Objective To evaluate the association of donor sex with transfusion-associated recipient immune responses in preterm newborns receiving unwashed and washed blood.

Design A cohort study using data collected during the Effect of Washed versus Unwashed Packed Red Blood Cell Transfusion on Immune Responses in the Extremely Preterm Newborn randomised trial.

Setting Participants were recruited from two South Australian hospitals between September 2015 and December 2020.

Patients Preterm newborns (<29 weeks).

Interventions Transfusion with unwashed and washed packed red blood cells (PRBCs) from either exclusively male or any female donor for the first three transfusions.

Main outcomes measures The primary outcome was the change from baseline in post-transfusion plasma cytokine concentrations, specifically interferon gamma, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12, IL-17A and tumour necrosis factor (TNF).

Results In total, 153 newborns were evaluated. By the third transfusion, the magnitude of pretransfusion to post-transfusion change in cytokines between the groups differed for IL-6 (p=0.003), IL-12 (p=0.008), IL-17A (p=0.003) and TNF (p=0.007). On post hoc comparison, compared with the unwashed–any female donor group, IL-6 (p<0.05), IL-12 (p<0.05) and IL-17A (p<0.01) were lower in the washed–exclusively male donor group, and IL-6 (p<0.01), IL-12 (p<0.05) and TNF (p<0.01) were lower in the washed–any female donor group.

Conclusion These findings suggest that transfusion with unwashed PRBCs from female donors is associated with an increased recipient immune response, an effect that can be ameliorated with pretransfusion washing. Larger randomised controlled studies confirming this mechanistic link between donor sex and transfusion-associated morbidity are warranted.

Trial registration number ACTRN12613000237785.