losartan-potassium and Infant--Premature--Diseases

Retinopathy of prematurity (ROP) is a leading cause of vision impairment and blindness in premature infants. Oxidative stress is implicated in its pathophysiology. NADPH oxidase (NOX), a major enzyme responsible for reactive oxygen species (ROS) generation in endothelial cells, has been studied for its involvement in physiologic and pathologic angiogenesis. Erythropoietin (EPO) has gained interest recently due to its tissue protective and angiogenic effects, and it has been shown to act as an antioxidant. In this review, we summarize studies performed over the last five years regarding the role of various NOXs in physiologic and pathologic angiogenesis. We also discuss the effect of EPO in tissue and vasoprotection, and the intersection of EPO and NOX-mediated oxidative stress in angiogenesis and the pathophysiology of ROP.

Topics: Endothelial Cells; Erythropoietin; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; NADP; NADPH Oxidases; Neovascularization, Pathologic; Retinopathy of Prematurity

Pre-term infants have one of the highest transfusion requirements within the hospital-setting. The vast majority of blood transfusions performed in Neonatal Intensive Care Units (NICUs) are for medically stable pre-term infants with anaemia of prematurity, with the aim of improving oxygen delivery to the vital organs during the crucial phase of growth and development. However, despite the frequency of transfusion in this population, the potential benefits and harms of 'top up' transfusion are not fully understood, leading to practice variation between clinicians, institutions and countries. Significant advances have been made in the prevention of anaemia of prematurity, with recent emphasis on optimising infants' circulatory volume at birth via placental transfusion and preserving infants' own blood volume through innovative minimal sampling techniques. More research is urgently needed to establish optimal transfusion thresholds for these high-risk pre-term infants, for whom benefits as well as adverse outcomes may have consequences that extend for decades throughout the recipients' life-course. In this review, we will discuss some of the consensus and controversies regarding optimal management of anaemia in pre-term infants and highlight potential areas for future research.

Topics: Anemia; Constriction; Delivery, Obstetric; Disease Management; Erythrocyte Transfusion; Erythropoietin; Fetal Blood; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Ligation; Risk Factors; Time Factors; Umbilical Cord

Erythropoietin (EPO) plays an important role in the development and maturation of the gastrointestinal tract. Recombinant EPO (rEPO) has been used to prevent anemia of prematurity. The gastrointestinal trophic effects of EPO may reduce feeding intolerance and necrotizing enterocolitis (NEC) in preterm neonates. The aim of this systematic review of randomized controlled trials (RCTs) was to evaluate the effects of rEPO on clinical outcomes such as feeding intolerance, stage II or higher NEC, any stage NEC, sepsis, retinopathy of prematurity, and bronchopulmonary dysplasia in preterm neonates. Twenty-five RCTs (intravenous: 13; subcutaneous: 10; enteral: 2; n = 4025) were eligible for inclusion. Meta-analysis of data from 17 RCTs (rEPO compared with placebo) with the use of a fixed-effects model showed no significant effect of rEPO on stage II or higher NEC (RR: 0.87; 95% CI: 0.64, 1.19; P = 0.39). Meta-analysis of data from 25 RCTs (rEPO compared with placebo) showed that rEPO significantly decreased the risk of any stage NEC [cases/total sample: 120/2058 (5.83%) compared with 146/1967 (7.42%); RR: 0.77; 95% CI: 0.61, 0.97; P = 0.03]. Only one RCT reported on time to full feedings. Meta-analysis of data from 15 RCTs showed a significant reduction in late-onset sepsis after rEPO administration (RR: 0.81; 95% CI: 0.71, 0.94; P = 0.004). Meta-analysis of 13 RCTs showed no significant effect of rEPO on mortality, retinopathy of prematurity, and bronchopulmonary dysplasia. Prophylactic rEPO had no effect on stage II or higher NEC, but it reduced any stage NEC, probably by reducing feeding intolerance, which is often labeled as stage I NEC. Adequately powered RCTs are required to confirm these findings.

Topics: Bronchopulmonary Dysplasia; Enterocolitis, Necrotizing; Erythropoietin; Gastrointestinal Tract; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Retinopathy of Prematurity; Sepsis

Prematurity remains the major cause of neonatal morbidity and mortality, with 15 million preterm births occurring worldwide in 2010. Infants born less than 37 weeks gestation are at high risk of abnormal neurodevelopmental outcomes, given that the central nervous system is extremely sensitive to an abnormal intra- and extra-uterine environment. Children born preterm have multiple neurodevelopmental sequelae involving dynamic and complex cognitive deficits. Former preterm infants have difficulty with each domain of cognition, including executive function, language, learning and memory, complex attention, perceptual-motor function and social cognition when compared to children born at term. Although deficits are not always severe, even mild delays can be impactful, resulting in a spectrum of outcomes from difficulties in school to an inability to lead an independent adult life. Here, we review current literature on the cognitive outcomes of infants born preterm with a focus on how specific disruption in crucial neurodevelopmental pathways render these children vulnerable to dynamic deficits in cognition as they mature. Further, we highlight promising therapies and intervention strategies aimed at mitigating these deficits, including the use of erythropoietin. With an increasing number of preterm infants surviving, understanding developmental deficits will allow therapies to be developed and optimized, in order to ensure the best outcome for this vulnerable patient population.

Topics: Cognition; Cognition Disorders; Developmental Disabilities; Erythropoietin; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases

This article explains the mechanisms underlying choices of pharmacotherapy for hypoxic-ischemic insults of both preterm and term babies. Some preclinical data are strong enough that clinical trials are now underway. Challenges remain in deciding the best combination therapies for each age and insult.

Topics: Acetylcysteine; Allopurinol; Antioxidants; Ascorbic Acid; Biopterins; Erythropoietin; Excitatory Amino Acid Antagonists; Free Radical Scavengers; Fructose; Humans; Hypoxia-Ischemia, Brain; Infant, Extremely Premature; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Melatonin; Memantine; Neuroprotective Agents; Nitric Oxide Synthase Type III; Resveratrol; Stilbenes; Topiramate; Vitamin E; Xenon

The decision to transfuse a neonate can be approached by addressing a series of questions that cover the cause of anaemia, alternatives to transfusion, the need for transfusion and the risks. Recent clinical trials of red cell transfusions have started to inform evidence-based transfusion practice, but have raised uncertainties about neurological outcomes when policies advocating use of fewer red cell transfusions at lower haemoglobin concentration (Hb) thresholds were tested. Red cell transfusions should be considered when the Hb <120 g/l for premature neonates requiring mechanical ventilation support, with lower thresholds applying for oxygen-dependent neonates not requiring ventilation or for late anaemia (Hb <70-100 g/l, depending on gestational and post-natal age). There is no recent high quality evidence to inform thresholds for prophylactic platelet transfusions in stable non-bleeding premature neonates with platelet count levels of 50 × 10(9) /l, although common practice has become more restrictive, using lower safe thresholds for platelet transfusion between 20 and 30 × 10(9) /l. A more appropriate transfusion strategy for fresh frozen plasma (FFP) in neonates is one that emphasizes the therapeutic use of FFP in the face of bleeding, rather than prophylactic use in stable non-bleeding neonates who often have mild to moderate apparent abnormalities of standard coagulation tests, after allowing for appropriate reference ranges.

Topics: Anemia, Neonatal; Blood Grouping and Crossmatching; Constriction; Decision Making; Diagnosis, Differential; Erythrocyte Transfusion; Erythropoietin; Evidence-Based Medicine; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Platelet Transfusion; Practice Guidelines as Topic; Professional Practice; Umbilical Cord

This review summarizes target populations of neonates for which erythropoietin (Epo) neuroprotective therapy might be of benefit, and the mechanisms by which Epo functions as a neuroprotective agent. Potential risks of Epo are reviewed. Finally, the progression of Epo neuroprotection from preclinical studies to translational studies is discussed.

Topics: Brain; Erythropoietin; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature, Diseases; Nervous System Diseases; Neuroprotective Agents; Risk Factors

Topics: Anemia; Erythrocyte Transfusion; Erythropoietin; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Recombinant Proteins; Transfusion Reaction

Red blood cell (RBC) transfusions convey benefits but they also carry risks. Among NICU patients, some transfusion risks are well defined and their occurrence odds can be estimated and weighed against benefits. However other risks are poorly defined and it is not currently possible to estimate their occurrence adds or weigh these against benefits.. We reviewed publications in the past 15 years, listed in PubMed, dealing with risks and benefits of RBC transfusions to newborn infants.. Risks of RBC transfusion to adult patients decreased significantly with the advent of nucleic acid testing for viral pathogens. However, new or previously unknown risks of transfusions have been suggested for neonatal recipients. These include developmental delay, intraventricular hemorrhage, and necrotizing enterocolitis. These potential transfusion risks are all currently in the form of statistical associations, and cause-and-effect relationships have not been proven. Mean of reducing transfusions, tested during the past 15 years, include adopting transfusions guidelines, erythropoietic stimulating agents, delayed cord clamping, cord stripping, drawing all NICU admission blood tests from the placenta, and limiting phlebotomy losses for blood testing.. We advocate always attempt to weigh benefits and risks when ordering a transfusion for a neonatal patient. Certainly some such are life-saving or otherwise clearly beneficial. Perhaps others carry risks unbalanced by meager benefit. Efforts to improve NICU transfusion practice have been proposed and appear to be working to diminish costs and improve outcomes.

Topics: Adult; Anemia; Blood Transfusion, Autologous; Cerebral Hemorrhage; Developmental Disabilities; Enterocolitis, Necrotizing; Erythrocyte Transfusion; Erythropoietin; Fetal Blood; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Risk Assessment; Risk Factors; Umbilical Cord

To review causes of anemia in preterm infants and to suggest potential preventive measures.. Data for this review is obtained from review of the literature.. An approach to investigating and treating causes of neonatal anemia is outlined.. Clinical practices can significantly impact anemia in premature infants. Delayed cord clamping, decreasing phlebotomy loss and optimizing nutritional support are practices that may decrease the severity of anemia, thereby decreasing the need for transfusions or erythropoietin treatment.

Topics: Anemia; Blood Specimen Collection; Constriction; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Nutritional Support; Time Factors; Umbilical Cord

Erythropoietin (Epo) has long been recognised for its role in the control of erythropoiesis and therefore in the treatment of anemia including anemia of prematurity. The erythropoietin receptor (Epo-R) though is expressed in many other organs including the CNS. This review focuses on the role of erythropoietin during the development of the CNS and its potential role as a neuroprotective agent. Epo-R is expressed in many different cellules of the CNS during development including neural progenitor cells, neurons, astrocytes and oligodendrocytes. In the event of hypoxia CNS cells respond with increase of erythropoietin release with subsequent stimulation of neurogenesis through Epo-R on neural progenitor cells. In an Epo-R knock-out model therefore cerebral development is severely impaired. In models of hypoxia-ischemia exogenous Epo has been shown to reduce lesion size and improve structural and functional recovery. Human studies are emerging using Epo as a neuroprotective agent both for the term infant with hypoxia-ischemia as well as for the extremely preterm infant.

Topics: Brain; Erythropoietin; Gene Knockout Techniques; Humans; Infant, Newborn; Infant, Premature, Diseases; Neuroprotective Agents; Receptors, Erythropoietin

Since the late 1980s recombinant human erythropoietin (r-EPO) has been studied as an alternative to packed red blood cell (RBC) transfusion for the treatment of anemia of prematurity in very low birth weight infants. Initial trials and reports focused on r-EPO's ability to prevent or treat anemia of prematurity with the goal of eliminating RBC transfusion but achieved limited success. New concerns about the safety of r-EPO administration have emerged. Past cost-benefit analyses of r-EPO administration versus transfusion for the treatment of anemia of prematurity have been nearly balanced. Autologous transfusion, blood-sparing technologies, changes in RBC transfusion technique and safety, and further elucidation of the risk-benefit ratio of r-EPO therapy may change the cost-benefit analysis.

Topics: Anemia; Erythrocyte Transfusion; Erythropoietin; Hematinics; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Recombinant Proteins

Preterm infants, especially those with extremely low birth weight (ELBW) are exposed to frequent blood draws as part of their care in the neonatal intensive care unit. ELBW infants develop the anemia of prematurity (AOP), a hypo-proliferative anemia marked by inadequate production of erythropoietin (Epo). Treatment of AOP includes red blood cell transfusions, which are given to preterm infants based on indications and guidelines (hematocrit/hemoglobin levels, ventilation and oxygen need, apneas and bradycardias, poor weight gain) that are relatively non-specific. In this article we review recent studies evaluating transfusion guidelines, discuss ways to decrease phlebotomy losses and examine the use of red cell growth factors such as Epo in preventing and treating anemia in preterm infants.

Topics: Anemia, Neonatal; Blood Transfusion; Erythropoietin; Hematocrit; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases

Newborn infants in intensive care units, especially those born premature, are at particular risk for blood transfusion adverse effects. Aside improvements in the preparation of specific blood products for the neonatal period, such as multiple packed cells preparations from a single donor for multiple transfusions in premature infants, progress has involved prophylaxis of anemia of prematurity as well. Recombinant human erythropoietin has proven to be beneficial with high range evidence. Also, alternative methods have been proposed to compensate for the delay in the effect of rHuEPO, such as delayed clamping of umbilical cord at birth, or autologous placental blood transfusion. However, a better understanding of the indications of blood transfusion and the provision of practice guidelines may justify a re-evaluation of prophylactic strategies for anemia of prematurity.

Topics: Anemia; Antigens, Human Platelet; Blood Component Transfusion; Combined Modality Therapy; Erythrocyte Transfusion; Erythropoietin; Exchange Transfusion, Whole Blood; Granulocytes; Humans; Immunity, Maternally-Acquired; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Intensive Care, Neonatal; Leukocyte Transfusion; Plasma; Platelet Transfusion; Practice Guidelines as Topic; Recombinant Proteins; Thrombocytopenia

The introduction of recombinant human erythropoietin (RHuEPO) has dramatically changed the therapeutic approach to the anemia of chronic renal failure. Clinical studies have also demonstrated that RHuEPO is effectiveness in various non-uremic conditions, such as anemia associated with onco-hematological disorders, prematurity, HIV infection and to reduce the exposure to allogeneic blood in surgical patients. In this review, we briefly analyze the main clinical applications of RHuEPO, with particular attention to the potential complications deriving from its use.

Topics: Adult; Anemia; Anemia, Neonatal; Blood Transfusion, Autologous; Child; Clinical Trials as Topic; Erythropoietin; Female; HIV Infections; Humans; Infant, Newborn; Infant, Premature, Diseases; Kidney Failure, Chronic; Male; Multicenter Studies as Topic; Neoplasms; Randomized Controlled Trials as Topic; Recombinant Proteins

There is a high incidence of hypoxic-ischaemic brain injury and intraventricular haemorrhage in newborn infants, particularly those born preterm. Many die during the newborn period or suffer permanent neurodevelopmental handicaps. Hypoxic brain injury develops over several hours and could potentially be influenced by intervention. At present, no drug exists that effectively prevents infant brain injury or ameliorates detrimental neurodevelopmental effects. The hypothesis is put forward that systemic administration of recombinant human erythropoietin positively affects the neurodevelopmental outcome of high risk preterm infants affected by brain injury. A multicentre, randomised, placebo controlled study is proposed to prospectively test this hypothesis.

Topics: Erythropoietin; Humans; Hypoxia, Brain; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Neuroprotective Agents; Recombinant Proteins

New drugs, recently available for treatment of different forms of anaemia, have somehow changed the therapeutic scenario in paediatric haematology. The aim of this review is to focus on the newest molecules discussing indications, clinical usefulness and related problems. Erythropoietin, the specific growth factor of red cell precursors, is now an established option for anaemia of chronic renal failure, prematurity, bone marrow transplantation and chemotherapy. Anti-CD20 monoclonal antibody, a novel cytotoxic molecule for mature B lymphocytes, has proven to be effective in the treatment of refractory autoimmune cytopenias. Haemoglobin analogues are currently under investigation, in order to obtain a synthetic oxygen-carrier that can substitute blood transfusions. Finally drugs that are able to increase the production of haemoglobin F have been used in thalassemias and haemoglobinopathies. For patients with sickle cell disease, hydroxyurea is no longer an experimental tool; it has given rise to several trials, where it has proven to be effective in terms of both clinical and haematological improvement.

Topics: Adult; Age Factors; Anemia; Anemia, Hemolytic, Autoimmune; Anemia, Sickle Cell; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antisickling Agents; Blood Substitutes; Bone Marrow Transplantation; Butyrates; Child; Clinical Trials as Topic; Erythropoietin; Fetal Hemoglobin; Forecasting; Hemoglobinopathies; Hemoglobins; Humans; Hydroxyurea; Infant, Newborn; Infant, Premature, Diseases; Kidney Failure, Chronic; Organ Transplantation; Rituximab; Thalassemia; Tissue Donors

Many unanswered issues regarding rhEPO therapy in prematurity remain, including which premature infants best respond to rhEPO, what the long-term effect of decreased erythrocyte transfusions is, how nutritional supplementation optimizes the effect of rhEPO, whether or not rhEpo therapy causes iron deficiency later in life, and whether or not it is safe to supplement with parenteral iron. Further study of rhEPO therapy and iron status in prematurity is necessary.

Topics: Anemia; Erythrocyte Transfusion; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Iron; Recombinant Proteins

Physiologic anemia is a common and normal finding in newborn infants. In preterm infants, anemia of prematurity is the result of this normal physiologic process compounded by the morbidity of prematurity. Premature infants reach their nadir hematocrit sooner and at a lower level than term. This article reviews the physiology of stem cell differentiation and the structure and function of the red blood cell, as well as examining red blood cell indices. It also addresses the etiology, symptomatology, diagnostic workups and treatment/prevention modalities of anemia of prematurity. Treatment for and prevention of anemia of prematurity remain controversial, and specific criteria are lacking.

Topics: Anemia, Neonatal; Blood Transfusion; Cell Differentiation; Erythrocyte Count; Erythrocyte Indices; Erythropoietin; Ferrous Compounds; Hematopoiesis; Hematopoietic Stem Cells; Humans; Infant, Newborn; Infant, Premature, Diseases; Risk Factors

Transfusion-dependent anemia remains a problem for preterm infants, particularly those with a birth weight less than 1.0 kg. Several studies have documented the efficacy and safety of transfusing red blood cells stored up to 42 days as a means to diminish donor exposures. Recombinant erythropoietin therapy has not been widely adopted because it does not consistently reduce the need for red blood cell transfusions in very low-birth weight preterm infants.

Topics: Anemia, Neonatal; Erythrocyte Transfusion; Erythropoietin; Hematocrit; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

Human recombinant erythropoietin was first cloned in 1985, and is currently available for clinical use for a variety of anemias. Following successful clinical trials using erythropoietin to treat adults with the anemia of end-stage renal disease, the first clinical trial evaluating the use of erythropoietin in preterm infants to treat anemia was published in 1990. Since that initial report, numerous clinical trials have reported various levels of success in the treatment of this anemia. Most recently, erythropoietin has been used in the first weeks of life in an attempt to prevent the anemia of prematurity. This review describes mechanisms of erythropoiesis in the fetus and neonate, and focuses on recent clinical trials evaluating the use of erythropoietin to prevent and treat anemia in preterm infants.

Topics: Anemia, Neonatal; Clinical Trials as Topic; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases

Topics: Anemia, Neonatal; Blood Transfusion; Clinical Trials as Topic; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Recombinant Proteins; Time Factors

Recently, recombinant human erythropoietin (rhEPO) has been claimed to diminish red blood cell transfusions in premature infants. After a year of experience, we investigated whether early rhEPO treatment would reduce the need for transfusion.. Fifty premature infants of gestational age < or = 32 weeks admitted to our NICU in 1997, received rhEPO 750 UI/kg/week from day 3 to 5 for six weeks. They were compared with 50 untreated controls admitted in 1996.. The treatment and control groups did not differ for gestational age, weight at birth, CRIB score, and blood losses. We were not able to detect any difference in the number of transfused infants, and in the number of transfusions per infant until discharge. However, treated infants received significantly fewer transfusions per infant between day 16 and day 45 (0.42 +/- 0.67 vs. 0.8 +/- 0.99). Infants with a birth weight between 1,000-1,250 g received fewer transfusions in the EPO group.. rhEPO treatment can be useful, but in association with other procedures: conservative transfusion criteria, minimization of phlebotomy losses and early iron supplementation.

Topics: Erythrocyte Transfusion; Erythropoietin; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Male; Recombinant Proteins; Retrospective Studies; Treatment Outcome

Neonatal erythropoiesis is limited by a relatively inadequate production of erythropoietin. This is likely the result of dependence on the hepatic production of erythropoietin and an incomplete switchover to renal production. The present model of neonatal erythropoiesis suggests that the use of exogenous erythropoietin should correct the early anemia of prematurity that is observed at 6 weeks of age in premature newborns. Randomized, controlled trials of erythropoietin use in very low birthweight infants are reviewed. The data support the conclusion that erythropoietin at doses of > or = 750 u/kg/wk started at less than 7 days of age results in improved reticulocyte counts and hemoglobin levels, but does not reduce the number of infants who will be exposed to blood products. Erythropoietin at doses of > or = 600 u/kg/wk started at an average of 21 days of life improves reticulocyte counts and hemoglobin levels, and reduces the number of infants will will require late transfusion, but does nothing for the bulk of infants who are transfused before that age.

Topics: Anemia, Neonatal; Erythropoiesis; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Randomized Controlled Trials as Topic

Anemia of prematurity (AOP) is an exaggerated form of the normal physiologic anemia of infancy. The primary pathophysiologic abnormality implicated in the development of AOP is inadequate production of erythropoietin, whose function is the regulation of red blood cell production. Recent studies into the safety and efficacy of recombinant human erythropoietin in infants with AOP have demonstrated consistently a rise in hematocrits and reticulocyte counts, fewer blood transfusions, reduced transfused volume of blood per kilogram body weight, and a decrease in bioavailable iron. Current dose recommendations are 200 U/kg subcutaneously or intravenously daily or every other day.

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Recombinant Proteins

Recombinant human erythropoietin (rHuEpo) has been increasingly used in preterm infants in the last 3 to 4 years. Recent studies have indicated a reduction in blood transfusion requirements in infants receiving rHuEpo. No significant adverse effects have emerged, apart from iron deficiency (if iron supplementation is inadequate), and the risk of transfusion-related infection is decreased. Nevertheless, rHuEpo is relatively expensive (a 6-week course costs approximately the same as 2 blood transfusions), so its use requires careful consideration; it is logical to target rHuEpo therapy to those babies who are most likely to be transfused. Using this strategy, 1 study involving stable growing preterm infants has shown that direct costs of blood transfusion and rHuEpo were similar, and the use of rHuEpo was recommended. In addition, use of high-dosage rHuEpo early in the course of management on the neonatal intensive care unit has been shown to reduce direct treatment costs in ill preterm infants. Further studies will continue to identify infants who are likely to benefit from rHuEpo therapy and to define its cost effectiveness in more detail.

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

Topics: Clinical Trials as Topic; Erythrocyte Transfusion; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Recombinant Proteins

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins; Risk Factors

Anemia of prematurity (AOP) affects almost all infants that are born prematurely. Excessive phlebotomy in the NICU setting has exacerbated this condition. Until recently, erythrocyte transfusion has been the only therapy for AOP. Recombinant human erythropoietin (rh-EPO) has been shown to be effective in reducing erythrocyte transfusions in premature infants with AOP. Various studies have utilized rh-EPO as a treatment modality or as prophylaxis for AOP. The results of these studies have shown that rb-EPO is a complementary strategy along with restriction of phlebotomy and less liberal transfusion policies, to decreasing the number of transfusions that an infant may need. Trials are necessary to document the cost-effectiveness of rh-EPO as well as its long term effects on the premature infant.

