Superoxide dismutase for preventing chronic lung disease in mechanically ventilated preterm infants

Free oxygen radicals have been implicated in the pathogenesis of chronic lung disease in preterm infants. Superoxide dismutase is a naturally occurring enzyme which provides a defence against such oxidant injury. Exogenously administered superoxide dismutase has been tested in clinical trials to prevent chronic lung disease in preterm infants.

To determine if exogenously administered superoxide dismutase is efficacious in the prevention of chronic lung disease in preterm infants who are mechanically ventilated, and efficacious in decreasing the following outcomes: bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, patent ductus arteriosus and mortality. To determine the frequency and nature of adverse effects of superoxide dismutase.

We searched Medline (1966 - 2000) and the Cochrane Controlled Trials Register (CCTR) using the following keywords: [bronchopulmonary dysplasia OR chronic lung disease] AND superoxide dismutase, limited to human studies in newborn infants (infant, newborn). We hand searched the reference lists of articles located and the abstracts of the Society for Pediatric Research (USA) (published in Pediatric Research) from 1980 - 2000.

Randomized controlled trials where subjects were preterm infants who had developed or were at risk of developing respiratory distress syndrome requiring assisted ventilation and who were randomly allocated to receive either superoxide dismutase (in any form, by any route) or placebo or no treatment. We included studies which reported any of the following outcomes: chronic lung disease, bronchopulmonary dysplasia, any intraventricular hemorrhage, intraventricular hemorrhage grades III/IV, patent ductus arteriosus, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, neonatal mortality, death prior to discharge and neurodevelopmental outcome.

We extracted and assessed separately all data for each study and entered final data into RevMan. We did not perform subgroup analyses (which were originally planned) because only two studies were eligible for inclusion. We assessed the methodological quality of the studies by assessing the risk for bias. We pooled the outcomes of infants who had developed bronchopulmonary dysplasia at 28 days with those who had died at 28 days to derive the combined outcome of bronchopulmonary dysplasia or death at 28 days. Similarly we pooled the outcomes of infants who had respiratory problems after discharge with those who had died prior to discharge to derive the combined outcome of respiratory problems after discharge or death. We used the standard method of the Cochrane Neonatal Review Group for statistical analysis, using a fixed effect model.

Two randomized controlled trials were included for analysis. No differences were found in either study or in the pooled data in death prior to discharge, oxygen dependency at 36 weeks corrected age, oxygen dependency at 28 days of life or in other outcomes. In one study (Rosenfeld 1984), survivors who had been treated with superoxide dismutase had a shorter duration of continuous positive airway pressure (4.9 vs 9.7 days), a lower frequency of respiratory problems after discharge (relative risk 0.33, 95% confidence limits 0.11, 0.96) and a lower frequency of chest radiograph abnormalities (relative risk 0.30, 95% confidence limits 0.11, 0.87) compared to survivors who received placebo. A third study was available only in abstract form and will be evaluated for inclusion after publication.

Based on currently available published trials, there is insufficient evidence to draw firm conclusions about the efficacy of superoxide dismutase in preventing chronic lung disease of prematurity. Data from a small number of treated infants suggest that it is well tolerated and has no serious adverse effects.