A Placebo-Controlled, Blinded Comparison Between Betamethasone and Dexamethasone to Enhance Lung Maturation in the Fetal Mouse

Abstract

OBJECTIVE

TO compare the effects of betamethasone and dexamethasone used to enhance lung maturity of the fetal mouse.

METHODS

Adult CD-I mice were administered a single dose of either a placebo or different strengths of betamethasone (0.01, 0.025, or 0.10 mg) or dexamethasone (0.025 or 0.10 mg) on day 14.0 (74%) of gestation. The eight gravid mice in each treatment cohort were killed on day 16.5 to assess fetal lung maturity (histologic changes and respiratory patterns) in a blinded manner. Another ten gravid mice in each treatment group were allowed to deliver spontaneously to assess perinatal outcomes.

RESULTS

Compared with the effects from placebo exposure, the 0.10-mg doses of both betamethasone and dexamethasone demonstrated enhanced histologic maturational changes and improved neonatal respiratory efforts. Betamethasone was twofold to threefold more potent than dexamethasone. The fetal crown-rump lengths and the fetal body, lung, and heart weights were indistinguishable among the three treatment groups. Compared with the fetal liver weight in the placebo group (55.0 ±2.2 mg), the liver was less heavy after exposure to 0.10 mg of betamethasone (45.6 ±2.0 mg; P <.005), 0.025 mg of dexamethasone (41.6± 1.7 mg; P <.02), or 0.10 mg of dexamethasone (43.8 ± 1.5 mg; P <. 001). No significant differences were observed between the 0.10-mg treatments of either corticosteroid and placebo for the duration of gestation, litter size, survival rate, birth weights, or weight gains to postnatal day 26.

CONCLUSION

A single subcutaneous dose of 0.10 mg of betamethasone was twofold to threefold more potent than dexamethasone in accelerating fetal lung maturity without impairingfetal survival or weight gain. The unexpected finding of a reduced fetal liver weight with either corticosteroid warrants clinical correlation.