Topics: Anemia, Neonatal; Erythrocyte Transfusion; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Neonatal Nursing

It has been well established that erythropoietin (EPO) in the dosage range of 500 units/kilo/week and perhaps slightly lower doses will produce a brisk reticulocyte response in infants with anemia of prematurity. Controlled clinical trials to demonstrate that this therapy can result in significant reductions in transfusion in these babies face several complex issues of experimental design. 1. Should the study population be relatively bigger, healthier babies (< 1500 grams birth weight, not on ventilatory support) who have lower transfusion requirements, or smaller sicker infants (< 1250 grams birth weight and on ventilators) who have higher transfusion requirements? These infants will need adequate nutrition and liberal supplementation with iron if they are to respond adequately, but the sicker smaller infants will take longer to meet these nutritional goals. 2. Timing is important because spontaneous recovery occurs at about 35 to 36 weeks of corrected gestational age, so to be effective, therapy must start before 33 weeks of gestational age and preferably earlier than that. 3. Since the end point is transfusion, the criteria used for transfusions become a critical issue. If liberal transfusion criteria are used, the study will be doubly biased in favor of EPO efficacy. There will be an increased number of transfusion events in the control population and spontaneous recovery from the anemia of prematurity will be overly suppressed in the control population. It's likely that the current transfusion criteria are too liberal thus introducing these biases to experimental design.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anemia, Neonatal; Blood Transfusion; Clinical Trials as Topic; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins; Research Design

To review and evaluate current research on the use of recombinant human erythropoietin (rhEPO) for the treatment of anemia of prematurity (AOP).. A MEDLINE search (1985-September 1994) was used to identify and retrieve pertinent data about erythropoietin's use in premature neonates. Bibliographies in the relevant literature and International Pharmacy Abstracts were reviewed as well.. The authors extrapolated data from trials and other literature in which the entire paper or abstract was published. Because of the paucity of data on the use of rhEPO in neonates, all available literature was reviewed and cited, regardless of study methodology.. Most data support that rhEPO is efficacious in treating AOP. Until recently, the published investigations have included only small numbers of patients. Larger, multicenter, placebo-controlled trials suggest that infants weighing less than 1500 g benefit from rhEPO therapy. Questions remain concerning the rhEPO dose and nutrient requirements for optimal efficacy.. Published clinical trials that have examined the efficacy of rhEPO in the treatment of AOP vary considerably with regard to methodology, rhEPO dose, nutrient doses, and outcome measurement. At present, many questions remain to be answered including ascertaining rhEPO's long-term benefit versus cost/risk as well as its potential contribution to improving the care of the premature neonate.

Topics: Anemia, Neonatal; Clinical Trials as Topic; Economics, Pharmaceutical; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Randomized Controlled Trials as Topic; Recombinant Proteins

Anemia of prematurity (AOP) results from several interacting processes, including phlebotomy losses, a temporary failure to release erythropoietin in response to anemia, a short life span of erythrocytes, and rapid growth of body mass and, hence, blood volume after the first few weeks of life. Infants with AOP have erythroid progenitors that respond to erythropoietin in vitro, suggesting that treatment with recombinant erythropoietin might reduce the need for transfusions for AOP. Many pilot studies were needed to define the dose of recombinant erythropoietin (500 to 750 U/kg/wk) that stimulated the early onset of erythropoiesis in infants with AOP. Three large controlled trials have demonstrated that recombinant erythropoietin therapy reduces transfusions in AOP and is apparently safe. Unresolved issues include the ideal dose, the optimal nutrition needed during therapy, the target population, and timing of the start of treatment.

Topics: Anemia, Neonatal; Clinical Trials as Topic; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Recombinant Proteins

Recombinant human erythropoietin (r-HuEPO) is a new therapeutic modality for the treatment of neonatal anemia. The results of three large controlled trials were published within the past year. This article reviews the physiologic rationale underlying the use of r-HuEPO in preterm infants, addresses how the design of clinical trials affects outcomes and conclusions, and discusses the recent trials in this context. The article concludes with a summary of questions that require further investigation.

Topics: Anemia, Neonatal; Clinical Trials as Topic; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

Recombinant human erythropoietin has been available for clinical use since 1985. It was an immediate success in treating the anemia of chronic renal failure and has also enjoyed some objective success in the treatment of other anemias in either a therapeutic or prophylactic setting, but the issues of appropriate patient selection and cost-benefit ratios are still unresolved. This review discusses the most recent literature concerning the use of recombinant human erythropoietin for the anemia associated with cancer, HIV infection, myelodysplasia, prematurity, autologous blood transfusion, bone marrow transplantation, and chronic renal failure.

Topics: Anemia; Blood Transfusion, Autologous; Erythropoietin; HIV Infections; Humans; Infant, Newborn; Infant, Premature, Diseases; Kidney Failure, Chronic; Myelodysplastic Syndromes; Neoplasms; Recombinant Proteins

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Recombinant Proteins

Topics: Anemia, Neonatal; Erythrocyte Transfusion; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Recombinant Proteins; Risk

Topics: Anemia, Neonatal; Blood Transfusion; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins; Research Design

Cytokines play key roles in the control of hemopoiesis and immunity. As they become available in increasing quantities and purity through improved recombinant technology, cytokines hold great clinical promise. This article focuses on recent clinical experience with a wide variety of cytokines. For example, newer uses of recombinant human erythropoietin include treatment of anemia of prematurity, AIDS, and some hemoglobinopathies. The myeloid-stimulating factors have established a niche in the treatment of chemotherapy-induced neutropenias and as an adjunct to bone marrow transplantation. Combinations of cytokines that act at different levels of hemopoietic proliferation are being evaluated for the treatment of other causes of neutropenia and thrombocytopenia and also as biologic response modifiers.

Topics: Anemia; Bone Marrow Transplantation; Child; Cytokines; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Neutropenia; Recombinant Proteins

Topics: Anemia, Neonatal; Blood Transfusion; Contraindications; Erythropoietin; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Recombinant Proteins

Recombinant human erythropoietin administration may prove to be a valuable adjunct in the treatment of the anemia of prematurity. This report provides an overview of fetal and neonatal erythropoiesis, the biology of erythropoietin, and the pathophysiology of the anemia of prematurity. The clinical trials using recombinant human erythropoietin in the treatment of anemia of prematurity are reviewed. Important considerations of this therapy are discussed.

Topics: Adult; Anemia; Erythropoiesis; Erythropoietin; Fetus; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

There is a high level of erythropoiesis in the growing fetus. In utero relative hypoxia results in a relatively high haematocrit and predominant synthesis of haemoglobin F, with erythropoietin (EPO) produced in the liver regulating erythropoiesis. At birth after full-term pregnancy, fetal EPO concentrations are high, but decline progressively thereafter. In pre-term infants the expected postnatal decline in haemoglobin is more prolonged than in full-term infants and the premature infants may become anaemic. It has been shown in a randomized, double-blinded, placebo-controlled trial that recombinant human erythropoietin (r-HuEPO) at a dose of 100 U/kg given intravenously twice weekly for 6 weeks to infants with anaemia of prematurity produced an earlier increase in reticulocyte counts compared with placebo; however, the difference between treatments was not significant. r-HuEPO therapy did not suppress subsequent release of endogenous EPO. It is concluded that a higher dose of r-HuEPO may be required to treat anaemic premature infants.

Topics: Anemia; Erythropoiesis; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

The anemia of prematurity is defined by a progressive decline in hemoglobin level occurring over the first 2 months of life. Unlike term newborns whose "physiologic anemia" rarely if ever necessitates any treatment, preterm infants may become anemic enough to have clinical symptoms that indicate a need for red blood cell transfusions. Various factors contribute to the development of this anemia. Some of these factors, such as the short life span of erythrocytes in preterm infants, increased sensitivity of the erythrocytes to oxidative injury, and the blood losses caused by repeated phlebotomies, would normally be expected to induce corrective reticulocytosis. Characteristically, however, this anemia is hyporegenerative. Thus, it is associated with relative reticulocytopenia, low serum erythropoietin levels, and bone marrow erythroid hypoplasia. The recent availability of recombinant human erythropoietin has opened new perspectives in the management of a variety of anemias. Based on current knowledge of the regulation and pathophysiology of fetal and neonatal erythropoiesis, recombinant erythropoietin may represent a logical and efficient alternative to giving red blood cell transfusions in the treatment of the anemia of prematurity. Clinical trials have been initiated in several countries using different approaches and methodology. At this early stage these trials do not yet fully affirm that recombinant erythropoietin can be used as the first-line therapy in infants with the anemia of prematurity. Our own observations, however, suggest that this agent is well tolerated by preterm infants and may exert a corrective effect on the anemia of prematurity.

Topics: Anemia, Neonatal; Blood Cell Count; Blood Transfusion; Combined Modality Therapy; Drug Evaluation; Erythropoiesis; Erythropoietin; Hematocrit; Humans; Immunologic Factors; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Injections, Subcutaneous; Iron; Iron Deficiencies; Longitudinal Studies; Pilot Projects; Recombinant Proteins; Reticulocytes

Topics: Anemia; Arthritis, Rheumatoid; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

Recombinant human erythropoietin (r-HuEPO) is of interest to pediatric hematologists and neonatologists because it may prove to be an effective alternative to blood transfusions in preventing and treating anemia in premature infants. The anemia of prematurity is the most promising setting for initial clinical trials. However, it is conceivable that recombinant erythropoietin will be given at birth to low-birth-weight infants in an effort to stimulate endogenous erythropoiesis and thereby prevent some of the erythrocyte transfusions required to replace blood sampled for laboratory tests. Beyond its appeal as a therapeutic alternative to red blood cell transfusions, recombinant human erythropoietin is likely to be the first member of an entirely new class of drugs to be used widely in neonatal medicine. These are drugs produced by cloning normal human genes and expressing them in the laboratory. Because many of the problems of premature birth are caused by developmental immaturity, transiently replacing crucial proteins with exact copies produced by the techniques of recombinant DNA technology is an approach that may have a major impact on morbidity and mortality of neonates. Carefully designed, controlled clinical trials will be essential to determine the role of new agents like r-HuEPO in the treatment of medical problems of premature infants.

Topics: Anemia; Animals; Blood Transfusion; Erythrocyte Transfusion; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Macaca mulatta; Recombinant Proteins

Recombinant human erythropoietin represents a potential therapeutic alternative to red blood cell transfusions in a number of pediatric anemias. It is effective in correcting anemia associated with chronic renal failure and may significantly reduce the morbidity associated with childhood CRF. Most exposures to allogeneic blood products in pediatrics for treatment of anemia with blood transfusions occur in neonatal intensive care units. If proven effective in treating anemia in premature babies, r-HuEPO will be responsible for a major reduction in the use of blood transfusions in clinical neonatology. Carefully designed, placebo-controlled clinical trials will be required to establish the role of r-HuEPO in anemia of prematurity. Recombinant human erythropoietin also may be useful to increase the amount of blood that can be collected before elective surgical procedures. Another potential indication is to raise the hematocrits of infants with large intracardiac shunts who develop congestive heart failure coincident with the developmental fall in hemoglobin concentration after birth. Finally, r-HuEPO may one day play a role in modifying the expression of globin genes and, thereby, ameliorate the course of sickle cell disease and beta thalassemia. Many questions surrounding the use of r-HuEPO in infancy and childhood are being addressed in ongoing clinical trials.

Topics: Anemia; Anemia, Sickle Cell; Blood Transfusion, Autologous; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Kidney Failure, Chronic; Recombinant Proteins

At no other time of life is the decision to transfuse potentially as difficult as in the newborn period. Superimposed upon complex "physiologic" changes in the ability to deliver and release oxygen are varying requirements among infants in terms of oxygen need. These are compounded by changes brought about as a direct consequence of frequent phlebotomy in the most ill of preterm infants. Despite the confusion overlying many of the changes occurring at this time of life, certain principles can be applied. Unlike that of the adult, an infant's ability to make oxygen available in response to a specific demand is almost as dependent upon the modifiers of oxygen uptake and release by hemoglobin as upon the hemoglobin concentration itself. These modifiers are constantly changing, sometimes in a predictable fashion, sometimes not. As discussed, some attention to the status of a particular infant's capability in providing oxygen relative to need will assist in the decision when to transfuse. If specific parameters of these assessments can not be determined, it may be necessary to proceed with transfusion based on the clinical presentation of an infant. With regard to the above, any infant sufficiently ill to require frequent blood sampling should have such blood losses replaced, certainly before ten percent of blood volume has been exceeded. This is particularly true in infants who are unable to maintain adequate arterial oxygen tensions with or without the use of supplemental inspired oxygen. At several weeks of age, when the clinical status of a preterm infant may have stabilized, transfusion may or may not be needed during the nadir of the anemia of prematurity. Infants who had been previously transfused or who had earlier received frequent simple transfusions should be able to tolerate lower levels of hemoglobin. Infants without compromised cardiopulmonary function and in whom no unusual metabolic needs exist are unlikely to be aided by transfusions when the hemoglobin concentration is greater than 10 to 11 g/dl. At lower levels of hemoglobin, simple calculations of "available oxygen" may be helpful when it is difficult to determine whether clinical signs and symptoms of anemia exist. Such signs and symptoms may include poor feeding, dyspnea, tachycardia, tachypnea, diminished activity, and pallor. Apnea has not unequivocably been shown to improve following transfusion. Clearly, our current concepts regarding indications for transfusion, even when based upon

Topics: Anemia, Neonatal; Blood Transfusion; Erythropoietin; Hematocrit; Hemoglobins; Humans; Infant, Newborn; Infant, Premature, Diseases; Oxygen; Risk

Topics: Anemia, Neonatal; Blood Transfusion; Erythropoiesis; Erythropoietin; Hemoglobins; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Oxygen; Oxygen Consumption; Regional Blood Flow

To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months of corrected gestational age (cGA) compared with those randomized to placebo.. We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs.. ELGANs have high rates of in-hospital AKI and kidney-related problems at 22-26 months of cGA. Recombinant erythropoietin may protect ELGANs against long-term elevated SBP but does not appear to protect from AKI, low eGFR, albuminuria, or elevated DBP at 22-26 months of cGA.

Topics: Acute Kidney Injury; Albuminuria; Double-Blind Method; Erythropoietin; Female; Gestational Age; Glomerular Filtration Rate; Humans; Hypertension; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Male; Recombinant Proteins; Renal Insufficiency, Chronic

Intraventricular hemorrhage (IVH) is a common complication in preterm infants that has poor outcomes, especially in severe cases, and there are currently no widely accepted effective treatments. Erythropoietin has been shown to be neuroprotective in neonatal brain injury.. The objective of this study was to evaluate the protective effect of repeated low-dose recombinant human erythropoietin (rhEPO) in preterm infants with IVH.. This was a single-blinded prospective randomized controlled trial. Preterm infants ≤ 32 weeks gestational age who were diagnosed with IVH within 72 h after birth were randomized to receive rhEPO 500 IU/kg or placebo (equivalent volume of saline) every other day for 2 weeks. The primary outcome was death or neurological disability assessed at 18 months of corrected age.. A total of 316 eligible infants were included in the study, with 157 in the rhEPO group and 159 in the placebo group. Although no significant differences in mortality (p = 0.176) or incidence of neurological disability (p = 0.055) separately at 18 months of corrected age were seen between the rhEPO and placebo groups, significantly fewer infants had poor outcomes (death and neurological disability) in the rhEPO group: 14.9 vs. 26.4%; odds ratio (OR) 0.398; 95% confidence interval (CI) 0.199-0.796; p = 0.009. In addition, the incidence of Mental Development Index scores of < 70 was lower in the rhEPO group than in the placebo group: 7.2 vs. 15.3%; OR 0.326; 95% CI 0.122-0.875; p = 0.026.. Treatment with repeated low-dose rhEPO improved outcomes in preterm infants with IVH.. The study was retrospectively registered on ClinicalTrials.gov on 16 April 2019 (NCT03914690).

Topics: Cerebral Hemorrhage; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Neuroprotective Agents; Prospective Studies; Recombinant Proteins; Single-Blind Method; Treatment Outcome

High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established.. In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age. Placebo was administered as intravenous saline followed by sham injections. The primary outcome was death or severe neurodevelopmental impairment at 22 to 26 months of postmenstrual age. Severe neurodevelopmental impairment was defined as severe cerebral palsy or a composite motor or composite cognitive score of less than 70 (which corresponds to 2 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition.. A total of 741 infants were included in the per-protocol efficacy analysis: 376 received erythropoietin and 365 received placebo. There was no significant difference between the erythropoietin group and the placebo group in the incidence of death or severe neurodevelopmental impairment at 2 years of age (97 children [26%] vs. 94 children [26%]; relative risk, 1.03; 95% confidence interval, 0.81 to 1.32; P = 0.80). There were no significant differences between the groups in the rates of retinopathy of prematurity, intracranial hemorrhage, sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, or death or in the frequency of serious adverse events.. High-dose erythropoietin treatment administered to extremely preterm infants from 24 hours after birth through 32 weeks of postmenstrual age did not result in a lower risk of severe neurodevelopmental impairment or death at 2 years of age. (Funded by the National Institute of Neurological Disorders and Stroke; PENUT ClinicalTrials.gov number, NCT01378273.).

Topics: Brain; Child, Preschool; Double-Blind Method; Erythropoietin; Female; Follow-Up Studies; Humans; Infant; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Male; Neurodevelopmental Disorders; Ultrasonography

To evaluate the effects of enteral administration of recombinant human erythropoietin (rhEPO) on feeding-related complications in preterm infants.. This double-blind, randomized controlled pilot study enrolled 120 preterm infants born ≤ 32 weeks' gestation who were admitted to the neonatal intensive care unit in a tertiary hospital; 60 patients randomly received recombinant human erythropoietin while the other 60 received placebo. Newborns who underwent cardiopulmonary resuscitation, infants with genetic syndromes, infants with inborn errors of metabolism, infants with major congenital or acquired gastrointestinal tract malformations, infants with previous use of parenteral growth factors such as recombinant human erythropoietin and granulocyte-macrophage colony-stimuating factor (GM-CSF) and infants previously treated with intravenous immunoglobulin were excluded. Overall, 48 patients withdrew from the study because of intravenous haematopoietic growth factor intake or death before treatment was completed. A total of 72 preterm infants remained in the study: 36 preterm infants in the erythropoietin (EPO) group, and 36 preterm infants in the placebo group. The day that enteral feeding was successfully started, the time to establishing one-half, two-thirds, and full enteral feedings (reaching at least 150 mL/kg/day), the number of episodes of feeding intolerance, the time to regain birth weight and the incidence of necrotizing enterocolitis (NEC) were recorded.. Both groups showed no significant difference in the time to achieve one-half, two-thirds, or full enteral feeding, no signs of feeding intolerance, and no cases of NEC were recorded.. Enteral erythropoietin does not appear to affect feeding intolerance or NEC incidence.

Topics: Double-Blind Method; Enteral Nutrition; Enterocolitis, Necrotizing; Erythropoietin; Female; Food Intolerance; Humans; Incidence; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Pilot Projects; Recombinant Proteins; Survival Rate

Extremely preterm infants are among the populations receiving the highest levels of transfusions. Erythropoietin has not been recommended for premature infants because most studies have not demonstrated a decrease in donor exposure.. To determine whether high-dose erythropoietin given within 24 hours of birth through postmenstrual age of 32 completed weeks will decrease the need for blood transfusions.. The Preterm Erythropoietin Neuroprotection Trial (PENUT) is a randomized, double-masked clinical trial with participants enrolled at 19 sites consisting of 30 neonatal intensive care units across the United States. Participants were born at a gestational age of 24 weeks (0-6 days) to 27 weeks (6-7 days). Exclusion criteria included conditions known to affect neurodevelopmental outcomes. Of 3266 patients screened, 2325 were excluded, and 941 were enrolled and randomized to erythropoietin (n = 477) or placebo (n = 464). Data were collected from December 12, 2013, to February 25, 2019, and analyzed from March 1 to June 15, 2019.. In this post hoc analysis, erythropoietin, 1000 U/kg, or placebo was given every 48 hours for 6 doses, followed by 400 U/kg or sham injections 3 times a week through postmenstrual age of 32 weeks.. Need for transfusion, transfusion numbers and volume, number of donor exposures, and lowest daily hematocrit level are presented herein.. A total of 936 patients (488 male [52.1%]) were included in the analysis, with a mean (SD) gestational age of 25.6 (1.2) weeks and mean (SD) birth weight of 799 (189) g. Erythropoietin treatment (vs placebo) decreased the number of transfusions (unadjusted mean [SD], 3.5 [4.0] vs 5.2 [4.4]), with a relative rate (RR) of 0.66 (95% CI, 0.59-0.75); the cumulative transfused volume (mean [SD], 47.6 [60.4] vs 76.3 [68.2] mL), with a mean difference of -25.7 (95% CI, 18.1-33.3) mL; and donor exposure (mean [SD], 1.6 [1.7] vs 2.4 [2.0]), with an RR of 0.67 (95% CI, 0.58-0.77). Despite fewer transfusions, erythropoietin-treated infants tended to have higher hematocrit levels than placebo-treated infants, most noticeable at gestational week 33 in infants with a gestational age of 27 weeks (mean [SD] hematocrit level in erythropoietin-treated vs placebo-treated cohorts, 36.9% [5.5%] vs 30.4% [4.6%] (P < .001). Of 936 infants, 160 (17.1%) remained transfusion free at the end of 12 postnatal weeks, including 43 in the placebo group and 117 in the erythropoietin group (P < .001).. These findings suggest that high-dose erythropoietin as used in the PENUT protocol was effective in reducing transfusion needs in this population of extremely preterm infants.. ClinicalTrials.gov Identifier: NCT01378273.

Topics: Adult; Blood Transfusion; Dose-Response Relationship, Drug; Double-Blind Method; Erythropoietin; Female; Gestational Age; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Male

Hosseini M, Azampour H, Raeisi S, Behtari M, Valizadeh H, Saboohi R. The effects of enteral artificial amniotic fluid-containing erythropoietin on short term outcomes of preterm infants. Turk J Pediatr 2019; 61: 392-398. Necrotizing Enterocolitis (NEC) is a common devastating gastrointestinal disease, which usually develops in premature infants. Erythropoietin (EPO) as a hematopoietic hormone produced by the kidney can also be naturally found in amniotic fluid and breast milk. There is some evidence that supports the contribution of EPO in the prevention of inflammation and intestinal tissue repair. This study was aimed to determine if oral administration of artificial amniotic fluid with or without EPO would protect preterm infants against NEC and improve the certain neonatal outcomes. In this study, 150 preterm infants with gestational age 28 weeks or less and birth weight 1250 grams or less were enrolled. The infants were divided randomly into 3 groups: 1) Control group (n=50) with routine feeding protocol without any administration; 2) Amniotic fluid group (n=50) with 5mL/kg synthetic amniotic fluid; 3) EPO group (n=50) with RhuEPO dissolved in the synthetic amniotic fluid. The administrations of the study solution were started 3 days after the birth and were continued for 3 weeks (21 days). The infants in the study groups were followed up until discharge and the frequency of NEC, mortality, and other complications of the disease among the groups were compared. The mortality rate in preterm infants of the amniotic fluid and EPO groups were significantly lower than in the control group (p=0.027). We couldn`t find any significant differences in the frequency of NEC and other complications among the three study groups. The administration of synthetic amniotic fluid (with or without EPO) in preterm infants may decrease the mortality rate. Use of EPO in synthetic amniotic fluid did not affect the frequency of NEC.

Topics: Amniotic Fluid; Birth Weight; Breast Feeding; Erythropoietin; Female; Gestational Age; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Milk, Human

We explored the clinical efficacy of vitamin A combined with vitamin B in the prevention and treatment of premature infants with anemia.. One hundred fifty cases of premature infants were divided into three groups. Vitamin A combined with recombinant human erythropoietin (group A), vitamin B combined with recombinant human erythropoietin (group B), vitamin A combined with vitamin B combined with recombinant human erythropoietin treatment (recorded as group C). Levels of serum ferritin (SF), hemoglobin (Hb), hematocrit (Hct) and reticulocyte (Ret) in the serum of children before and after treatment were compared with those of three different treatments.. After treatment, the levels of SF, Hb and Ret in group C were higher than those in group A and B, and the level of Hct in group C was lower than that in group A and B (P<0.05) There was no significant difference in SF, Hb, Hct and Ret between the two groups (P>0.05). The ratio of blood transfusion in group C was lower than that in group A and B (P<0.05). There was no significant difference between the two groups (P>0.05).. Vitamin A combined with vitamin B can effectively prevent anemia in premature infants, which has important clinical significance.

Topics: Anemia, Neonatal; Drug Therapy, Combination; Erythropoietin; Female; Ferritins; Hematocrit; Hemoglobins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Recombinant Proteins; Reticulocytes; Treatment Outcome; Vitamin A; Vitamin B Complex

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.. 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.. 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.. 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.

Topics: Child Development; Child, Preschool; Cognition; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Erythropoietin; Female; Follow-Up Studies; Hematinics; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Injections, Subcutaneous; Male; Neurodevelopmental Disorders; Time Factors; Treatment Outcome

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.. 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.. 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.. 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.

