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THE MAJORITY OF premature infants, especially very low birth weight (birth weight < 1500 g) infants, receive ≥ 1 red blood cell transfusion for anemia of prematurity during their first [...], OBJECTIVES. Erythropoietin is frequently administered to premature infants to stimulate erythropoiesis. The primary goal of erythropoietin therapy is to reduce transfusions, but the efficacy of erythropoietin has not been convincingly demonstrated in this regard. The aim of this trial was to investigate whether combined administration of vitamin [B.sub.12], folic acid, iron, and erythropoietin could decrease transfusion requirements in extremely low birth weight infants. PATIENTS AND METHODS. In a randomized, controlled trial, extremely low birth weight infants with a birth weight ≤ 800g and a gestational age ≤ 32 weeks were randomly assigned to a group receiving combination treatment or a control arm. RESULTS. The treatment increased levels of folate in red blood cells, vitamin [B.sub.12], ferritin, transferrin receptor levels in plasma, and reticulocyte counts. The proportion of infants requiring no transfusions was lower in the treatment group (38%) as compared with controls (5%). The treatment group and the need for mechanical ventilation were independent predictors of the number of transfusions in multiple regression analysis. Cox regression analysis indicated that combined therapy resulted in a 79% risk reduction for any transfusion. CONCLUSION. Combined treatment with erythropoietin, intravenous iron, folate, and vitamin [B.sub.12] during the first weeks reduces the need for transfusion in extremely low birth weight infants. Key Words folate, vitamin [B.sub.12], erythropoietin, iron, ELBW infant, transfusions Abbreviations RBC--red blood cell GA--gestational age ELBW--extremely low birth weight TFR--transferrin receptor CI--confidence interval IRF--immature reticulocyte fraction MCV--mean corpuscular volume ROP--retinopathy of prematurity

HYPERGLYCEMIA IS ASSOCIATED with increased mortality and morbidity rates among nondiabetic adults admitted to ICUs for treatment of myocardial infarction, (1) stroke, (2) or trauma (3,4) and among adults admitted [...], OBJECTIVES. The objectives of this study were to determine the prevalence of hyperglycemia in extremely low birth-weight infants and to determine whether hyperglycemia increases the risk of early adverse outcomes (death or intraventricular hemorrhage of grade 3 or 4) and/or affects the length of hospital stay among survivors without intraventricular hemorrhage. METHODS. The charts of all extremely low birth-weight infants (n = 93) admitted to Texas Children's Hospital (Houston, TX) during 2001 were reviewed. The highest daily blood glucose concentrations, highest dopamine infusion rates, highest daily percentage of inspired oxygen, and mean blood sodium concentrations were averaged over the first week of life or before death or occurrence of grade 3 or 4 intraventricular hemorrhage. Among survivors without severe intraventricular hemorrhage, the time ratio for blood glucose concentrations of > 150 mg/dL was calculated. RESULTS. More than 50% of the infants had persistent blood glucose concentrations of >150 mg/dL during their first week of life. Early adverse outcomes were associated with the average highest daily blood glucose concentration through interaction with the Clinical Risk Index for Babies score and with the average highest daily percentage of inspired oxygen. The length of hospital stay was associated with the time ratio for blood glucose concentrations of >150 mg/dL through interaction with birth weight and the average highest daily percentage of inspired oxygen. CONCLUSION. These data confirm the high prevalence of hyperglycemia among parenterally fed, extremely low birth-weight infants and show that high blood glucose concentrations increase the risk of early death and grade 3 or 4 intraventricular hemorrhage and the length of hospital stay among survivors without intraventricular hemorrhage, which suggests that prevention and treatment of hyperglycemia may improve the outcomes of extremely low birth-weight infants. www.pediatrics.org/cgi/doi/10.1542/ peds.2006-0628 doi:10.1542/peds.2006-0628 Key Words hyperglycemia, outcomes, extremely low birth weight Abbreviations IVH--intraventricular hemorrhage ELBW--extremely low birth weight CRIB--Clinical Risk Index for Babies LOS--length of stay PMAD--postmenstrual age at discharge

