Plug the lung until it grows (PLUG): A new method to treat congenital diaphragmatic hernia in utero

Abstract

Fetal lungs normally produce fluid that flows through the upper airway into the amniotic fluid. In fetuses with congenital diaphragmatic hernia (CDH), obstructing the flow of lung fluid may expand the lungs and propel the viscera from the chest, alleviating the pulmonary hypoplasia associated with CDH. To test this hypothesis, left-sided diaphragmatic hernias were created in sixteen 75-day-gestation fetal lambs (full-term, 145 days). At 120 days, the trachea was ligated in eight lambs; it was left unligated in the other eight. At 135 to 140 days, the fetuses were delivered, and a tracheostomy performed. Newborns were ventilated for 1 hour and then killed. Blood gas analysis was performed at 0, 5, 20, 40, and 60 minutes. Lung dry weight, DNA, protein, and lipid analyses, as well as plasma cortisol measurements were performed. At autopsy, in the ligated lamb, the abdominal viscera was reduced from the thorax; however, the unligated lambs had viscera completely occupying the left chest. The lungs of the ligated lambs had a higher dry weight (4.22 ± 1.37 g/kg v 1.95 ± 0.59 g/kg; P = .001), DNA (193.8 ± 90.5 mg/kg v 91.5 ± 66.4 mg/kg; P = .02), and protein (1798 ± 691.6 mg/kg v 766.6 ± 201 mg/kg; P = .004). Lung saturated phosphatidyl choline (SPC) levels, DNA:protein ratio, and plasma cortisol were not different between the groups. Neonatal Po 2 at 60 minutes was higher in the ligated group (179.4 ± 127.0 mm Hg v 60.9 ± 62.4 mm Hg; P < .05), and Pco 2 was lower (44.1 ± 21.4 v 83.9 ± 23.5; P < .05) in the ligated group. The authors conclude that tracheal occlusion or “plugging” the upper airway in the fetal lamb with diaphragmatic hernia (1) reduces the abdominal viscera from the chest, (2) accelerates fetal lung growth, and (3) improves oxygenation and ventilation after birth. This technique may have important implications for the future of human fetal therapy for CDH.