Steroid Trial

Purpose
To compare the effect of early postnatal dexamethasone to selective late dexamethasone therapy in ventilated extremely low birth weight (ELBW) premature infants

Study Design
Multicenter, randomized, double-blinded controlled clinical trial at 41 neonatal intensive care units in the Vermont Oxford Network

Methods
Infants weighing 501 to 1000 grams were eligible for enrollment at 12 hours of age if they required assisted ventilation, had received surfactant replacement therapy, were physiologically stable, had no obvious life-threatening congenital anomaly, and had blood cultures obtained and antibiotic therapy initiated

Intervention
Infants were randomly assigned to dexamethasone or saline placebo. Intravenous dexamethasone was administered for 12 days according to the following dosing schedule: 0.5 mg/kg/day for three days, 0.25 mg/kg/day for three days, 0.10 mg/kg/day for three days, 0.05 mg/kg/day for three days. Infants in either group could receive treatment with selective late postnatal steroids beginning on day 14 of life if they were on assisted ventilation with supplemental oxygen greater than 30%.

Primary Outcome
Chronic lung disease or death at 36 weeks postmenstrual age

Results
The study was stopped prior to completion of sample size goals due to concern regarding serious side effects in the early steroid treatment group. 542 infants were enrolled (early treatment n=273, selective treatment n=269). The two groups had similar demographic characteristics. No differences were noted in the primary outcome of chronic lung disease or death at 36 weeks postmenstrual age (early treatment 50% vs. late treatment 53%, relative risk 0.93, 95%CI 0.79, 1.09). Fewer infants who received early steroid treatment had a patent ductus arteriosus (relative risk 0.78, 95%CI 0.63, 0.96) and fewer infants in the early steroid group received indomethacin therapy (relative risk 0.74, 95%CI 0.64, 0.86) or late steroid treatment (relative risk 0.69, 95%CI 0.58, 0.81). However, more infants who received early steroid treatment had complications associated with therapy including an increase in hyperglycemia (relative risk 1.29, 95%CI 1.13, 1.46), and an increase in the use of insulin therapy (relative risk 1.62, 95%CI 1.36, 1.94). A trend toward increased gastrointestinal hemorrhage (relative risk 1.55, 95%CI 0.92, 2.61), gastrointestinal perforation (relative risk 1.53, 95%CI 0.89, 2.61) and an increased systolic blood pressure (relative risk 1.34, 95%CI 0.97, 1.85) was noted. In infants receiving cranial ultrasound examinations, a marginal increase in periventricular leukomalacia was noted in the early steroid treatment group (relative risk 2.23, 95%CI 0.99, 5.04). Infants who received early steroid therapy had fewer days in supplemental oxygen, but experienced poorer weight gain.

Conclusions
A 12-day course of early postnatal steroid therapy given to extremely low birth weight infants did not decrease the risk of chronic lung disease or death at 36 weeks postmenstrual age and was associated with an increased risk of serious complications and poor weight gain.

Citation
Vermont Oxford Network Steroid Study Group. Early postnatal dexamethasone therapy for the prevention of chronic lung disease. Pediatrics. 2001;108(3):741-748. PubMed: 11533345

Sponsor
Children’s Miracle Network