Fetoscopic Interventions for severe congenital diaphragmatic hernia: selection of cases and proposal of an optimal trial design
Foetoscopische behandeling van van ernstige congenitale hernia diafragmatica:selectie criteria en voorstel voor een optimale trial
Jani, Jacques; M0330587
The studies reported in this thesis are part of a programme on fetal therapy established in the University of Leuven over a number of years. Weconducted a series of animal studies which have confirmed previous knowledge but have also used new methods to highlight some of the remaining problems in fetal lung development. Diaphragmatic hernia causes pulmonary hypoplasia which only in part can be prevented by intrauterine intervention. The animal model that was developed for functional studies lends itself to further investigation for development of new strategies to improve the outcome of such interventions. In the human fetal therapy has often been undertaken in the absence of essential knowledge on appropriate patient selection, the use of minimally invasive techniques and adequate methodologies to test effectiveness.It was essential to involve multiple centres throughout the world to contribute their data to a central Registry established in the University of Leuven as the basis for formulating a strategy of patient selection for fetal surgery. Despite the great limitations of retrospective, multicentre studies providing data derived from over a decade it was possible to establish and validate the use of the LHR as a useful prenatal predictor of postnatal outcome. However, it became obvious that the technique for such measurements should be improved and adjustments should be made to take into account changes with gestation. The observed to expected LHR using the tracing method was shown to be at the moment the best method in the prenatal prediction of postnatal survival in fetuses with left and right sided diaphragmatic hernia. It was also shown to be predictive of postnatal morbidity in survivors of diaphragmatic hernia. Once a gold standard was established it made it possible to investigate the potential value of thenew imaging modalities of 3D ultrasound and magnetic resonance imaging and to highlight the new challenges for future research. 3D ultrasound was shown not to be superior in the prediction of postnatal outcome in diaphragmatic hernia fetuses as compared to observed to expected LHR and although magnetic resonance imaging was shown to be very promising, the extent to which this technique would be superior needs further investigation. In the last part of this thesis, we described the clinical application of fetoscopic endoluminal tracheal occlusion (FETO). We documented a homogeneous series of left-sided diaphragmatic hernia treated by FETO in terms of fetal and maternal complications as well as results. Furthermore, we documented lung responsiveness to tracheal occlusion and we were able to predict postnatal outcome from pre-FETO antenatal findings. On the basis of these results it became possible to define the entry criteria for a randomised study to investigate the potential value of fetal intervention and future research to improve outcome in fetuses that do not at present fulfil the entry criteria for such trial.