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

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.

Comparison between oral and intramuscular dexamethasone in suppressing unconjugated estriol levels during the third trimester.

OBJECTIVES: Unconjugated estriol production depends on fetal adrenal androgen precursors. Fetal exposure to exogenous glucocorticoids results in adrenal suppression with a subsequent decrease in maternal serum unconjugated estriol levels. We compared the efficacy between oral and intramuscular dexamethasone in maternal serum unconjugated estriol suppression at 48 hours after the initial dose among women at risk for preterm delivery. STUDY DESIGN: Twenty-four gravidas at risk for preterm delivery were randomized to receive either 6 mg intramuscular or 8 mg oral dexamethasone every 12 hours for a total of 4 doses. Blood samples (9 mL) were obtained before the initial dexamethasone administration and again after the fourth dose. Serum was separated and frozen at -70 degreesC and subsequently underwent batch analysis. Unconjugated estriol levels were determined by radioimmunoassay with intra-assay and interassay coefficients of variation of 7.9% and 5.5%, respectively. All values are reported as mean +/- SD. The primary statistical analysis was a t test, with P <.05 considered significant. RESULTS: At the time of dexamethasone administration, gestational ages in both groups were similar. Predexamethasone and postdexamethasone unconjugated estriol levels were also similar between the intramuscular and oral groups (5.39 +/- 3.99 vs 1.80 +/- 2.49 ng/mL and 6.05 +/- 3.00 vs 1.61 +/- 1.03 ng/mL, respectively, P >.05). No difference in percent decrease in unconjugated estriol levels was found between the intramuscular (0.67 +/- 0.24) and oral (0.65 +/- 0.39) groups. CONCLUSION: Oral dexamethasone (8 mg) produces similar maternal serum unconjugated estriol suppression compared with intramuscular dexamethasone (6 mg) when evaluated 48 hours after administration.