BACKGROUND AND PURPOSE:

• Based on observational studies, fetoscopic endoluminal tracheal occlusion (FETO) may increase survival rates among infants with severe pulmonary hypoplasia due to isolated left-sided congenital diaphragmatic hernia
  • FETO procedure: Insertion of an inflatable balloon that is removed a few weeks later | Can be  performed under local anesthesia
  • Fetal tracheal obstruction stimulates lung growth | Lung maturation following prenatal reversal of the occlusion and administration of glucocortocoids
• Deprest et al. (NEJM, 2021) present data from a randomized controlled trial that was designed to assess whether the use of FETO results in increased postnatal survival

METHODS:

• Open-label randomized trial
  • Tracheal Occlusion to Accelerate Lung Growth (TOTAL) trial
• Participants
  • Singleton fetuses
  • Severe isolated congenital diaphragmatic hernia on the left side
  • Severe malformation: Observed-to-expected lung-to-head ratios of <25.0%, irrespective of liver position
• Interventions
  • FETO at 27 to 29 weeks of gestation
  • Expectant care
• Study design
  • A group-sequential design was used
  • Five prespecified interim analyses for superiority
  • Maximum sample size: 116 women
• Primary outcome
  • Infant survival to discharge from the NICU

RESULTS:

• 80 women
  • Trial was stopped early for efficacy after the third interim analysis
• More infants in the FETO group survived to discharge
  • FETO: 40%
  • Expectant care: 15%
  • Relative risk (RR) 2.67 (95% CI, 1.22 to 6.11); P=0.009
• Survival to 6 months of age was the same as the survival to discharge
  • RR 2.67 (95% CI, 1.22 to 6.11)
• Women in the FETO group experienced higher incidences of
  • Preterm, prelabor rupture of membranes
    • FETO: 47%
    • Expectant care: 11%
    • RR 4.51 (95% CI, 1.83 to 11.9)
  • Preterm birth
    • FETO: 75%
    • Expectant care: 29%
    • RR 2.59 (95% CI, 1.59 to 4.52)
• Adverse events
  • One neonatal death occurred after emergency delivery for placental laceration from fetoscopic balloon removal
  • One neonatal death occurred because of failed balloon removal (delivered at non-FETO center)
• Analysis including 11 participants whose data was available after the RCT was stopped
  • FETO: 36%
  • Expectant care: 14%
  • RR 2.65 (95% CI, 1.21 to 6.09)

CONCLUSION:

• The use of FETO at 27 to 29 weeks in pregnancies with isolated severe congenital diaphragmatic hernia on the left side significantly increased survival to discharge, compared to expectant management
  • This increase survival persisted to 6 months of age
• However, FETO increased the risk of PPROM and preterm birth
• Trial not powered for secondary outcomes such as duration of NICU stay or ventilatory support
• The authors conclude

Because the trial involved experienced fetal surgery units, the findings should not be generalized to centers without extensive experience in fetoscopy and FETO or to centers that cannot ensure availability of a team that can perform safe and effective balloon retrieval 

Learn More – Primary Sources:

Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia

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