Abstract
<title>Abstract</title> <p>Background Very low birthweight (VLBW) infants frequently require red blood cell (RBC) transfusions during early postnatal life. Emerging evidence suggests that transfusions may modulate immune responses, but its impact on immune development remains incompletely understood. Methods 136 VLBW infants participating in the prospective “Immune Regulation of the Newborn Study” (IRON study) were analzed during the first 42 postnatal days with serial immune phenotyping. Infants were stratified by RBC transfusion exposure. Group differences were assessed using Mann-Whitney U tests at each postnatal week and multivariable linear regression models were used to evaluate the association between RBC transfusion and log-transformed CD8 + T-cell counts. For a dose-dependent effect, log-transformed CD8 + T-cell counts were regressed on the number of transfusions and on the cumulative transfusion burden. Results Transfused infants were more premature and had higher morbidity. Longitudinal analysis demonstrated persistently lower CD8 + T-cell counts in transfused infants. At day 42, RBC transfusion was independently associated with reduced CD8 + T-cell levels in multivariable regression (β = −0.312, 95% CI − 0.578 to − 0.045, p = 0.022), corresponding to approximately 27% lower CD8 + T-cell counts among transfused infants. Across all six weekly windows, a higher number of transfusions is consistently associated with lower CD8 + T-cell counts reaching statistical significance in week 2 and week 5. Conclusions RBC transfusion exposure in VLBW infants is independently associated with altered adaptive immune development, particularly reduced CD8 + T-cell levels over time. Our findings indicate an RBC-specific effect supporting the concept of RBC transfusion-related immunomodulation in preterm infants and warrant further investigation.</p>