Does non-transferrin bound iron contribute to transfusion related immune-modulation in preterms?

OBJECTIVE: There is increasing awareness that allogeneic transfusion is potentially harmful in preterm neonates secondary to transfusion related immunomodulation (TRIM). Non-transferrin bound iron (NTBI) may contribute to TRIM by promoting oxidative damage and pro-inflammatory cytokine release. The current study aimed to determine if transfusion early in the neonatal period resulted in an increase in circulating NTBI, oxidative stress and immune activation.
DESIGN: Prospective observational study.
SETTING: One transfusion event was studied in infants ≤28 weeks gestation between 2 and 6 weeks postnatal age (n=33) admitted to a tertiary neonatal intensive care unit.
METHODS: Serum NTBI, inflammatory cytokines and malondialdehyde (MDA) were measured from the donor pack, prior to and at 2-4 and 24 h post-transfusion.
RESULTS: Median (range) age at transfusion was 17 (14-39) days with the pretransfusion haemoglobin level 9.6 (7.4-10.4) g/dl. NTBI was detectable in 18 (51%) of the transfusion packs. NTBI levels were higher after transfusion (p<0.01) returning to pretransfusion levels by 24 h. Post-transfusion NTBI level correlated with the age of transfused blood (p<0.001) and was positively correlated with plasma MDA (p=0.01) but not IL-1β, IL-6, IL8 or TNFα.
CONCLUSIONS: Circulating NTBI is transiently elevated following blood transfusion in preterm newborns. This increase was related to the age of blood transfused and correlated with increases in oxidative stress but not pro-inflammatory cytokines. While further studies are necessary to determine whether these transient effects influence clinical outcome, the current data do not support a significant role in the very preterm neonate for NTBI in TRIM.