Topics: Blood Transfusion; Cognition; Concept Formation; Darbepoetin alfa; Developmental Disabilities; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Erythropoietin; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Injections, Subcutaneous; Male; Memory, Short-Term; Neurologic Examination; Neuropsychological Tests; Problem Solving; Prospective Studies

To evaluate the efficacy and safety of enteral recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human erythropoietin (rhEPO) in preventing feeding intolerance.. An interventional randomized control trial was conducted in 90 preterm infants born at ≤33 weeks gestational age. The neonates were assigned to 4 groups; 20 received rhG-CSF, 20 received rhEPO, 20 received both, and 30 received distilled water (placebo control). The test solution was given at the beginning of enteral feeding and was discontinued when enteral intake reached 100 mL/kg/day or after a maximum of 7 days, whichever came first. Feeding tolerance and adverse effects of treatment were assessed. Serum granulocyte colony-stimulating factor and erythropoietin levels were measured on days 0 and 7 of treatment.. All neonates tolerated the treatment without side effects. Neonates who received rhG-CSF and/or rhEPO had better feeding tolerance, as reflected by earlier achievement of 75 mL/kg/day, 100 mL/kg/day, and full enteral feeding of 150 mL/kg/day with earlier weight gain and a shorter hospital stay (P < .05). The risk of necrotizing enterocolitis was reduced from 10% to 0% in all treatment groups (P < .05). There was a shorter duration of withholding of feeding secondary to feeding intolerance among neonates receiving both rhG-CSF and rhEPO compared with those receiving placebo (P < .05). Serum levels of granulocyte colony-stimulating factor and erythropoietin at 0 and 7 days did not differ across the treatment groups.. Enteral administration of rhG-CSF and/or rhEPO improves feeding outcome and decreases the risk of necrotizing enterocolitis in preterm neonates. The mechanism may involve the prevention of villous atrophy.

Topics: Enterocolitis, Necrotizing; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Recombinant Proteins

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).. 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.. 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.. 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.

Topics: Anemia, Neonatal; Darbepoetin alfa; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Female; Guideline Adherence; Hematinics; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Injections, Subcutaneous; Male; Reticulocyte Count; Therapeutic Equivalency

To compare reticulocyte responses of once-per-week erythropoietin (EPO) dosing with 3-times-a-week dosing in preterm infants.. Infants weighing ≤ 1500 g and ≥ 7 days of age were randomized to once-per-week EPO, 1200 U/kg/dose, or 3-times-a-week EPO, 400 U/kg/dose, subcutaneously for 4 weeks, along with iron and vitamin supplementation. Complete blood counts, absolute reticulocyte counts (ARCs), transfusions, phlebotomy losses, and adverse events were recorded.. Twenty preterm infants (962 ± 55 g, 27.9 ± 0.4 weeks, 17 ± 3 days of age) were enrolled. Groups were similar at baseline. Infants in both groups had increased ARCs, which were similar between treatment groups at the start and end of 4 weeks. Hematocrit remained stable, and similar numbers of transfusions were administered. No adverse effects of either dosing schedule were noted.. Preterm infants respond to weekly EPO by increasing ARCs and maintaining hematocrit. We speculate that once-per-week EPO dosing might be beneficial to preterm infants requiring increased erythropoiesis.

Topics: Anemia, Neonatal; Blood Cell Count; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythrocyte Count; Erythropoiesis; Erythropoietin; Female; Follow-Up Studies; Hematocrit; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Injections, Subcutaneous; Intensive Care Units, Neonatal; Iron Compounds; Male; Pilot Projects; Risk Assessment; Severity of Illness Index; Treatment Outcome; Vitamins

To compare transfusion requirements and erythropoietic response in preterms between schedules of rEPO administration once or three times per week, using the same weekly dose.. Prospective, randomized trial including infants weighing <1500 g at birth and/or were 32 weeks' gestation: Group 1 (60 infants) received subcutaneous rEPO at 250 units kg(-1) per dose, three times weekly for 6 weeks; Group 2 (59 infants), at 750 units kg(-1) per dose, once weekly for 6 weeks. Efficacy was evaluated based on the transfusion requirement, hemoglobin changes, reticulocyte counts, serum transferrin receptor (sTfR) and serum ferritin. The frequency of adverse effects was registered in both groups.. A total of 13 infants were transfused in each group (relative risk: 0.98; 95% confidence interval: 0.4 to 2.3). Phlebotomy loss and red blood cell transfusion volumes received were similar in both groups. Hemoglobin levels were lower at end of study in Group 2 (10.6±1.5 g dl(-1) versus 11.5±1.4 g dl(-1); P<0.003). At end of study, reticulocyte counts and sTfR values increased and serum ferritin values decreased, without significant differences between the two groups. Incidence of complications was similar in both groups.. The once-weekly rEPO schedule for very low birth weight infants proved as effective as the three-times-weekly schedule, in relation to erythropoietic stimulus and transfusion requirement.

Topics: Anemia, Neonatal; Blood Transfusion; Drug Administration Schedule; Drug Monitoring; Erythropoiesis; Erythropoietin; Ferritins; Hemoglobins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Injections, Subcutaneous; Receptors, Transferrin; Recombinant Proteins; Reticulocyte Count; Thrombocytosis; Transfusion Reaction; Treatment Outcome

The primary outcome measure of this study was the ability of rHuEPOα therapy to reduce transfusion needs, whereas secondary outcome measures were NICU-LOS and ventilation need.. All babies with BW <1250 g and GA <30 were eligible. Thirty premature neonates were enrolled in the study (10 treated, 20 controls). rHuEPOα was administered as 300 IU/kg/dose 3 times/week subcutaneously. Iron, folic acid and Vitamin E supplementation were administered in both groups. Hematologic variables and blood sampling were recorded during the study.. In rHuEPO group, only four (40%) premature infants required a transfusion, averaging 0.4 ± 0.52 transfusions/pts. A total of 23 transfusions were administered to controls; 11 (55%) infants received one transfusion at least, 55% required multiple transfusions. The average number of transfusions/pts was statistically different (1.15  ±  1.46 vs. 0.4 ± 0.52; p = 0.02), as the cumulative number of transfused patients (55% vs. 40%; p<0.001). NICU stay was not statistically different, whereas ventilation-free days were increased in EPO group (p<0.05).. R-Hu-EPO treatment in first post-natal weeks markedly enhanced erythropoiesis in severely premature infants compared with matched controls, with a significant impact on transfusion needs. EPO group experienced also a reduction of ventilation time and, possibly, a decreased occurrence of clinical BPD.

Topics: Anemia; Blood Transfusion; Case-Control Studies; Combined Modality Therapy; Drug Administration Schedule; Erythropoietin; Folic Acid; Hematinics; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Iron; Length of Stay; Respiration, Artificial; Treatment Outcome

Erythropoietin has been reported to possess neuroprotective properties in animal studies. No previous studies have investigated the neurodevelopmental outcome of extremely low birth weight (ELBW) infants treated with recombinant human erythropoietin (rEpo) and evaluated it at school age.. Of 200 ELBW infants treated from 1993 to 1998, 171 (86%) survived, and 148 (87%) were followed up to the age of 10 to 13 years. The neurodevelopmental and school outcome of the ELBW infants receiving rEpo treatment for stimulation of erythropoiesis in the first weeks of life (n = 89) was compared to that of untreated children (n = 57). To test for a neuroprotective effect of erythropoietin therapy, analyses of variance (ANOVAs) were conducted with erythropoietin treatment and intraventricular hemorrhage (IVH) as independent variables and Hamburg-Wechsler Intelligence Test for Children-III (HAWIK-III) intelligence quotient (IQ) scores as dependent variables.. The rEpo group scored significantly better than untreated children in the overall developmental assessment (55% vs 39% normally developed, p < 0.05) as well as in the psychological examination (mean composite HAWIK-III IQ score, 90.8 vs 81.3, p < 0.005). The results of ANOVAs show that these differences were ascribable to children with IVH. Whereas those children with IVH treated with rEpo scored significantly better than untreated children (52% vs 6% normally developed, composite HAWIK-III IQ score, 90.3 vs 67.0), treated and untreated children without IVH did not differ in their outcome. The treatment and control groups were comparable in perinatal parameters relevant to prognosis.. The results of our observational study confirm the hypothesis of a neuroprotective effect of rEpo in ELBW infants with IVH. This offers a promising preventative therapeutic option for the treatment of these high-risk infants.

Topics: Adolescent; Age Factors; Analysis of Variance; Chi-Square Distribution; Child; Developmental Disabilities; Erythropoietin; Female; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Intelligence Tests; Longitudinal Studies; Male; Nervous System Diseases; Neuropsychological Tests; Recombinant Proteins; Treatment Outcome; Ultrasonography

Erythropoietin has been shown to be protective against hypoxic-ischemic and inflammatory injuries in cell culture, animal models of brain injury, and clinical trials of adult humans. The rationale for our study was that early administration of high-dose recombinant human erythropoietin may reduce perinatal brain injury (intraventricular hemorrhage and periventricular leukomalacia) in very preterm infants and improve neurodevelopmental outcome. We investigated whether administration of high-dose recombinant human erythropoietin to very preterm infants shortly after birth and subsequently during the first 2 days is safe in terms of short-term outcome.. This was a randomized, double-masked, single-center trial with a 2:1 allocation in favor of recombinant human erythropoietin. Preterm infants (gestational age: 24 to 31 weeks) were given recombinant human erythropoietin or NaCl 0.9% intravenously 3, 12 to 18, and 36 to 42 hours after birth.. The percentage of infants who survived without brain injury or retinopathy was 53% in the recombinant human erythropoietin group and 60% in the placebo group. There were no relevant differences regarding short-term outcomes such as intraventricular hemorrhage, retinopathy, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia. For 5 infants who were in the recombinant human erythropoietin group and had a gestational age of <26 weeks, withdrawal of intensive care was decided (3 of 5 with severe bilateral intraventricular hemorrhage, 2 of 5 with pulmonary insufficiency); no infant of the control group died. Recombinant human erythropoietin treatment did not result in significant differences in blood pressure, cerebral oxygenation, hemoglobin, leukocyte, and platelet count.. No significant adverse effects of early high-dose recombinant human erythropoietin treatment in very preterm infants were identified. These results enable us to embark on a large multicenter trial with the aim of determining whether early high-dose administration of recombinant human erythropoietin to very preterm infants improves neurodevelopmental outcome at 24 months' and 5 years' corrected age.

Topics: Apgar Score; Brain Diseases; Cerebral Hemorrhage; Developmental Disabilities; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Erythropoietin; Female; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Male; Maximum Tolerated Dose; Probability; Recombinant Proteins; Reference Values; Retinopathy of Prematurity; Risk Assessment; Survival Analysis; Treatment Outcome

High-dose recombinant erythropoietin is neuroprotective in animal models of neonatal brain injury. Extremely low birth weight infants are at high risk for brain injury and neurodevelopmental problems and might benefit from recombinant erythropoietin. We designed a phase I/II trial to test the safety and determine the pharmacokinetics of high-dose recombinant erythropoietin in extremely low birth weight infants.. In a prospective, dose-escalation, open-label trial, we compared 30 infants who were treated with high-dose recombinant erythropoietin with 30 concurrent control subjects. Eligible infants were <24 hours old,

Topics: Analysis of Variance; Brain Diseases; Developmental Disabilities; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Follow-Up Studies; Gestational Age; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Infusions, Intravenous; Male; Prospective Studies; Recombinant Proteins; Reference Values; Risk Assessment; Single-Blind Method; Survival Analysis; Treatment Outcome

To evaluate the effect of the early use of recombinant human erythropoietin (rhu-EPO) on neurobehavioral development in preterm infants.. Forty-four preterm infants (30 males and 14 females) were randomly divided into two groups: Rhu-EPO treatment and untreated control (n=22 each). From postnatal day 7, the Rhu-EPO treatment group received intravenous rhu-EPO (250 IU/kg3 times weekly) for 4 weeks. A Neonatal Behavioral Neurological Assessment (NBNA) was performed at 40 weeks of corrected gestational age. A Gesell Development Schedule was used to evaluate neurological development 6 and 12 months after birth.. The NBNA score in the rhu-EPO treatment group (36.20+/-0.75) was significantly higher than that in the control group (34.40+/-1.05) at 40 weeks of corrected gestational age (P<0.05). The developmental quotient of fine motor in the rhu-EPO treatment group was significantly higher than that in the control group 6 months after birth (P<0.05). By 12 months after birth, the developmental quotient of gross motor, fine motor and language in the rhu-EPO treatment group was significantly higher than that in the control group (P<0.05).. Early use of Rhu-EPO can promote neurobehavioral development in preterm infants.

Topics: Anemia; Brain; Child Development; Erythropoietin; Female; Humans; Infant Behavior; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Recombinant Proteins

Hematopoietic and non-hematopoietic effects of recombinant erythropoietin (Epo) given to preterm infants are controversially discussed. Because renal loss of Epo was significantly higher after intravenous versus subcutaneous Epoetin-beta administration, we suggest a reconsideration of whether subcutaneous recombinant Epo is more efficient and safer because of lower peaks of circulating Epo.

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Injections, Intravenous; Injections, Subcutaneous; Longitudinal Studies; Recombinant Proteins

Suppression of erythropoiesis due to low plasma erythropoietin levels is an important factor in the development of anaemia of prematurity. Premature infants may therefore be treated with recombinant human erythropoietin (rhEPO). This prospective, randomised and controlled study was designed to find out whether rhEPO treatment improves erythrocyte deformability in preterm infants.. Sixteen infants were treated with rhEPO (250 IU/kg three times weekly) a total of 15 times beginning on day of life 5 whereas fifteen infants served as controls. Haemoglobin concentration, haematocrit, reticulocyte count, ferritin level and erythrocyte deformability were measured on days 5, 14, 28, 42 and 63. Erythrocyte elongation was determined as an indicator of erythrocyte deformability using a shear stress diffractometer (Rheodyn SSD) at shear forces of 0.3 to 60 Pa.. Haemoglobin concentration was significantly higher on days 28 and 42 and reticulocyte percentage on day 28 in the rhEPO group compared to the controls. Serum ferritin was lower in the rhEPO group on day 28. Erythrocyte deformability was significantly increased on days 28 and 42 in the infants receiving rhEPO. We found a strong relationship between erythrocyte elongation and reticulocyte count.. RhEPO markedly increases the erythropoiesis in preterm infants in the critical first weeks of life and the anaemia of prematurity is obviously reduced. The erythrocyte deformability improved under rhEPO treatment. Erythrocyte deformability was significantly related to the reticulocyte count indicating that the improvement of erythrocyte deformability was due to the formation of well-deformable young erythrocytes.

Topics: Anemia, Neonatal; Erythrocyte Deformability; Erythropoietin; Hematinics; Hematocrit; Hemoglobins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Prospective Studies; Recombinant Proteins; Reticulocyte Count

Premature infants, especially those with birth weights of <1500 g, often suffer from anemia of prematurity and associated problems. Erythropoietin therapy is a safe effective way to prevent and to treat anemia of prematurity. We hypothesized that combined administration of vitamin B12 and folate with erythropoietin and iron would enhance erythropoietin-induced erythropoiesis.. 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 B12 (3 microg/kg per day) and folate (100 microg/kg per day) (treatment group) or a lower dose of folate (60 microg/kg per day) (control group).. During the 4-week observation period, vitamin B12 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 B12 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.. With the limitation of a slight imbalance in baseline data between the study groups, combined therapy with vitamin B12, 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.

Topics: Anemia, Neonatal; Blood Transfusion; Drug Therapy, Combination; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Folic Acid; Gestational Age; Hematocrit; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Parenteral Nutrition; Vitamin B 12; Vitamin B Complex

To determine the effectiveness of a 10-day subcutaneous erythropoietin (rHuEpo) course of 300 units per kg per dose plus oral iron compared to oral iron alone in anemic infants during their convalescent phase of illness.. Prospective, randomized trial performed at a 40-bed, teaching, referral, level III, neonatal intensive care unit. Infants with a gestational age at birth of less than 32 weeks, hematocrit of less than or equal to 28% with a corrected reticulocyte count of less than or equal to 5%, postconceptual age of less than 48 weeks or 5 months chronological age, and a diagnosis of anemia of prematurity were considered for inclusion. Major outcome parameters included hematocrit, corrected reticulocyte count and red cell transfusion requirements.. A total of 60 infants were enrolled (n=30 per group). Infants randomized to rHuEpo had a significantly higher post-treatment hematocrit and corrected reticulocyte count than infants in the iron only group (p<0.001). There was a trend towards fewer red cell requirements in the rHuEpo group.. The rHuEpo regimen studied here was associated with an acute improvement in hematocrit and corrected reticulocyte counts. This study did not demonstrate a statistically significant decrease in transfusion therapy, in part related to increased subsequent use of rHuEpo in the control group. Taken together, these data demonstrate that this regimen can effectively treat anemia in convalescent premature infants.

Topics: Anemia, Neonatal; Convalescence; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hematinics; Hematocrit; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Injections, Subcutaneous; Prospective Studies; Recombinant Proteins; Reticulocyte Count; Treatment Outcome

This study aimed to detect the effectiveness of recombinant human erythropoietin therapy in preventing premature anemia in low-birthweight preterm infants.. A total of 292 premature infants who were born earlier than 33 gestational weeks and smaller than 1500 g birthweight were enrolled into the study. In addition to their conventional supportive therapy (medications), recombinant human erythropoietin 200 U/kg twice a week, subcutaneously, was given to randomly selected 142 premature infants for 6 weeks. The blood count variables and need for transfusions were compared with the remaining 150 premature infants during 6 months follow up.. Serum erythropoietin levels were 11.3 +/- 6.1 mU/mL and 38.3 +/- 19.1 mU/mL in the erythropoietin group before and at the fourth week of the study, respectively (P < 0.001). Reticulocyte counts of the group treated with erythropoietin were 146 x 10(6) +/- 28 x 10(6)/mL and 122 x 10(6) +/- 27 x 10(6)/mL at the fourth and seventh week of the study, respectively, and these values were significantly higher when compared with the control group (P < 0.001 and P < 0.001). At the same period, hematocrit values were also found to be higher in the treatment group than the control group (P < 0.001). Serum ferritin levels were lower in the treatment group compared with the control group at the fourth week of the study. No side-effects related to erythropoietin usage were encountered. The need for packed cell transfusions were 47% in the group treated with erythropoietin and 62.6% in the control group. A statistically significant difference was found for transfusion needs between the control and treatment groups (P < 0.001).. Recombinant erythropoietin is effective therapy for maintaining stable hematocrit levels in low-birthweight preterm infants and prevents the need for blood transfusions.

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Prospective Studies; Recombinant Proteins

Premature infants<1500 g were randomly assigned to study and control groups. In the study group, 42 premature infants received recombinant human erythropoietin (r-Hu EPO) 750 U/kg per week subcutaneously from day 5 to 40 and enteral iron supplementation of 2 to 6 mg/kg/d beginning on day 14 provided that they were receiving at least 50% energy intake orally. In the control group, 51 infants received the same dose of enteral iron supplementation beginning at the end of the fourth week. At the end of a 12-week monitoring period, r-Hu EPO combined with early enteral iron reduced transfusion needs only in the subgroup<1000 g. r-Hu EPO and early iron treatment had no effect on the development of severe retinopathy of prematurity, intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia. We suggest that r-Hu EPO combined with early enteral iron is both effective and safe in infants<1000 g.

Topics: Anemia, Neonatal; Child Development; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Follow-Up Studies; Humans; Infant Mortality; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Injections, Subcutaneous; Male; Recombinant Proteins; Risk Assessment; Treatment Outcome

To compare the analgesic effects of non nutritive pacifier sucking, oral administration of a 30% saccharose solution, local application of Emla and their association for subcutaneous injection of erythropoietin (EPO) in preterm infants.. Our study was a randomised, prospective study conducted over 5 months. Neonates with a gestational age below 33 weeks of gestation and older than 8 days of life were included if they were treated with EPO (three subcutaneous injections per week during 6 weeks). For each consecutive EPO injection, patients were randomised between four groups of intervention: non nutritive pacifier sucking (T), oral administration of 0.2-0.5 ml of a 30% saccharose solution with non nutritive pacifier sucking (S), local application of Emla with non nutritive pacifier sucking (E), and oral administration of 0.2-0.5 ml of a 30% saccharose solution with local application of Emla and with non nutritive pacifier sucking (S + E). Each child was its own control. Pain was assessed with the Newborn Acute Pain scale (DAN) and with the Neonatal Facial Coding System (NFCS).. Thirty-three neonates were included, representing 265 injections. Distribution was: 41 in group T, 71 in group E, 86 in group S and 67 in group E + S. Mean DAN and NFCS scores were statistically different between groups T, E and S. Analgesic effect of saccharose (-1.05) was greater than Emla (-0.56). Used together, effects were adding up without potentialisation.. This study shows that the association of non nutritive pacifier sucking with oral administration of saccharose and local application of Emla has a better analgesic effect than each of these three interventions alone for subcutaneous injection of EPO.

Topics: Administration, Cutaneous; Administration, Oral; Analysis of Variance; Anesthetics, Combined; Anesthetics, Local; Combined Modality Therapy; Drug Therapy, Combination; Erythropoietin; Facial Expression; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature, Diseases; Injections, Subcutaneous; Lidocaine; Lidocaine, Prilocaine Drug Combination; Male; Pacifiers; Pain; Pain Measurement; Prilocaine; Prospective Studies; Solutions; Sucking Behavior; Sucrose; Treatment Outcome

To comprehensively identify preterm infants likely to require blood transfusion and to investigate the effectiveness of recombinant erythropoietin in this high risk subgroup.. Double blind randomised controlled trial.. Neonatal Intensive Care Unit, Middlemore Hospital, Auckland, New Zealand.. Preterm infants < 33 weeks gestation and < 1700 g birth weight meeting specific criteria indicating a high possibility of requiring blood transfusion.. Predictors of blood transfusion were determined by analysis of preterm infants admitted to a neonatal intensive care unit over a two year period. Using the criteria developed, high risk infants entered the study and received erythropoietin or sham treatment until 34 weeks completed gestation. The sample size was calculated to detect a reduction of one blood transfusion per infant (significance level 5%, power 80%).. The selection criteria had a positive predictive value for transfusion of 91% and a negative predictive value of 94%. Mean birth weights and gestational ages were similar in the two groups. Absolute reticulocyte counts and haemoglobin values were higher in the group receiving erythropoietin. There was no significant difference in the number of blood transfusions received in the treatment and control groups. However, comparing transfusions given to < 1000 g infants after 30 days of age, there were significantly fewer transfusions in the erythropoietin group (mean (SD) 0.5 (0.7) in those receiving erythropoietin and 1.6 (1.1) in the controls). No adverse effects were noted.. The selection criteria for the study were highly predictive of subsequent transfusion. In the group receiving erythropoietin, a reduction in transfusion requirements was apparent only in the < 1000 g birthweight group after 1 month of age.

Topics: Blood Cell Count; Blood Donors; Blood Transfusion; Double-Blind Method; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Recombinant Proteins

To evaluate the effects of vitamin E supplementation on haemoglobin concentration and the requirement for transfusion in premature infants treated with erythropoietin and iron.. Randomised, double blind, placebo controlled trial. Thirty infants

Topics: Anemia, Neonatal; Double-Blind Method; Erythrocyte Transfusion; Erythropoietin; Hemoglobins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Iron; Recombinant Proteins; Reticulocyte Count; Treatment Failure; Vitamin E

To compare iron sufficiency in premature infants receiving high-dose recombinant human erythropoietin (r-HuEPO), 1200 IU/kg per week, supplemented with 6 or 12 mg/kg per day of enteral iron.. We conducted a prospective, double-blind, controlled study of premature infants receiving r-HuEPO therapy, randomly assigned to receive 2 different doses of iron. Measurements of ferritin, iron, total iron-binding capacity, reticulocyte count, hemoglobin level, and hematocrit were obtained at baseline, 4, and 6 weeks. Transferrin saturation was calculated; the number of blood transfusions and the incidences of sepsis were recorded.. This study was performed in the neonatal intensive care unit at Loma Linda University Children's Hospital, Loma Linda, Calif.. Infants with a gestational age of 32 weeks or younger, older than 7 days, and receiving r-HuEPO therapy from March 1, 1997, to June 30, 1998, were eligible for the study. Infants were randomly assigned to receive 6 mg/kg per day or 12 mg/kg per day of enteral iron during a course of r-HuEPO therapy for 4 to 6 weeks.. Sixty-four infants were enrolled in the study. Twelve infants did not complete the study; 52 completed 4 weeks and 41 completed 6 weeks of the study. While ferritin levels and transferrin saturation decreased in both groups over the study period, there were no differences between the 2 study groups.. Infants receiving high-dose r-HuEPO therapy (1200 IU/kg per week) decrease their ferritin levels (measure of iron stores) even when receiving high enteral iron supplementation. Given that the ferritin levels were similar between the 2 groups, we speculate that the additional iron either was not absorbed or was not stored.

