April 15, 1998
A new study conducted by researchers in the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network suggests that the steroid dexamethasone, which is commonly prescribed to help premature infants get off mechanical ventilators, may have serious side effects.
The study, which was published in the April 16 issue of the New England Journal of Medicine, was an attempt to learn if earlier treatment of ventilator-dependent premature infants with the drug dexamethasone is beneficial. The investigators enrolled 371 very-low-birth-weight infants who weighed between 1 and 3 pounds from 12 centers of the NICHD Neonatal Research Network. The infants were 13 to 15 days old and were on mechanical ventilators because they were unable to breathe on their own. Because ventilator therapy can cause serious long-term problems such as chronic lung disease, neonatologists try to wean infants from ventilators as soon as possible.
Dexamethasone is a therapy that neonatologists use because it improves the function of premature infants' lungs so that they get off the ventilator earlier. Although steroids have been used to treat ventilator-dependent premature infants who were developing chronic lung disease at one month of age, recently they have been used much earlier in an attempt to prevent chronic lung disease.
The trial tested whether giving the drug to premature infants on a ventilator at two weeks of age was more effective than waiting until four weeks of age. Babies were randomized to one of two groups: the first group started a two-week course of dexamethasone treatment immediately while the second group received a placebo. After the initial two-week treatment period the treatments were switched: babies in group one received placebo for two weeks and babies in group two who were still on the ventilator received a two-week course of dexamethasone.
The researchers found that there was no benefit to the earlier steroid treatment: there was no difference in the number of days that it took the babies in the two groups to breathe without a ventilator. Both groups of babies breathed unassisted at an average of 36 days. The two groups also had a similar frequency of chronic lung disease: 66% in the babies treated with dexamethasone at two weeks and 67% in the group treated at four weeks.
More worrisome was the effect on infections and growth. The infants who were treated with dexamethasone at two weeks of age had an infection rate that was 50% higher than the infants who received placebo at two weeks of age. Moreover, both groups of infants gained weight more slowly and had slower head growth while they received dexamethasone. The authors questioned whether current dexamethasone regimens in premature infants who require ventilator support are potentially more harmful than beneficial.
"Additional randomized trials using lower steroid doses or shorter courses and long-term follow-up are needed to determine if steroid treatment is really beneficial," said Linda Wright, M.D., a study author and investigator from the NICHD.
Others authors of the paper were Lu-Ann Papile, M.D., University of New Mexico, Albuquerque; Jon E. Tyson, M.D., University of Texas Southwestern Medical Center; Barbara J. Stoll, M.D. Emory University; Edward F. Donovan, the University of Cincinnati; Charles R. Bauer, M.D., University of Miami; Heidi Krause-Steinrauf, M.S. and Joel Verter, Ph.D., George Washington University Biostatistics Center; Sheldon B. Korones, M.D., University of Tennessee at Memphis; James A. Lemons, M.D., Indiana University; Avroy A. Fanaroff, M.B, B.Ch, Case Western Reserve University; David K. Stevenson, M.D., Stanford University; William Oh, M.D., Women and Infants Hospital, Brown University; Richard A. Ehrenkranz, M.D., Yale University; and Seetha Shankaran, M.D., Wayne State University.