BACKGROUND: The first randomized controlled trial (RCT) of A1PI supplementation for the prevention of CLD was recently completed by our group. The incidence of CLD in survivors, defined by the requirement for supplemental oxygen at 36 weeks' corrected gestational age, was lower in the treated group but the difference did not reach statistical significance (RR=.48, CI.23-1.00). Although treatment groups were comparable with respect to demographic factors such as gestational age, birth weight and sex ratio, other variables that might influence the risk of a baby developing CLD were not considered in the original analysis. OBJECTIVE: To examine the influence of different demographic or treatment variables on the development of CLD in the cohort of premature neonates enrolled in the above trial. METHODS: Data were collected prospectively after factors potentially affecting the risk of CLD were identified. The SAS procedure LOGISTIC was used with stepwise progression on data from 94 babies with birth weights of 600-1250g. Demographic variables entered into the model were: birth weight, gestational age, sex, center, PDA, antenatal steroid exposure and ureaplasma culture. Treatment variables included: mean airway pressure x FIO2 on day 1, lowest and mean pCO2 in the first 2 days, total fluid intake, volume of packed red blood cells (PRBC), FFP or platelets transfused, amount of A1PI, amount of intravenous lipid and volume of breast milk/formula given in the first week of life. RESULTS: The model rejected all variables except the total amount of PRBC and A1PI given in the first week of life. A decreased volume of transfused PRBC's was associated with a decrease in the risk of developing CLD(OR=.91, p<.0001) while decreased volume of A1PI infused was associated with a increased risk (OR 1.28, p<.005). CONCLUSIONS: Supplementary analyses of data from a RCT of A1PI supplementation for the prevention of CLD strongly support the efficacy of this therapy. While alternative explanations should be explored, increased risk of CLD with increased PRBC transfusion is likely due to greater underlying disease severity.