Topics: Anemia; Double-Blind Method; Drug Therapy, Combination; Erythrocyte Count; Erythropoietin; Hematocrit; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Iron

To test the efficacy and safety of combining intravenous iron in amounts approximating the in utero iron accretion rate and the postnatal iron loss with erythropoietin (EPO) in very low birth weight (VLBW) infants.. A prospective, controlled, randomized, unmasked trial lasting 21 days was performed in 29 clinically stable VLBW infants <31 weeks' gestation and <1300 g birth weight not treated with red blood cell transfusions during the study period. Mean (+/- standard error of the mean) age at study entry was 23 +/- 2.9 days. After a 3-day run-in baseline period in which all participants received oral supplements of 9 mg/kg/day of iron polymaltose complex (IPC), participants were randomized to receive 18 days of treatment with: 1) oral IPC alone (oral iron group); 2) 300 U of recombinant human EPO (r-HuEPO) kg/day and daily oral IPC (EPO + oral iron group); 3) 2 mg/kg/day of intravenous iron sucrose, r-HuEPO, and oral iron (intravenous iron + EPO group). To assess efficacy of the 3 treatments, serial blood samples were analyzed for hemoglobin (Hb), hematocrit (Hct), reticulocyte count, red blood cell indices and plasma levels of transferrin, transferrin receptor (TfR), ferritin, and iron. Oxidant injury was assessed before and after treatment by plasma and urine levels of malondialdehyde (MDA) and o-tyrosine.. At the end of treatment, Hb, Hct, reticulocyte count, and plasma TfR were markedly higher in both of the EPO-treated groups, compared with the oral iron group. At study exit a trend toward increasing Hb and Hct levels and significantly higher reticulocyte counts were observed in the intravenous iron + EPO group, compared with the EPO + oral iron group. During treatment, plasma ferritin levels increased significantly in the intravenous iron + EPO group and decreased significantly in the other 2 groups. By the end of treatment, ferritin levels were significantly higher in the intravenous iron + EPO group compared with the other 2 groups. Although plasma and urine MDA or o-tyrosine did not differ among the 3 groups, plasma MDA was significantly greater in the subgroup of intravenous iron + EPO participants sampled at the end of the 2-hour parenteral iron infusion, compared with values observed immediately before and after parenteral iron-dosing.. In stable VLBW infants receiving EPO treatment, parenteral supplementation with 2 mg/kg/day of iron sucrose results in a small, but significant, augmentation of erythropoiesis beyond that of r-HuEPO and enteral iron alone. However, to reduce the potential adverse effects of parenteral iron/kg/day on increasing plasma ferritin levels and on causing oxidative injury, we suggest that the parenteral iron dose used should be reduced and/or the time of infusion extended to maintain a serum iron concentration below the total iron-binding capacity.

Topics: Administration, Oral; Ascorbic Acid; Blood Cell Count; Drug Therapy, Combination; Erythrocyte Indices; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Ferric Compounds; Ferric Oxide, Saccharated; Glucaric Acid; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Injections, Intravenous; Iron; Malondialdehyde; Prospective Studies; Tyrosine

Topics: Anemia, Neonatal; Double-Blind Method; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins; Treatment Outcome

To assess whether a high intake of oral iron would increase the effect of recombinant human erythropoietin (rHuEPO) on hemoglobin synthesis.. We studied 30 preterm infants (gestational age 29+/-1.8 weeks, birth weight 1161+/-200 g, at age of 28+/-10 days) who were randomly assigned to receive either 8 mg/kg per day (n=15) or 16 mg/kg per day of oral iron during a course of rHuEPO therapy (900 microg/kg per week) for a duration of 4 weeks. Both groups were comparable in regard to clinical and laboratory data at the time of enrollment.. rHuEPO caused a significant increase in reticulocyte count in the low- and high-dose iron groups, 17.1+/-5.3 to 34.7+/-9.2 and 16.3+/-3.3 to 42.5+/-5.6 (10(9)/l), respectively (p<0.05). However, in both groups, hematocrit values remained stable at the end of the study as compared to baseline (0.35+/-0.03% vs. 0.30+/-0.03%, 0.35+/-0.05% vs. 0.30+/-0.03%, NS) and in both groups there was a comparable and significant decrease in ferritin level (259+/-109 to 101+/-40 and 168+/-54 to 69+/-38 microg/l, respectively; p<0.01). The rates of bloody stools without any evidence of necrotizing enterocolitis were not significantly different between the two treatment groups (1/15 vs. 4/15, NS).. We conclude that a higher dose (16 mg/kg per day) of oral iron is not more beneficial when compared to a lower dose (8 mg/kg per day) during rHuEPO therapy for anemia of prematurity. Further studies will define the optimal dosage and route of administration of iron supplementation during rHuEPO therapy.

Topics: Administration, Oral; Analysis of Variance; Anemia, Neonatal; Drug Synergism; Erythropoietin; Female; Ferritins; Hematocrit; Humans; Infant, Newborn; Infant, Premature, Diseases; Iron; Male; Recombinant Proteins

Infants of

Topics: Anemia, Neonatal; Blood Transfusion; Child Development; Erythropoiesis; Erythropoietin; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Iron; Male; Placebos

Extremely low birth weight (ELBW) infants frequently undergo transfusion because they are critically ill, often need artificial ventilation, and have the highest blood sampling loss in relation to their weight. During the last decade our transfusion guidelines were changed 3 times to become more restrictive. We hypothesized that these modifications substantially decreased the number of transfusions in our ELBW infants.. We performed a single-center analysis of 256 infants with birth weights from 500 to 999 g who were admitted from 1989 to 1997 and included 3 study periods, each starting with newly modified transfusion guidelines in April 1989, September 1991, and January 1995. We evaluated prospectively recorded clinical data and retrospective chart analysis for transfusion-related information.. The median number of transfusions per infant decreased from 7 in the first period to 2 in the third period, whereas donor exposure decreased from 5 to 1 and blood volume transfused decreased from 131 to 37 mL/kg birth weight (P <.01). The median venous hematocrit measured before transfusion decreased from 43% to 35% in infants who underwent ventilation and from 41% to 31% in spontaneously breathing infants. The median birth weight decreased from 870 to 740 g and the median gestational age from 27 to 25 completed weeks (P <.01). The overall survival rate was 75% and did not change. The incidences of retinopathy, intraventricular hemorrhage, and patent ductus arteriosus remained unchanged.. Over this 9-year period with increasingly restrictive transfusion guidelines, the transfusion number decreased by 71% and the donor exposure by 80% in ELBW infants without adverse clinical effects.

Topics: Blood Donors; Erythrocyte Transfusion; Erythropoietin; Female; Hematocrit; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Practice Guidelines as Topic; Prospective Studies; Recombinant Proteins; Survival Rate

The administration of recombinant human erythropoietin (rHuEPO), started after the first 2 weeks of life, reduces the transfusion requirement in premature infants. However, its use throughout the first 2 weeks of life, when anemia results predominantly from phlebotomy losses, remains controversial. We investigated whether early use of rHuEPO would reduce the total transfusion requirement and/or the number of transfusions throughout the first 2 weeks of life.. We randomized 114 infants with birth weight (BW) <1250 g to receive rHuEPO (1250 units/kg/week; IV; early group: n = 57) or placebo (late group: n = 57) from day 2 to day 14 of life; subsequently, all the patients received rHuEPO (750 units/kg/week, subcutaneously) for 6 additional weeks. All infants were given oral iron (6 mg/kg/day) and folic acid (2 mg/day).. The early group showed higher hematocrit and reticulocyte counts than the late group in the first 3 weeks of life, but there was no difference in the total number of transfusions (early: 1.8 +/- 2.3 vs late: 1.8 +/- 2.5 transfusion/patient) or the transfusion requirement throughout the first 2 weeks of life (early:.8 +/- 1.1 vs late:.9 +/- 1.3) could be demonstrated. In infants with BW <800 g and total phlebotomy losses >30 mL/kg (n = 29), a lower number of transfusions was received by infants in the early group, compared with late group, from the second week to the end of the treatment (early: 3.4 +/- 1.1 vs late: 5.4 +/- 3.7 transfusion/patient). No clinical adverse effects were observed. Thrombocytosis was detected during the treatment with rHuEPO in 31% of the infants.. In the whole population, the early administration of rHuEPO induced a rise of reticulocyte counts, but not enough to reduce the transfusion requirement. The most severely ill infants (BW <800 g and phlebotomy losses >30 mL/kg) seemed to benefit from early use of rHuEPO, and this deserves additional study.

Topics: Anemia, Neonatal; Blood Transfusion; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Iron; Recombinant Proteins; Time Factors

To compare the erythropoietic response between two and five times a week dosages of recombinant human erythropoietin (r-EPO) using the same weekly dose, 500 U/kg, in very low birth weight (VLBW) infants.. Eighty VLBW infants were stratified into two gestational age groups and randomized to receive 500 U/kg of r-EPO either two or five times a week; 72 infants completed at least 4 weeks of study. The primary outcome variable was absolute reticulocyte counts at 4 weeks. Secondary outcome variables were hematocrits, transfusions, iatrogenic blood losses, infections, and serum ferritins. Multiple regression analysis was used to evaluate the secondary outcome variables.. By 4 weeks, absolute reticulocyte counts were higher in the infants given r-EPO five times a week [mean (SEM)]: 173 000/mm(3) (15 000) vs 220 000/mm(3) (18 000), two versus five doses per week, respectively. Hematocrits, 34.9% (0.9) vs 34.1% (0.8), and transfusions per infant, 2.06 (0.4) vs 2.11 (0.4), were not different between the groups. Additionally, 79% of the variance in the amount of blood transfused was accounted for by iatrogenic blood loss, the latter primarily associated with number of days ventilated. Episodes of sepsis and necrotizing enterocolitis were significantly associated with decreased absolute reticulocyte counts and increased transfusions.. More frequent dosing of the same weekly amount of r-EPO produced a significant and sustained increase in stimulated erythropoiesis in VLBW infants. The importance of this finding on reducing transfusions was not able to be demonstrated because this study was not intended to differentiate transfusions. In this population of infants and at the dose level of r-EPO, iatrogenic blood loss contributed more to transfusions than a lower level of erythropoiesis, the former primarily associated with mechanical ventilation. Based on this and other studies, when VLBW infants are at risk for greater phlebotomy losses, it may be justifiable to use more vigorous r-EPO treatment, and when at lower risk to use less frequent dosing to enhance cost-effectiveness.

Topics: Anemia; Dose-Response Relationship, Drug; Erythropoietin; Female; Ferritins; Hematocrit; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Recombinant Proteins; Reticulocyte Count; Treatment Outcome

Recently, recombinant human erythropoietin (rhEPO) has been claimed to diminish red blood cell transfusions in premature infants. After a year of experience, we investigated whether early rhEPO treatment would reduce the need for transfusion.. Fifty premature infants of gestational age < or = 32 weeks admitted to our NICU in 1997, received rhEPO 750 UI/kg/week from day 3 to 5 for six weeks. They were compared with 50 untreated controls admitted in 1996.. The treatment and control groups did not differ for gestational age, weight at birth, CRIB score, and blood losses. We were not able to detect any difference in the number of transfused infants, and in the number of transfusions per infant until discharge. However, treated infants received significantly fewer transfusions per infant between day 16 and day 45 (0.42 +/- 0.67 vs. 0.8 +/- 0.99). Infants with a birth weight between 1,000-1,250 g received fewer transfusions in the EPO group.. rhEPO treatment can be useful, but in association with other procedures: conservative transfusion criteria, minimization of phlebotomy losses and early iron supplementation.

Topics: Erythrocyte Transfusion; Erythropoietin; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Male; Recombinant Proteins; Retrospective Studies; Treatment Outcome

A few years ago recombinant human erythropoietin (rh-EPO) has been introduced for the prophylaxis of anaemia of prematurity. Aim of this controlled study was a cost-effectiveness analysis of the prophylaxis with rh-EPO versus sole transfusion with packed red blood cells. In the study group 33 infants (gestational age 30 +/- 2 weeks, birthweight 1217 g +/- 244 g) were treated with rh-EPO beginning on the fifth day of life for a six week period. They received 750 IE rh-EPO/kg/week and transfusion with packed red blood cells when indicated. In the historic control group 33 infants (gestational age 29.2 +/- 1.9 weeks, birthweight 1181 g +/- 205 g) did not receive rh-EPO, patients were only transfused. Indication and guidelines for transfusion were identical for both groups. The number of transfusions was registered after 2 and 4 weeks of life and by the time of hospital discharge. The cost analysis was carried out by using current prices for packed red blood cells including material and processing and prices for rh-EPO (Neo-Recormon, Boehringer Mannheim). Infants in the study group received 1.39 +/- 1.94 transfusions per patient while patients in the control group needed 2.7 +/- 1.93 transfusions per patient (p < 0.05). Cost for treatment was slightly increased in the study group (DM 536,- vs. DM 459,-). Prophylaxis of anaemia of prematurity with recombinant human erythropoietin proved to be effective. Compared with sole blood transfusion treatment, expenses for the prophylaxis with rh-EPO were only little higher.

Topics: Anemia, Neonatal; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Recombinant Proteins

To evaluate safety and efficacy of recombinant human erythropoietin (r-HuEPO)in reducing the need for red cell transfusions in anemia of prematurity.. forty -two preterm infants (gestational age <32 weeks) were randomly assigned to a "treatment" group (r-HuEPO 400 units/kg every alternate day * 10 doses) or "no treatment" (control) group. All infants on enteral feeds received oral iron 3 mg/kg/day, graded up to 6 mg/kg/day.. Higher reticulocyte counts in week 2 and 3 and higher hemoglobin levels in week 4 were noted after treatment with r-HuEPO. Despite stumulated erythropoiesis, the frequency of transfusions could not be reduced with r-HuEPO therapy.Overall, Phlebotomy losses, frequency and volume of redcell transfusions were significantly more in neonates with birthweight <1000 grams compared with those with birthweight >1000 grams (p<0.05). Associated side effects of r-HuEPO such as neutropenia,sepsis, hypertension or increased risk of late death did not occur.. r-HuEPO therapy was safe without any side effects. Inability of r-HuEPO therapy to minimize red cell transfusions for anemia of prematurity may be explained by a relatively strict red-cell transfusion policy and the desired degree of treatment effect.

Topics: Administration, Oral; Anemia; Birth Weight; Enteral Nutrition; Erythrocyte Count; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Hypertension; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Iron; Male; Neutropenia; Phlebotomy; Recombinant Proteins; Reticulocytes; Safety; Sepsis; Survival Rate

To investigate whether a weekly 1500 IU/kg dose of recombinant human erythropoietin (rhEPO) is more effective than a dose of 750 IU/kg/week in preventing anemia and reducing the transfusion need in infants with birth weights less than 1000 gm.. In a randomized, double-blind, multicenter trial, 184 infants with birth weights between 500 and 999 gm were treated with either rhEPO 750 (low-dose group) or 1500 IU/kg/week (high-dose group) from day 3 of life until 37 weeks' corrected age.. Thirty-two percent of the infants in each group did not receive any transfusion during the treatment period. The total volume of erythrocytes received was similar in each group. The success rate, defined as no transfusion needed and hematocrit value 0.30 L/L or greater, was 27.6% in the low-dose and 29.5% in the high-dose group (p = 0.96).. Doubling the rhEPO dose of 750 IU/kg/week is not indicated in infants with birth weights less than 1000 gm.

Topics: Anemia; Blood Transfusion; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Erythropoietin; Female; Gestational Age; Hematocrit; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Iron; Male; Recombinant Proteins

Theophylline administration has been shown to attenuate erythropoietin (EP) production in adults; the effect of caffeine is not known. Our aim was to determine whether caffeine and theophylline had similar effects on EP production in the premature newborn. If caffeine was found to have a greater effect, this would influence prescribing habits. Fifty preterm infants (mean gestational age 28 weeks) who had clinically significant apnoea were randomized to receive theophylline (4 mg/kg then 2 mg/kg twice daily) or caffeine (10 mg/kg then 2.5 mg/kg once daily). The methylxanthines were continued at least until discharge from the NICU and the dosage altered to keep the levels within the therapeutic range. As an assessment of EP production, serum EP concentrations were measured. Blood for EP, haemoglobin, reticulocyte count, theophylline and caffeine levels was obtained prior to treatment and at least during weeks 3 and 7. There was no significant difference in the mean EP level in the two groups taken prior to treatment at a median age of 2 days of life. There were similar falls in haematocrit and haemoglobin in the two groups during the study period compared to pre-treatment values. At that time, however, the median reticulocyte count was higher in the caffeine compared to the theophylline treated infants (P < 0.05). This was associated with a rise compared to baseline (median 10.0-0.2 mU/ml) in the mean EP levels in the caffeine group and a decrease from a median of 10.1 to 8.3 mU/ml in the theophylline group, but the EP levels in the two groups at week 7 did not differ significantly.. These results suggest that caffeine does not have a greater impact than theophylline on EP production.

Topics: Anemia; Apnea; Caffeine; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Theophylline

To assess the efficacy and the optimum dose of recombinant human erythropoietin (rhEpo) on the anemia of premature, 45 preterm infants with a gestational age of less than 35 weeks and birth weight of less 1,800 g were randomly assigned to treatment group 1 (n = 15, receiving subcutaneous rhEpo 150 U/kg.time), treatment group 2 (n = 15, receiving 250 U/kg.time), three times a week for 6 weeks, and control group (n = 15, no treatment was given). All preterm infants received supplements of vitamin E (20 IU) and iron (20 mg) each day. Our results showed that postnatal decline of hemoglobin (Hb) and hematocrit (Hct) were lessened in the treatment groups, particularly in the group 2 and the differences were very significant (P < 0.0001 for all). Treated infants had significantly higher reticulocyte counts (Ret) (P < 0.0001 for all), but there was no significant difference between the two treatment groups (P > 0.05). Serum iron dropped significantly in the treatment groups as compared with control group (P < 0.01 for all), but no dose-dependent relationship was observed in treated infants (P > 0.05). After treatment, serum levels of erythropoietin was higher in group 2 than those in group 1 and control group (P < 0.0001, P < 0.01 and P < 0.05, respectively). There was no significant difference between group 1 and control group (P > 0.05). No side effects related to rhEpo therapy were observed. Our study suggested that rhEpo therapy stimulates endogenous erythropoiesis and enhances Ret, Hct and level of Hb in a dose-dependent manner in premature infants. The therapy is more efficient when given in higher dosages.

Topics: Anemia, Iron-Deficiency; Erythropoietin; Ferrous Compounds; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

To evaluate the role of recombinant human erythropoietin (R-HuEpo) in reducing iron infusion, which may exacerbate free radical damage, leading to chronic lung disease.. A multicentre, randomised, placebo controlled, double blind study was carried out in four neonatal intensive care units in Yorkshire. Infants were randomly allocated and received either R-HuEpo (480 U/kg/wk) or placebo by twice weekly subcutaneous injection. The primary outcome measure was the number of days on respiratory support and a secondary outcome the number of blood transfusions required.. Forty two very low birthweight (VLBW) infants were randomly allocated. There was little difference in the need for respiratory support one month after randomisation, but subsequently there was a trend towards a reduction in the proportion requiring respiratory support in the R-HuEpo group (difference at three months -0.50, 95% confidence interval -1.00, 0.17). During stay in hospital, the median number of blood transfusions was lower for infants in the R-HuEpo group (difference in medians -2, 95% CI -4, 0). The study was stopped early because of failure to recruit babies at the expected rate.. R-HuEpo seems to reduce the number of days in oxygen for ill VLBW infants. These data could be used to construct a larger multicentre study to evaluate this effect further.

Topics: Blood Transfusion; Chronic Disease; Double-Blind Method; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Iron; Lung Diseases; Oxygen Inhalation Therapy; Recombinant Proteins; Respiration, Artificial

The purpose of this study was to test the therapeutic effect of human recombinant erythropoietin (rH-EPO) on anemia of prematurity.. Fifty-eight preterm infants less than 34 weeks of gestational age from three different hospitals were studied. Transfusional policies were similar in all three centers. Infants with ABO or Rh incompatibility were excluded. At 28 days after birth, 28 infants (48.3%) had hemoglobin levels under 10.5 g/dL and were randomized to receive rH-EPO or standard care. Those infants ascribed to the treatment group received 200 U/kg of body weight of rH-EPO subcutaneously once a day, three days a week for 4 weeks together with oral supplements of ferrous sulfate at a dosage of 4 mg/kg/day. Both groups received daily doses of 50 micrograms of folic acid and 5U of vitamin E per os. Erythropoietin and ferritin were determined at randomization and at 60 days of age. Hemoglobin, reticulocytes, leucocytes, granulocytes and platelets were measured once a week, from the beginning of the treatment until 60 days of age.. At randomization into treatments, there were no significant differences between the groups with respect to weight, gestational age, hemoglobin (9.42 +/- 0.73 vs 9.26 +/- 0.68 g/dL), reticulocytes (61.7 +/- 32.2 vs 68.0 +/- 61.0 x 10(9)/L), ferritin, EPO1 leucocytes or platelets. At 60 days of age, the treatment group showed higher hemoglobin values (10.5 +/- 1.73 vs 9.1 +/- 1.0 g/dL, p < 0.05). There were no significant differences between reticulocyte counts (176.4 +/- 91.1 vs 112.6 +/- 85.0 x 10(9)/L), granulocytes (2,351 +/- 868 vs 2,075 +/- 856 x 10(9)/L), platelets (400 +/- 138 vs 316 +/- 164 x 10(9)/L) or ferritin (209 +/- 177 vs 393 +/- 328 micrograms/mL). Of the infants in the nontreated group, 13.3% received blood transfusions between 30 and 60 days of age, while only 6.7% of the treatment group did (p = 0.31).. We have been able to find 11 controlled studies in the medical literature which deal with the clinical usage of rH-EPO in newborns. Six use the hormone in an early phase and 5 in a posterior one. Our study should be included in the later and, as happens in most of them, demonstrates the efficacy of rH-EPO in the treatment of late anemia of the preterm newborn as shown by an increment in the hemoglobin levels and a trend towards the diminution in the use of blood transfusions. We have not observed substantial adverse effects.

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases

Clinical trials of erythropoietin (EPO) administration to preterm infants have not focused on infants weighing 750 gm or less, the population most likely to receive multiple transfusions because of large phlebotomy losses. It is unknown whether preterm infants weighing 750 gm or less will respond to EPO by accelerating erythropoiesis, or whether EPO administered to this population will decrease blood transfusions.. We randomly assigned 28 extremely low birth weight preterm infants (mean +/- SEM: 24.7 +/- 0.3 weeks' gestation, 662 +/- 14 gm birth weight), in the first 72 hours of life, to receive either EPO (200 U/kg/day) or placebo for 14 days and administered transfusions only according to protocol over a 21-day study period. All infants received 1 mg/kg/day iron dextran in their total parenteral nutrition solution during the 14-day treatment period.. During the 21-day study period, a lower number and volume of transfusions were received by the EPO recipients (4.7 +/- 0.7 transfusions per patient and 70 +/- 11 ml/kg per patient) than by the placebo recipients (7.5 +/- 1.1 transfusions per patient and 112 +/- 17 ml/kg per patient; p < 0.05, EPO vs placebo), whereas hematocrits remained similar in the two groups. Reticulocyte counts were similar in both groups on day 1 but were greater in the EPO recipients on day 14 (EPO day 1, 351 +/- 53; EPO day 14, 359 +/- 40 x 10(3)/microl; placebo day 1, 334 +/- 64; placebo day 14, 120 +/- 10 x 10(3)/microl; p < 0.01, EPO vs placebo). Serum ferritin concentrations were similar in both groups at the beginning of the study but were greater in the placebo recipients by day 14 (EPO, 262 +/- 44 microg/L; placebo, 593 +/- 92 microg/L; p < 0.01). No adverse effects of EPO or iron were noted.. The combination of EPO and parenteral iron stimulates erythropoiesis in preterm infants weighing 750 gm or less and results in fewer transfusions during their first 3 weeks of life.

Topics: Anemia, Hemolytic; Blood Transfusion; Combined Modality Therapy; Double-Blind Method; Erythropoietin; Ferritins; Gestational Age; Hematocrit; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Iron; Parenteral Nutrition, Total; Recombinant Proteins; Reticulocyte Count

To examine the effect of protein intake on the erythropoietic response of very low birth weight infants to treatment with recombinant human erythropoietin (rHuEPO).. Twenty very low birth weight infants were enrolled in the study and 19 completed the 6 weeks of study. Weekly absolute reticulocyte counts, protein intakes, and growth, as well as selected markers of protein metabolism--prealbumin, albumin, and transferrin--were analyzed. Iron stores were estimated for each infant to exclude iron deficiency as a cause of anemia. The relationship between protein intake and absolute reticulocyte count was evaluated with a linear breakpoint analysis to account for any plateau in the relationship at higher protein intakes.. Adequate iron stores were present in all infants, and transferrin concentrations correlated with measured total iron-binding capacity (r = 0.95, p = 0.0001). In the rHuEPO-treated infants, absolute reticulocyte count was significantly associated with protein intake up to 3.1 gm/kg per day and extending to 3.5 gm/kg per day (p = 0.041 to 0.032); beyond this point there was no longer any effect. Moreover, in comparison with the infants who received placebo, the rHuEPO-treated infants had a better daily percent weight gain for a protein intake up to 3.5 gm/kg per day (p = 0.016).. In VLBW infants treated with rHuEPO, higher protein intake up to 3.1 to 3.5 gm/kg per day improved the erythropoietic response, and protein utilization for growth was improved. During treatment with rHuEPO, infants who receive adequate protein to achieve satisfactory growth also receive sufficient protein for erythropoiesis.

