PLACEBO-CONTROLLED COMPARISON BETWEEN A SINGLE-DOSE AND A MULTIDOSE OF BETAMETHASONE IN ACCELERATING LUNG MATURATION OF MICE OFFSPRING

OBJECTIVE: Our purpose was to determine, in a placebo-controlled manne r with a mouse model, whether a multidose of betamethasone is more ben eficial than a single dose in accelerating fetal lung maturation. STUD Y DESIGN: Ninety gravid CD-1 mice were randomly assigned to 1 of 3 gro ups (n = 30) to receive either a placebo (0.25 mL subcutaneously) or b etamethasone (0.1 mg subcutaneously) as a single dose on gestational d ay 14 or as a multidose twice daily on gestational day 14 and 15. Ten pregnancies in each group were terminated at gestational day 16.5 to o bserve the neonatal breathing pattern (scale 0 to 5; 5 is unlabored br eathing) and the lung histologic findings (scale 0 to 5; 5 is alveolar budding). The lungs of the offspring belonging to the remaining 20 pr egnancies in each group were removed and weighed at postnatal day 1, 3 , 5, or 120. RESULTS: Fetuses exposed to a multidose of betamethasone displayed a higher breathing score at gestational day 16.5 than either to a single dose or to the placebo (mean score 4.6 vs 3.8 or 1.3, P < .001). Alveolar development was greater after exposure to a multidose of betamethasone than after a single dose or after a placebo (mean sc ore 4.4 vs 3.5 or 1.6; P < .001). The lung weights at gestational day 16.5 were less after a multidose of betamethasone than after a single dose of either betamethasone or a placebo (18.3 +/- 1.0 g vs 21.4 +/- 1.3 g or 23.3 +/- 1.3 g; P < .02). The lung/body weight ratio was simi larly affected. This reduced weight of the lungs persisted postnatally into adulthood. CONCLUSIONS: With a CD-I mouse model, a multidose of antenatal betamethasone accelerated fetal lung maturation more than af ter a single dose but was accompanied with a decrease in lung weight t hat persisted into adulthood.