A randomized, controlled trial of oral and intramuscular dexamethasone in the prevention of neonatal respiratory distress syndrome

Abstract

Objective: The study's objective was to compare the efficacies of oral and intramuscular antenatal administration of dexamethasone in reducing neonatal respiratory distress syndrome.

Study design: Subjects at high risk for preterm delivery between 24 and 33 weeks' gestation were prospectively randomly assigned to receive either 6 mg intramuscular dexamethasone or 8 mg oral dexamethasone every 12 hours for 4 doses. The regimen was repeated weekly until 34 weeks' gestation if delivery had not yet occurred. A blinded data review was performed. The primary outcome of the trial was respiratory distress syndrome. Data were analyzed in an intent to treat fashion. Comparisons were made with an unpaired t test, chi2 or Fisher exact test, and survival analysis. P <.05 was considered significant.

Results: The study was discontinued at 39% enrollment after a blinded review of available outcomes. A total of 170 women with 188 fetuses were randomly assigned. The oral and intramuscular groups had similar mean gestational ages at enrollment (29.9 weeks vs 29.2 weeks) and similar median latencies (9.5 vs 10 days). No difference in the frequency of respiratory distress syndrome was found between the oral and intramuscular groups, (34.3% vs 29.8%). Neonatal sepsis (10.1% vs 1.2%, P =.01) and intraventricular hemorrhage (10.1% vs 2. 4%, P =.04) were significantly higher in the oral group. There were no statistical differences in the frequencies of necrotizing enterocolitis or neonatal death. A subgroup analysis of 112 patients who were delivered at <34 weeks' gestation revealed no statistical difference in respiratory distress syndrome between the groups; however, oral dexamethasone was associated with a significant increase in sepsis (15.9% vs 1.6%, P =.009) and intraventricular hemorrhage (15.9% vs 3.3%, P =.03).

Conclusion: Oral administration increases neonatal morbidity without demonstrable benefit and should not at this time be used clinically for induction of fetal pulmonary maturation.