Topics: Anemia, Neonatal; Dietary Proteins; Double-Blind Method; Erythropoiesis; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Recombinant Proteins

In a double-blind placebo-controlled study we showed a 3-fold decrease in blood transfusions (BTFs) given to preterm infants with anaemia of prematurity who received recombinant erythropoietin. However, only 50% of placebo recipients required a BTF. Data from the placebo group indicated that either mean daily weight gain < or = 7.5 g/day before study entry or haematocrit < or = 50% at birth was associated with BTFs (P < 0.001). We calculated that giving erythropoietin to patients in the treatment group with either of these variables prevented 24 of 28 BTFs and that it would cost R184 to prevent 1 BTF. The cost of each BTF was R187 (blood filtered to remove white cells and reduce cytomegalovirus transmission). Therefore, the costs of the two treatments were similar, but as the risk of transmitting infection is lower with erythropoietin, we recommend its use in selected preterm infants.

Topics: Anemia, Neonatal; Blood Transfusion; Combined Modality Therapy; Cost-Benefit Analysis; Double-Blind Method; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins; Treatment Outcome

The effect of recombinant human (r-Hu) erythropoietin (Epo) (300 IU/Kg per week for 4 weeks) was studied in healthy preterm infants (n = 14) fed human milk with additional milk protein and high doses of iron. The controls (n = 15) were in themselves a study group and were used to follow the natural course of anaemia of prematurity on such nutrition. Serum immunoreactive Epo (SiEpo) increased significantly 24 h after r-HuEpo injections (range 36 to > 128 mU/ml) and remained at these levels throughout the treatment period. r-HuEpo in such moderate doses kept haemoglobin above 11 g/dl. Bodyweight gain, protein and iron parameters indicated adequacy of dietary protein and iron. In controls, siEpo increased during the first weeks after nutritional supplementation, with a concommitant rise in reticulocyte count. At age 3 weeks, despite low siEpo levels, reticulocyte counts indicated active erythropoiesis. Following further moderate increases in siEpo, the reticulocyte count increased to high levels (7%). The reticulocyte response suggests that erythropoiesis in preterm infants is less dependent upon Epo levels than in adults.

Topics: Anemia, Neonatal; Combined Modality Therapy; Dietary Proteins; Erythropoietin; Ferrous Compounds; Growth; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins; Reticulocyte Count

Erythropoietin (rHuEPO) therapy has been shown to be beneficial in preventing and treating anaemia of prematurity and to decrease the need for blood transfusions. There is, however, only scanty data on the effect of rHuEPO therapy on iron metabolism. We studied 29 preterm infants (age 34 +/- 14 days) who were randomly assigned to receive either rHuEPO 900 U kg-1 week-1 with 6 mg kg-1 day-1 of iron for 4 weeks (n = 15) or no therapy. The following parameters were evaluated and compared between and within groups at the beginning, during and at the end of the study: Haematocrit (SI), reticulocytes (10(9) micrograms l-1), serum ferritin (microgram 1-1) and iron (mumol l-1). The results were as follows. At the baseline, erythropoietin levels were similar in both groups: 7.2 +/- 5.6 versus 6.2 +/- 3.2 mU ml-1 (NS). In the treated infants the haematocrit remained stable during the study and was significantly higher than in the control group by the end of the study: 0.34 +/- 0.03 versus 0.28 +/- 0.05 (p = 0.001). rHuEPO therapy increased the reticulocyte count from 130 +/- 70 to 430 +/- 200 (p = 0.0002). However, rHuEPO therapy depleted both serum ferritin and iron levels from 321 +/- 191 to 76 +/- 58 micrograms l-1 (p = 0.04) and from 18 +/- 5 to 13 +/- 4 mumol l-1 (p = 0.03), respectively. We conclude that rHuEPO therapy prevented anaemia and its sequelae; however, serum ferritin and iron levels were depleted. We suggest that the effect of rHuEPO may be further increased by higher iron supplementation.

Topics: Anemia, Neonatal; Body Weight; Combined Modality Therapy; Erythropoietin; Ferritins; Ferrous Compounds; Hematocrit; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Iron; Recombinant Proteins; Reticulocyte Count

To determine whether intravenously administered iron supplements would improve the hematologic response to recombinant erythropoietin in stable preterm infants.. Forty-two preterm infants (<33 weeks' gestation, birth weight < 1500 gm, hematocrit <38%) were treated with recombinant human erythropoietin (Eprex), 600 U/kg per week, and randomly assigned to receive either an oral preparation of ferrous lactate (elemental iron, 12 mg/kg per day) or an intravenous preparation of iron sucrose (6 mg/kg per week).. Hematocrits, reticulocyte counts, and transfusions were similar in the oral group (OG) and the intravenous group (IVG). However, markedly higher serum ferritin concentrations were noted in the IVG (p <0.001), and by completion of the study the arithmetic mean values were 265 +/- 127 microg/L versus 137 +/- 65 microg/L in the IVG and the OG, respectively. The numbers of hypochromic erythrocytes increased in both groups during the study but were significantly higher in the OG (p = 0.04). Mean daily weight gain in the IVG (27 +/- 6.4 gm/day) was greater than in the OG (22.9 +/- 4.78 gm/day; p = 0.04).. High doses of both orally administered iron and intravenously administered iron sucrose appear to supply sufficient iron for erythropoiesis in stable infants. Storage iron may become depleted after oral supplementation. The intravenous preparation appears to be safe and maintains serum ferritin concentrations, and it may be indicated for patients with low ferritin levels and for those not established on enteral feedings.

Topics: Administration, Oral; Anemia, Neonatal; Blood Cell Count; Blood Transfusion; Erythrocyte Count; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Ferric Compounds; Ferric Oxide, Saccharated; Ferritins; Ferrous Compounds; Glucaric Acid; Hematocrit; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Injections, Intravenous; Iron; Lactates; Male; Recombinant Proteins; Reticulocytes

Topics: Anemia, Neonatal; Dose-Response Relationship, Drug; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Injections, Subcutaneous; Male; Prospective Studies; Recombinant Proteins; Treatment Outcome

Twenty-four premature infants, < 32 weeks gestational age, were randomly assigned in a double-blind, placebo-controlled trial to 6 weeks of treatment with either recombinant human erythropoietin (rHuEpo) 150 U/kg three times per week given sc (n = 12) or placebo (n = 12). The infants were fed a diet rich in protein (3.2 g/kg/day) and energy (130 kcal/kg/day) based on their own mother's milk fortified with bovine protein together with moderate iron supplementation (4 mg/kg/day). During the treatment (rHuEpo versus placebo) significant differences in mean (+/- SD) reticulocyte count (4.8 +/- 1.2 versus 2.7 +/- 1.4%; p < 0.01), mean packed red cell volume (PCV) (0.38 +/- 0.03 versus 0.34 +/- 0.04, p < 0.05) and mean haemoglobin concentration (12.6 +/- 1.1 versus 11.5 +/- 1.2 g/100 ml; p < 0.05) were found. Within the rHuEpo group, PCV and haemoglobin concentration remained unaltered from entry to 1 week after cessation of treatment whereas a significant decline was observed in the placebo group. No indications of iron deficiency were seen. We conclude that moderate doses of rHuEpo given to infants fed a diet rich in protein and energy are effective in ameliorating anaemia of prematurity. High iron supplementation does not seem to be essential for a significant erythropoietic response. No adverse effect attributable to rHuEpo was observed.

Topics: Analysis of Variance; Anemia; Animals; Cattle; Double-Blind Method; Electrolytes; Erythropoiesis; Erythropoietin; Food, Fortified; Humans; Infant, Newborn; Infant, Premature, Diseases; Milk Proteins; Milk, Human; Placebos; Radioimmunoassay

Treatment with recombinant human erythropoietin (rHuEPO) stimulates erythropoiesis and reduces the need for transfusions in hospitalized preterm infants. The aim of our study was to follow very low birth weight infants after the initial 6 weeks of rHuEPO treatment.. We randomly assigned 97 very low birth weight infants with a gestational age of 31 weeks or less and birth weight of 1500 gm or less to receive rHuEPO, 300 units/kg per week (erythropoietin (EPO) 300, n = 33), rHuEPO, 750 units/kg per week (EPO 750; n = 28), or no treatment (control, n = 36). The rHuEPO was administered from the first week of life for 6 weeks. After EPO therapy was discontinued, 75 neonates were followed weekly until discharge and at 3, 6, and 12 months of age.. Mean numbers (+/- SD) of packed erythrocyte transfusions per patient from the time rHuEPO therapy was discontinued until discharge were 0.38 +/- 0.64 (EPO 300), 0.23 +/- 0.52 (EPO 750), 0.9 +/- 1.1 (control) (p < 0.05 in both EPO groups vs control). Mean reticulocyte counts at the sixth week were 6% +/- 2.2% (EPO 300), 6.9% +/- 2.2% (EPO 750), and 3.1% +/- 2.6% (control) in the three groups (p < 0.01 in both EPO groups vs control), and at the eighth week were 4.7% +/- 2.8% (EPO 300), 5.4% +/- 2.7% (EPO 750), and 2.6% +/- 2.2% (control) (p < 0.01 in both EPO groups vs control). Serum ferritin levels were significantly higher at the sixth week, and the percentage of hemoglobin F was significantly lower at 6, 8, and 10 weeks in the control group versus EPO groups. At 3, 6, and 12 months of age, there were no differences in reticulocytes, ferritin, HbF, and growth among groups.. Preterm infants who received rHuEPO had a normal pattern of erythropoiesis after the drug was discontinued. These data provide strong evidence that the anemia of prematurity is the result of a transient developmental abnormality in EPO production.

Topics: Anemia, Neonatal; Drug Administration Schedule; Erythropoiesis; Erythropoietin; Ferritins; Follow-Up Studies; Hematocrit; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins; Time Factors; Treatment Outcome

We investigated the question whether there is a difference in the response to high dose human recombinant erythropoietin (rhEPO) given twice or three times weekly in premature infants. 48 premature infants were randomly assigned to receive 300 U/kg rhEPO three times a week or 450 U/kg two times a week for at least 4 weeks and up to 6 weeks. Concomitant oral iron supplementation was compulsory, median daily dosage reached 6.6 mg/kg, doses exceeding 8 mg/kg/d were not tolerated. Our data showed no differences in the two groups in regard to hematocrit (HCT), reticulocytes and ferritin levels. A marked increase in reticulocyte counts could be observed in both groups. Serum ferritin decreased as expected. Premature infants starting with a baseline HCT lower than 32% showed a steady increase in HCT without any initial decline. No adverse effects could be observed in either group. Since there is no difference in the response to high dose rhEPO given two or three times weekly, we therefore conclude that the twice weekly regimen is compatible with outpatient treatment.

Topics: Anemia; Blood Transfusion; Erythropoietin; Hematocrit; Humans; Infant, Newborn; Infant, Premature, Diseases; Iron; Recombinant Proteins

We hypothesized that treatment with recombinant human erythropoietin (r-HuEPO) would stimulate erythropoiesis and would thereby reduce the need for erythrocyte transfusions in preterm infants. We treated 157 preterm infants born at 26.9 +/- 1.6 weeks of gestation who weighed 924 +/- 183 g at birth with either subcutaneous r-HuEPO (100 U/kg/d, 5 days per week) or placebo for 6 weeks in a randomized, double-blind, controlled clinical trial. All patients received oral iron and were managed according to uniform conservative transfusion guidelines.. Treatment with r-HuEPO was associated with fewer erythrocyte transfusions (1.1 +/- 1.5 per infant in the r-HuEPO group versus 1.6 +/- 1.7 per infant in the placebo group; P = .046) and with a reduction in the volume of packed erythrocytes transfused (16.5 +/- 23.0 mL versus 23.9 +/- 25.7 mL per infant; P = .023). Overall, 43% of the infants in the r-HuEPO group and 31% of placebo-treated infants were transfusion-free during the study (P = .18). The volume of blood removed for laboratory tests and the need for respiratory support at the start of treatment had major effects on transfusion requirements independent of r-HuEPO. Reticulocyte counts were higher during treatment in the r-HuEPO group (P = .0001), and r-HuEPO-treated infants had higher hematocrit values at the end of the study (32% versus 27.3% in the placebo group; P = .0001). We found no differences in the incidence of major complications of prematurity between the treatment groups.. We conclude that treatment with r-HuEPO at a weekly dose of 500 U/kg stimulates erythropoiesis, moderates the course of anemia, is associated with a reduction in erythrocyte transfusions, and appears safe in very low birth weight preterm infants who are receiving iron supplements. Conservative transfusion criteria, minimization of phlebotomy losses, and treatment with r-HuEPO are complementary strategies to reduce erythrocyte transfusions in these infants.

Topics: Anemia; Bloodletting; Double-Blind Method; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Hematocrit; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Logistic Models; Recombinant Proteins; Reticulocyte Count

Topics: Anemia; Bilirubin; Blood Transfusion; Carboxyhemoglobin; Double-Blind Method; Erythropoietin; Hematocrit; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Recombinant Proteins

Seventy premature infants (birthweight 1.75 kg or less, gestational age 33 weeks or less) with hemoglobin less than 10 g/dL and hematocrit less than 30% were studied and randomly divided into three groups. All of them received oral elemental iron 3 mg/kg/day and vitamin E 5 mg/kg/day during the study period. Recombinant human erythropoietin (rHuEPO) 150 U/kg was administered intravenously twice a week for 4 weeks in group A (26 infants). Infants in group A received a total of 4 erythrocyte transfusions because of frequent apnea. Infants in group B (25 infants) received erythrocyte transfusion when their hemoglobin levels was less than 10 g/dL with signs and symptoms (including tachycardia, tachypnea, poor feeding, apnea, poor weight gain) attributed to anemia or who had a hemoglobin less than 8 g/dL even if asymptomatic. Infants in group B received a total of 36 erythrocyte transfusions. Infants in group C (19 infants) were assigned to a non-rHuEPO and nontransfusion group. Three of the 19 premature infants in group C received erythrocyte transfusions later because of frequent and prolonged apneic episodes and were excluded from this study. Our data revealed that reticulocyte and serum erythropoietin values were higher (p < 0.01) in rHuEPO-treated group than transfusion group and hemoglobin and hematocrit values were lower in group C than the other two groups during the rHuEPO treatment period. No significant difference (p > 0.05) was found in neutrophil and platelet counts among these three groups. Serum ferritin values were found lower in the rHuEPO-treated group than the other two groups. Lower weight gain was found in infants in group C. We conclude that rHuEPO administration can reduce the need for blood transfusion. Poor weight gain can be found in infants with anemia of prematurity who do not receive rHuEPO or blood transfusion therapy.

Topics: Anemia, Neonatal; Erythrocyte Transfusion; Erythropoietin; Ferritins; Hematocrit; Hemoglobins; Humans; Infant, Newborn; Infant, Premature, Diseases; Iron; Leukocyte Count; Neutrophils; Platelet Count; Recombinant Proteins; Reticulocyte Count; Vitamin E

We evaluated the results of administering recombinant human erythropoietin (rHuEPO) and iron in 19 randomly selected premature infants, who had no infections, did receive oxygen support or aminophylline. rHuEPO was administered intravenously from days to 37 (biweekly) in a dose of 100 U/kg (group I) or 400 U/kg (group II). Also, infants in both groups were supplemented with 10 mg/kg/week of iron intravenously. Seven of 19 infants did not receive either rHuEPO or iron (group III). Infants of all groups had similar birth weights, gestational age and hematocrit, RBC count as well as total and fetal hemoglobin concentrations in blood obtained within the first hour of life. However, infants treated with 400 U/kg of rHuEPO required a significantly (p < 0.04) lower volume of packed erythrocytes in comparison to untreated infants, both between days 7 and 37 of life (18.6 ml vs 46.8 ml; p < 0.04) and between day 7 of life and the day of discharge (35.8 ml vs 94.2 ml; p < 0.04). No difference in neutrophil count, fetal hemoglobin concentration and no toxicity were observed in infants treated with rHuEPO in comparison to untreated prematures.

Topics: Anemia, Neonatal; Drug Administration Schedule; Erythropoietin; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Injections, Intravenous; Iron; Recombinant Proteins

The aim of this study is to evaluate how many blood transfusions can be saved by the treatment of anemia in preterm infants (eg < or = 33 weeks) with HUEPO. VLBW infants are at high risk of receiving blood transfusions, following the blood transfusion criteria most applied (45-50% of VLBW infants need blood transfusions). A review of the most recent studies shows that we can save a remarkable number and quantity of blood transfusions in the VLBW infants treated with HUEPO.

Topics: Anemia; Blood Transfusion; Erythropoietin; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Male; Recombinant Proteins

Anemia of prematurity is characterized by low reticulocyte counts and inadequate erythropoietin response, for which many very-low-birth-weight infants receive multiple blood transfusions. We investigated whether early treatment of such infants with recombinant human erythropoietin would reduce their need for transfusions.. We performed a controlled, blinded trial in 241 infants with very low birth weights at 12 centers in six European countries. When three days old, the infants were randomly assigned either to the epoetin group or to the control group. Those in the epoetin group received 250 IU of epoetin beta per kilogram of body weight subcutaneously three times a week from day 3 to day 42 (for a total of 17 doses); those in the control group did not receive this drug. Infants in both groups received oral iron (2 mg per day) from day 14 onward.. The control infants needed a mean of 1.25 transfusions each, as compared with 0.87 transfusion for epoetin-treated infants (P = 0.013). The median cumulative volume of blood transfused per kilogram per day was 0.41 ml in the control group (first quartile, 0 ml; third quartile, 0.8 ml) and 0.09 ml in the epoetin group (first quartile, 0 ml; third quartile, 0.8 ml) (P = 0.044). The rate of success, defined as an absence of need for transfusions and a hematocrit that never fell below 32 percent, was 4.1 percent in the control group and 27.5 percent in the epoetin group (P = 0.008). Epoetin was most beneficial in boys with birth weights of 1200 g or more and a base-line hematocrit of 48 percent or more. No toxic effects were observed in the epoetin group; as compared with the control group, the epoetin group had an increased incidence of septicemia (14 vs. 7 episodes, P not significant) and reduced weight gain (520 vs. 571 g, P = 0.02).. Infants with very low birth weights have less need of transfusions if given epoetin beta during the first six weeks of life (250 IU per kilogram three times a week). We recommend early epoetin treatment for all such infants, but further studies of nutrition and iron supplementation during treatment are needed.

Topics: Anemia, Neonatal; Blood Transfusion; Cost-Benefit Analysis; Erythropoietin; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Injections, Subcutaneous; Iron; Male; Recombinant Proteins; Treatment Outcome

To assess the efficacy of recombinant human erythropoietin (rHuEpo) in the treatment of the anemia of prematurity.. A double-blind, placebo-controlled study was conducted on 80 preterm infants (< or = 32 weeks; postnatal age, 2 to 8 weeks; central hematocrit < or = 35%). Patients were randomly assigned to receive subcutaneous rHuEpo (Eprex, 600 U/kg per week) or an equivalent volume of placebo, for up to 6 weeks. All patients received supplements of vitamin E (25 IU) and iron (3 mg/kg per day). The iron supplement was increased if declining serum ferritin measurements were noted.. Treatment and placebo groups did not differ significantly with respect to mean gestational age, birth weight, hematocrit, or reticulocyte count at study entry. Fewer transfusions were administered to those receiving erythropoietin (7 compared with 21; P = .002). Compared with the placebo group, the infants receiving rHuEpo had a higher mean hematocrit (32.3 +/- 4% vs 29.3 +/- 6.2%; P = .014) and absolute reticulocyte count (223 +/- 73 vs 124.9 +/- 73 x 10(9)/L; P < .001) at the end of the study. The mean neutrophil count was not significantly reduced at study exit (P = .8), nor at any other period during the trial in the rHuEpo group. Intercurrent events (mostly infections) were not increased in the treatment group, although there was one case of sudden infant death syndrome at age 4 months.. Using a dose of rHuEpo of 600 U/kg per week, this study has shown a clear reduction in the requirement for blood transfusion in preterm infants.

Topics: Anemia, Neonatal; Blood Cell Count; Blood Transfusion; Double-Blind Method; Erythropoietin; Hematocrit; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Iron; Recombinant Proteins; Vitamin E

To evaluate the costs relative to the benefits of using recombinant human erythropoietin (rHuEPO) therapy as an alternative to red blood cell (RBC) transfusions in infants with anemia of prematurity.. A cost-benefit analysis of rHuEPO therapy was performed based on its use in very-low-birth-weight premature infants.. Data were drawn from published studies or were provided by the University of Iowa Hospitals and Clinics, Iowa City.. Costs and benefits were analyzed as a comparison of incurred costs to averted costs. Incurred and averted costs of rHuEPO therapy and RBC transfusions included direct product costs and estimates of costs of adverse events. The analysis was viewed in terms of net savings. Sensitivity analysis was performed.. The base case analysis yielded a net loss of $299.48 per infant. A 54% reduction in the direct product costs of rHuEPO therapy yielded a break-even point. No other variations in the sensitivity analysis resulted in a net savings.. Using assumptions based on the current state of clinical research, it appears that routine use of rHuEPO with supplemental RBC transfusions would not generate any cost savings as an alternative to RBC transfusions alone. As further evidence is compiled on the efficacy of rHuEPO therapy in very-low-birth-weight premature infants, the true costs may be better established.

Topics: Anemia, Neonatal; Costs and Cost Analysis; Delivery of Health Care; Drugs, Investigational; Erythrocyte Transfusion; Erythropoietin; Health Care Costs; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins; Treatment Outcome

Mean erythropoietin levels were somewhat higher in premature infants receiving theophylline than in untreated infants with a comparable degree of anemia. These results differ from those in adults and may reflect the oxygenation of the theophylline-treated patients or the developmental regulation of erythropoietin production in response to adenosine receptor antagonists.

Topics: Apnea; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Theophylline

The effectiveness of recombinant human erythropoietin (r-HuEpo) in raising haemoglobin concentrations in very low birthweight infants was examined in a randomised multicentre study. Twenty nine 'healthy' appropriate for gestational age infants with birth weights 900-1400 g entered the study at 3 weeks of age. All infants received breast milk supplemented with 9 g/l human breast milk protein from 3 to 8 weeks of age. Eighteen mg iron was given daily from week 3 and was doubled if serum iron concentration fell below 16.0 mumol/l. Fourteen infants were randomised to receive 100 U/kg r-HuEpo subcutaneously three times a week from week 3 to week 7; 15 infants served as controls. After one week reticulocyte and haemoglobin concentrations were significantly higher in the r-HuEpo treated group and the haemoglobin values remained significantly higher throughout r-HuEpo treatment and at the concentrations observed in full term infants. No adverse effects were associated with the treatment. In stable very low birthweight infants with optimal iron and protein intakes, moderate dose r-HuEpo can produce significant gains in red cell production that may be clinically useful.

Topics: Anemia, Neonatal; Cell Count; Erythropoietin; Female; Hemoglobins; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Iron; Male; Proteins; Recombinant Proteins; Reticulocytes

The specific objectives of this study were (1) to assess the safety and efficacy of recombinant human erythropoietin (rhEPO) in reducing postnatal hemoglobin decline in premature infants of less than 33 weeks' gestation, and thus reducing the need for transfusion; and (2) to determine the optimal dosage of rhEPO.. Three groups of premature infants of less than 33 weeks' gestation were treated with rhEPO: group 1 (n = 10) received 300 U/kg per week; group 2 (n = 11), 600 U/kg per week; and group 3 (n = 10), 900 U/kg per week. These three groups were compared to a reference group of 20 infants of the same gestational age and birth weight. Treatment started on the 10th day of life and lasted 6 weeks. All infants were given oral iron and vitamin E supplements.. Treated infants had significantly higher reticulocyte counts, and the effect was dose dependent (P = .009). Postnatal decline of hemoglobin and hematocrit was lessened in the treated groups; the percent of decrease of hemoglobin and hematocrit was significantly reduced in the treated infants at 35 days of age (P = .0025 and P = .0036, respectively). The need for blood transfusion was also reduced in the rhEPO-treated groups: 19% of treated vs 45% of reference infants received transfusions, and the treated infants received less blood. Serum iron and transferrin saturation percentage dropped significantly during the study and a dose-dependent relationship in treated infants was displayed, suggesting high iron consumption (P = .0008 and P = .006, respectively). No dose effect on hemoglobin level and the need for blood transfusion was found, possibly because of the higher degree of illness severity and iron consumption in groups 2 and 3. No side effects related to rhEPO therapy were observed.. It is concluded that rhEPO therapy is safe in premature babies when given in the three dosages used in this study; in addition, it enhances erythropoiesis and reduces the need for blood transfusions. rhEPO therapy seems more efficient when given in higher dosages; however, illness severity and iron consumption represent major limiting factors. Controlled, randomized studies are warranted to confirm these data and to determine precise modalities and indications of rhEPO therapy in premature infants.

