135 PRENATAL HORMONAL THERAPY IMPROVES PULMONARY MORPHOLOGY IN RA WITH NTTROFEN-INDUCED CONGENITAL DIAPHRAGMATIC HERNIA

Abstract

The high mortality of Congenital Diaphragmatic Hernia (CDH) is due in large part to the pulmonary hypoplasia, which resembles that seen in premature neonates with respiratory distress syndrome (RDS). Using therapies extrapolated from RDS, we applied quantitative stereologic morphometric techniques to evaluate pulmonary development following prenatal hormonal therapy in the nitrofen CDH rat model. Antenatal hormonal therapy was administered on days 18.5 and 19.5 prior to delivery on day 21.5, using dexamethasone (Dex), thyrotropin releasing hormone (TRH), Dex-TRH, or normal saline (NS) as control. Lungs from CDH rats (n=5) in each treatment group were studied, ten morphometric airspace parameters determined by point-counting 18-30 fields/lung/animal, and analysis of variance with post hoc testing was performed.Equivalent striking maturational changes were observed in the lungs of Dex and Dex-TRH treated animals (Figure). Total internal surface area, the volume fraction of airspaces, and radial alveolar counts were all significantly improved by Dex and Dex-TRH compared to NS treated controls (p=0.0001), as were five other parameters. TRH therapy had minimal beneficial effects.Prenatal corticosteroid ± TRH treatment of CDH significantly improved multiple morphometric parameters of lung maturity in the rat model, further supporting the potential use of hormonal therapy for in utcro treatment of human CDH.