Use of antenatal steroids to counteract the negative effects of tracheal occlusion in the fetal lamb model

Tracheal occlusion (TO) in fetal lambs induces pulmonary hyperplasia but ha s negative effects on type Il cells. The purpose of this study was to deter mine whether antenatal steroids could reverse the adverse effects of TO on lung maturation in fetal lambs. Sixteen time-dated pregnant ewes (term, 145 d) and 24 of their fetuses were divided into six groups: 1) TO at 117 d ge station; 2) TO at 117 d with a single maternal intramuscular injection of 0 .5 mg/kg betamethasone 24 h before delivery; 3) TO at 117 d and release of the occlusion 2 d before delivery: 4) TO and release of the occlusion with maternal steroids; 5) unoperated controls without antenatal steroid treatme nt; and 6) unoperated controls, littermates of groups 1-4, treated with ant enatal steroids. All fetuses were killed at 137 d gestation. Outcome measur ements consisted of lung weight-to-body weight ratio; lung morphometry dete rmined by mean terminal bronchial density; and assessment of type II pneumo cytes by in situ hybridization to the mRNA of surfactant proteins B and C. Lung weight-to-body weight ratio and mean terminal bronchial density were s ignificantly different among groups with TO and controls, indicating increa sed lung growth and structural maturation. The density of type II pneumocyt es was markedly decreased by TO. Release 2 d before sacrifice significantly increased the density and surfactant activity of type, II pneumocytes, but to levels still far from controls. Steroids alone had an effect similar to release. An additive effect was noted with steroids and 2-d release result ing in type II cell density comparable to controls. After fetal TO, a singl e maternal intramuscular dose of 0.5 mg/kg of betamethasone 24 h before del ivery allows partial recuperation of the type II pneumocytes, an effect tha t is potentiated by 2-d release.