Topics: Anemia, Neonatal; Blood Transfusion; Dose-Response Relationship, Drug; Erythropoietin; Hematocrit; Hemoglobins; Humans; Infant, Newborn; Infant, Premature, Diseases; Iron; Pilot Projects; Recombinant Proteins

Twenty four infants between 27 and 33 weeks' gestation were recruited into a double blind study to investigate the use of recombinant human erythropoietin (r-HuEpo) for the prevention of anaemia of prematurity. Between 50 and 150 U of r-HuEpo (n = 16) or placebo was administered subcutaneously twice a week from 7 days of age until discharge. There was a significant increase in the reticulocyte count in infants receiving r-HuEpo sustained from the second week of treatment until discharge compared with placebo. There was a reduction in the number of transfusions required in the r-HuEpo group with only 47% requiring a transfusion compared with 87% in the placebo group. During treatment with r-HuEpo there was a significant rise in the red cell folate concentration, a significant fall in the ferritin concentration, and a significantly higher percentage of haemoglobin F at discharge suggesting active erythropoiesis. The study provides strong evidence for the efficacy of r-HuEpo in stimulating erythropoiesis and reducing the requirement for transfusions for anaemia of prematurity.

Topics: Anemia, Neonatal; Double-Blind Method; Drug Administration Schedule; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Injections, Subcutaneous; Male; Recombinant Proteins

There is a high level of erythropoiesis in the growing fetus. In utero relative hypoxia results in a relatively high haematocrit and predominant synthesis of haemoglobin F, with erythropoietin (EPO) produced in the liver regulating erythropoiesis. At birth after full-term pregnancy, fetal EPO concentrations are high, but decline progressively thereafter. In pre-term infants the expected postnatal decline in haemoglobin is more prolonged than in full-term infants and the premature infants may become anaemic. It has been shown in a randomized, double-blinded, placebo-controlled trial that recombinant human erythropoietin (r-HuEPO) at a dose of 100 U/kg given intravenously twice weekly for 6 weeks to infants with anaemia of prematurity produced an earlier increase in reticulocyte counts compared with placebo; however, the difference between treatments was not significant. r-HuEPO therapy did not suppress subsequent release of endogenous EPO. It is concluded that a higher dose of r-HuEPO may be required to treat anaemic premature infants.

Topics: Anemia; Erythropoiesis; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

The anemia of prematurity is defined by a progressive decline in hemoglobin level occurring over the first 2 months of life. Unlike term newborns whose "physiologic anemia" rarely if ever necessitates any treatment, preterm infants may become anemic enough to have clinical symptoms that indicate a need for red blood cell transfusions. Various factors contribute to the development of this anemia. Some of these factors, such as the short life span of erythrocytes in preterm infants, increased sensitivity of the erythrocytes to oxidative injury, and the blood losses caused by repeated phlebotomies, would normally be expected to induce corrective reticulocytosis. Characteristically, however, this anemia is hyporegenerative. Thus, it is associated with relative reticulocytopenia, low serum erythropoietin levels, and bone marrow erythroid hypoplasia. The recent availability of recombinant human erythropoietin has opened new perspectives in the management of a variety of anemias. Based on current knowledge of the regulation and pathophysiology of fetal and neonatal erythropoiesis, recombinant erythropoietin may represent a logical and efficient alternative to giving red blood cell transfusions in the treatment of the anemia of prematurity. Clinical trials have been initiated in several countries using different approaches and methodology. At this early stage these trials do not yet fully affirm that recombinant erythropoietin can be used as the first-line therapy in infants with the anemia of prematurity. Our own observations, however, suggest that this agent is well tolerated by preterm infants and may exert a corrective effect on the anemia of prematurity.

Topics: Anemia, Neonatal; Blood Cell Count; Blood Transfusion; Combined Modality Therapy; Drug Evaluation; Erythropoiesis; Erythropoietin; Hematocrit; Humans; Immunologic Factors; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Injections, Subcutaneous; Iron; Iron Deficiencies; Longitudinal Studies; Pilot Projects; Recombinant Proteins; Reticulocytes

To assess the risks and benefits of erythropoietin versus erythrocyte transfusion in the treatment of the anemia of prematurity, we randomly assigned 19 anemic preterm infants (birth weight 988 +/- 227 gm; gestational age 27.6 +/- 1.2 weeks; age 41 +/- 15 days; all values mean +/- SD) to receive either transfusion or subcutaneously administered erythropoietin (200 units/kg every other day for 10 doses). In the 10 erythropoietin recipients, corrected reticulocyte counts increased from 2% +/- 1% to 7% +/- 2% (p less than 0.001) and hematocrits increased from 27% +/- 2% to 30% +/- 4% (p less than 0.05). In the nine infants who underwent transfusion, reticulocyte counts did not increase, but hematocrits increased from 28% +/- 4% to 41% +/- 2% after initial transfusion (p less than 0.001) and had decreased to 34% +/- 5% by day 20. Signs attributed to anemia (tachycardia, apnea with bradycardia, and poor weight gain) declined in both the erythropoietin recipients and those who underwent transfusion. However, five of nine infants who underwent transfusion had symptoms within 10 to 14 days and were given further transfusions. Marrow aspiration performed after 7 to 10 days of treatment showed that infants receiving erythropoietin had greater percentages of erythropoietic precursors (p less than 0.01), greater concentrations of mature erythroid progenitors (p less than 0.001), and higher cycling rates of erythroid progenitors (p less than 0.001). The percentage of mature stored neutrophils in marrow was lower in the erythropoietin group than in the transfusion group, resulting in an inverse myeloid/erythroid ratio (0.5:1 vs 6.2:1; p less than 0.001). After 20 days, absolute blood neutrophil counts were lower in the erythropoietin recipients (1.8 +/- 0.9 x 10(3) cells/microliters) than in the infants who underwent transfusion (3.9 +/- 1.9 x 10(3) cells/microliters; p less than 0.05). Administration of erythropoietin thus stimulated erythropoiesis and relieved signs attributed to anemia; the significance of the relative neutropenia remains to be determined. We conclude that erythropoietin administration offers promise as an alternative to erythrocyte transfusion in neonates with symptomatic anemia of prematurity.

Topics: Anemia, Neonatal; Blood Cells; Blood Component Transfusion; Bone Marrow; Erythropoietin; Ferritins; Hematocrit; Hematopoietic Stem Cells; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Prospective Studies; Recombinant Proteins; Recurrence; Risk Factors

To study the safety and efficacy of administering human recombinant erythropoietin (rHuEPO) to infants with anaemia of prematurity, a combined phase I/II trial of weekly intravenous injections for 4 weeks was undertaken. We treated 16 infants with 10, 25, 50, 100 or 200 units/kg body weight in groups of two to four patients per dose level. They were all born prematurely (mean gestational age: 29 weeks; range 27-32), had a mean post-natal age of 42 days (range: 25-59) and haemoglobin concentration of 87 g/l (range: 72-94) when treatment was started. Four patients (25%) needed a transfusion during the trial, one at day 7 treated with 10 units/kg and 3 at days 15, 25, 29 with 100 units/kg. In the others, a progressive rise in mean haemoglobin values was seen in each group after 21 days of treatment, without a dose-dependent effect. A positive change in absolute reticulocyte counts with a peak after 7-14 days of therapy was observed with low (25-50 units/kg) but not with higher doses, with a significant difference at day 14 between 25 and 100 units/kg (P less than 0.01). A dose-limiting severe neutropenia (absolute neutrophil count less than 0.5 x 10(9)/l) occurred transiently in five patients, with doses greater than 25 units/kg. No infectious complication and no sign of iron deficiency were observed. Weekly low doses of rHuEPO appear safe, convenient to administer and able to induce a reticulocytic response in infants with anaemia of prematurity. A phase III placebo-controlled trial is needed to confirm these results. Neutropenia associated with rHuEPO administration in infants might be related to their stage of human ontogeny.

Topics: Anemia, Neonatal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation; Erythropoietin; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Injections, Intravenous; Iron; Neutropenia; Recombinant Proteins

Topics: Anemia; Erythropoiesis; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Recombinant Proteins

Topics: Anemia; Erythropoiesis; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Recombinant Proteins

To determine if trial-related blood sampling increases the risk of later red blood cell (RBC) transfusion in very preterm infants, we compared the volume of clinical- and trial-related blood samples, in a specific trial and correlated to subsequent RBC transfusion.. For 193 very preterm infants, participating in the FortiColos trial (NCT03537365), trial-related blood volume drawn was in accordance with ethical considerations established by the European Commission. Medical records were reviewed to assess the number and accumulated volume (mL/kg) of blood samples (both clinical- and trial-related). Data were compared with the need of RBC transfusions during the first 28 days of life.. Mean (SD) gestational age and birth weight was 28 ± 1 weeks and 1168 ± 301 g. In total, 11% of total blood volume was drawn for sampling (8.1 ± 5.1 mL/kg) and trial-related sampling accounted for 1.6 ± 0.6 mL/kg. Trial-related blood sampling had no impact on RBC transfusion (p = 0.9).. Clinical blood sampling in very preterm infants is associated with blood loss and subsequent need for RBC transfusions. In a specific trial requiring blood samples, we found no additional burden of trial-related blood sampling. The study suggests that trial-related sampling is safe if European criteria are followed.

Topics: Anemia, Neonatal; Erythrocyte Transfusion; Erythropoietin; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight

Anemia of prematurity is common in extremely preterm neonates, and oxygen exposure may participate to anemia by inhibiting erythropoietin secretion. We aimed to determine whether hyperoxia exerts an independent role in the occurrence of the anemia of prematurity.. Sprague-Dawley pups were exposed to 80% oxygen or room air from days 3 to 10 of life. Main outcome was the difference in hemoglobin and circulating erythropoietin levels in animals exposed to hyperoxia at 10 days of life. We performed a complete blood count analysis using fluorescent laser flow cytometry and measured circulating erythropoietin levels using ELISA.. We found lower hemoglobin in the hyperoxia group, compared to the normoxia group, both in males (70 ± 3 versus 78 ± 2 g/l) and in females (71 ± 2 versus 81 ± 3 g/l) at 10 days of life. Reticulocyte count was not increased in the hyperoxia group. Circulating erythropoietin levels were lower at 10 days of life in the animals exposed to hyperoxia, both in males (33 ± 7 versus 73 ± 6 pg/ml) and in females (37 ± 5 versus 66 ± 3 pg/ml), but were similar at 28 days of life.. Neonatal exposure to hyperoxia decreases hematopoiesis in rats.. Mechanisms leading to anemia of prematurity are not well known and their study in humans is complicated due to multiple confounders. This study shows for the first time that exposure to high concentrations of oxygen in the neonatal period decreases hematopoiesis in rats, providing insight on the pathophysiological mechanisms of the anemia of prematurity. This research paves the way for future therapeutic developments aiming to reduce the burden of anemia of prematurity and the necessity of red blood cell transfusions in extremely preterm neonates.

Topics: Animals; Animals, Newborn; Erythropoietin; Female; Humans; Hyperoxia; Infant, Newborn; Infant, Premature, Diseases; Male; Oxygen; Rats; Rats, Sprague-Dawley

Iron deficiency during infancy is associated with poor neurological development, but iron overload causes severe complications. Appropriate iron supplementation is therefore vital. Reticulocyte hemoglobin content (RET-He) provides a real-time assessment of iron status and chracterezes hemoglobin synthesis in preterm infants. However, the existing literature lacks detailed reports assessing chronological changes in RET-He. The aim of this study was to assess the chronological changes in RET-He during oral iron dietary supplementation, and concomitant therapy with recombinant human erythropoietin (rHuEPO) in preterm very low birthweight infants.. Very low birthweight infants, admitted to our neonatal intensive care unit were analyzed retrospectively. Hemoglobin (Hb), reticulocyte percentage (Ret), mean corpuscular volume, RET-He, serum iron (Fe), and serum ferritin were recorded. Data at birth (T0), the initial day of rHuEPO therapy (T1), the initial day of oral iron supplementation (T2), 1-2 weeks (T3), 3-4 weeks (T4), 5-6 weeks (T5), and 7-8 weeks (T6) from the initial day of oral iron supplementation were extracted, and their changes over time were examined.. Reticulocyte hemoglobin content was highest at birth and declined rapidly thereafter, especially after starting rHuEPO therapy. There was no upward trend in RET-He after the initiation of oral iron supplementation, with a slower increase during 5-6 weeks after the initiation of iron therapy.. During the treatment of anemia of prematurity, low RET-He levels may be prolonged. Anemia of prematurity should therefore be assessed and treated on a case-by-case basis, while considering the iron metabolic capacity of preterm infants.

Topics: Anemia; Anemia, Iron-Deficiency; Erythropoietin; Hemoglobins; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Iron; Reticulocytes; Retrospective Studies

Topics: Child, Preschool; Erythropoietin; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Neuroprotection; Recombinant Proteins

Endogenous erythropoietin (EPO) concentrations vary widely in preterm infants and may be associated with perinatal risk factors and neurological outcomes. Erythropoietin is elevated in fetal hypoxia but is also a potential neuroprotectant.. In a prospective study of 27 infants ≤ 30 weeks gestation, serum erythropoietin concentrations were measured during the first month of life, on day 1 and weeks 1, 2, and 4, and related to perinatal risk factors and outcomes including retinopathy of prematurity and cerebral injury evaluated near term-equivalent post menstrual age using magnetic resonance imaging with quantitative scoring.. Lower birth weight was associated with higher EPO concentrations throughout the first 2 weeks of life (r = -0.6, p < 0.01). Higher day 1 and week 1 EPO concentrations were associated with lower Apgar score at 1 minute (r = - 0.5) and 5 minutes (r = -0.7), respectively (p < 0.01). Higher day 1 EPO concentrations and 2-week area under the curve were associated with increased risk (p = 0.01) and severity (r = 0.5, p < 0.02) of retinopathy of prematurity. Higher EPO concentrations at 2 weeks were associated with increased total brain injury score (r = 0.5, p < 0.05).. Elevated endogenous erythropoietin concentrations in the first two weeks of life are associated with lower birth weight and increased risk of adverse outcomes.

Topics: Age Factors; Apgar Score; Brain Injuries; Erythropoietin; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Male; Pregnancy; Prospective Studies; Retinopathy of Prematurity

Topics: Anemia, Neonatal; Combined Modality Therapy; Erythrocyte Transfusion; Erythropoietin; Hematinics; History, 20th Century; History, 21st Century; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Iron

Topics: Books; Brain; Erythropoietin; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Magnetic Resonance Imaging; Negative Results

The aim of this study was to assess the incidence and risk factors of intraventricular hemorrhage (IVH) as well as the role of cord blood erythropoietin (EPO) level in predicting the possibility of IVH in premature neonates.. This prospective study included 140 preterm neonates born at hospitals affiliated to Shiraz University of Medical Sciences from May 2014 to April 2015. Complete blood count and cord blood EPO level was measured after birth. Brain ultrasonography was performed at 3 and 7-10 days after birth in these newborns.. Brain ultrasonography showed IVH in 8.57% (12/140) until the third day and 20% (28/140) at 7-10 days of life in premature neonates. Early gestational age, low birth weight, low Apgar score, and failure to give prenatal steroid were significant risk factors for developing IVH. The mean level of cord blood EPO was 20.95 ± 21.09 mIU/mL in premature newborns without IVH and 15.82 ± 17.11 mIU/mL with IVH. There was no correlation between the cord blood EPO and IVH in premature newborns.. Antenatal steroids therapy should be encouraged among women at risk of premature delivery. Our results showed that the cord blood EPO was not correlated with IVH in preterm neonates and further research is required to assess this relationship.

Topics: Biomarkers; Cerebral Intraventricular Hemorrhage; Erythropoietin; Female; Fetal Blood; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Prospective Studies

Thrombocytosis is more prevalent in pediatric than in adult patients and is associated with complications or worsened outcomes after vascular events. This study aimed to determine the prevalence of thrombocytosis in very preterm infants who had not received human recombinant erythropoietin treatment (rHuEPO) and its relationship with other hematological parameters and clinical complications.. We performed a retrospective study of hematological and clinical data of very preterm infants who were admitted to our unit in their first 48 hours of life and stayed for longer than 1 week.. Thrombocytosis was prevalent (32.6% of patients) in very preterm infants (≤32 weeks of gestational age, n = 193) who had not received rHuEPO. The platelet count was positively correlated with calendar age. Infants with thrombocytosis were significantly more premature (28.0 ± 2.1 versus 29.6 ± 2.2 weeks) and had a lower birth weight (1036 ± 304 versus 1303 ± 304) than those without thrombocytosis. Thrombocytosis was associated with retinopathy of prematurity after adjusting for gestational age and comorbidities, but not with other prematurity-associated complications.. Late asymptomatic thrombocytosis is common in very preterm infants at approximately 1 month of postnatal age and it may be associated with retinopathy of prematurity.

Topics: Erythropoietin; Follow-Up Studies; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Prognosis; Recombinant Proteins; Retinopathy of Prematurity; Retrospective Studies; Spain; Thrombocytosis

Strategies to prevent anaemia in preterm infants include drawing fewer blood samples, the use of recombinant human erythropoietin and iron supplementation. Although iron sulfate is the most commonly used pharmaceutical formulation for iron supplementation, there are few studies comparing different iron salts in infants.. This is a study of retrospective data comparison of two groups of preterm infants receiving erythropoietin to evaluate the efficacy of iron bisglycinate chelate to iron sulfate.. Three-hundred infants of gestational age ≤32 weeks were enrolled: 225 were supplemented with iron sulfate (3 mg/kg/day) and 75 were supplemented with iron bisglycinate chelate (0.75 mg/kg/day). The effect on erythropoiesis was assessed with a general linear model that estimates the response variables (values for Haemoglobin, Haematocrit, absolute values and percentage Reticulocytes, Reticulocyte Haemoglobin content) based on treatment, time, birth weight, and gestational age.. Supplementation with iron bisglycinate chelate at a dose of 0.75 mg/kg/day demonstrated an efficacy comparable to iron sulfate at a dose of 3 mg/kg/day in both populations of preterm infants. The two cohorts had similar erythropoietic response, without significant differences.. The higher bioavailability of iron bisglycinate chelate resulted in a lower load of elemental iron, a quarter of the dose, and achieved equivalent efficacy compared to iron sulfate. Iron bisglycinate chelate may appear to be an alternative to iron sulfate in the prevention and treatment of preterm newborn anaemia.

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Drug Therapy, Combination; Erythropoietin; Female; Ferrous Compounds; Hematinics; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Retrospective Studies; Treatment Outcome

Iron (Fe) status of neonates born to women carrying multiple fetuses might be compromised as a consequence of the high prevalence of maternal Fe deficiency and anemia coupled with an increased risk of preterm birth. This study aimed to characterize and identify determinants of anemia in this neonatal population.. Umbilical cord blood obtained from 183 neonates was utilized to assess hemoglobin (Hb), ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, serum Fe, erythropoietin, folate, vitamin B-12, C-reactive protein, and interleukin-6. Associations with maternal Fe status were explored.. Cord Hb or SF did not change significantly as a function of gestational age at birth (25-38 wks). Neonates born to women who were obese prior to pregnancy or smoked cigarettes during pregnancy had a 4-5-fold greater odds of anemia at birth. Cord sTfR was the strongest indicator of cord Hb (P < 0.0001), and it was significantly associated with maternal sTfR at mid-gestation (P = 0.01) and delivery (P = 0.002). Cord Fe indicators were significantly associated with cord hepcidin, but not maternal hepcidin.. Screening for Fe status in neonates born to women carrying multiple fetuses is warranted, especially for those born to smokers or to women who are obese at entry into pregnancy.

Topics: Adult; Anemia; Anemia, Iron-Deficiency; C-Reactive Protein; Cohort Studies; Erythropoietin; Female; Ferritins; Fetal Blood; Folic Acid; Hemoglobins; Hepcidins; Humans; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Interleukin-6; Iron; Obesity; Pregnancy; Pregnancy Complications; Pregnancy, Multiple; Premature Birth; Receptors, Transferrin; Smoking; Tobacco Use Disorder; Vitamin B 12; Young Adult

Low birthweight infants have a reduced number of nephrons and are at high risk of chronic kidney disease. Preterm birth and/or intrauterine growth restriction (IUGR) may also affect peritubular capillary development, as has been shown in other organs.. We report two patients with a history of preterm birth and extremely low birthweight who showed polycythemia and renal capillary rarefaction. Patient 1 and 2, born at 25 weeks of gestation with a birthweight of 728 and 466 g, showed mild proteinuria at age 8 and 6 years, respectively. In addition to increasing proteinuria, hemoglobin levels became elevated towards adolescence and their serum erythropoietin (EPO) was high despite polycythemia. Light microscopic examination of renal biopsy specimens showed glomerular hypertrophy, focal segmental glomerulosclerosis, and only mild tubulointerstitial fibrosis. A decrease in the immunohistochemical staining of CD31 and CD34 endothelial cells in renal biopsy specimens was consistent with peritubular capillary rarefaction.. Since kidney function was almost normal and fibrosis was not severe, we consider that the capillary rarefaction and polycythemia associated with elevated EPO levels were largely attributable to preterm birth and/or IUGR.

Topics: Adolescent; Angiotensin II Type 1 Receptor Blockers; Antigens, CD34; Apgar Score; Biopsy; Child; Endothelial Cells; Erythropoietin; Female; Fibrosis; Glomerulosclerosis, Focal Segmental; Hemoglobins; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Kidney Glomerulus; Kidney Tubules; Male; Microvascular Rarefaction; Nephrons; Platelet Endothelial Cell Adhesion Molecule-1; Polycythemia; Pregnancy; Premature Birth; Proteinuria; Valsartan

Intraventricular hemorrhage (IVH) is an important cause of death in premature infants. This study aimed to assess the association of the umbilical cord plasma levels of interleukin-6 (IL-6) and erythropoietin (EPO) with the occurrence and severity of IVH in premature infants.. Fifty premature newborns of mothers with chorioamnionitis risk factor were selected via nonprobability sampling. The concentration of the cord plasma's IL-6 and erythropoietin were measured by enzyme-linked immunosorbent assay (ELISA) for 3 days. Finally, all samples underwent sonography for the diagnosis of IVH. Results analyzed statistically.. Among the samples, 68.98% of them were diagnosed with IVH grade 1. The most severe IVH cases were detected on the second day. The mean and standard deviation of IL-6 level was 74.71 ± 50.53 in the case group and 24.10 ± 46.10 in the control group. There was a correlation between IL-6 levels and IVH (p = 0.0005). The mean and standard deviation of EPO level was 18.38 ± 15.23 in the IVH group and 6.45 ± 13.48 in samples without IVH. A correlation was detected between EPO level and IVH (p = 0.005).. The concentration of IL-6 and EPO levels of the cord plasma was higher in the premature newborns with IVH.

Topics: Biomarkers; Cerebral Intraventricular Hemorrhage; Chorioamnionitis; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Fetal Blood; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-6; Iran; Male; Pregnancy; Pregnancy Complications, Infectious; Ultrasonography; Umbilical Cord

We investigated the effects of glucocorticoids, erythropoietin (EPO) and spironolactone (SPL) n human fetal lung fibroblasts and human alveolar epithelial cells exposed to tracheal aspirate fluid (TAF) from extremely premature infants with chronic lung disease (CLD), characterized by fibrosis and changes in the alveolar epithelium.. Fibroblasts and epithelial cells (FHs 738Lu and A549, respectively) were treated with different concentrations of hydrocortisone (HDC), dexamethasone (DEX), betamethasone (BET), SPL, and EPO in the absence or presence of TAF from infants with CLD (gestational age, 25.3 ± 0.8 weeks; birthweight, 658 ± 77 g; postnatal age, 0-28 days) and assayed for proliferation.. Exposure to TAF resulted in a concentration-dependent proliferation of fibroblasts and epithelial cells. Proliferation of TAF-exposed fibroblasts was suppressed most significantly by 100 μmol/L DEX (21%, P = 0.046) and 300 mIU/mL EPO (18%, P = 0.02) and promoted most significantly by 0.4 μmol/L HDC (10%, P = 0.04). Epithelial proliferation was promoted by 4 μmol/L HDC (15%, P = 0.04), 10 μmol/L DEX (53%, P < 0.01), 0.2 μmol/L BET (56%, P < 0.01), and 300 mIU/mL EPO (35%, P < 0.01) in the presence of TAF. Treatment with glucocorticoids alone did not significantly affect fibroblast proliferation.. Glucocorticoids and EPO reduced fibroproliferation while promoting epithelial cell growth in vitro within certain dose ranges. Appropriate doses of glucocorticoids and EPO may be useful in the prevention and resolution of CLD in extremely premature infants.

