Association of anemia and necrotizing enterocolitis in neonates: Systematic review and meta-analysis of transfusion thresholds, erythropoietin trials, and observational studies.

In 30 seconds

This systematic review and meta-analysis examined whether anemia is associated with necrotizing enterocolitis (NEC) in preterm infants, combining randomized trials of transfusion thresholds and erythropoietin or darbepoetin with case-control studies. Transfusion-threshold trials found no difference in NEC incidence between lower- and higher-hemoglobin groups (OR: 1.14 (CI: 0.89, 1.46), p 0.647). In erythropoietin trials, NEC incidence was higher in the lower- versus higher-hemoglobin group (OR: 1.43 (CI: 1.13, 1.80), p 0.003); case-control studies also found lower hematocrit in NEC cases than controls.

Key findings

• Four transfusion-threshold RCTs (3307 participants) found no difference in NEC incidence between low- and high-hemoglobin groups: OR: 1.14 (CI: 0.89, 1.46), p 0.647.
• Eleven rEPO-versus-placebo RCTs (4173 participants) reported higher NEC incidence in the low- versus high-hemoglobin group: OR: 1.43 (CI: 1.13, 1.80), p 0.003.
• Three case-control studies (1016 participants) found lower hematocrit in NEC cases than controls (standardized mean difference -0.28; CI -0.56, -0.002; p 0.048).

Why it matters

The findings suggest that lower hemoglobin may be associated with NEC, but results differ across study types and interventions. Distinguishing an association from a causal effect is important when interpreting anemia and NEC risk in preterm infants. The review highlights uncertainty that prospective studies will need to address before the relationship can be established more firmly.

What to keep in mind

The authors state that well-designed, adequately powered prospective studies are needed to confirm the findings.