The pros and cons of repeat steroids

February 1, 2004

Giving weekly courses of corticosteroids to women at risk for spontaneous preterm delivery may reduce infant mortality, especially when delivery occurs before 32 weeks, according to this randomized trial presented at SMFM's annual meeting. But it also significantly reduces birthweight.

To reach that conclusion, Ronald Wapner and his associates gave at-risk women who were initially less than 32 weeks pregnant—and had already received a single course of betamethasone—either weekly courses of the drug or placebo. Among women on multiple courses who delivered before 32 weeks, the overall incidence of stillbirth, neonatal death, severe respiratory distress syndrome, and related complications was 21.3%, compared to 38.5%, a marginally significant difference (P=0.083). When the research team looked more closely at the data, however, they found that repeat doses apparently reduced the need for surfactant (12.5% vs. 18.4%, P=0.02) and mechanical ventilation (15.5% vs. 23.5%, P=0.005).

On the other hand, infants who had been exposed to four or more courses weighed significantly less at birth (2,396 g vs. 2,561 g P= 0.01). But when investigators analyzed the data for all infants on repeat steroids, including those who had been exposed to more than one and less than four courses of therapy—the drop in birthweight became statistically insignificant. That led researchers to conclude that: "...further investigation of limited repeated steroid administration to women at high risk for early preterm birth is warranted." (Italics added)

Wapner RJ for the NICHD MFMU Network. A randomized trial of single vs. weekly course of corticosteroids. (Abstract 2).

Commentary by Charles J. Lockwood, MD:Until further clinical trials are conducted, I would recommend that a second course of corticosteroids be considered only in infants at immediate risk of preterm delivery prior to 28 weeks. The research presented at the SMFM meeting parallels the work done by Guinn DA, et al., (JAMA. 2001;286:1581-1587), who compared rates of respiratory distress syndrome (RDS), necrotizing enterocolitis, severe intraventricular hemorrhage, bronchopulmonary dysplasia, periventricular leukomalacia, sepsis, and perinatal death among infants whose mothers had received single versus weekly courses of antenatal corticosteroids. These investigators observed that these complications occurred in 22.5% of the weekly-course group versus 28.0% of the single- course group. While this difference was not statistically significant overall, it was significant among neonates delivered before 28 weeks. In particular, the rate of severe RDS in neonates delivered before 28 weeks was lower in the weekly steroid group (65.6%) compared with the single-course steroid (89.3%) group. However, the weekly steroid group had significantly higher rates of preterm deliveries between 24 and 27 weeks, shorter intervals from enrollment to delivery, and trends toward lower birthweights and increased maternal infections. So there's evidence that multiple courses of corticosteroids may reduce some indices of neonatal morbidity among infants born prior to 28 to 32 weeks but may have deleterious effects on growth.