Topics: Cell Proliferation; Cells, Cultured; Chronic Disease; Epithelial Cells; Erythropoietin; Female; Fibroblasts; Gestational Age; Glucocorticoids; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lung Diseases; Male; Pulmonary Alveoli; Trachea

To explore the association between concentrations of endogenous erythropoietin (EPO) in blood the first 2 weeks of life and neonatal disorders in extremely low gestational age newborns (ELGANs).. Prospective cohort study.. Neonatal care units at 14 participating hospitals in the USA.. 867 children born before the 28th week of gestation from the ELGAN study cohort.. EPO blood concentrations were measured on postnatal days 1, 7 and 14. The following neonatal characteristics and disorders were registered: blood gases, early and late respiratory dysfunction, pulmonary deterioration, retinopathy of prematurity (ROP), necrotising enterocolitis (NEC) and bronchopulmonary dysplasia (BPD). We calculated the gestational age-adjusted ORs for having each disorder associated with an EPO blood concentration in the highest or lowest quartile, compared with infants whose EPO concentration was in the middle two quartiles on the corresponding day.. Newborns whose day-1 EPO was in the highest quartile were at increased risk for early and persistent respiratory dysfunction during the first 2 weeks of life, and NEC requiring surgery. The lowest EPO quartile on day 1 was associated with a decreased risk of moderate BPD. The association between low EPO and decreased risk of respiratory complications persisted on day 7. On day 14, being in the highest EPO quartile was associated with increased risk of ROP, and BPD not requiring ventilation assistance.. EPO blood concentrations in extremely preterm newborns during the first 2 weeks of life convey information about increased risks of bowel, lung and retinal diseases.

Topics: Bronchopulmonary Dysplasia; Enterocolitis, Necrotizing; Erythropoietin; Gestational Age; Humans; Infant, Extremely Premature; Infant, Premature, Diseases; Prospective Studies; Respiratory Distress Syndrome, Newborn; Retinopathy of Prematurity; Risk Factors; Time Factors

To evaluate the incidence, onset, duration, characteristics and importance of late-onset neutropenia (defined as absolute neutrophil count<1500 μl(-1) at 3 weeks of age or later) in a group of very low birth weight (VLBW) infants.. Routine complete blood cell counts (CBCs) obtained from VLBW infants over a period of 7 years were gathered retrospectively, including those of newborns with weekly CBCs taken over a duration of at least 3 weeks. Data were obtained from between January 2003 and December 2009.. CBCs of 399 newborns were included. Values were obtained from birth to 36 weeks of postnatal age. Late-onset neutropenia was observed in 259 cases (65%). Neutropenic infants had a mean of 0.5 weeks lower gestational age. Late-onset neutropenia was more frequent in children with intraventricular hemorrhage but not in patients who received erythropoietin. The median age of neutropenia onset was 7 weeks in extremely low birth weight infants and 6 weeks in VLBW infants. The fifth percentile of neutrophils between weeks 3 and 4 was 1280 μl(-1) and between weeks 13 and 15 was 500 μl(-1). The average duration was 2 weeks with normalized values after 18 weeks.. A neutrophil count <1500 μl(-1) after the third week of life is frequently observed in VLBW infants and should not be used as a lower reference limit. The fifth percentile varies according to postnatal age from around 1300 μl(-1) in week 4 of life, decreasing to a nadir of 500 μl(-1) between 3 and 4 months of age. Values normalize in the first year of life.

Topics: Age of Onset; Cerebral Hemorrhage; Erythropoietin; Female; Humans; Incidence; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Leukocyte Count; Male; Neutropenia; Retrospective Studies

Topics: Anemia, Neonatal; Erythropoietin; Female; Hematinics; Humans; Infant, Premature, Diseases; Male

Our patient is a 26-week-old preterm female infant delivered by caesarean section secondary to severe maternal preeclampsia who had been receiving subcutaneous recombinant erythropoietin (r-EPO) for anemia of prematurity. At 8 weeks of age after 8 doses of r-EPO, the infant developed numerous non-blanching erythematous macules and patches located on the back, posterior shoulder, and posterior arms, concerning for late-onset blueberry muffin lesions. Biopsy of the lesions confirmed dermal hematopoiesis. After r-EPO was discontinued all skin lesions gradually resolved over a period of 2 weeks and never recurred.

Topics: Anemia; Dermis; Erythroblasts; Erythropoietin; Female; Fetal Growth Retardation; Hematopoiesis, Extramedullary; Humans; Infant; Infant, Premature; Infant, Premature, Diseases; Intracranial Hemorrhages; Recombinant Proteins; Respiratory Distress Syndrome, Newborn; Skin Diseases

The benefit to risk ratio of the treatment with erythropoietin (EPO) as a means of limiting the number of transfusions in very preterm infants during hospitalization, seems to be modest since the adoption of restrictive transfusion criteria and of policy limiting phlebotomy losses. We therefore aim to evaluate the factors associated with the number of late blood transfusion in very preterm infants in a unit where the routine use of EPO has been discontinued.. A comparative "before-after" study was carried out in premature infants born before 32 weeks postmenstrual age (PMA), over a period of one year before (EPO group) and one year after (non-EPO group) the discontinuation of EPO therapy.. A total of 48 infants were included in the study (EPO = 21; non-EPO = 27). The number of infants transfused after the 15 day of life (D15) and the number of transfusions per infant after D15 were not significantly different between the two groups. In a multivariate analysis, the gestational age and the volume of blood drawn off during the first month of life significantly influenced the need for transfusions after the 15th day of life, independently of the treatment with EPO. The hemoglobin levels measured at different times of hospitalization (median postnatal age: 16, 33 and 67 days) were not significantly different between the two groups.. Our study shows that the discontinuation of EPO did not change the number of late transfusions. Even when a policy limiting phlebotomy losses is used, blood loss is an important and independent risk factor for late transfusion of very preterm infants.

Topics: Anemia; Blood Transfusion; Edetic Acid; Erythropoietin; Female; Ferric Compounds; Fetal Growth Retardation; Follow-Up Studies; Gestational Age; Hemoglobins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Male; Phlebotomy; Retrospective Studies; Risk Assessment; Unnecessary Procedures

Infantile haemangiomas are benign vascular neoplasms that occur frequently in premature infants. The authors hypothesised that in addition to gestational age and birth weight, erythropoietin therapy may influence the incidence of these soft tissue tumours in preterm infants.. 2563 infants born prematurely and admitted to the Division of Neonatology, University of Heidelberg Medical School were investigated in a retrospective analysis. Hospital charts for all infants were reviewed for clinical data. The primary endpoint was the percentage of infants who had received erythropoietin treatment and were diagnosed with a haemangioma.. Haemangiomas were diagnosed in 4.3% (n=110) of the 2563 preterm infants. These 110 infants had a median gestational age of 29 weeks (IQR 27-33 weeks) and the female:male ratio was 1.8:1. A higher incidence of haemangiomas (12-15%) was detected in premature infants with a lower gestational age (<31 weeks). Erythropoietin therapy was shown to be an independent risk factor after adjusting for all other known factors and oxygen therapy in multivariable analysis (HR 2.82, 95% CI 1.55 to 5.12). Subgroup analysis revealed that the effect was more pronounced in male than female infants (HR 3.61, 95% CI 1.52 to 8.57).. This retrospective study demonstrates that erythropoietin treatment is associated with an increase in the incidence of these benign vascular tumours after adjusting for all other factors.

Topics: Birth Weight; Erythropoietin; Female; Germany; Gestational Age; Hemangioma; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Prevalence; Recombinant Proteins; Retrospective Studies

To evaluate cord blood erythropoietin (EPO) and interleukin-6 (IL-6) levels to predict preterm infants at risk of developing intraventricular hemorrhage (IVH).. Levels of umbilical cord EPO, acid-base status and IL-6 were analyzed in 116 consecutive, preterm newborns (GA at delivery: 29 [23-34 ] weeks) born to mothers who had a clinically indicated amniocentesis to rule out infection. Early-onset neonatal sepsis (EONS) was diagnosed using symptoms, hematological criteria and blood cultures.. IVH was diagnosed by cranial ultrasounds. The prevalence of IVH in our population was 25% (29/116). There was a direct relationship between cord blood EPO and cord blood IL-6 concentration (r = 0.225, p = 0.014), independent of GA at birth. Elevated cord blood EPO levels (r = 0.182, p = 0.016) and GA at birth (r =  -0.236, p = 0.004) remained significant independent factors associated with the risk of IVH, when evaluated with stepwise logistic regression analyses. Cord blood IL-6, pH, and EONS were not associated with IVH. These relationships remained following correction for GA at birth (p = 0.027).. Our results suggest that elevation in cord blood EPO may predict newborns at risk for IVH, independent of fetal inflammatory status. Further studies are warranted to confirm this association.

Topics: Adult; Biomarkers; Chorioamnionitis; Erythropoietin; Female; Fetal Blood; Humans; Infant, Newborn; Infant, Premature, Diseases; Interleukin-6; Intracranial Hemorrhages; Pregnancy; Premature Birth; Prospective Studies; Sepsis; Young Adult

Newborns and particularly preterm infants are a population at high risk of transfusion. The implementation of strategies to prevent transfusion by reducing blood loss, use of recombinant human erythropoietin, administration of iron and vitamins and delayed umbilical cord clamping have reduced the frequency of transfusions neonatal periods. The emergence of more stringent recommendations on indications for transfusion has been involved in this development. Various transformations and qualifications for red cell concentrates, platelet concentrates and fresh frozen plasma must be known to better adapt the blood products to newborn term and preterm according to their pathologies. Preparing pediatric units from a single donor for repeated transfusions reduces the allo-immune and infectious risks.

Topics: Animals; Blood Component Transfusion; Blood Grouping and Crossmatching; Blood Preservation; Blood Safety; Blood Transfusion; Constriction; Erythropoietin; Exchange Transfusion, Whole Blood; France; Gestational Age; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Newborn, Diseases; Infant, Premature; Infant, Premature, Diseases; Iron; Neonatology; Neuroprotective Agents; Practice Guidelines as Topic; Recombinant Proteins; Risk; Umbilical Cord

Topics: Brain Diseases; Child Development; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Neuroprotective Agents

Topics: Erythropoietin; Female; Fetal Diseases; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Infant, Premature, Diseases; Pregnancy

In the early weeks of life, very low birth weight (VLBW) infants experience intense laboratory blood sampling leading to clinically significant anemia and the need for red blood cell transfusion. Although controversial, treatment with recombinant human erythropoietin (EPO) and iron has been recommended to stimulate erythropoiesis; optimal dosing of EPO and iron is still uncertain.. To assess the validity of a four-quadrant diagnostic plot of iron availability (ferritin index) versus iron demand for erythropoiesis (reticulocyte hemoglobin content, CHr) for differentiating iron status in anemic VLBW infants.. Study subjects were enrolled in a previously reported randomized controlled trial of clinically stable VLBW infants <31 weeks' gestation and <1,300 g at birth to receive 18 days of treatment with: group 1: oral iron; group 2: EPO + oral iron, and group 3: EPO + intravenous + oral iron.. At the end of treatment the ferritin index was significantly higher in both EPO groups compared to the control group. By day 18, CHr of the control group declined into the quadrant of the diagnostic plot characteristic of functional iron deficiency and anemia of chronic disease. Both EPO groups ended in the quadrants that are characteristic for latent iron deficiency and iron deficiency anemia, respectively.. The diagnostic plot for differentiating anemia in VLBW infants may be an informative, clinically useful tool for iron status assessment under different physiologic and therapeutic erythropoietic states. Larger additional studies in difficult patient populations are needed before the clinical utility of this diagnostic procedure can be unequivocally confirmed.

Topics: Administration, Oral; Anemia, Iron-Deficiency; Body Weight; Drug Therapy, Combination; Erythropoietin; Ferric Compounds; Ferritins; Hemoglobins; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Injections, Intravenous; Iron; Nomograms; Randomized Controlled Trials as Topic; Recombinant Proteins; Reticulocytes

Oxygen-carrying capacity of blood is reduced in anemic infants because of low hemoglobin levels. Red blood cell transfusions become necessary if low hematocrit causes tissue hypoxia. No reliable parameters exist for detecting chronic tissue hypoxia. Vascular endothelial growth factor is upregulated by hypoxia; hence, elevated vascular endothelial growth factor levels may be a marker for tissue hypoxia and may indicate the need for red blood cell transfusions.. In a prospective study, plasma vascular endothelial growth factor levels were measured in 3 groups of infants suspected of requiring red blood cell transfusions to find a vascular endothelial growth factor cutoff value indicative of tissue hypoxia. The 3 groups were acute anemic (an episode of acute bleeding [hematocrit drop > 5%] per day); chronic anemic (hematocrit drop < 5% per day); and nontransfused (hematocrit drop < 5% per day) but not meeting clinical criteria for a transfusion. Blood was sampled before transfusion and again 48 hours after transfusion if required. Plasma vascular endothelial growth factor and erythropoietin concentrations were measured.. Vascular endothelial growth factor concentrations were lower in acutely anemic compared with chronically anemic infants, whereas erythropoietin levels did not differ between these groups. The vascular endothelial growth factor concentration was <140 pg/mL in all acutely anemic infants, and this was deemed the threshold level indicating sufficient tissue oxygenation in subsequent analysis. We found that 30% of chronically anemic and 43% of nontransfused infants had vascular endothelial growth factor levels of >140 pg/mL. In transfused infants, with elevated vascular endothelial growth factor levels, red blood cell transfusion resulted in lowering of vascular endothelial growth factor concentrations.. Vascular endothelial growth factor concentrations of >140 pg/mL may indicate insufficient oxygen delivery to tissues and may serve as a marker of the need for transfusion or of tissue hypoxia in other diseases.

Topics: Anemia, Neonatal; Biomarkers; Erythrocyte Transfusion; Erythropoietin; Female; Hematocrit; Hemorrhage; Humans; Hypoxia; Infant, Newborn; Infant, Premature, Diseases; Male; Predictive Value of Tests; Prospective Studies; Reference Values; Vascular Endothelial Growth Factor A

Holder pasteurization renders donor human milk safe for consumption. Because human milk reduces the risk of necrotizing enterocolitis in preterm infants, we tested whether Holder pasteurization affects certain factors in human milk that protect the intestines: epidermal growth factor (EGF), transforming growth factor (TGF)-beta1, erythropoietin (EPO), and interleukin (IL)-10. Donor human milk from a milk bank was examined.. The aqueous phase of 17 samples of donor term human milk (mean duration of lactation, 8 +/- 3.5 months) was examined before and after Holder pasteurization. In the case of IL-10, lesser degrees of pasteurization were also evaluated. The agents were quantified using enzyme immunoassays. The function of IL-10 was also tested.. Concentrations of EGF and IL-10 were markedly lower than previously reported values in human milk from earlier phases of lactation. Holder pasteurization significantly reduced the concentrations of EPO and IL-10, whereas lesser degrees of heating increased the detection of IL-10. The immunosuppression of T-cell proliferation by human milk, thought to be attributed to IL-10 alone, persisted after Holder pasteurization.. Holder pasteurization greatly decreased concentrations of EPO and IL-10 in human milk. These decreases may impact the ability of human milk to protect against necrotizing enterocolitis. Evidence of possible binding of IL-10 to other proteins in human milk was also found. Experiments to test whether Holder pasteurization affects the function of IL-10 in human milk produced evidence for an agent in human milk other than IL-10 that inhibits T-cell proliferation and resists Holder pasteurization.

Topics: Adult; Enterocolitis, Necrotizing; Epidermal Growth Factor; Erythropoietin; Female; Food Preservation; Hot Temperature; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Interleukin-10; Lactation; Milk, Human; Transforming Growth Factor beta1

A primary objective was to evaluate whether addition of enteral iron supplementation will facilitate a systemic erythropoietic effect when feeding erythropoietin (Epo) to suckling rats. A secondary objective was to confirm that iron does not alter the previous finding that enteral Epo exerts local trophic effects on the small intestine.. Four-day-old Sprague-Dawley rats underwent gastrostomy and were fed a cow's milk-based rat milk substitute for 8 days. We studied rats fed rat milk substitute alone (control), enteral Epo 425 U x kg(-1) x day(-1), and enteral Epo 1700 U x kg(-1) x day(-1), and the effects of oral iron sulfate (Fe) therapy (6 mg x kg(-1) x day(-1)). Blood was collected to measure hemoglobin (Hb), reticulocytes, red cell indices, and zinc protoporphyrin/heme. To confirm previous work describing trophic effects of enteral Epo on the intestine, duodenal villous height was measured.. Hb levels in control (84 +/- 1 g/L) were similar to Epo 425 (87 +/- 1 g/L). Hb levels in control+Fe (97 +/- 1 g/L), Epo 425+Fe (97 +/- 1 g/L), and Epo 1700 (94 +/- 1 g/L) were higher than control, P < 0.001, but mean Hb level in Epo 1700+Fe was higher (105 +/- 1 g/L) than the other groups, P < 0.003. Mean cell volume was higher in rats receiving iron supplementation, compared with those without iron, P < 0.005. Duodenal villous height was taller in Epo 1700+Fe compared with control + Fe, P < 0.01.. If combined with sufficient iron supplementation, high-dose Epo artificially fed to suckling rats exerted a systemic erythropoietic effect in addition to the previously reported local trophic effects.

Topics: Animals; Animals, Suckling; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Duodenum; Enteral Nutrition; Erythrocyte Indices; Erythropoiesis; Erythropoietin; Gastrostomy; Hemoglobins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Iron, Dietary; Random Allocation; Rats; Rats, Sprague-Dawley; Recombinant Proteins

The purpose of the present paper was to detect the clinical factors most predictive of red blood cell (RBC) transfusion in extremely low-birthweight (ELBW) infants in the recombinant human erythropoietin era.. Between 1995 and 2000, 66 ELBW infants were admitted to a level III neonatal intensive care unit. Fifty-four of 66 infants were eligible for enrollment in the present study. Infants were treated with erythropoietin 200 IU/kg per dose s.c. twice a week with 4-6 mg/kg per day iron supplement.. The mean gestational age and birthweight were 26.5 +/- 2.1 weeks and 776 +/- 134 g, respectively. Ten of 54 ELBW infants (18.5%) died during the first 21 days. Eight of 10 dead infants (80.0%) and 27 of 44 surviving infants (61.4%) received one or more RBC transfusions. The overall requirement for RBC transfusions in the surviving infants was 3.0 +/- 3.2 per infant/hospital course (range: 0-9) . There were significant differences in gestational weeks, birthweight, initial hemoglobin value, 5 min Apgar score, phlebotomy loss, phlebotomy loss/birthweight, duration of mechanical ventilation, duration of oxygen supplement, and incidence of both intraventricular hemorrhage and chronic lung disease between the transfused and non-transfused group. The predictive variables, initial hemoglobin level (odds ratio [OR] 2.61; 1 g/dL), birthweight (OR 3.00; 100 g), and gestational week (OR 1.89; 1 week), were found to be most predictive for transfusion on logistic regression analysis.. ELBW infants are still the population at greatest risk for repeated blood transfusions after introduction of erythropoietin treatment. If labor develops, it is often impossible to extend the pregnancy period, therefore efforts should be made to increase hemoglobin level at birth.

Topics: Algorithms; Anemia, Neonatal; Erythrocyte Transfusion; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Japan; Male; Practice Guidelines as Topic; Predictive Value of Tests; Recombinant Proteins; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome

Anaemia of prematurity is a common problem encountered in most special care baby units warranting often repeated blood transfusions with its inherent dangers. We present three patients in Nigeria who were very low birth weight premature babies on whom recombinant erythropoietin was used as an efficient replacement for blood transfusions. All three patients showed a progressive drop in haemoglobin concentration from the first to the sixth to eight week of life with development of heamic murmurs and insignificant reticulocyte responses, and were planned for transfusion therapy. The parents of all the patients strongly refused transfusion therapy (one on religious grounds) warranting the use of recombinant erythropoietin to which there was a significant response in all three patients with elevation of haemoglobin concentration, PCV, and reticulocyte counts, and obviating the planned transfusions. No significant side effects were also noticed. We suggest further controlled trials to establish this mode of therapy.

Topics: Anemia, Neonatal; Erythropoietin; Female; Hemoglobins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Nigeria; Recombinant Proteins; Reticulocyte Count

Darbepoetin is longer acting and more potent than recombinant erythropoietin (rEpo). In certain situations, preterm neonates might benefit from rEpo, and for such patients darbepoetin would require fewer doses at a lower cost. However, the proper dose and dosing interval have not been established.. We performed a prospective trial in two level III Neonatal Intensive Care Units. Patients <32 weeks gestation at birth, with a birth weight (BW) <1500 g, were eligible for participation if they were >21-days-old and had a hemoglobin (Hgb) concentration

Topics: Anemia, Neonatal; Area Under Curve; Biological Availability; Darbepoetin alfa; Erythropoietin; Half-Life; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Pilot Projects; Prospective Studies; Reticulocyte Count

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Recombinant Proteins

Topics: Blood Transfusion; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases

Topics: Blood Transfusion; Controlled Clinical Trials as Topic; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Multicenter Studies as Topic

Severe congenital myotonic dystrophy (CMD) is an autosomal dominant condition characterized by hypotonia and respiratory insufficiency at birth. Terminal outcome has been reported in infants requiring ventilation for longer than 30 days. The case is reported of an infant born at 34 weeks' gestation with severe CMD. Infant survived following ventilatory support from birth until day 67 of life. Subcutaneous erythropoietin (600 units, three times weekly) was commenced on day 6 as the Jehovah's Witness parents were strongly opposed to blood transfusions. Haemoglobin fell to 5.8 g/dL without adverse effects and then progressively rose to 15.4 g/dL. No blood transfusions were necessary. This case illustrates that infants with severe CMD requiring ventilation for more than 30 days do not have a universally fatal outcome. Low haemoglobin was well tolerated which calls for re-examination of the indications for blood transfusions in ventilated neonates.

Topics: Adult; Anemia; Blood Transfusion; Christianity; Erythropoietin; Female; Hemoglobins; Humans; Infant, Newborn; Infant, Premature, Diseases; Myotonic Dystrophy; Parents; Patient Selection; Pedigree; Prognosis; Respiration, Artificial; Severity of Illness Index; Survival Analysis; Treatment Refusal

Topics: Erythropoietin; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Neutropenia; Recombinant Proteins

In order to determine the factors responsible for eosinophilia during the neonatal period, we counted the eosinophils of premature infants every week and compared the medical profiles of infants with eosinophil counts above the 95th percentile and those below that percentile during the course of study. Medical treatments such as mechanical ventilation, antibiotics administration and intravenous catheterization had no significant effects on the increase of eosinophils. Furthermore, the incidence of eosinophil counts above the 95th percentile was not different between breast-fed and formula-fed infants. The infants treated with erythropoietin had greater eosinophil counts than those with no treatment. It is probable that medical manipulation using foreign bodies such as intratracheal tube, intravenous catheter, antibiotics and artificial formula had no significant effects on the increase of eosinophil counts, except for exogenous erythropoietin.

Topics: Disease Progression; Eosinophilia; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Intensive Care, Neonatal; Leukocyte Count; Male

Topics: Diseases in Twins; Erythropoietin; Hemangioma; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Recombinant Proteins

To evaluate the effectiveness of recombinant human erythropoietin (rH-EPO) in the prophylactic treatment of anemia of prematurity.. We performed a non-randomised, retrospective case control study of 108 premature babies with birth weights of less than 1500 grams and gestational age of less than 34 weeks. Infants with hemolytic or hemorrhagic disease and those who died in the first days of life were excluded. Fifty-four patients were treated with rH-EPO (250 U/kg subcutaneously, 3 times a week) for 6 weeks. A ferrous sulfate supplement was also administered orally (4-6 mg/kg/day) with a multivitamin complex.. There were no differences between groups in gestational age, birth weight, ferritin levels, hematocrit and hemoglobin on admission, amount of blood sampled and days with ventilatory support. The number of transfusions per patient were 1.46 +/- 1.38 in control group versus 0.69 +/- 1.19 in rH-EPO-treated infants (p < 0.002). Sixty-three percent of infants in the treated group did not require blood transfusions compared with only 29.7% in the nontreated group (p < 0.001). The lowest mean hemoglobin was 8.72 +/- 2.62 gr/dl in the control group versus 9.70 +/- 2.08 gr/dl in the rH-EPO group.. Prophylactic treatment with rH-EPO was effective in reducing the number of transfusions, mainly in stable newborn infants with a birth weight greater than 1000 grams.

