Preschool Assessment of Preterm Infants Treated With Darbepoetin and Erythropoietin.

BACKGROUND: We previously reported improved neurodevelopmental outcomes at 2 years among infants treated with the erythropoiesis-stimulating agents (ESAs) darbepoetin alfa (darbepoetin) or erythropoietin. Here we characterize 4-year outcomes. METHODS: Former preterm infants randomly assigned to receive darbepoetin (10 µg/kg, once per week), erythropoietin (400 U/kg, 3 times/week), or placebo through 35 weeks' postconceptual age were evaluated at 3.5 to 4 years of age. For comparison, healthy children formerly delivered full term (term controls [TCs]) were also recruited. All participants were assessed by using measures of full-scale IQ (FSIQ) and general language from the Wechsler Preschool and Primary Scale of Intelligence, Third Edition, and an overall measure of executive function, on the basis of tests evaluating inhibitory control and spatial working memory. Rates of neurodevelopmental impairment were compared across groups. RESULTS: Multivariate analysis of variance compared children randomly assigned to ESAs (n = 39), placebo (n =14), and TCs (n = 24). FSIQ and performance IQ were significantly higher in the ESA group than in the placebo group (FSIQ: 91.1 ± 17.5 vs 79.2 ± 18.5, P = .036; performance IQ: 93.0 ± 17.0 vs 79.5 ± 19.5, P = .018). Follow-up analyses revealed that the children receiving ESAs performed better than those who received placebo on executive function tasks. The ESA group's performance was below that of TCs, but the results did not reach significance on executive function. The incidence of neurodevelopmental impairment was greater in the placebo group than in the ESA group. CONCLUSIONS: ESA-treated infants had better cognitive outcomes and less developmental impairment at 3.5 to 4 years of age compared with placebo-treated infants. ESAs show promise in improving long-term cognitive outcomes of infants born prematurely.

A randomized, masked, placebo-controlled study of darbepoetin alfa in preterm infants.

BACKGROUND: A novel erythropoiesis stimulating agent (ESA), darbepoetin alfa (Darbe), increases hematocrit in anemic adults when administered every 1 to 3 weeks. Weekly Darbe dosing has not been evaluated in preterm infants. We hypothesized that infants would respond to Darbe by decreasing transfusion needs compared with placebo, with less-frequent dosing than erythropoietin (Epo). METHODS: Preterm infants 500 to 1250 g birth weight and ≤48 hours of age were randomized to Darbe (10 µg/kg, 1 time per week subcutaneously), Epo (400 U/kg, 3 times per week subcutaneously) or placebo (sham dosing) through 35 weeks' gestation. All received supplemental iron, folate, and vitamin E, and were transfused according to protocol. Transfusions (primary outcome), complete blood counts, absolute reticulocyte counts (ARCs), phlebotomy losses, and adverse events were recorded. RESULTS: A total of 102 infants (946 ± 196 g, 27.7 ± 1.8 weeks' gestation, 51 ± 25 hours of age at first dose) were enrolled. Infants in the Darbe and Epo groups received significantly fewer transfusions (P = .015) and were exposed to fewer donors (P = .044) than the placebo group (Darbe: 1.2 ± 2.4 transfusions and 0.7 ± 1.2 donors per infant; Epo: 1.2 ± 1.6 transfusions and 0.8 ± 1.0 donors per infant; placebo: 2.4 ± 2.9 transfusions and 1.2 ± 1.3 donors per infant). Hematocrit and ARC were higher in the Darbe and Epo groups compared with placebo (P = .001, Darbe and Epo versus placebo for both hematocrit and ARCs). Morbidities were similar among groups, including the incidence of retinopathy of prematurity. CONCLUSIONS: Infants receiving Darbe or Epo received fewer transfusions and fewer donor exposures, and fewer injections were given to Darbe recipients. Darbepoetin and Epo successfully serve as adjuncts to transfusions in maintaining red cell mass in preterm infants.

Implementing a program to improve compliance with neonatal intensive care unit transfusion guidelines was accompanied by a reduction in transfusion rate: a pre-post analysis within a multihospital health care system.

BACKGROUND: We previously reported that in the year 2006, approximately 35% of the transfusions administered in the Intermountain Healthcare neonatal intensive care units (NICU) were noncompliant with our transfusion guidelines. In January 2009 we instituted an electronic NICU transfusion ordering and monitoring system as part of a new program to improve compliance with transfusion guidelines. STUDY DESIGN AND METHODS: In the four largest NICUs of Intermountain Healthcare, we performed a pre-post analysis of compliance with transfusion guidelines and transfusion usage. RESULTS: After beginning the new transfusion compliance program all four NICUs had an increase in compliance from 65% to 90%. Accompanying the improved compliance, all four NICUs had a reduction in transfusions administered. Specifically, compared with 2007 and 2008, there were 984 fewer NICU transfusions given in 2009. This included 554 fewer red blood cell (RBC) transfusions, 174 fewer platelet transfusions, and 256 fewer frozen plasma infusions. We calculate that in 2009, a total of 200 NICU patients who in previous years would have received one or more transfusions instead received none. Applying specific Intermountain Healthcare billing data to the observed transfusion reductions, this new program resulted in an annual decrease of $780,074 in blood bank charges (blood administration charges were not included). During the 3-year period, January 2007 through December 2009, we detected no change in NICU demographics, major morbidities, length of hospital stay, or mortality rate. CONCLUSION: Implementing a systemwide NICU program to improve compliance with already-established transfusion guidelines increased compliance from 65% to 90%. Improved compliance with transfusion guidelines was accompanied by a significant reduction in transfusions given, with no increase in NICU length of stay or mortality rate.