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


METHODS
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.
Davis
Jonathan M
JM
Department of Pediatrics (Neonatology), CardioPulmonary Research Institute, Winthrop University Hospital, SUNY Stony Brook School of Medicine, Mineola, New York 11501, USA. jdavis@winthrop.org
Parad
Richard B
RB
Michele
Theresa
T
Allred
Elizabeth
E
Price
Anita
A
Rosenfeld
Warren
W
D000367:Age Factors; D001997:Bronchopulmonary Dysplasia / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007442:Intubation, Intratracheal; D008297:Male; D010919:Placebos; D011663:Pulmonary Surfactants / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D012121:Respiration, Artificial; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000627:therapeutic use*; D016896:Treatment Outcome
D016166:Free Radical Scavengers; D010919:Placebos; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; D013482:Superoxide Dismutase