Topics: Anemia, Neonatal; Case-Control Studies; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Recombinant Proteins; Retrospective Studies

Subcutaneous injection of active principles must be performed through a short and thin needle and an insuline syringe (because of the few quantity of drug to administrate). In our Centre, to prevent preterm chronic anemia wc practice subcutaneous therapy with recombinant human erythropoietin. 300 UI three times a week, to all the newborns weighing < 1500 g at birth. Injections to the newborns are performed in correspondence of their gluteal and deltoid muscles, and in the outer part of their thigh. To prevent atrophy, it is important to change every time the site of Injection. For this goal, we have created the shape of a newborn, nained Puntino, and we have located 24 points on it. Each point has received a number between 0 and 23. During the treatment we have followed the guide of Puntino to locate each time the correct site of injection. Thanks to Puntino's aid, there were no cases of skin adverse reaction and atrophy, even in newborns weighing < 1000 g.

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Injections, Subcutaneous; Recombinant Proteins

Topics: Anemia; Birth Weight; Erythropoietin; Gestational Age; Hemoglobins; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Recombinant Proteins; Risk Factors; Transfusion Reaction

Our objective was to analyze the utility of treatment with erythropoietin (EPO) plus iron in decreasing the need of late transfusions and reaching hematocrit > or = 32% in preterm infants of < or = 32 weeks of gestation.. Between March 1996 and October 1998, preterm infants of one unit were considered as the control group, while another group in another unit in the same hospital were treated with EPO (250 U/Kg, 3 times a week, subcutaneously) from day 7 of life until 37 weeks 37 post-conception. Oral iron was added to treatment one week later (5 mg/Kg, and increased in order to keep ferritin levels > 100 ng/ml). More strict transfusion criteria were established. Weights were stratified in < 1,000 g, 1,000-1,249 g and > or = 1,250 g.. Blood losses during the first 2 weeks were higher in the control group and that was probably the reason for the increased number of transfusions during the first 10 days of life. Late transfusions decreased in the EPO treated group (p < 0.0003). This was significant after the 3rd week and in the 1,000-1,249 g weight group. The EPO-treated group showed lower hematocrit < or = 32% (p < 0.001). When EPO-treated infants were separately analyzed it was clear that late transfusions were more frequent in infants that were smaller, more immature and sicker and with higher blood losses. The reticulocyte count increase was similar in both groups of late transfused vs. Not transfused EPO-treated infants, being higher at 4 weeks after EPO was started (30/1000). EPO and ferritin values were always higher in late transfused EPO-treated infants than in non-transfused infants.. The EPO plus iron treated group of preterm infants had a 40% decrease in the need for late transfusions in comparison with the control group. The best results were obtained in the 1000-1249 g group of preterm infants.

Topics: Age Factors; Anemia, Neonatal; Birth Weight; Blood Transfusion; Data Interpretation, Statistical; Erythropoietin; Gestational Age; Hematocrit; Humans; Infant, Newborn; Infant, Premature, Diseases; Iron

The effects of anemia of prematurity during bronchopulmonary dysplasia (BPD) as well as on the metabolic and erythropoietic functions were determined before and after a transfusion. Fourteen anemic (Hb range: 65-88 gm/L), oxygen dependent (fraction of inspired oxygen < or = 35%), nonventilated, preterm infants with BPD were studied at a postnatal age of 6 +/- 2 weeks.. Cardiac output, heart rate, mean velocity of circumferential fiber shortening, shortening fraction (SF), and stroke volume were assessed by pulsed and continuous wave Doppler echocardiography. Values for resting oxygen consumption, carbon dioxide production, and energy expenditure were obtained by indirect calorimetry. The affinity of oxygenated hemoglobin was determined by a blood oxygen dissociation analyzer.. An increased hemoglobin level resulted in a suppression of erythropoietin secretion (p < 0.001), whereas heart rate, cardiac output, stroke volume, and SF decreased (p < 0.05). Weight gain before and after transfusion were similar. Plasma lactate levels decreased from 1.6 +/- 0.3 to 1.2 +/- 0.3. Oxygen consumption, carbon dioxide production, and energy expenditure were not affected.. Anemia of prematurity and BPD increase heart rate, cardiac output, stroke volume, and SF. These hemodynamic compensatory responses are normalized by transfusion.

Topics: Adaptation, Physiological; Anemia, Neonatal; Blood Transfusion; Bronchopulmonary Dysplasia; Echocardiography, Doppler; Erythropoietin; Hemodynamics; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Myocardium; Oxygen Consumption; Oxygen Inhalation Therapy

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases

Topics: Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Neutropenia; Recombinant Proteins; Risk

Topics: Anemia, Neonatal; Blood Transfusion; Erythropoietin; Evaluation Studies as Topic; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Risk Factors

Topics: Anemia, Neonatal; Erythrocyte Count; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Recombinant Proteins

Topics: Erythropoietin; Fluid Therapy; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Informed Consent; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Time Factors

Iron is an important catalyst for free oxygen radicals and lipid peroxidation reactions which may play a role in the pathogenesis of several diseases in premature infants. During the early neonatal period, extracellular iron is available in excessive amounts. We hypothesized that administration of erythropoietin (EPO) mobilizes iron from plasma and inhibits iron-catalyzed reactions. To evaluate this hypothesis, recombinant human EPO (rhEPO) was administered s.c. to premature rabbits delivered at 29-d gestation: one group was kept in room air (RA) and the other in a 100% oxygen environment. Within each group, the animals were randomized to receive placebo or rhEPO at 400 or at 800 U/kg on d 0 and 2 of life. On d 3 or 4, plasma iron and iron saturation of transferrin were assessed. Lipid peroxidation was analyzed in plasma and bronchoalveolar lavage fluid (BAL). Nonsedimentable protein (NSP) and phospholipid content were measured in BAL. Erythropoiesis was evaluated in liver and bone marrow. Treatment with rhEPO decreased plasma iron, decreased iron saturation of transferrin, increased reticulocytes, and increased erythropoiesis in liver and bone marrow in both RA and hyperoxia group. Oxygen exposure increased NSP in BAL and decreased the ability of BAL to inhibit lipid peroxidation as measured by malondialdehyde (MDA) generation compared with RA exposure. In O2-exposed animals, EPO treatment increased the ability of both plasma (EPO 800) and BAL (EPO 400 and 800) to inhibit lipid peroxidation and decreased NSP in BAL (EPO 400). In addition, rhEPO treatment decreased alveolar thickening and proteinaceous exudate in the hyperoxia group. We propose that by stimulating erythropoiesis, rhEPO mobilizes non-heme iron and decreases oxidant injury that depends on the availability of transient metal.

Topics: Animals; Animals, Newborn; Antioxidants; Catalysis; Disease Models, Animal; Drug Evaluation, Preclinical; Erythropoiesis; Erythropoietin; Free Radicals; Gestational Age; Humans; Hyperoxia; Infant, Newborn; Infant, Premature, Diseases; Iron; Lung Diseases; Oxidative Stress; Rabbits; Recombinant Proteins

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Recombinant Proteins

Topics: Anemia, Neonatal; Erythrocyte Transfusion; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases

The anaemia of prematurity has been attributed to an insufficient erythropoietin (Epo) level. However, haemopoiesis is known to be regulated by a cohort of growth factors including interleukin-3 (IL-3), IL-6, stem cell factor (SCF), granulocyte monocyte-colony stimulating factor (GM-CSF) and insulin-like growth factors-I and -II (IGF-1, IGF-II). Circulating levels of these growth factors were measured in cord blood at the following gestational ages: 25-28 weeks, 29-32 weeks, 33-36 weeks and > 37 weeks. This study indicates that low concentrations of IGFs as well as a low Epo level in early gestational ages may play a role in anaemia of prematurity.

Topics: Anemia, Neonatal; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Fetal Blood; Gestational Age; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Cell Growth Factors; Humans; Infant, Newborn; Infant, Premature, Diseases; Interleukins; Somatomedins

A preterm baby, whose mother received chemotherapy for acute leukaemia during pregnancy, required intensive care because of profound anaemia and neutropenia. Haemopoietic progenitor cell studies showed fetal marrow suppression. Those caring for such mothers and babies should know the possible serious effects chemotherapy for malignancies can have on a developing fetus. Long term follow up of the baby is imperative.

Topics: Acute Disease; Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Erythropoietin; Etoposide; Female; Granulocyte Colony-Stimulating Factor; Humans; Infant, Newborn; Infant, Premature, Diseases; Leukemia, Myeloid; Neutropenia; Pregnancy; Pregnancy Complications, Neoplastic; Prenatal Exposure Delayed Effects

Topics: Anemia; Endothelins; Erythropoietin; Female; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins; Stimulation, Chemical

Three neonates (a male and two females of gestational ages 27, 27 and 29 weeks with birthweight 985, 660 and 1130 g), born to parents who are Jehovah's Witnesses, were admitted to our neonatal intensive care unit over a 2 month period in 1992. Human recombinant erythropoietin (rHuEpo, 200 u/kg sc. on alternate days for 6-8 weeks) was started early in conjunction with strict control of blood sampling in an attempt to avoid the need for blood transfusion. The lowest haemoglobin recorded was 95 g/L at 35 days of age in the first infant. The amount of blood withdrawn for sampling was 21.4 mL, 20.7 mL and 5.5 mL, respectively. All were discharged near their expected birthdate, never having received a blood transfusion in the Nursery. It is possible to manage sick, very preterm, very low birthweight neonates in a neonatal intensive care setting without the use of blood transfusions by the early use of rHuEpo in conjunction with strict control of blood sampling.

Topics: Anemia, Neonatal; Blood Transfusion; Erythropoietin; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Recombinant Proteins; Religion and Medicine

We determined the effects of anemia of prematurity on myocardial, metabolic, and erythropoietic functions. Twelve anemic (hemoglobin range, 65 to 78 gm/L) infants without symptoms (gestational age, (mean +/- SD) 28 +/- 2 weeks; birth weight, 1178 +/- 326 gm) were studied at a postconceptional age of 35 +/- 1.6 weeks. All measurements were done before and 36 to 48 hours after a transfusion of packed erythrocytes. Cardiac output, heart rate, and myocardial function were assessed. Oxygen consumption, carbon dioxide production, resting energy expenditure, arterial oxygen pressure for 50% hemoglobin saturation, and the concentrations of erythropoietin and 2,3-diphosphoglycerate were also determined. After transfusion, increased hemoglobin level (75 +/- 4 to 150 +/- 16 gm/L) and decreased oxyhemoglobin affinity (20.8 +/- 1.7 to 23.6 +/- 2.1 gm/L; p < 0.05) caused a decrease in plasma erythropoietin concentration (from 21.1 +/- 6.2 to 5.8 +/- 1.5 mU/ml; p < 0.01). There was a decrease in heart rate (from 155 +/- 10 beats/min to 146 +/- 7 beats/min) and cardiac output (from 281 +/- 73 ml/kg per minute to 199 +/- 62 ml/kg per minute; p < 0.05). Myocardial function indexes, weight gain, and metabolic demands were normal before and after transfusion. These results suggest that oxygenation is adequately maintained in symptom-free infants with anemia of prematurity.

Topics: Anemia, Neonatal; Energy Metabolism; Erythrocyte Transfusion; Erythropoietin; Heart; Hemodynamics; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Oxygen

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

Topics: Anemia; Christianity; Erythropoietin; Humans; Iatrogenic Disease; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Recombinant Proteins

Topics: Anemia; Christianity; Erythropoietin; Female; France; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Religion and Medicine

Topics: Anemia, Neonatal; Blood Transfusion; Erythropoietin; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Recombinant Proteins

Topics: Anemia, Neonatal; Clinical Trials as Topic; Conflict of Interest; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Recombinant Proteins; Sudden Infant Death

Topics: Anemia, Neonatal; Blood Transfusion; Clinical Trials as Topic; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

Pharmacokinetics of recombinant human erythropoietin (rHuEPO) were studied in a group of very low birth weight infants after both intravenous and subcutaneous administration. The volume of distribution was larger and the clearance more rapid than those reported in adults. The maximum concentration of erythropoietin after subcutaneous doses of rHuEPO was variable, but bioavailability was high (42%) compared with values reported in adults. These observations could be useful in optimizing treatment of the anemia of prematurity with rHuEPO.

Topics: Anemia, Neonatal; Biological Availability; Erythropoietin; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Injections, Intravenous; Injections, Subcutaneous; Recombinant Proteins

Recombinant human erythropoietin (rHuEPO) was administered subcutaneously three times a week to 18 infants with the anaemia of prematurity at doses of 75, 150, 300, or 600 units/kg per week for 4 weeks, starting at 3-4 weeks of postnatal age. A significant and dose-dependent increase in reticulocyte count was observed from a mean baseline value of 71 x 10(9)/l to 200 x 10(9)/l after 3 weeks of therapy, compared with a change from 69 to 97 x 10(9)/l in 66 historical controls. The haematocrit value remained unchanged during rHuEPO treatment, whereas it steadily declined until 9 weeks of postnatal age in the controls. These effects were accompanied by a marked reduction in serum iron concentration and transferrin saturation in patients receiving standard-dose iron supplements, but not in those given larger doses. Only 3 of 18 patients required a red blood cell transfusion. These infants were among the most anaemic at entry into the study and 2 of them were unable to complete rHuEPO therapy, while the third developed iron deficiency anaemia. These data indicate that rHuEPO with appropriate iron supplementation may accelerate the recovery from anaemia of prematurity. Larger scale placebo-controlled studies are now needed to confirm these findings and verify their impact on transfusion requirements of premature infants.

Topics: Anemia, Neonatal; Blood Component Transfusion; Blood Platelets; Cell Count; Erythropoiesis; Erythropoietin; Hematocrit; Humans; Infant, Newborn; Infant, Premature, Diseases; Iron; Neutrophils; Recombinant Proteins; Reticulocytes

Topics: Adult; Anemia, Neonatal; Animals; Child; Erythropoiesis; Erythropoietin; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases

A comparison was carried out between a series of neonates who weighed less than 1500 g at birth and received red cell transfusions for symptomatic anaemia of prematurity (group 1, n = 14) and controls of similar gestational age and weight, who remained well and were not transfused during their nursery stay (group 2, n = 10). Mean (SD) haemoglobin concentrations at birth were 163 (12) g/l and 183 (17) g/l (p = 0.004), respectively. Transfusion resulted in significantly better weight gain in six infants who had been growing poorly:mean (SE) 8.8 (2.8) g/day improved to 23.3 (2.1) g/day (p less than 0.002). Geometric mean (SD) serum immunoreactive erythropoietin (SiEp) concentrations (17.7 (1.3) U/l) for the whole group of infants were similar to those of normal adults (17.4 (4.7) U/l) despite considerably reduced haemoglobin values. There was a significant inverse correlation between haemoglobin and log SiEp concentrations in the infants requiring transfusion (r = -0.43; p less than 0.01), but this was not apparent in the untransfused babies. Moreover, at haemoglobin concentrations below 120 g/l the mean (SE) SiEp concentration of 20 (1.08) U/l in group 1 was significantly higher than in group 2 (14 (1.06) U/l; p = 0.002). These data suggest that an increased concentration of SiEp early in the course of the anaemia of prematurity helps to identify those infants who would benefit from red cell transfusions, but that clinical criteria, although ill defined, do so equally well.

Topics: 2,3-Diphosphoglycerate; Anemia, Neonatal; Blood Cell Count; Blood Transfusion; Chi-Square Distribution; Diphosphoglyceric Acids; Erythrocyte Transfusion; Erythropoietin; Ferritins; Hemoglobins; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Time Factors

Topics: Adult; Anemia; Clinical Trials as Topic; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

Circulating erythroid progenitors (BFU-E) in five anaemic preterm infants (haemoglobin less than 100 g/l) were about 2 and 4.4 times as abundant as in 10 preterm infants who were not anaemic and five healthy adults, respectively, and were significantly more responsive to low concentrations of recombinant human erythropoietin (rHuEpo) than those from healthy adults. These results encourage further studies in the use of rHuEpo for the treatment of the anaemia of prematurity.

Topics: Adult; Anemia, Neonatal; Dose-Response Relationship, Drug; Erythrocyte Count; Erythroid Precursor Cells; Erythropoietin; Fetal Blood; Humans; Infant, Newborn; Infant, Premature, Diseases; Recombinant Proteins

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases

We used cells from marrow aspirations that had been performed on 10 infants with the "anemia of prematurity" and tested the responsiveness of their erythroid colony-forming units (CFU-E) to recombinant human erythropoietin. For comparison, we also tested marrow-derived CFU-E from five healthy adults, and circulating CFU-E from cord blood of five healthy neonates. CFU-E from the anemic infants had a 50% maximal response at 0.073 +/- 0.024 U erythropoietin per milliliter (mean +/- SD). They were therefore at least as responsive as were CFU-E from adults, which displayed a 50% maximal response at 0.118 +/- 0.076 U/ml, and as were circulating CFU-E of cord blood origin, which had a 50% maximal response at 0.109 +/- 0.047 U/ml. Because CFU-E from infants with the "anemia of prematurity" appeared highly sensitive to erythropoietin in vitro, we propose that its administration to these patients would likely result in a significant increase in erythrocyte production in vivo.

Topics: Anemia, Neonatal; Bone Marrow; Erythropoietin; Fetal Blood; Humans; In Vitro Techniques; Infant, Newborn; Infant, Premature, Diseases; Stem Cells

Topics: Anemia; Erythropoiesis; Erythropoietin; Female; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Male

We studied erythropoiesis in infants with the anemia of prematurity by counting the number of colonies derived from erythroid burst-forming units (BFU-E) in the blood of 11 premature infants before they received transfusions. Colony growth in blood from the infants was compared with growth in blood from adults and umbilical-cord blood from term infants, in the presence of erythropoietin, 0 to 2000 mU per milliliter. Addition of increasing concentrations of erythropoietin resulted in a stepwise increase in the number of colonies derived from BFU-E (P less than 0.0005) of all three groups of subjects. Cultures stimulated with 2000 mU of erythropoietin yielded 28.1 +/- 7.6, 88.0 +/- 19.4, and 121.0 +/- 22.5 bursts (mean +/- SE) per 10(5) cells plated in blood from adults, blood from premature infants, and cord blood, respectively. Although more BFU-E-derived colonies appeared when 200 or 2000 mU were present per milliliter in cultures of the infants' blood and cord blood, the intrinsic responsiveness of BFU-E to erythropoietin was similar in all groups. Although the mean hematocrit was 26 percent, mean serum erythropoietin concentrations (+/- SD) in the infants (20.7 +/- 10.0 mU per milliliter) were not significantly different from those in the adult controls (24.0 +/- 6.5). We conclude that progenitor cells committed to erythroid differentiation are present during the anemia of prematurity, and that the intrinsic responsiveness of the circulating BFU-E pool to erythropoietin is normal. These results implicate inadequate production of erythropoietin as the cause of the anemia of prematurity and suggest that recombinant erythropoietin might provide a therapeutic alternative to transfusion for symptomatic babies with this condition.

Topics: Anemia; Blood Transfusion; Erythrocyte Count; Erythropoiesis; Erythropoietin; Globins; Hematopoietic Stem Cells; Humans; Infant, Newborn; Infant, Premature, Diseases

Topics: Anemia, Neonatal; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases

Topics: Anemia; Erythropoiesis; Erythropoietin; Humans; Hypoxia; Infant, Newborn; Infant, Premature, Diseases

This study was undertaken to determine the factors that are important in determining the erythropoietin response in low-birth-weight infants during the period of so-called anemia of prematurity. In the first weeks of life oxygen consumption in a group of 21 infants gradually increased as hemoglobin level fell. The magnitude of the erythropoietin response inversely varied with the central venous oxygen tension (P-vO2) (r = -0.55, P less than 0.001). When the P-vO2 declined to less than 30 torr, erythropoietin values were uniformly increased above the "normal" range (defined as the values associated with P-vO2 greater than 38 torr). Erythropoietin values varied inversely with hemoglobin but in general did not exceed the values observed for normal adult men. The erythropoietin values in the infants were remarkably lower at any given hemoglobin level when compared with those of older children with anemia resulting from bone marrow failure. In general, elevations of erythropoietin were seen when the hemoglobin concentration declined to less than 10.0 gm/dl. Change in heart rate did not appear to be a reliable indicator of the presence of anemia; rather, it correlated best with oxygen consumption.

Topics: Adult; Anemia; Central Venous Pressure; Erythropoietin; Heart Rate; Hemoglobins; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Oxygen Consumption

Erythropoietin, hemoglobin, hematocrit, oxygen affinity (P50), and reticulocyte counts were measured weekly starting at 1 week of age in 10 very-low-birth-weight infants and on a single occasion in 15 healthy men. In the adults, "available oxygen" (derived from oxygen carrying capacity and P50) averaged 13.1 ml/dl blood and the mean erythropoietin level was 15.2 mU/ml. Erythropoietin levels in the infants were inversely related to concentration of hemoglobin, P50, and available oxygen. However, despite the much lower mean "available oxygen" of 9.3 ml/dl in the infants compared with that in adults (P less than 0.001), the mean erythropoietin value of 8.2 mU/ml in the infants was less than in adults (P less than 0.001). Furthermore, the erythropoietin response to decreased "available oxygen" was lowest in the least mature infants. VLBW infants often develop clinical evidence of hypoxia during the anemia of prematurity. The relatively low erythropoietin levels in relation to "available oxygen" are compatible with a decreased erythropoietin response to hypoxia compared with that in adults. Such a difference in response could be a contributing factor to the anemia of prematurity.

Topics: Adult; Aging; Anemia; Blood Transfusion; Erythropoietin; Hemoglobins; Humans; Infant, Newborn; Infant, Premature, Diseases; Male; Middle Aged; Oxygen; Partial Pressure

Plasma erythropoietin concentrations were studied in 11 preterm appropriate for gestational age infants at the age of 3-14 weeks. Their birth weights ranged from 860-1 690 g. Erythropoietin was measured by a cell culture technique. Significant concentrations of erythropoietin was detected in 18 out of 29 samples, at all stages of the early anemia. The highest levels were found at 3-9 weeks. Individual erythropoietin values did not correlate with hemoglobin concentrations, hematocrit levels or 'corrected' reticulocyte counts, nor did the 'corrected' reticulocyte count correlate with hemoglobin or hematocrit. The lack of correlation with hemoglobin concentration most likely reflects the importance of other factors as well as the hemoglobin in determining the oxygenation status of the infant. A significant positive correlation (r = 0.60, p less than 0.01) was found between erythropoietin concentration and weight gain in the preceding week. The study shows that small preterm infants are capable of erythropoietin production during their early anemia, and indicates that the hormone plays a role in the regulation of erythropoiesis also at this time of life.

Topics: Anemia, Neonatal; Body Weight; Erythrocyte Count; Erythropoietin; Hemoglobins; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Reticulocytes

Erythropoietin (EPO) titres in the serum of premature infants were determined by an in vitro method using radioiron incorporation into haem in fetal mouse liver cells in culture. The serum EPO titres in 12 premature infants at birth were significantly lower than those of normal adults. In those premature infants who developed anaemia the serum EPO titres increased significantly by 4-6 weeks after birth, confirming that EPO production increases in premature infants in early days of life.

Topics: Adult; Anemia, Neonatal; Erythropoietin; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Male; Time Factors

Topics: Adult; Anemia, Neonatal; Bone Marrow; Erythrocyte Aging; Erythrocyte Count; Erythropoiesis; Erythropoietin; Female; Hematopoiesis; Hemoglobins; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Pregnancy

Topics: Adult; Anemia; Erythropoiesis; Erythropoietin; Humans; Infant, Newborn; Infant, Premature, Diseases; Oxygen Consumption

Topics: Anemia; Erythropoiesis; Erythropoietin; Fetal Hemoglobin; Humans; Hypoxia; Infant, Newborn; Infant, Premature, Diseases

Urinary erythropoietin was determined sequentially in four premature infants throughout their period of physiologic anemia. After the first day of life, no erythropoietin was found, even though there was a marked fall in hematocrit. Among seven premature infants with severe respiratory disease, three excreted elevated amounts of erythropoietin. Premature infants appear able to respond to hypoxia by increasing erythropoietin production. In the absence of hypoxia, however, diminution of erythropoiesis in the early weeks of life is not accompanied by elevated excretion of erythropoietin.

Topics: Anemia; Animals; Erythropoiesis; Erythropoietin; Female; Hematocrit; Humans; Hypoxia; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Iron Radioisotopes; Male; Mice

Topics: Adolescent; Anemia, Neonatal; Animals; Child; Child, Preschool; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Hematocrit; Hemoglobins; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Iron Radioisotopes; Mice; Polycythemia; Pregnancy

Topics: Adult; Anemia; Animals; Biological Assay; Erythrocytes; Erythropoiesis; Erythropoietin; Humans; Infant; Infant, Newborn; Infant, Premature, Diseases; Iron; Iron Radioisotopes; Male; Mice; Polycythemia