A higher hemoglobin threshold does not improve survival outcomes without neurodevelopmental impairment for preterm infants with anemia, according to results of a study published in The New England Journal of Medicine.

An open, multicenter trial (ClinicalTrials.gov Identifier: NCT01702805) evaluated outcomes following red-cell transfusions given to infants with birth weights of 1000 g or less and gestational ages of 22 weeks to 28 weeks and 6 days. Infants were considered eligible for study inclusion if they were under 48 hours of postnatal age. They were randomly assigned (1:1) to be transfused based on either higher or lower hemoglobin transfusion thresholds until either discharge or 36 weeks of postmenstrual age.

Transfusion thresholds in each group varied by postnatal age and need for respiratory support, but the mean difference in pretransfusion hemoglobin levels between groups was anticipated to be 2.0 g/dL to 2.5 g/dL. The primary composite outcome included death or prematurity-corrected neurodevelopmental impairment at 22 to 26 months of age.

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A total of 1692 infants were evaluable for the primary outcome, with 845 in the higher-threshold group and 847 in the lower-threshold group. The mean (+ standard deviation [SD]) initial hemoglobin levels at randomization were 13.8 + 2.6 g/dL in the higher-threshold group and 13.7 + 2.6 g/dL in the lower-threshold group.

Across the treatment period, the difference in mean pretransfusion hemoglobin levels between groups was 1.9 g/dL (P <.001), and there was a separation in the means of measured hemoglobin levels between groups throughout the study. The mean (+ SD) number of transfusions was 6.2 + 4.3 in the higher-threshold group, compared with 4.4 + 4.0 transfusions in the lower-threshold group.

Rates of death or neurodevelopmental impairment at 2 years were similar between the groups. Of the infants in the higher-threshold group, 50.1% died or remained alive with neurodevelopmental impairment, compared with 49.8% in the lower-threshold group (adjusted relative risk [aRR], 1.00; 95% CI, 0.92-1.10; P =.93).

Rates of death at 2 years were 16.2% in the higher-threshold group and 15.0% in the lower-threshold group (aRR, 1.07; 95% CI, 0.87-1.32). Neurodevelopmental impairment at 2 years occurred at rates of 39.6% in the higher-threshold group and 40.3% in the lower-threshold group (aRR, 1.00, 95% CI, 0.88-1.13). Rates of survival without severe complications at discharge were also similar between groups (28.5% vs 30.9%, respectively), and serious adverse events occurred at similar rates (22.7% vs 21.7%, respectively).

“In our trial, a higher hemoglobin threshold for transfusion was associated with an increase in the number of transfusions administered. However, it did not improve survival without neurodevelopmental impairment at 22 to 26 months of age among extremely-low-birth-weight infants,” the study investigators concluded in their report.

Disclosure: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Kirpalani H, Bell EF, Hintz SF, et al for the Eunice Kennedy Shriver NICHD Neonatal Research Network. Higher or lower hemoglobin transfusion thresholds for preterm infants. N Engl J Med. 2020;383(27):2639-2651. doi:10.1056/NEJMoa2020248