ALPHA1-PROTEINASE INHIBITOR (A1PI) THERAPY FOR THE PREVENTION OF BRONCHOPULMONARY DYSPLASIA (BPD) IN PREMATURE INFANTS. • 1466

Abstract

Background/Objectives: An imbalance between increased neutrophil elastase and a decreased antiprotease shield has been suggested as a factor contributing to the development of BPD. We hypothesized that administration of exogenous A1PI to premature neonates would inhibit neutrophil elastase and attenuate the development of BPD. Methods: A randomized, placebo-controlled, prospective study of A1PI (Prolastin/Bayer) supplementation was performed. Neonates less than 24 hours of age with birth weights 600-1000 g on respiratory support, and 1001-1250 g with respiratory distress syndrome (RDS) were eligible. A1PI (60 mg/kg IV) or placebo was infused on Days 0, 4, 7 and 14. Primary outcome was BPD in survivors, defined as oxygen requirement on Day 28. Results: 106 patients were recruited. There were no significant differences between groups in birth weight, gestational age, sex ratio or incidence of RDS. Status on Day 28 and incidence of intraventricular and pulmonary hemorrhage (IVH & PH) are shown below. Statistical analysis is by chi-squared test. A1PI therapy significantly reduced the incidence of PH (p=.03, RR.22, CI.05-.98). The incidence of BPD in survivors was lower in the treated group but the difference did not reach statistical significance (p=.06, RR.79, CI.60-1.02). No side effects were noted other than a trend towards increased total, but not severe IVH. Conclusion: A1PI therapy appears to reduce the incidence of PH and may impede the development of BPD in some neonates born prematurely. Further work on dosage, timing and adjunctive therapies is indicated. (Funding received from Bayer/CRCS R&D Fund)Table