Abstract

Objective

To compare the effect of early postnatal dexamethasone to selective late dexamethasone therapy in ventilated extremely low birthweight premature infants.

Design

Multicenter randomized double blinded controlled clinical trial.

Setting

Forty-one Neonatal Intensive Care Units in the Vermont Oxford Network.

Participants

Infants weighing 501-1000 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%.

Outcome Measurements

The primary outcome measure was 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 poor 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.