Dexamethasone Therapy in VLBW Infants at Risk of CLD

Ventilator-dependent premature infants are often treated with dexamethasone. However, the
optimal timing of therapy is unknown. We compared the benefits and hazards of initiating
dexamethasone therapy at two weeks of age and at four weeks of age in 371
ventilator-dependent very-low-birth-weight infants (501 to 1500 grams) who had
respiratory-index scores (mean airway pressure x the fraction of inspired oxygen) of greater
than or equal 2.4 at two weeks of age. The primary outcome was the number of days from
randomization to extubation not requiring reintubation (extubation score or death). The
secondary outcomes were death before discharge from the hospital; the duration of assisted
ventilation, supplementary oxygen therapy and hospital stay; the incidence of chronic lung
disease (defined as the need for supplemental oxygen at 36 weeks postconceptional age by best
obstetrical estimate) and rates of morbidity and mortality from respiratory causes during the
first year. Additional secondary endpoints were hyperglycemia, hypertension, growth,
bacteremia, necrotizing enterocolitis and upper GI bleeding.

The sample size of 370 was based on a 0.60 probability that the extubation score of late
treatment was greater than early treatment, a 5% two-sided type 1 error, 85% power, and 10%
treatment noncompliance.

Infants were randomized to either receive dexamethasone for two weeks followed by saline
placebo for two weeks, or saline placebo for two weeks followed by either dexamethasone or
additional placebo for two weeks (if they still met entry criteria). Dexamethasone was given
at a dose of 0.25 mg per kilogram of body weight twice daily intravenously or orally for five
days, and the dose then tapered.

The median time to ventilator independence was 36 days in the dexamethasone-placebo group and
37 days in the placebo-dexamethasone group. The incidences of chronic lung disease (defined
as the need for oxygen supplementation at 36 weeks postconceptional age) were 66 percent and
67 percent, respectively. Dexamethasone was associated with an increased incidence of
nosocomial bacteremia (relative risk, 1.5; 95 percent confidence interval, 1.1 to 2.1) and
hyperglycemia (relative risk, 1.9; 95 percent confidence interval, 1.2 to 3.0) in the
dexamethasone-placebo group, elevated blood pressure (relative risk, 2.9; 95 percent
confidence interval, 1.2 to 6.9) in the placebo-dexamethasone group, and diminished weight
gain and head growth (P less than 0.001) in both groups. Treatment of ventilator-dependent
premature infants with dexamethasone at two weeks of age is more hazardous and no more
beneficial than treatment at four weeks of age.

Inclusion criteria:

- 501 to 1500 grams

- 13 to 15 days old

- Respiratory-index score of greater than or equal to 2.4 that had been increasing or
minimally decreasing during the previous 48 hours or a score of greater than or equal
to 4.0 even if there had been improvement during the preceding 48 hours

Exclusion criteria:

- Received glucocorticoid treatment after birth

- Had evidence or suspicious signs of sepsis as judged by the treating physician

- Major congenital anomaly of the cardiovascular, pulmonary, or central nervous system