Abstract 1901 Neonatal Pulmonology I: Mechanical Influences on Lung Development Platform, Tuesday, 5/4

Introduction: Congenital Diaphragmatic Hernia (CDH) is a major cause of refractory respiratory failure in the newborn. Pulmonary hypoplasia (PH) is the major factor limiting survival. Vitamin A plays an important role during lung development. We hypothesized that antenatal treatment with vitamin A would stimulate lung growth and decrease mortality in experimental CDH, induced in rats by ingestion of the herbicide, Nitrofen (2,4-dichloro-phenyl-p-nitrophenyl-ether).

Methods: Nitrofen was administered to pregnant rats on day 12 of gestation (term, 22 days). Rats were assigned to 5 groups: 3 groups received one dose of oral antenatal vitamin A (15 000 IU) before (day 10), concomitant with (day 12), or after (day 14) Nitrofen; 1 group received only Nitrofen; a control group received vehicle (olive oil). Protocol 1: Rats were allowed to deliver spontaneously and survival was monitored until 72 hours at which time point any surviving animal was sacrified. The incidence of CDH was verified. Protocol 2: Rats were delivered by C-section at day 21. Rat pups were sacrified and weighed. PH was assessed by a lung/body weight ratio (LW/BW), radial saccular count (RSC) and DNA/protein ratio.

Results: The incidence of CDH was markedly lower in all groups receiving vitamin A (day 10-44%, day 12-20%, day 14-40%) compared to the Nitrofen group (84%, p<0.05). The 72-hour survival was higher in all 3 vitamin A groups (day 10-40%, day 12-58% and day 14-70%) compared to the Nitrofen group (16%, p<0.05). The LW/BW and the RSC were significantly increased by vitamin A. There was no difference in the DNA/protein ratio.

Conclusion: Antenatal treatment with vitamin A lowers the incidence and severity of experimental CDH and increases lung growth and maturation. The mechanisms by which vitamin A exerts its beneficial effects are currently under investigation.