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.

Erythropoietin increases reticulocyte counts and maintains hematocrit in neonates requiring surgery.

BACKGROUND: Limited erythropoietin (Epo) production diminishes neonates' ability to regenerate blood removed by phlebotomy. Neonates requiring surgery are at risk to receive multiple transfusions. We sought to determine if recombinant Epo administration to neonates requiring surgery would stimulate erythropoiesis. METHODS: Infants were randomized in double-masked fashion to receive Epo (200 units kg(-1) d(-1)) or placebo for 14 days. Complete blood count, absolute reticulocyte count (ARC), phlebotomy losses, and transfusions were measured during the study period. Infants were transfused using a strict transfusion protocol. RESULTS: In the Epo group (n = 10, 2034 +/- 308 g, 8 +/- 2 days old; mean +/- SEM), ARC increased significantly, whereas in the placebo group (n = 10, 2400 +/- 184 g, 7 +/- 2 days old), ARC remained low. Hematocrits in the Epo group trended upward from 34.4 1.7% to 37.3 1.9% (although not statistically significant) despite phlebotomy losses of 53 +/- 12 mL/kg. Hematocrits in the placebo group were 35.9 1.8% and 33.2 1.6% on days 1 and 15, respectively, with phlebotomy losses of 27 +/- 5 mL/kg. There were no differences in absolute neutrophil counts or platelet counts between groups at the end of the study. No adverse effects were noted. CONCLUSIONS: Infants randomized to Epo increased reticulocyte counts and hematocrits without adverse effects. Erythropoietin administration may provide an adjunct to present care in decreasing or eliminating erythrocyte transfusions in surgical neonates.

A randomized, controlled trial of nasal phenylephrine in infants hospitalized for bronchiolitis.

OBJECTIVE: To examine the hypothesis that pharmacologic treatment of nasal obstruction, specifically alpha-adrenergic nose drops, will decrease objective signs of respiratory distress in infants with bronchiolitis. STUDY DESIGN: Forty-one infants aged 3 weeks to 12 months hospitalized for viral bronchiolitis were enrolled in this double-blinded, placebo-controlled trial of topical 0.5% phenylephrine drops. The primary outcome measure was change in oxygen saturation. Secondary outcomes were changes in respiratory scores and vital signs. RESULTS: There were no statistical differences in any of the outcome measures between groups. No adverse events were observed. Overall, participants showed an average 1.6 percentage point increase in their oxygen saturations (P = .002) and a 0.5-point improvement in respiratory score (P = .003) over the 30 minutes of the study. CONCLUSIONS: Topical nasal phenylephrine did not produce significant short-term improvements in clinical status in infants hospitalized for acute bronchiolitis.

A randomized, controlled trial of smoking cessation counseling provided during child hospitalization for respiratory illness.

The impact of parental smoking on children is enormous. Injury and illness related to parental smoking result in 6,200 excess pediatric deaths per year, which places smoking as the leading preventable cause of death in US children. Parental smoking doubles the risk of child hospitalization for respiratory illness therefore pediatricians have frequent contact with smoking parents. A single study has previously investigated the effect of child hospitalization on parental smoking cessation. Smoking caregivers of children hospitalized for respiratory illness at the University of New Mexico were offered a smoking cessation intervention during the child's hospitalization. Participants were randomized to receive either a brief anti-smoking message or more extensive counseling based on current clinical practice guidelines. Forty-two parents enrolled in the study. Fourteen percent of participants in the counseling group and 5% in the brief message group were self-reported quitters at 6 months. A significant percentage of smoking parents of children hospitalized for respiratory illness are willing to receive smoking cessation counseling while their child is in the hospital. Abstinence rates appear similar to other pediatric office-based interventions. Child hospitalization should be considered an important opportunity to provide parents with smoking cessation services, particularly since many smoking parents will not have access to these services elsewhere.