Fetal tracheal occlusion for the treatment of congenital diaphragmatic hernia.
BACKGROUND
Congenital diaphragmatic hernia (CDH) continues to be associated with significant mortality and morbidity rates despite advances in neonatal care. Fetal intervention for CDH has been studied for 25 years. After initial difficulties encountered with open fetal repair, attention has turned to tracheal occlusion (TO) as a method to correct pulmonary hypoplasia before birth. This article reviews our contribution to this field of research and outlines the current status of this treatment modality.


METHODS
Using the fetal lamb model, we have studied the effects of fetal TO on tracheal fluid pressure, lung growth and type II pneumocyte maturation, and surfactant production. We developed a minimally invasive and reversible technique of TO, using a detachable balloon placed using single-port tracheoscopy. We examined differential lung growth, structural maturation, pulmonary artery remodeling, and lung function during an 8-h resuscitation period in lambs, comparing normal controls, lambs with a surgically created CDH, those with CDH+TO, and those with CDH+TO and release of TO 1 week before delivery. We also studied the potential benefits of maternal betamethasone administration and the administration of surfactant at birth. Using a neonatal piglet model, we examined the effect of postnatal pulmonary distension with perfluorocarbon on lung growth. More recently, we turned to the rat nitrofen-induced CDH model to study the effects of TO on bronchial branching and some molecular markers of lung growth (Shh and LGL1).


CONCLUSIONS
Fetal TO is being used to treat human CDH, but its application remains limited by the absence of reliable and widely reproducible prenatal prognostic criteria. A better understanding of the molecular events guiding the lung growth seen with TO may help to refine its use in humans.
Laberge
Jean-Martin
JM
Department of Surgery, The Montreal Children's Hospital of the McGill University Health Center, 2300 rue Tupper, H3H 1P3, Montreal, QC, Canada. jean-martin.laberge@muhc.mcgill.ca
Flageole
Hélène
H
D000818:Animals; D021721:Balloon Occlusion / Q000379:methods*; D001623:Betamethasone / Q000627:therapeutic use; D005315:Fetal Diseases / Q000628:therapy*; D005938:Glucocorticoids / Q000627:therapeutic use; D006548:Hernia, Diaphragmatic / Q000503:physiopathology / Q000628:therapy*; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D008168:Lung / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism; D023421:Models, Animal; D011379:Prognosis; D011663:Pulmonary Surfactants / Q000378:metabolism; D051381:Rats; D012756:Sheep; D013552:Swine; D014132:Trachea; D016896:Treatment Outcome
D005938:Glucocorticoids; D011663:Pulmonary Surfactants; D001623:Betamethasone