Multiple Courses of Antenatal Corticosteroids Are Associated With Early Severe Lung Disease in Preterm Neonates

Abstract

Administering a single course of antenatal corticosteroids (ANCS) to women at risk of delivering prematurely has numerous positive neonatal effects including decreases in respiratory distress syndrome, intraventricular hemorrhage, and mortality. Although benefit lasts at least 7 to 10 days, there are no trials confirming benefit beyond this time, so that some obstetricians choose to recommend repeated courses of ANCS. The authors reviewed findings of the thyrotropin-releasing hormone (TRH) trial for prevention of lung disease in preterm infants to determine, in 595 trial neonates born at 26 to 32 weeks' gestation, whether three or more courses of ANCS correlated with infant mortality. The trial, using a randomized design, took place at 13 North American centers in the years 1992 to 1996. All participants received a course of ANCS when enrolled, either two 12-mg intramuscular doses of betamethasone given 24 hours apart or four 6-mg doses of dexamethasone at 6-hour intervals. Women randomized to receive TRH or placebo were given repeated courses of ANCS at the direction of the attending obstetrician. Mortality was 9.2% for neonates exposed to three or more courses of maternal ANCS therapy and 4.8% for those whose mothers received one or two courses. The odds ratio for death in the former group was 3.2 after adjusting for gestational age and multiple gestations. The time of delivery after the last steroid dose did not significantly influence mortality. Multicourse ANCS remained significantly associated with mortality after controlling for tocolytic exposure. Whether the mother received TRH or placebo was not a factor. Early severe lung disease (ESLD) correlated with three or more courses of ANCS, but nonrespiratory neonatal morbidity related to prematurity did not. An increased incidence of ESLD explained the association between mortality and multicourse ANCS therapy. Survival time after birth was significantly shorter when three or more courses of ANCS were administered. The present findings suggest that repeat courses are warranted only in the setting of a clinical trial.