Enhancement of erythropoiesis by recombinant human erythropoietin in low birth weight infants: a pilot study.

We randomly assigned eight concurrently symptom-free premature infants (birth weight less than or equal to 1250 gm) at high risk of requiring erythrocyte transfusions for anemia of prematurity to 6 weeks of intensive treatment with either subcutaneous recombinant human erythropoietin (r-HuEPO group) or a placebo (control group). Treatment with r-HuEPO was initiated at a dose of 100 units/kg per day 5 days a week, and was increased to 200 units/kg per day after 2 or 3 weeks if target reticulocyte counts were not achieved. All patients were given supplemental oral iron therapy at a dose of 6 mg/kg per day, as tolerated. Mean reticulocyte counts in r-HuEPO-treated and control infants were 64,600 versus 67,500 cells/mm3 at entry; were 245,600 versus 78,000 cells/mm3 after 1 week; and averaged 262,600 versus 136,400 cells/mm3 during the study. Mean reticulocyte counts in r-HuEPO-treated infants were 251,200 cells/mm3 during the week when r-HuEPO, 100 units/kg per day, was given, and were 269,500 cells/mm3 after the dose was increased to 200 units/kg per day. Mean hematocrit values at entry were 33.4% in babies who received r-HuEPO versus 33.6% in the control subjects, and were 31.4% in r-HuEPO-treated and 25.2% in the control subjects at the end of treatment. One r-HuEPO-treated and three control babies received transfusions during the study; the total volume of blood given was 17 ml in the r-HuEPO group and 101 ml in the control subjects. The percentage of hemoglobin F increased in infants not given transfusions. We conclude that r-HuEPO stimulates endogenous erythropoiesis in small premature babies who are receiving supplemental oral iron therapy. A controlled multicenter trial has been undertaken to confirm these promising preliminary observations.

Recombinant human erythropoietin in the anemia of prematurity: results of a placebo-controlled pilot study.

Experimental and clinical data implicate inadequate erythropoietin production as an important reason that infants acquire this anemia and suggest that recombinant human erythropoietin (r-HuEPO) might be used to treat or prevent it. We therefore randomly assigned 20 small premature infants (birth weight less than or equal to 1250 gm) who were highly likely to require erythrocyte transfusions for anemia of prematurity to receive 6 weeks of treatment with either intravenously administered r-HuEPO (at a dose of 100 units/kg twice each week) or a placebo. Hematologic measurements, transfusion requirements, and growth were followed during therapy and for 6 months thereafter. Treated (EPO) and control babies did not differ with respect to weight, hematocrit, overall mean absolute reticulocyte count, calculated erythrocyte mass, or rate of growth. However, reticulocyte counts increased earlier in patients given r-HuEPO. Six of ten babies in the EPO group, and 8 of 10 assigned to the control group, received at least one erythrocyte transfusion during treatment. For all infants the amount of blood sampled for laboratory tests was strongly predictive of the volume of packed erythrocytes transfused (r = 0.890; p = 0.0001). Of nine infants who had less than 20 ml packed erythrocytes removed for laboratory tests, none of four given r-HuEPO received a transfusion, whereas three of five infants assigned to the placebo group received one. No toxic effects were attributable to r-HuEPO, and no significant changes in leukocyte or platelet counts occurred during treatment. Reticulocyte counts were correlated with simultaneous platelet counts and were inversely related to absolute neutrophil counts in both study groups. We conclude that r-HuEPO administration is safe and feasible at the dose studied. Additional controlled trials utilizing higher doses of r-HuEPO and larger numbers of patients are justified.

Acquired immune deficiency syndrome in childhood.

The acquired immunodeficiency syndrome has been observed with increasing frequency in children with associated hemophilia, high-risk environmental backgrounds, and blood transfusions. AIDS should be considered in the differential diagnosis of childhood immunodeficiency, and it must be distinguished from congenital disorders. We emphasize the importance of epidemiologic, clinical, and laboratory data in diagnosis and aggressive management of infectious complications. The relationship between human retrovirus infection and AIDS remains to be precisely defined, especially with regard to cofactors that may play a role in the development of severe immunodeficiency following exposure to the agent.

PIP: To date, the acquired immunodeficiency syndrome (AIDS) has been identified in over 50 children in the US, including those with associated hemophilia, high-risk environmental factors (Haitian background, parental intravenous drug abuse, or prostitution), and blood transfusions. The evaluation of an infant or young child in whom AIDS is suspected requires exclusion of congenital disorders of immune function. A specific test is not currently available, but inclusion criteria for childhood AIDS have been developed. The diseases accepted as indicative of underlying cellular immunodeficiency children are the same as those used in defining AIDS in adults, with the exclusion of congenital infections such as toxoplasmosis or herpes simplex virus infection in the 1st month of life or cytomegalovirus infection in the 1st 6 months of life. Specific conditions that must be excluded in children are primary immunodeficiency diseases (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome, ataxia-telangiectasia, neutrophil function abnormality) and secondary immuno-deficiency associated with immunosuppressive therapy, lymphoreticular malignancy, or starvation. Almost all young children with AIDS have hepatosplenomegaly, interstitial pneumonitis, and poor growth. The average age of 36 US child AIDS victims studied in detail was 5 months at presentation with findings suggestive of severe immunodeficiency. Mucocutaneous candidiasis was present in 75% of these 36 children, and Pneumocystis carinii and cytomegalovirus were each isolated from 30% of cases. Normal T4:T8 ratios occur in about 15% of pediatric AIDS cases. Laboratory evidence of polyclonal hypergammaglobulinemia generally supports the AIDS diagnosis. Recurrent infection and malnutrition are major problems in the clinical management of child AIDS patients.