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Cardiac surgery on neonates for the correction of congenital heart defects is usually associated with the transfusion of packed red blood cells (PRBCs) into the cardiopulmonary bypass (CPB) circuit. We hypothesised that such transfusions of stored PRBCs directly into the arterial system may increase postoperative morbidity when compared to intravenous transfusion.In this retrospective cohort study, data from 122 consecutive neonates who received transfusions of PRBCs in the course of corrective surgery for congenital heart defects were analysed. Group assignment was according to the timing of the first transfusion: during CPB (On-CPB) or after weaning from CPB (Post-CPB). Chi Square and rank sum tests were applied to compare clinical characteristics. Times until extubation and release from the intensive care unit were analysed by Kaplan-Meier curves and by multivariate Cox regression.Transfusion of PRBCs during CPB was associated with greater 48 hour blood loss (mean±standard deviation, 86±125 versus 32±16 mL/kg, p<0.001), longer duration of mechanical ventilation (214±268 versus 99±75 h, p<0.001) and longer stay on the intensive care unit (10.9±12.1 versus 5.3±3.5 days, p<0.001). However, the groups also differed in many characteristics, such as bodyweight, complexity of surgery or preoperative haemoglobin concentration, which may also affect outcome. Yet, multivariate analyses confirmed an independent association of transfusion On-CPB with an adverse clinical outcome.Our results are consistent with the hypothesis that the transfusion of PRBCs during CPB may increase postoperative morbidity. However, due to the limitations of this retrospective analysis, further studies are needed to confirm a causal relationship between the timing of the transfusion and the clinical outcome and to elucidate putative mechanisms of such an association.