The fetal respiratory system as target for antenatal therapy

The widespread use of prenatal ultrasound has made the fetus a patient. A number of conditions diagnosed as such may require therapy prior to birth. Herein we describe past, current and potential future procedures designed to treat pulmonary conditions in the antenatal period. When congenital cystic adenomatoid malformation (CCAM) is associated with fetal hydrops, treatment is required. Prior to viability this may be in utero resection of the pathologic lung lobe or shunting of cystic lesions. More recently, fetuses with isolated congenital diaphragmatic hernia (CDH) with lethal lung hypoplasia have been offered percutaneous fetal tracheal occlusion to provoke lung growth. A very rare condition is laryngeal atresia, which requires peripartum re-establishment of the airways. As we get more experience with access to the fetal airways, this may open the doors for novel therapies. One of these is gene delivery to treat fetuses with serious monogenic disorders or to induce transient overexpression of certain proteins. We review the individual hurdles that are being met by researchers when designing fetal gene therapeutic strategies, in particular for the fetal lung. Also the use of stem cells for pulmonary disorders is currently explored.