Cognitive outcomes of preterm infants randomized to darbepoetin, erythropoietin, or placebo.

BACKGROUND: We previously reported decreased transfusions and donor exposures in preterm infants randomized to Darbepoetin (Darbe) or erythropoietin (Epo) compared with placebo. As these erythropoiesis-stimulating agents (ESAs) have shown promise as neuroprotective agents, we hypothesized improved neurodevelopmental outcomes at 18 to 22 months among infants randomized to receive ESAs. METHODS: We performed a randomized, masked, multicenter study comparing Darbe (10 µg/kg, 1×/week subcutaneously), Epo (400 U/kg, 3×/week subcutaneously), and placebo (sham dosing 3×/week) given through 35 weeks' postconceptual age, with transfusions administered according to a standardized protocol. Surviving infants were evaluated at 18 to 22 months' corrected age using the Bayley Scales of Infant Development III. The primary outcome was composite cognitive score. Assessments of object permanence, anthropometrics, cerebral palsy, vision, and hearing were performed. RESULTS: Of the original 102 infants (946 ± 196 g, 27.7 ± 1.8 weeks' gestation), 80 (29 Epo, 27 Darbe, 24 placebo) returned for follow-up. The 3 groups were comparable for age at testing, birth weight, and gestational age. After adjustment for gender, analysis of covariance revealed significantly higher cognitive scores among Darbe (96.2 ± 7.3; mean ± SD) and Epo recipients (97.9 ± 14.3) compared with placebo recipients (88.7 ± 13.5; P = .01 vs ESA recipients) as was object permanence (P = .05). No ESA recipients had cerebral palsy, compared with 5 in the placebo group (P < .001). No differences among groups were found in visual or hearing impairment. CONCLUSIONS: Infants randomized to receive ESAs had better cognitive outcomes, compared with placebo recipients, at 18 to 22 months. Darbe and Epo may prove beneficial in improving long-term cognitive outcomes of preterm infants.

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.

A low-sodium solution for airway care: results of a multicenter trial.

BACKGROUND: Normal saline is sometimes instilled into the endotracheal tube preparatory to airway suctioning, to assist in removing thick secretions. However, saline can damage the antimicrobial properties of airway secretions. We previously described a low-sodium physiologically based solution for airway care and reported a small (n = 60) randomized trial in neonates, which showed trends toward less ventilator-associated pneumonia (VAP) and less chronic lung disease with the new solution. We now report a multicenter trial of that solution. METHODS: We conducted a before-and-after study with a parallel control group, in 4 level-3 neonatal intensive care units (NICUs). During year 1, all 4 NICUs used saline for airway care. During year 2, one NICU used the test solution exclusively while the other NICUs used saline exclusively. The 2 study outcomes were VAP (cases/1,000 ventilator days) and chronic lung disease, defined 3 ways: supplemental oxygen at 28 days; supplemental oxygen at 36 weeks gestation; and supplemental oxygen on hospital discharge. RESULTS: During the study period 1,116 neonates had endotracheal intubation for respiratory management. Of those, 1,029 received the standard saline for airway suctioning, and the 87 in NICU 4 received the test solution. NICU 4 had a decrease in VAP rate, from 4.2 VAPs/1,000 ventilator days with saline, to 1.6 VAPs/1,000 ventilator days with the test solution (P = .04), and also had the lowest prevalence of chronic lung disease (P < .001 for each definition). CONCLUSIONS: The test solution significantly reduced the VAP and chronic lung disease rates.

Very high users of platelet transfusions in the neonatal intensive care unit.

BACKGROUND: In neonatal intensive care unit (NICU) practice, a small percentage of the patients receive a large proportion of the platelet (PLT) transfusions administered. This study sought to better define this very-high-user group. To accomplish this, records of all NICU patients in a multihospital health care system who, during a recent 5(1/2)-year period, received 20 or more PLT transfusions were examined. STUDY DESIGN AND METHODS: Electronic medical record repositories of Intermountain Healthcare neonates with dates of birth from January 1, 2002, through June 30, 2007, who received 20 or more PLT transfusions were identified. The causes of the thrombocytopenia were sought, whether each transfusion given was a treatment for bleeding versus prophylaxis was determined, whether each transfusion was compliant with our transfusion guidelines was judged, and the outcomes were tabulated. RESULTS: During this period, 45 patients received 20 or more PLT transfusions (median, 29; range, 20-79). Medical conditions could be categorized into six diagnoses: 1) extracorporeal membrane oxygenation (ECMO) for congenital diaphragmatic hernia (CDH; n = 13), 2) fungal sepsis (n = 8), 3) ECMO for reasons other than CDH (n = 8), 4) necrotizing enterocolitis (n = 7), 5) bacterial sepsis (n = 7), and 6) congenital hyporegenerative thrombocytopenia (n = 2). Nineteen percent of the transfusions were ordered for oozing, bruising, or bleeding and 81 percent for prophylaxis. Thirty-six percent of transfusions were given in violation of our transfusion guidelines. Forty-nine percent of the high users died, but no deaths were due to hemorrhage. All survivors developed chronic lung disease, and all survivors weighing less than 1250 g at birth developed retinopathy of prematurity. CONCLUSIONS: Almost all patients that received 20 or more PLT transfusions had an acquired, consumptive thrombocytopenia. All could have received fewer transfusions had the guidelines already in place been observed. Eighty-one percent fewer PLT transfusions would have been administered had the paradigm been transfusing only if oozing, bruising, or bleeding was present.