It’s well known that NEC is more common in infants who are already ill or born prematurely, but what actually causes the condition — which is characterized by death of intestinal tissue, usually in the colon — is still speculation. The new research supports findings from smaller studies that have suggested a link between transfusions and NEC, but questions still remain, including the mechanism behind the association.
In the current study, researchers led by Dr. David Paul of the Christiana Care Health System in Newark, Delaware, retrospectively reviewed the medical records of all low birth weight infants admitted to Christiana Hospital between 1993 and 2007. They considered a total of 2,311 infants, all of whom were born under 1.5kg.
Treating neonatologists made the decision about whether or not to give a patient a transfusion. When they did, a volume of 10 to 20 mL/kg PRBCs was transfused over 2 to 4 hours, followed in some cases by furosemide at 1 mg/kg. There were 2,315 total transfusions given to approximately 50% of the infants.
A total of 122 infants (5.3%) developed NEC, and these patients were more likely to have a younger gestational age and lower birth weight and also had higher incidences of sepsis and patent ductus arteriosus (PDA) compared to patients who did not develop NEC.
In infants with NEC, 80% had received a PRBC transfusion at some point before their diagnosis, compared to 48% of infants without NEC that had received a transfusion. Of all NEC cases, 27% happened within 48 hours of a transfusion, 49% more than 48 hours following a transfusion, and 24% in infants who had not received a PRBC transfusion.
NEC developed within 48 hours of 1.4% of all PRBC transfusions.
A multivariate model showed that the odds of developing NEC in infants who received a transfusion were 2.3 times higher than those who did not receive a transfusion (95% CI: 1.2-4.2).
By determining the source of the blood transfusions, the researchers calculated that 83% of blood transfused before a diagnosis of NEC came from male donors, a finding which they could not explain.
PRBC transfusions may result in exaggerated intestinal immune response, the authors write, and such responses have been associated with NEC – a possible explanation behind the link. They also add that PRBC transfusion may affect the amount of oxygen being delivered to the intestine. One speculated cause of NEC is too little oxygen or blood flow going to the intestines.
It’s also possible that the association between transfusions and NEC is not causal, and that the transfusions were “indicative of other factors that may be causal for NEC,” Dr. Paul and his colleagues write.
“Our study results add to a growing body of data that confirm the association of PRBC transfusion and NEC,” they conclude, adding that future research is still needed. “Prospective studies to determine causality may prove difficult to perform,” the authors write. “Prospective study designs with NEC as a primary outcome would include randomized studies in which PRBC transfusions are administered at different thresholds or enteral feeds are discontinued during PRBC transfusions.”
Pediatrics, online March 14, 2011.