March 01, 2016
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Necrotizing enterocolitis linked to severe anemia, not transfusion, in very low-birth-weight infants

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Severe anemia appeared associated with an increased risk for developing necrotizing enterocolitis among very low-birth-weight infants, according to the results of an observational cohort study.

However, the receipt of red blood cell transfusions did not appear to increase risk for necrotizing enterocolitis in this patient population, results showed.

“Necrotizing enterocolitis is a leading cause of mortality among preterm infants, with case-fatality rates of 20% to 30%,” Ravi M. Patel, MD, MSc, assistant professor of pediatrics and neonatology at Emory University School of Medicine, and colleagues wrote. “The pathogenesis of necrotizing enterocolitis remains unclear, with conflicting data regarding the role of two risk factors, red blood cell transfusion and anemia, on the development of necrotizing enterocolitis.”

To determine the relationship between these risk factors and necrotizing enterocolitis, Patel and colleagues conducted a secondary, prospective, multicenter observational study of 598 very low-birth-weight (≤ 1,500 g) infants.

Between January 2010 and February 2014, the researchers enrolled infants (mean gestational age, 27.9 weeks; 50.5% boys; 57.9% black) within 5 days of birth from three neonatal ICUs in Atlanta. They followed infants until 90 days, hospital discharge, transfer to a non–study-affiliated hospital or death, whichever occurred first.

Red blood cell transfusion served as the primary exposure, with severe anemia (hemoglobin level, ≤ 8 g/dL) serving as the secondary exposure.

The incidence of necrotizing enterocolitis served as the primary endpoint, with mortality observed as a competing risk.

During the course of the study, 44 infants developed necrotizing enterocolitis and 32 died of any cause.

Fifty-three percent (n = 319) of the study population received a total of 1,430 red blood cell transfusions. The researchers observed an unadjusted cumulative incidence of necrotizing enterocolitis among transfusion-exposed infants of 9.9% (95% CI, 6.9-14.2) by week 8, compared with 4.6% (95% CI, 2.6-8) among nonexposed infants.

However, in a multivariable analysis adjusted for birth weight, breastfeeding duration, illness severity and antibiotic exposure, the receipt of a red blood cell transfusion in any given week did not appear to significantly affect the rate of necrotizing enterocolitis (cause-specific HR = 0.44; 95% CI, 0.17-1.12) or mortality (cause-specific HR = 1.36; 95% CI, 0.27-6.82).

Based on an evaluation of 4,565 longitudinal measurements of hemoglobin (median per infant, 7), severe anemia vs. no anemia appeared to significantly increase the risk for necrotizing enterocolitis in any given week (adjusted cause-specific HR = 5.99; 95% CI, 2-18).

The researchers acknowledged study limitations, including their inability to determine causality between red blood count or anemia exposure and necrotizing enterocolitis. They further noted their inability to control for other potential confounding factors.

“Among very low-birth-weight infants, severe anemia but not red blood cell transfusion was associated with an increased risk for necrotizing enterocolitis,” Patel and colleagues wrote. “Further studies are needed to evaluate whether preventing severe anemia is more important than minimizing red blood cell transfusion.” – by Cameron Kelsall

Disclosure: The researchers report no relevant financial disclosures.