Repeated doses of antenatal corticosteroids in animals: A systematic review

OBJECTIVE: The purpose of this review was to assess the effects of repeated doses of antenatal corticosteroids on lung and brain function and on growth restriction in animals. STUDY DESIGN: MEDLINE and EMBASE were searched for randomized controlled trials that compared repeated doses of antenatal corticosteroids versus a single dose, with or without placebo, in pregnant animals. RESULTS: Nineteen studies were included. The animals that were studied included sheep, monkeys, rabbits, and mice. There were 8 studies that assessed the effects of repeated doses of antenatal corticosteroids on lung function. All the studies reported improvement in lung function after repeated doses of antenatal corticosteroids. Seven studies investigated the effects of repeated doses of antenatal corticosteroids on brain or nervous system function or growth; all the studies found adverse effects with repeated doses of antenatal corticosteroids. Eleven studies looked at the effect of repeated doses of antenatal corticosteroids on fetal growth. Nine studies found evidence of fetal growth restriction with repeated doses of antenatal corticosteroids. One study assessed long-term behavioral outcomes in mice and found no effect. CONCLUSION: Evidence from randomized controlled trials in animals suggests that repeated doses of antenatal corticosteroids may have beneficial effects in terms of lung function but may have adverse effects on brain function and fetal growth. Because of the differences between animals and humans, it is difficult to extrapolate directly the results of these studies to humans. Therefore, randomized controlled trials in humans are needed to assess the effects of repeated courses of antenatal corticosteroids for pregnant women who are at increased risk of preterm birth in terms of important perinatal, neonatal, and maternal outcomes.