Randomized Trial of a Single Repeat Dose of Prenatal Betamethasone Treatment in Imminent Preterm Birth

Abstract

Morbidity in preterm infants is reduced by a single course of corticosteroid treatment, administered prenatally. This randomized, blinded, placebo-controlled study was designed to show whether a single additional dose of 12-mg betamethasone, given with preterm birth imminent before 34 weeks' gestation and at least a week after the full treatment course, would further lower the risk of respiratory distress syndrome (RDS) and severe (grade 3 or 4) intraventricular hemorrhage (IVH). The initial course of therapy consisted of two 12-mg doses of betamethasone. Of 249 mothers enrolled in the study before it was discontinued, 125 were randomized to an additional 12-mg dose of betamethasone and 124 to placebo. All 159 infants born to actively treated mothers and all 167 whose mothers received placebo were born before 36 weeks' gestation. The mean gestational ages at delivery were 30.7 and 31.0 weeks, respectively. Additional steroid treatment did not influence the intact survival rate. In fact, the rate was lower than expected because the incidence of RDS, adjusted for gestational age, was higher than that in the general population. More infants in the steroid group required surfactant therapy. Posthoc analysis of data on 206 infants who were delivered within 1 to 24 hours indicated that the additional steroid dose tended to increase the risk of RDS and reduce the rate of intact survival. No differences were found between the steroid and placebo groups in mortality rates or rates of severe IVH. Six of the 11 infants who died were multiple births, and four of these were cases of twin-to-twin transfusion. Rather than augmenting the benefit of initial steroid therapy when preterm birth is imminent, an additional dose of steroid-administered just before preterm birth-may compromise respiratory adaptation. The findings of this study dictate caution in the use of repeat glucocorticoid therapy in high-risk pregnancies.