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
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