NEW ORLEANS -- Repeated weekly courses of prenatal steroids reduce infant morbidity in certain cases, but the overall risks of this approach outweigh the benefits, Dr. Ronald J. Wapner said at the annual meeting of the Society for Maternal-Fetal Medicine.
In a trial of 492 women at 23-32 weeks' gestation who were at risk for spontaneous preterm birth, the use of repeated weekly courses of prenatal steroids did not improve overall neonatal morbidity. In addition, repeated courses led to a reduction in birth weight and an increase in the frequency of small-for-gestational-age infants, compared with babies of women who were given an initial steroid dose followed by placebo doses.
"Based on these observations, we believe that weekly administration of prenatal corticosteroids should not be utilized," said Dr. Wapner of the National Institute of Child Health and Human Development, Rockville, Md.
Study participants were randomized to receive weekly courses of betamethasone or a single dose followed within 10 days by weekly placebo. There were no significant overall differences between groups in these primary outcomes: stillbirth or neonatal death, severe respiratory distress syndrome, grade III or IV intraventricular hemorrhage, periventricular leukomalacia, or chronic lung disease. Among those who delivered before 32 weeks' gestation, however, multiple steroid doses were associated with a trend toward reduction in the risk of the primary outcomes.
Overall, multiple courses were associated with significant reductions in most secondary outcomes related to lung function.
At least one of the primary outcomes occurred in 8% of the 250 women who received weekly steroid doses and 9% of the 242 women in the placebo group.
Among those who delivered before 32 weeks' gestation, at least one of the primary outcomes occurred in 21% of 60 women in the weekly steroid group, and 39% of 52 women in the placebo group.
The study was initiated following a National Institutes of Health consensus conference that found a lack of evidence to argue either for or against the use of repeat doses of steroids in women at risk for spontaneous preterm birth. Initially, the NICHD planned to enroll 2,200 women for the study, but after the second interim analysis, enrollment was halted because of reduced birth weights among those receiving multiple steroid doses, emerging literature showing a risk of reduced birth weights, and a lack of identifiable improvement or reduction in morbidity associated with repeat doses of steroids, Dr. Wapner explained.
Overall, there was an insignificant trend toward reduced birth weight (2,194 g vs. 2,289 g) and length (44.2 cm vs. 44.7 cm) in those who received weekly steroids. Among those infants whose mothers received at least four courses of betamethasone, however, birth weight was significantly reduced (2,396 g vs. 2,561 g).
Although these findings are tempered by the early termination of study enrollment and the concomitant reduction in power, and while further study of alternative corticosteroid treatment approaches is warranted, there are currently insufficient data in regard to the efficacy or safety of any alternative approach, he said.
Until further data are available, existing recommendations to limit steroid exposure to a single course should be followed, he said.
BY SHARON WORCESTER
COPYRIGHT 2004 International Medical News Group
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