Infant pulmonary function in a randomized trial of fetal tracheal occlusion for severe congenital diaphragmatic hernia

Abstract

Congenital diaphragmatic hernia (CDH) carries a high mortality risk secondary to pulmonary hypoplasia and respiratory failure. In experimental animals, fetal tracheal occlusion (TO) induces lung growth and morphologic maturation. We measured indicators of pulmonary function in 20 infants who were enrolled in a randomized trial of fetal TO as treatment for severe CDH [nine with conventional treatment (controls); 11 with TO]. We hypothesized that TO would improve lung function. At birth, the TO group had a lower mean gestational age (30.8 +/- 2.0 versus 37.4 +/- 1.0 wk; p=0.0002). All infants required assisted ventilation. Mortality did not differ between groups (64 versus 78%, TO and control, respectively; p=0.64). We measured respiratory mechanics at four study points: 1) first 24 h, 2) before CDH operative repair (5.9 +/- 2.2 d), 3) immediately after repair (7.0 +/- 2.2 d), and 4) before elective extubation (32.5 +/- 16.1 d). We calculated perioperative oxygenation index and alveolar-arterial oxygen difference to assess efficiency of pulmonary gas exchange. Data were analyzed by univariate and repeated measures techniques. Respiratory system compliance (Crs) was low. The rate of increase in Crs over the four study points was greater in the TO group than in control subjects. Crs in the TO group was significantly greater at study 2 (0.28 +/- 0.12 versus 0.17 +/- 0.04 mL.cm H2O(-1).kg(-1); p=0.02) and study 4 (0.93 +/- 0.45 versus 0.51 +/- 0.16 mL.cmH2O(-1).kg(-1); p=0.02). oxygenation index did not differ between groups, but alveolar-arterial oxygen difference was lower in the TO infants. We conclude that fetal TO for severe CDH results in modest improvements in neonatal pulmonary function that are of questionable clinical significance.