A Placebo-Controlled Comparison of Effects of Repetitive Doses of Betamethasone and Dexamethasone on Lung Maturation and Lung, Liver, and Body Weights of Mouse Pups

Abstract

The aim of this study was to compare in vivo effects of single and repetitive doses of betamethasone (BETA) and dexamethasone (DEX) administered to pregnant mice on lung maturation and lung, liver, and body weights (LLBW) of their pups. One hundred and eighty gravid Swiss albino mice were randomly assigned to 1 of 6 groups (n = 30) and administered either BETA, DEX, or saline as a single dose at 14 d gestation or repetitive doses twice daily at 14 and 15 d gestation. All the study groups were then divided into three sets (n = 10). The mice in the second sets were redivided into three subsets randomly (including four, three, and three mice). All gestations in the first sets were terminated at 16.5 d gestation to observe the neonatal breathing pattern (scale to 0-5; 5 is unlabored breathing) of male and female pups whereas other sets had normal delivery. The pups in first, second, and third sets were killed for evaluation in the first set after the evaluation of breathing pattern, in the subsets of second set on postnatal d 1, 3, and 5, and in the third set on postnatal d 90. We recorded maternal body weights at 0 and 16.5 d gestation, and LLBW, the lung/body weight ratio of pups, sex, and the amount of live and dead births per litter. Pups exposed to BETA and DEX had significantly lower maternal weight compared with the saline groups. The death litter size was significantly higher in pups exposed to repetitive doses of DEX than the other treatments. Sex had no significant effect on breathing score and LLBW. Pups exposed to repetitive doses of BETA and DEX presented a higher breathing score than the other groups. The breathing score was significantly higher with BETA than DEX after their repetitive use. The LLBW were significantly less in the treatment groups, especially in the group exposed to repetitive doses of DEX. In conclusion, repetitive doses of BETA and DEX lead to increased fetal lung maturation, but this may be at the expense of fetal and neonatal growth. DEX is less potent in accelerating lung maturation than BETA but it causes more reduction in fetal and neonatal growth.

Controversy: Antenatal Steroids

“…The few direct comparisons of dexamethasone with betamethasone in developing annals also demonstrate differences in the drugs. For example, Ozdenir, et al, reported that betamethasone promoted more lung maturation with less growth restriction in fetal mice than did dexamethasone [10]. Pregnant sheep developed labor more consistently with fetal infusions with betamethasone than with dexamethasone, and the fetal betamethasone treatment decreased maternal progesterone more than dexamethasone [11].…”

Role of Secretoglobin 3A2 in Lung Development

“…Breathing scores were determined by two independent investigators by observing for 2 minutes pups placed on moistened filter paper at 378C immediately after removal from the mother. Scoring assignment was performed according to the criteria described by Ozdemir and colleagues (20).…”

Synthetic Glucocorticoids: Antenatal Administration and Long-term Implications

“…Early studies using rhesus monkeys demonstrated that maternal intramuscular betamethasone administration at 120-133 days of gestation (term is 167 days) resulted in significant reductions in fetal body weight of ~23% at 133 and 167 days of gestation. More recently, studies in sheep and mice demonstrated that clinically relevant doses of maternal betamethasone caused significant fetal growth restriction and reductions in the weight of most organs [87][88][89][90][91]. Growth restriction has also been shown in rats and rabbits treated with maternal dexamethasone [83][84][85][86].…”