SAN FRANCISCO — Three randomized, controlled trials now show evidence of beneficial effects from a limited number of repeat courses of prenatal corticosteroids for fetuses at risk of preterm delivery, according to Julian T. Parer, M.D.
Those aren't necessarily the official conclusions of the studies, however, he acknowledged at a meeting on antepartum and intrapartum management sponsored by the University of California, San Francisco.
Two of the three studies found no overall benefit from repeat prenatal steroids but reported significantly less respiratory distress and morbidity in babies born at younger gestational ages if they got more than one course of betamethasone prenatally.
The third study showed a benefit from repeat prenatal steroids, but the investigators will not draw conclusions about the results until after a 2-year follow-up period, said Dr. Parer, who is professor of ob.gyn. at the university.
Dr. Parer said he has no financial relationships with companies that make corticosteroids.
A consensus statement issued in 2000 by the National Institutes of Health says that repeat courses of corticosteroids should not be used routinely due to insufficient data from randomized clinical trials.
Data from these three more recent studies, however, support the administration of more than one course of prenatal corticosteroids for women who are at at high risk of delivering before 28 weeks, Dr. Parer said.
“It is possible to justify repeating at least a single course in those patients, particularly if given at a 2-week interval,” he said.
Dr. Parer relayed results of the third, and most recent, study that he heard presented at a conference in Australia earlier this year. That study included 982 pregnant women at risk for preterm delivery who had received one course of prenatal corticosteroids.
The women were randomized to weekly corticosteroids or placebo; treatment continued until 32 weeks' gestation only if the risk for preterm delivery continued.
The study included singletons, twins, and triplets for a total of 1,100 fetuses that were a mean of 28 weeks' gestation at enrollment. The risk factors for preterm birth were similar between groups.
Results showed significantly lower rates of respiratory distress syndrome (RDS) and severe RDS in the weekly corticosteroid group. With weekly corticosteroids, 33% developed RDS, and 12% had severe RDS, compared with 41% and 20%, respectively, in the placebo group.
The need for oxygen or mechanical ventilation fell less dramatically in the weekly corticosteroids group, compared with placebo, but it was not clear whether these differences were significant.
There were no significant differences between groups in the need for intensive care, duration of intensive care, rates of chronic lung disease or severe intraventricular hemorrhage, or maternal outcomes.
Although birth weights were somewhat lower in the steroid group, the weight differences between groups resolved by the time of hospital discharge, he said. Average neonatal length and head circumference did not differ between groups.
No harmful effects of repeat corticosteroids were noted. Of those women who received repeat courses, 24% received at least four courses. The investigators declined to present a conclusion until they've completed 2 years of neurodevelopmental follow-up, he said at the meeting.
A separate study, which was reported at the Society of Maternal and Fetal Medicine meeting in 2004, randomized 495 women after an initial course of prenatal corticosteroids to weekly courses or placebo.
The study was stopped prematurely at 23% of its expected enrollment due to concerns about birth weights, and no signs of a substantial reduction in overall morbidity in the steroid group.
The investigators concluded that there was no benefit to repeated courses of corticosteroids, but Dr. Parer highlighted the “much more impressive” results in infants delivered at less than 32 weeks. These babies had significantly less bronchopulmonary dysplasia and less need for mechanical ventilation or continuous positive airway pressure if they had received repeat corticosteroids, he noted. Birth weights were lower only in infants who had been exposed to more than four courses of corticosteroids.
A third study that randomized 502 women to a single course or weekly courses of corticosteroids also was stopped early and reported no benefit from weekly prenatal steroids (JAMA 2001;286:1581–7).
That study also reported a significantly lower incidence of RDS in babies born before 28 weeks whose mothers received repeated courses of corticosteroids, Dr. Parer noted.
Critics contend that both of these studies were too small and too short to detect significant differences in their primary end point of composite morbidity.