Association of Blood Donor Sex and Age With Outcomes in Very Low-Birth-Weight Infants Receiving Blood Transfusion

Abstract

IMPORTANCE There are conflicting data on the association between blood donor characteristics and outcomes among patients receiving transfusions.OBJECTIVE To evaluate the association of blood donor sex and age with mortality or serious morbidity in very low-birth-weight (VLBW) infants receiving blood transfusions. DESIGN, SETTING, AND PARTICIPANTSThis is a cohort study using data collected from 3 hospitals in Atlanta, Georgia. VLBW infants (Յ1500 g) who received red blood cell (RBC) transfusion from exclusively male or female donors were enrolled from January 2010 to February 2014. Infants received follow-up until 90 days, hospital discharge, transfer to a non-study-affiliated hospital, or death. Data analysis was performed from July 2019 to December 2020.EXPOSURES Donor sex and mean donor age. MAIN OUTCOMES AND MEASURESThe primary outcome was a composite outcome of death, necrotizing enterocolitis (Bell stage II or higher), retinopathy of prematurity (stage III or higher), or moderate-to-severe bronchopulmonary dysplasia. Modified Poisson regression, with consideration of covariate interactions, was used to estimate the association between donor sex and age with the primary outcome, with adjustment for the total number of transfusions and birth weight. RESULTSIn total, 181 infants were evaluated, with a mean (SD) birth weight of 919 (253) g and mean (SD) gestational age of 27.0 (2.2) weeks; 56 infants (31%) received RBC transfusion from exclusively female donors. The mean (SD) donor age was 46.6 (13.7) years. The primary outcome incidence was 21% (12 of 56 infants) among infants receiving RBCs from exclusively female donors, compared with 45% (56 of 125 infants) among those receiving RBCs from exclusively male donors. Significant interactions were detected between female donor and donor age (P for interaction = .005) and between female donor and number of transfusions (P for interaction < .001). For the typical infant, who received a median (interquartile range) of 2 (1-3) transfusions, RBC transfusion from exclusively female donors, compared with male donors, was associated with a lower risk of the primary outcome (relative risk, 0.29; 95% CI, 0.16-0.54). The protective association between RBC transfusions from female donors, compared with male donors, and the primary outcome increased as the donor age increased, but decreased as the number of transfusions increased. CONCLUSIONS AND RELEVANCEThese findings suggest that RBC transfusion from female donors, particularly older female donors, is associated with a lower risk of death or serious morbidity in VLBW infants receiving transfusion. Larger studies confirming these findings and examining potential mechanisms are warranted.

Immunologic effects of red blood cell and platelet transfusions in neonates

“…After the third transfusion, infants who received standard RBCs had elevated interleukin (IL)-17A and tumor necrosis factor (TNF), compared to pretransfusion levels, while infants transfused with washed blood showed reduced IL-17A, TNF, IL-6, IL-8, and IFN-γ levels, suggesting that the pro-inflammatory response to transfusion can be attenuated with washing, presumably by removing the free hemoglobin and other inflammatory mediators present in the supernatant of stored RBCs. Intriguingly, the sex and age of the donor also seem to affect neonatal outcomes, with one study showing that preterm infants transfused exclusively with RBCs from female donors had better outcomes than neonates transfused with RBCs from male donors [31 ▪ ]. The protective association of transfusions from female donors increased with advancing donor age, but decreased as the number of transfusions increased (likely reflecting increased severity of illness).…”

Red Blood Cell Donor Sex Associated Effects on Morbidity and Mortality in the Extremely Preterm Newborn

“…A different approach was taken by Patel and colleagues [ 45 ]. Here the authors included newborns previously recruited into the prospective Transfusion-Transmission of Cytomegalovirus cohort study [ 46 ].…”

“…Female donors represented 136 (27%) of the transfusions. The exclusively female donor group had a lower risk of death or serious morbidity (21% vs. 45%, adjusted OR 0.26 95% CI 0.09–0.65) [ 45 ]. Further, in a subset of 76 newborns a single RBC transfusion from a female donor was associated with the lowest risk of the primary composite outcome (RR 0.15, 95% CI 0.02–0.99) after adjustment for birthweight and donor age.…”

“…The most obvious methodological difference is the inclusion, rather than exclusion, of infants who received both male and female donor RBCs in the Murphy study [ 40 ]. Patel and colleagues argue that newborns who receive transfusions from both donor sexes, suggesting greater transfusion exposure, may have greater illness severity [ 45 ]. When comparing transfusion exposure between those newborns included versus those excluded due to exposure to both male and female donor RBC in their cohort, the difference in the median number of transfusions was of a factor of 3.…”

“…When comparing transfusion exposure between those newborns included versus those excluded due to exposure to both male and female donor RBC in their cohort, the difference in the median number of transfusions was of a factor of 3. However, both studies found an adverse interaction between female donor sex and the number of transfusions, resulting in an increase in the odds of any morbidity [ 40 ] versus a reduction in the protective effect of exposure to female donor RBCs for each additional transfusion [ 45 ].…”