Fetal therapy for congenital diaphragmatic hernia: past, present and future

Congenital diaphragmatic hernia (CDH) affects 1/2500-5000 infants and is associated with significant neonatal morbidity and mortality related to pulmonary hypoplasia and pulmonary hypertension. Current estimates of perinatal mortality are between 30-40%. With advances in neonatal and surgical management and now improvements in prenatal diagnosis and intervention, further reduction in mortality is anticipated. Data from the international Tracheal Occlusion to Accelerate Lung Growth (TOTAL) trials, have demonstrated the efficacy of fetal endoscopic tracheal occlusion (FETO) in severe left CDH (LCDH). Although promising, this intervention also has potential for significant morbidity related to prematurity and iatrogenic mortality if reversal of tracheal occlusion is unsuccessful. The implementation of FETO must proceed cautiously within Level III fetal therapy centers and with rigorous outcomes monitoring of centers offering this therapy, ensuring that they are experienced in antenatal severity assessment of CDH, FETO insertion and removal and are integrated with expert, standardized neonatal CDH centers with availability of Extracorporeal life support (ECLS). Further research is needed to better understand the impact of prematurity on FETO survivors, the role of FETO in moderate LCDH, Right CDH (RCDH) and non-isolated CDH in carefully selected circumstances as well as the development of alternative, less invasive, fetal therapies that can specifically target both pulmonary hypoplasia and pulmonary hypertension.