Antenatal Corticosteroids—Too Much of a Good Thing?
Authors: Edward E. Lawson
Journal: JAMA (2001)

CHANGES IN MANAGEMENT REGARDING CARE OF NEOnates resemble the swings of a pendulum. As the force of gravity keeps a pendulum from swinging too far, continuing medical research keeps management from becoming too extreme. Research permits evaluation of the risks and benefits of a particular treatment, advancing knowledge to refine the risk-benefit ratio and alter clinical care. Unfortunately, despite apparently proper research protocols, physicians do not always correctly understand risks and benefits regarding any specific issue. Therefore, occasionally the recommended management may become transiently out of phase with the ultimate “best practice.” For years, physicians have known that antenatal betamethasone or dexamethasone, when administered at least 24 hours before delivery, reduces the incidence of respiratory distress syndrome (RDS) in neonates between 24 and 32 weeks’ gestation. Consensus on this point swung through phases as early studies supported the use of antenatal corticosteroids, then a major National Institutes of Health (NIH)–sponsored, multicenter, randomized controlled trial failed to show benefit. Further studies and review of all available data resulted in general consensus that antenatal corticosteroid therapy is clearly efficacious in preventing RDS in both sexes and all racial groups. The 1994 NIH Consensus Development Conference on Effect of Corticosteroids for Fetal Maturation on Perinatal Outcomes concluded that antenatal corticosteroids reduce risk of death, RDS, and intraventricular hemorrhage. Use of antenatal betamethasone to enhance fetal pulmonary maturity is now established and generally considered to be standard of care. The 1994 NIH Consensus Development Report also recognized that the effect of antenatal corticosteroids apparently lasted only 7 days. This gave support to the concept that antenatal corticosteroids should be repeatedly administered if the preterm pregnancy persisted beyond 1 week after the first course of corticosteroids. However, the available literature reports variable results when comparing incidence of RDS following single or multiple courses of antenatal corticosteroids. Similarly, postnatal care of prematurely born neonates with dexamethasone to ameliorate the course of chronic lung disease has become commonplace. Again, the earliest articles on this topic were positive, and later articles, although generally continuing to support efficacy, now also demonstrate significant negative developmental effects. For premature infants who have been treated with long courses (up to 6 weeks) of daily dexamethasone, delay in growth of head circumference, reduced body weight, decreased length, and developmental abnormalities are now being reported. These findings are entirely consistent with data from earlier animal studies, as recently reviewed by Smith and associates. Clinically, however, neonatologists have considered that protracted courses of corticosteroids were necessary to prevent death secondary to chronic lung disease. Arguing that the doses were much smaller than those used in the animal studies, many neonatologists continued with this management. Some neonatologists, possibly out of concern for potential iatrogenic effects, modified the 6-week dexamethasone therapy to earlier or shorter (or both). Others used more intense treatments. Nevertheless, recent studies indicating negative outcomes for growth and development have forced reconsideration of postnatal corticosteroid management. The pendulum is definitely swinging back. In this issue of THE JOURNAL, Guinn and colleagues report the results from a randomized, double-blind, placebocontrolled clinical trial comparing repeated weekly betamethasone administration with a single initial dose administered to pregnant women at the onset of threatened preterm delivery. During the course of this trial, a second NIH consensus development conference was held (August 17-18, 2000) to determine whether repeated courses of corticosteroids had benefits and risks different from a single dose of antenatal corticosteroid administration. The studies regarding potential benefits or adverse effects of mul-