Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia (Known as the TOTAL Trial)

Observational studies have shown that fetoscopic endoluminal tracheal occlusion (FETO) has been associated with increased survival amongst infants with severe pulmonary hypoplasia due to isolated congenital diaphragmatic hernia (CDH) on the left side, but data from randomized trials are lacking. Methods: The tracheal occlusion to accelerate lung growth (TOTAL) trial was an open-label multicentre (n = 10) randomized trial of FETO in fetuses with severe leftsided CDH. Severity was defined by and observed to the expected lung-to-head ratio that predicted survivals of <25%, with FETO initiated at 27 to 29 weeks of gestation. Primary outcome was infant survival to discharge from the neonatal intensive care unit. Results: The trial was stopped early when a difference emerged after 80 women were recruited. In the FETO group, 16/40 (40%) of infants survived, as compared with 6/40 (15%) in the expectant care group (relative risk, 2.67; 95% confidence interval [CI], 1.22 to 6.11; two-sided P = 0.009). This difference persisted to survival at six months of age. As anticipated, the incidence of preterm rupture of membranes was higher in the FETO group (47% vs 11%; relative risk, 4.51; 95% CI, 1.83 to 11.9), as was the incidence of preterm birth (75% vs 29%; relative risk, 2.59; 95% CI, 1.59 to 4.52). There was one neonatal death that occurred after emergency delivery for placental laceration from fetoscopic balloon removal, and one neonatal death occurred because of failed balloon removal. Amongst the secondary outcomes examined, there was less use of extracorporeal membrane oxygenation (ECMO) (2/40 (5%) vs 11/38 (29%)). Conclusions: FETO offers improved survival in fetuses who have left-sided CDH and severe lung hypoplasia.