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Crawford TM, Andersen CC, Stark MJ. Effect of repeat transfusion exposure on plasma cytokine and markers of endothelial activation in the extremely preterm neonate [published online ahead of print, 2020 Jul 25]. Transfusion. 2020;10.1111/trf.15952. doi:10.1111/trf.15952

Background: Very preterm newborns receive up to three to five red blood cell (RBC) transfusions, often early, after birth. Despite awareness of the association of transfusion with increases in cytokines and markers of endothelial activation, research has focused on single transfusions weeks after birth. With pathophysiologic processes contributing to the development of morbidities starting soon after delivery, we investigated the response to early, repeated transfusion exposure.

Study design and methods: Three consecutive transfusion exposures were studied in transfusion-naive infants less than 30 weeks’ gestation (n = 46). Plasma cytokines and markers of endothelial activation were measured before and 2 to 4 hours after transfusion by multiplex enzyme-linked immunosorbent assay.

Results: The median (IQR) age was 3 (1-9) days at first transfusion, 7 (3-20) days at the second, and 18 (7-28) days at the third. Baseline concentrations did not differ between the three transfusions. Interleukin (IL)-17A and tumor necrosis factor (TNF)-α did not change after the first transfusion but increased after the second (P < .05) and third transfusions (P < .01). While IL-1β, IL-6, and IL-8 concentrations did not differ after the first and second transfusions, all increased after the third (IL-1β, P < .01; IL-6, P < .01; IL-8, P < .05). The magnitude of posttransfusion increase in IL-1β, IL-17A, and TNF-α increased between the first and third transfusion exposure.

Conclusion: Early, repeated transfusion results in alterations in proinflammatory cytokines and markers of endothelial activation in the very preterm newborn and suggests that the potential for transfusion-related immunomodulation is present in the initial days after birth rather than confined to later in the postnatal period.

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