The mean gestational age at birth of the 11 patients was 35.3±2.2 weeks, with a median interval time between balloon removal and puncture and birth of 7 (0–35) days (Table 2). Four of the 11 patients (36.4%) had a vaginal delivery, and 7 of 11 (63.6%) had a cesarean delivery for obstetric indications (including a single ex utero intrapartum treatment procedure with balloon removal). The median Apgar score at 5 minutes was 7.2–4 The median umbilical arterial pH of the 10 fetoscopically treated neonates at delivery was 7.30 (7.26–7.35).
In the 10 patients in whom the balloon was successfully placed, there were significant increases in all indicators of lung volume despite no significant change in liver herniation (Fig. 2). Postnatal surgical repair of the diaphragmatic defect was performed in all patients on day 2–4 of life. All neonates had very large diaphragmatic defects requiring a patch.
Eight of 10 (80%) fetuses undergoing fetoscopic tracheal occlusion survived to 6 months. One child died at 17 days of life as a result of severe pulmonary hypertension, and another died at 4 months from pulmonary hypertension associated with pulmonary capillary hemangiomatosis, an unrelated but typically lethal condition. Another child died at 8 months from persistent pulmonary hypertension and progressive respiratory failure. Of the remaining seven children, six have been discharged alive, and, at the time of manuscript submission, one patient remains hospitalized (23 months); thus, survival rates to 1 year and 2 years of life were 70% (7/10) and 67% (6/9), respectively (Table 3). The median length of stay to discharge for survivors was 87 days (range 56–133 days). At 6 months, four of eight (50%) of the surviving infants required supplemental oxygen.
When we considered only the most severe of our fetoscopic tracheal occlusion group compared with nontreated patients (Table 3) using all accepted measures (ultrasonography: lung-to-head ratio less than 1.0 and observed-to-expected and lung-to-head ratio less than 0.25 and liver herniation and MRI: observed-to-expected and total fetal lung volume less than 0.32 and liver herniation greater than 0.21), the survival rates to 6 months, to discharge, to 1 year of life, and to 2 years of life were all significantly higher in the fetoscopic-treated group. Extracorporeal membrane oxygenation utilization was also higher in the nontreated group. Figure 3 shows a Kaplan-Meier analysis for the fetoscopic tracheal occlusion and nontreated groups (P<.01).
Our study has demonstrated that, in an appropriately resourced U.S. setting, fetoscopic tracheal occlusion is feasible, safe, and may offer survival benefit in fetuses with severe isolated left-sided diaphragmatic hernia. These results are in agreement with a recent randomized controlled trial showing improved survival in the fetoscopically treated patients.10
The 6-month survival rate (80%) is higher when compared with a composite of comparable published outcomes on fetoscopic tracheal occlusion programs in European and South American centers (50%)5–7,10–12,21–25 and also higher than published series of similarly severe left diaphragmatic hernia managed without tracheal occlusion but with extracorporeal membrane oxygenation (20–50%).16,26–29
In our own center, our historical cases that would have met our inclusion criteria for fetoscopic tracheal occlusion had a lower 6-month survival when compared with our treated population (Table 2).16 In addition to improving the lung size and the 6-month survival rate, fetoscopic tracheal occlusion also reduced the need for extracorporeal membrane oxygenation in our unit (78–30%). These differences in survival and need for extracorporeal membrane oxygenation are even more pronounced if all prenatal measures of severity are used for inclusion (ultrasonography and magnetic resonance imaging; Table 3). Reducing the need for extracorporeal membrane oxygenation in these patients has important clinical and economic implications given the risks of this therapy (especially cerebral hemorrhage).
Safety was of primary interest in the design and implementation of this study. Measures were put in place to facilitate emergency balloon retrieval and to minimize any risk of airway obstruction at birth in fetuses with a balloon in place. A specialized team was on call 24/7 during the time the balloon was in place; training of this team included simulation of emergency balloon removal with a life-like model30 for all involved health care providers. Our system was tested in one patient in which ex utero intrapartum treatment was required because of rapidly progressive preterm labor and it functioned as planned.
This study was conducted under special oversight by the FDA under stringent conditions. During our study, the Goldvalve balloon, which was FDA-approved for neurosurgical use, was discontinued, precluding our off-label use for fetoscopic tracheal occlusion. The FDA office assisted in obtaining an Investigational Device Exemption for the Balt balloon, which is not FDA-approved.
Limitations of our study include a nonrandomized study design, small sample size, and the fact that these results represent a single center with a team that had prior fetoscopic tracheal occlusion experience. One particular issue that must be addressed is the potential for confounding as a result of changes in management over the 8 years during which patients in the control group were treated. Although this is a valid concern, in terms of neonatal intensive care unit protocols, use of ventilation and drug (ie, nitric oxide) strategies, extracorporeal membrane oxygenation availability, surgeons and surgical technique, and postdelivery management, there has been minimal change with the same team of surgeons managing all patients with diaphragmatic hernia since 2001.
In conclusion, our results suggest that fetoscopic tracheal occlusion may be a useful adjunctive prenatal therapy to improve the outcomes of fetuses with severe and extremely severe left- sided diaphragmatic hernia in a U.S.-based health care system with extracorporeal membrane oxygenation capability.
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