Medical Professional Publications

Does Feed Fortification or Blood Transfusion Quickly Lead to NEC?

Columbus, OH — January 2018

Many infants who ultimately develop necrotizing enterocolitis (NEC) receive enteral feeds and/or blood transfusions, but studies conflict on what that means. Do the feeds and transfusions increase the odds for developing the condition? One of the reasons studies conflict is that not accounting for all important variables – gestational age, birth weight, severity of illness (or degree of sickness) etc. – may confound outcomes.

Physician-researchers at Nationwide Children’s Hospital have potentially eliminated many of those confounders in a study examining the relationship among feed fortification, feed volume increases and transfusion on the short-term odds of developing NEC. The authors used a “case-crossover” design, first developed in the early 1990s to determine if exercise was related to myocardial infarctions that occurred soon after the exercise.    

The Nationwide Children’s study found no association between feeding advances, feeding fortifications or packed red blood cell transfusions and NEC onset in the infants they studied. But that’s not the end of the story, says Jonathan Slaughter, MD, member of the Division of Neonatology at Nationwide Children’s and senior author of the study.

“We believe the study’s method is very useful in determining if these variables are temporally associated with NEC,” says Dr. Slaughter, who is also an assistant professor of Pediatrics at The Ohio State University College of Medicine. “However, we have a very low-rate of NEC at Nationwide Children’s, a good thing for our patients. Thus, our available cohort was relatively small. We saw some relatively high odds ratios in our study, but there were wide confidence intervals involving feed fortification and blood transfusion. Since it’s possible that we might have seen associations with a larger cohort, we hope to collaborate with others in the future to repeat our investigation in a larger sample of infants. That would allow us to more precisely measure any associations.”

The case-crossover design essentially allows each infant to serve as his or her own control. All 63 infants included in the Nationwide Children’s study developed NEC. Researchers looked at the 48 hours before NEC onset, and compared that to a preceding 48-hour control period. Because the babies were the same, only changes in acute, transient exposures were thought to lead to NEC development.

“Before and after studies are difficult in this population over longer periods of time,” says Dr. Slaughter. “This technique works well for acute changes. It doesn’t tell you exactly what causes NEC, but it does tell you if a change in a baby’s care right before NEC, such as a feeding increase, is related to NEC onset.”

Whether feeding advances or blood transfusions lead to NEC is still an open question, Dr. Slaughter says. While this study might not provide the answer, its methodology may help in the future.

“To my knowledge, there has never been a case-crossover design like this in neonatal intensive care patients,” he says.


 Le VT, Klebanoff MA, Talavera MM, Slaughter JL. Transient effects of transfusion and feeding advances (volumetric and caloric) on necrotizing enterocolitis development: A case-crossover study. PLoS One. 2017 June 20; 12(6).

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