IMPROVED OXYGENATION AFTER birth results in systemic oxygen delivery that far exceeds oxygen consumption among newborns. Without hypoxic stimuli for erythropoietin production, (1) serum erythropoietin concentrations decrease and erythropoiesis declines [...], BACKGROUND. Premature infants, especially those with birth weights of METHODS. In a randomized, controlled trial, 64 premature infants (birth weight: 801-1300 g) receiving erythropoietin and iron supplementation were assigned randomly to receive either vitamin [B.sub.12] (3 µg/kg per day) and folate (100 µg/kg per day) (treatment group) or a lower dose of folate (60 µg/kg per day) (control group). RESULTS. During the 4-week observation period, vitamin [B.sub.12] and folate enhanced erythropoietin-induced erythropoiesis significantly, as indicated by a 10% increase in red blood cell counts, compared with folate alone. Hemoglobin and hematocrit levels remained stable in the treatment group, whereas they decreased in the control group. Vitamin [B.sub.12] levels in the treatment group increased over baseline and control values, whereas red blood cell folate levels were comparable between the groups. Subsequent analysis showed slight nonsignificant differences in baseline red blood cell count, hemoglobin level, hematocrit level, and mean corpuscular volume values, which must be addressed as a limitation. CONCLUSIONS. With the limitation of a slight imbalance in baseline data between the study groups, combined therapy with vitamin [B.sub.12], folate, erythropoietin, and orally and intravenously administered iron seemed more effective in stimulating erythropoiesis among premature infants, compared with erythropoietin, iron, and low-dose folate alone. Additional trials are necessary to confirm these data. www.pediatrics.org/cgi/doi/10.1542/ peds.2005-2475 doi:10.1542/peds.2005-2475 Key Words anemia of prematurity, erythropoietin, folic acid, vitamin [B.sub.12] Abbreviations RBC--red blood cell MCV--mean corpuscular volume TFR--transferrin receptor

Although glutamine is the most abundant amino acid in both plasma and human milk, (1) it is not included in standard intravenous amino acid solutions because of its limited stability [...], Background. Glutamine is one of the most abundant amino acids in both plasma and human milk, yet it is not included in standard intravenous amino acid solutions. Previous studies have suggested that parenteral nutrition (PN) supplemented with glutamine may reduce sepsis and mortality in critically ill adults. Whether glutamine supplementation would provide a similar benefit to extremely low birth weight (ELBW) infants is not known. Methods. We performed a multicenter, randomized, double-masked, clinical trial to assess the safety and efficacy of early PN supplemented with glutamine in decreasing the risk of death or late-onset sepsis in ELBW infants. Infants 401 to 1000 g were randomized within 72 hours of birth to receive either TrophAmine (control) or an isonitrogenous study amino acid solution with 20% glutamine whenever they received PN up to 120 days of age, death, or discharge from the hospital. The primary outcome was death or late-onset sepsis. Results. Of the 721 infants who were assigned to glutamine supplementation, 370 (51%) died or developed late-onset sepsis, as compared with 343 of the 712 infants (48%) assigned to control (relative risk: 1.07; 95% confidence interval: 0.97-1.17). Glutamine had no effect on tolerance of enteral feeds, necrotizing enterocolitis, or growth. No significant adverse events were observed with glutamine supplementation. Conclusions. Parenteral glutamine supplementation as studied did not decrease mortality or the incidence of late-onset sepsis in ELBW infants. Consequently, although no harm was demonstrated, routine use of parenteral glutamine supplementation cannot be recommended in this population. ABBREVIATIONS. PN, parenteral nutrition; ELBW, extremely low birth weight; RIK relative risk; CI, confidence interval.