Multiple Courses of Prenatal Steroids: No Added Benefits

OB/GYN News,  March 15, 2000  by Kate Johnson

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Other studies show higher risk of fetal death, neonatal sepsis, and endometritis.

MIAMI BEACH -- Multiple courses of prenatal corticosteroids given to women at risk of preterm delivery appear to offer no additional benefit, compared with single courses, and may actually increase rates of adverse neonatal outcomes, including death.

That was the message that emerged from several studies presented during the annual meeting of the Society for Maternal-Fetal Medicine.

Interim results of one study--the first prospective, randomized, double-blind, placebo-controlled trial to compare single versus multiple courses--showed that multiple courses conveyed no additional benefit, according to Dr. Debra Guinn, the study's lead author.

Results of previous smaller studies on prenatal steroids, many of which were retrospective, have had mixed results. At least two retrospective studies showed that multiple courses decrease the risk of neonatal respiratory distress syndrome (RDS). But other studies--including some presented at the meeting--suggested that multiple courses were associated with adverse outcomes such as an increased risk of fetal death, early-onset neonatal sepsis, and chorioamnionitis.

"There's a growing body of evidence that multiple courses do not improve outcome and evolving, evidence that perhaps they are detrimental, so, until more randomized trials are available, why risk it?" Dr. Stephen Vermillion, lead author of one of the current studies, said in an interview.

Dr. Guinn of the department of maternal-fetal medicine at Denver Health Medical Center and the University of Colorado Health Sciences Center echoed Dr. Vermillion's concerns. "If we were seeing a benefit in the nursery [from multiple courses], we could possibly offset that with the risk of long-term complications, but we're not seeing any [additional] benefit at all," she said.

"We're not willing to continue to expose children to weekly courses of steroids as part of this trial" when we can see no obvious benefit to it, so the study may be called off early she told this newspaper.

The benefits of a single course of prenatal steroids is firmly established. A 1994 National Institutes of Health consensus statement on prenatal steroids said that a single course has been shown to reduce the incidence of mortality, RDS, and intraventricular hemorrhage (IVH) in preterm babies and has not been associated with any serious detrimental effects. But the document stated there was no evidence to support or refute the benefits of repeat courses.

Nevertheless, some physicians have been administering additional courses if delivery does not occur within 7 days of treatment. A survey of U.S. maternal-fetal medicine specialists showed that 58% would repeat weekly doses six times or more if needed.

Dr. Guinn's study found no difference in composite morbidity or fetal lung maturation between 308 babies exposed to either one or multiple courses of betamethasone.

Women at risk for premature delivery who already had received one course of betamethasone were randomized to receive either weekly courses or placebo until delivery or 34 weeks' gestation.

Although the blind will not be broken until delivery of the 500th patient, the composite morbidity rates for the first 308 babies was the same for both treatment groups. Among the neonatal outcomes measured were RDS, IVH, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leucomalacia, necrotizing enterocolitis, sepsis, and death.

But two other studies presented at the meeting suggested that multiple courses actually may do serious harm.

One of the studies, conducted by Dr. Vermillion and his colleagues, showed that multiple courses were associated with an almost 3 times greater risk of neonatal death, a 5 times greater risk of early-onset neonatal sepsis, an almost 10 times greater risk of chorioamnionitis, and a 3.6 times greater risk of endometritis, compared with single courses.

The study, a prospective observational analysis of 453 infants delivered between 24 and 34 weeks' gestation, showed no significant differences in rates of RDS, severe IVH, and late-onset neonatal sepsis among groups, according to Dr. Vermilion, a maternal-fetal specialist at the Medical University of South Carolina in Charleston.

The second study a retrospective analysis of 429 low-birth-weight infants aged up to 18 months, showed that those exposed to multiple courses were more than twice as likely to have severe mental and psychomotor developmental delay compared with either babies whose mothers received a single course or unexposed babies.

All babies were assessed using the Bayley Scales of Infant Development, said Dr. Sean Esplin, the study's lead author and a fellow in maternal-fetal medicine at the University of Utah in Salt Lake City.

Babies exposed to a single course tested as well as or better than those who received no steroids.

"These findings support the continued use of a single course of steroids but raise serious questions about the continued use of multiple courses," he said.