Antenatal dexamethasone vs. betamethasone dosing for lung maturation in fetal sheep

Abstract

Background: Dexamethasone-phosphate (Dex-PO₄) and the combination betamethasone-phosphate (Beta-PO₄) + betamethasone-acetate (Beta-Ac) are the most used antenatal corticosteroids to promote fetal lung maturation. We compared fetal lung maturation induced by Beta-Ac+Beta-PO₄, Dex-PO₄, or Beta-PO₄ alone.

Methods: Pregnant ewes received two intramuscular doses 24 h apart of 0.25 mg/kg/dose of Beta-Ac+Beta-PO₄, Dex-PO4 or Beta-PO₄; or 2 doses of 0.125 mg/kg/dose of Beta-PO₄ at 6, 12, or 24 h intervals. Fetuses were delivered 48 h after the first dose and ventilated for 30 min. We assessed ventilatory variables, vital signs, and blood gas. After ventilation pressure-volume curves were measured and lungs were sampled for analysis.

Results: All treatments improved lung compliance and ventilation efficiency. Only Beta-Ac + Beta-PO₄ required lower positive inspiratory pressure compared with control. Beta-Ac + Beta-PO₄ and Beta-PO₄ alone, but not Dex-PO₄, increased the mRNA of surfactant proteins compared with control. Low-dose Beta-PO₄ did not increase mRNA of surfactant proteins. There were no differences among Beta-PO₄ treatment intervals.

Conclusion: Beta-Ac + Beta-PO₄ given as two doses 24 h apart was more effective in promoting fetal lung maturation than Dex-PO₄ or Beta-PO₄ alone, consistent with a prolonged exposure provided by the Beta-Ac + Beta-PO₄. These results support the clinical use of combined Beta-Ac + Beta-PO₄ preparations over phosphate corticosteroids alone for fetal lung maturation.