Pulmonary outcome at 1 year corrected age in premature infants treated at birth with recombinant human CuZn superoxide dismutase

Abstract

Objective: To examine whether treatment of premature infants with intratracheal recombinant human CuZn superoxide dismutase (r-h CuZnSOD) reduces bronchopulmonary dysplasia and improves pulmonary outcome at 1 year corrected age.

Design: Three hundred two premature infants (600-1200 g birth weight) treated with exogenous surfactant at birth for respiratory distress syndrome were randomized to receive either intratracheal r-h CuZnSOD (5 mg/kg in 2 mL/kg saline) or placebo every 48 hours (as long as intubation was required) for up to 1 month of age. Short-term, as well as longer-term pulmonary outcome was assessed.

Results: There were no differences between groups in the incidence of death or the development of bronchopulmonary dysplasia (oxygen requirement with an Edwards chest radiograph score of >or=3) at 28 days of life or 36 weeks' postmenstrual age. r-h CuZnSOD was well-tolerated and not associated with significant increases in any adverse event. At a median of 1 year corrected age, health assessments and physical examinations were performed on 209 (80%) surviving infants, with complete data available on 189 infants. Thirty-seven percent of placebo-treated infants had repeated episodes of wheezing or other respiratory illness severe enough to require treatment with asthma medications such as bronchodilators and/or corticosteroids compared with 24% of r-h CuZnSOD-treated infants, a 36% reduction. In infants <27 weeks' gestation, 42% treated with placebo received asthma medications compared with 19% of r-h CuZnSOD-treated infants, a 55% decrease. Infants <27 weeks' gestation who received r-h CuZnSOD also had a 55% decrease in emergency department visits and a 44% decrease in subsequent hospitalizations. Growth measurements and the results of physical examinations were comparable between groups.

Conclusions: These data indicate that treatment at birth with r-h CuZnSOD may reduce early pulmonary injury, resulting in improved clinical status when measured at 1 year corrected age. r-h CuZnSOD appears to be a safe and effective therapy that improves pulmonary outcome in high-risk premature infants.