Non–blood group-specific red blood cell transfusions in preterm infants and necrotizing enterocolitis

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To the Editor:

We were interested in the report by Blau et al¹ on transfusion-related gut injury (TRAGI) as an etiology for necrotizing enterocolitis (NEC). We hypothesized that TRAGI might be an immune-mediated antigenic response to receiving non group-specific red blood cell (RBC) transfusions. RBC alloantibody formation in infants aged <4 months is rare, and thus all neonates receive group O blood.² We used a prospective database of confirmed cases of NEC (Bell’s staging ≥2) from 2006-2010 in a level III neonatal intensive care unit. Out of 44 177 births over the 4-year study period, 602 infants (1.3%) were born at a weight of <1500 g, of whom 39 developed NEC. Nine infants with a birth weight (BW) of >1500 g also developed NEC, for a total of 48 cases of NEC.

A total of 779 RBC transfusions were performed, of which 367 (47%) were blood group-specific. In comparison, 17 of 30 transfusions (56.6%) were group-specific in the infants who developed NEC. The distribution of blood groups transfused was similar in infants who developed NEC and those who did not. However, 16 (53%) were O-positive developed NEC, whereas 291 (37%) did not. The mean day of onset of NEC was day of life 22 ± 14 in the unmatched group and day 24 ± 14 in the matched group (P = .70). The mean BW was 801 ± 230 g in the matched group and 931 ± 314 g in the unmatched group (P = .22).

We classified the timing of RBC transfusion and the onset of NEC as follows: RBC transfusion 48 hours before the onset of NEC symptoms (transfusion-associated NEC [TAN]), RBC transfusion >48 hours before the onset of NEC symptoms (non–transfusion-associated NEC [TIN]), and NEC with no RBC transfusion before onset of symptoms. Four neonates were in the TAN group, 26 were in the TIN group, and 18 did not undergo transfusion. The mean gestational age (GA) was 28 ± 3 weeks in the TAN group, 26 ± 2 weeks in the TIN group, and 31 ± 3 weeks in the never-transfused group (P < .001). Mean BW was 971 ± 522 g in the TAN group, 860 ± 244 g in the TIN group, and 1551 ± 815 g in the never-tranfused group (P < .001). The mean GA at symptom onset was 31 ± 1 weeks in the TAN group, 30 ± 3 weeks in the TIN group, and 32 ± 3 weeks in the never-transfused group (P < .003). The median day of onset of NEC was day 22 ± 15 in the TAN group, day 23 ± 14 in the TIN group, and 11 ± 8 days in the never-transfused group (P < .01).

Non–group-specific RBC transfusions were not associated with the development of NEC and thus remain a safe practice in neonatal blood transfusion. We had a lower incidence of TRAGI compared with Blau et al (8.3% vs 25%). We found that infants with TAN had lower BW, lower GA, and developed NEC later than infants who did not undergo transfusion.

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References 

1. Blau J, Calo JM, Dozor D, Sutton M, Alpan G, La Gamma E. Transfusion-related acute gut injury: necrotizing enterocolitis in very low birth weight neonates after packed red blood cells transfusion. J Pediatr. 2011;158:403–409
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2. Floss AM, Strauss RG, Goeken N, Knox L. Multiple transfusion fail to provoke antibodies against blood cell antigens in human infants. Transfusion. 1986;26:419–422
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