Fetuses with congenital diaphragmatic hernia (CDH) who have the liver herniated into the hemithorax and a low lung-to-head ratio have a very poor prognosis with the highest quality and most expensive postnatal treatment including extracorporeal membrane oxygenation, sophisticated ventilatory techniques, and surfactant therapy. The strategy of temporary tracheal occlusion to gradually enlarge the hypoplastic fetal lung was developed to salvage these severely affected fetuses. The early experience using hysterotomy and open fetal surgery was not successful, but when minimally invasive fetoscopic techniques were developed to accomplish tracheal occlusion, 70 out of 10 babies survived. However, the efficacy of this therapy cannot be established without a properly controlled prospective trial. Despite the ethical, logistical, and financial difficulties of assigning or withholding an innovative surgical procedure for a life-threatening fetal condition, it is imperative to establish the place of this promising new therapy early in its development before it becomes established without being scientifically tested. It is the general aim of this proposal to perform a clinical trial to assess the efficacy and safety of fetoscopic tracheal occlusion for the treatment of severe CDH. This will be a prospective randomized, controlled trial comparing two groups; those who undergo endoscopic fetal tracheal occlusion between 24 and 28 weeks' gestation, and those who deliver at or near term and receive standard tertiary postnatal care. The sample population is a subset of fetuses with CHD who, by applying selected criteria developed in previous experimental and clinical studies, are deemed to have an 80% mortality rate: isolated CDH diagnosed before 25 weeks' gestation with liver herniated into the hemithorax and a low lung-to-head ratio. There can be no other anomies demonstrated by ultrasonography, and the karyotype and fetal echocardiogram must be normal. The primary outcome variable is neonatal mortality. Secondary outcome variables will reflect long-term morbidity, mortality, and cost. Statistical analyses will use a logistic regression model based on neonatal mortality and long-to-head ratio as outcome predictors. Secondary analyses will be performed using the following statistical tests as appropriate; Cox proportional hazard model, analysis of variance, and logistic regression models. The study will employ an intent-to-treat analysis and provisions will be made for early limb closure if statistically significant differences in neonatal mortality occur between the groups or if maternal mortality occurs in the group randomized to fetal intervention. We hypothesize that fetal temporary tracheal occlusion, when compared to standard postnatal care for the treatment of severe CDH, will improve survival and quality of life. Although a controlled randomized trial of any fetal treatment poses great difficulties, it is time to establish whether this innovative therapeutic modality should be pursued or abandoned.
|Effective start/end date||4/1/99 → 3/31/04|
- National Institutes of Health: $181,555.00