Dose-response effects of betamethasone on maturation of the fetal sheep lung

Objective: Glucocorticoid administration to women in preterm labor improves neonatal mortality and morbidity. Fetal exposure to glucocorticoid levels higher than those appropriate to the current gestational stage has multiple organ system effects. Some, eg, fetal hypertension, are maximal at lower than the clinical dose. We hypothesized that the clinical dose has supramaximal lung maturational effects. Study Design: We evaluated the full, half, and quarter clinical betamethasone dose (12 mg/70 kg or 170 μg/kg intramuscularly twice 24 hours apart) on fetal sheep lung pressure volume curves (PVC) after 48 hours' exposure at 0.75 gestation. We measured key messenger RNAs and protein products that affect lung function and total lung dipalmitoyl phosphatidyl choline. Results: Full and half doses had similar PVC and total lung dipalmitoyl phosphatidyl choline effects. Messenger RNA for surfactant proteins A, B, and D and elastin increased in a dose-dependent fashion. Conclusion: Half the clinical betamethasone dose produces maximal PVC improvement in fetal sheep at 0.75 gestation.