Background: Ventilator-dependent premature infants are often treated with dexamethasone. However, the optimal timing of therapy is unknown. Methods: 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 g) who had respiratory- index scores (mean airway pressure x the fraction of inspired oxygen) of ≤2.4 at two weeks of age. One hundred eighty-two infants received dexamethasone for two weeks followed by placebo for two weeks, and 189 infants received placebo for two weeks followed by either dexamethasone (those with a respiratory-index score of ≤2.4 on treatment day 14) or additional placebo for two weeks. 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 was then tapered. Results: 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<0.001) in both groups. Conclusions: 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.
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