Critical thinking in red blood cell transfusion decisions: Donor, product, recipient, and outcomes.

Red blood cell (RBC) transfusion is a common and potentially lifesaving intervention in neonatal care, particularly for very low birth weight (VLBW) infants. Transfusion decisions are often guided by hemoglobin thresholds; however, these surrogate markers may incompletely capture the complex physiologic, immunologic, and developmental factors that influence transfusion benefit and risk. This review presents a critical thinking framework for neonatal RBC transfusion decision-making that integrates donor characteristics, blood product attributes, recipient vulnerability, and clinical outcomes. We summarize infectious and non-infectious risks of RBC transfusion. Contemporary strategies to mitigate transfusion-transmitted cytomegalovirus (CMV), including leukoreduction and CMV-seronegative donor selection, are discussed in the context of evidence demonstrating extremely low residual risk and maternal breast milk as the primary source of postnatal infection in VLBW infants. We also note variability in blood banking practices and clinical implications. Emerging physiological data suggests that storage-related changes, particularly following irradiation, may affect regional tissue oxygenation in preterm infants, although the clinical significance is uncertain. Evidence from randomized trials does not support routine use of fresh RBCs to improve major neonatal outcomes, underscoring the need to move beyond storage age alone when evaluating transfusion practices. Finally, we highlight future research directions, including vein-to-vein studies linking donor and product characteristics to recipient outcomes, and emphasize the importance of close collaboration between neonatologists and transfusion medicine specialists to optimize neonatal patient blood management and improve outcomes in this highly vulnerable population.