Device for Treatment of Congenital Diaphragmatic Hernia

H-Cubed, Inc., Olmsted Twp OH

Investigators

Abstract

? DESCRIPTION (provided by applicant): Congenital diaphragmatic hernia (CDH) affects 1 in 2000 newborns. CDH is a disorder in which part of the diaphragm fails to form, allowing abdominal organs to migrate into the chest, resulting in lung hypoplasia (underdevelopment) in affected infants. Although great strides have been made in the management of this disease, significant morbidity and mortality persist. Pooled results from over 50 centers worldwide indicate overall survival to be 68% with standard, postnatal therapy. Specific morbidities in survivors include neurodevelopmental, nutritional, sensorineural hearing, and pulmonary function deficiencies. The public health impact of this disease is also significant, as evidenced by a recent study that has identified CDH has the third most costly birth defect. The severe consequences of this congenital anomaly have led others to pursue methods of correcting CDH or its main consequence, lung hypoplasia, prior to birth, allowing for more normal postnatal function. The most promising in utero therapy developed thus far consists of complete occlusion of the fetal trachea (cTO), which has been shown to encourage lung growth. However, this procedure impairs the phasic mechanical forces that are known to critically regulate proper lung development. Despite progression from animal experiments to ongoing human trials, cTO has yet to be demonstrated as superior to standard postnatal therapy and is currently reserved for use in only the most severely affected fetuses. To overcome this, we have proposed the use of a miniature valve system to provide dynamic tracheal occlusion (dTO). For the Phase I project we propose the following Specific Aims: (1) Optimize dTO valve flow-dependence and outflow pressure settings for ideal lung development for severe lung hypoplasia; and (2) Optimize dTO valve flow-dependence and outflow pressure settings for ideal lung development for moderate lung hypoplasia.