulate lung growth in the nitrofen rat model for pulmonary hypoplasia, with particular interest on dosage, route and time-point of administration. If beneficial, the obtained results will provide a profound scientific basis for a pharmacological treatment modality that can be applied by fetoscopy or even via ultrasound-guided needle procedures in fetuses affected by CDH.
Clinical section: Few centers, including the former host institution, offer FETO and termination of affected pregnancies is still widely performed. We plan to perform advanced clinical evaluation of afflicted pregnancies in the framework of a specialized outpatient clinic in Graz, Austria, in close collaboration with the former host institution in Leuven, Belgium, with regards to transfer of patients and data. Advancing the national awareness for prenatal therapeutic options will complete our intentions to improve postnatal survival and morbidity in babies affected by CDH.
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