Search

Hemolytic disease of the fetus and newborn occurs when maternal IgG antibodies cross the placenta and cause hemolysis of fetal red blood cells. Kp(a) is a low frequency red blood cell antigen that has rarely been implicated in hemolytic disease of the fetus and newborn. The few reported cases attributed to anti-Kp(a) have typically had minimal clinical consequences. We report a critically ill neonate who presented with purpura, respiratory failure, severe liver dysfunction, hyperbilirubinemia, hypoglycemia and anemia. This case report broadens the spectrum of neonatal disease associated with anti-Kp(a), addresses the evaluation of hemolysis with liver failure in a neonate, and emphasizes the importance of screening for antibodies to low frequency red blood cell antigens in suspected hemolytic disease of the fetus and newborn.

Hepcidin is a regulatory peptide hormone acts by limiting intestinal iron absorption and promoting iron retention. Determining the level of hepcidin in anemia of prematurity might be important in preventing iron overload. This study aimed to determine serum levels of prohepcidin in newborns with anemia of prematurity, to assess the effect of a single erythrocyte transfusion on serum prohepcidin levels, and to determine the possible relationships between prohepcidin levels and serum iron and complete blood count parameters. Nineteen premature newborns with anemia of prematurity who had been treated with erythrocyte transfusions were included in this study. Just before, and 48 hours after, each transfusion, venous blood samples were collected from patients. Serum prohepcidin levels before and after erythrocyte transfusion were 206.5+/-27.3 and 205.7+/-47.1 ng/mL, respectively; no statistically significant differences were found. No significant differences existed before or after transfusion regarding serum total iron and ferritin levels, iron-binding capacity, or mean corpuscular hemoglobin concentration. No significant correlations existed between serum prohepcidin levels and other parameters, either before or after transfusions. Our results showed that there were no statistically significant differences between serum prohepcidin levels before and after a single erythrocyte transfusion in premature newborns.

Objective: 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., Methods: 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., Results: 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., Conclusions: 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.

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.

Background and Objective: Extremely low birth weight infants frequently receive red cell transfusions. We sought to determine whether a restrictive versus liberal hemoglobin transfusion threshold results in differences in death or adverse neurodevelopmental outcomes of extremely low birth weight infants., Patients and Methods: Extremely low birth weight infants previously enrolled in the Preterm Infants in Need of Transfusion Trial, a randomized, controlled trial of low versus high hemoglobin transfusion thresholds, were followed up at 18 to 21 months' corrected age. Erythrocyte transfusion was determined by an algorithm of low (restrictive) or high (liberal) hemoglobin transfusion thresholds, differing by 10 to 20 g/L and maintained until first hospital discharge. The primary composite outcome was death or the presence of cerebral palsy, cognitive delay, or severe visual or hearing impairment., Results: Of 451 enrolled infants, the primary outcome was available in 430. There was no statistically significant difference in the primary outcome, found in 94 (45%) of 208 in the restrictive group and 82 (38%) of 213 in the liberal group. There were no statistically significant differences in preplanned secondary outcomes. However, the difference in cognitive delay (Mental Development Index score < 70) approached statistical significance. A posthoc analysis with cognitive delay redefined (Mental Development Index score < 85) showed a significant difference favoring the liberal threshold group., Conclusions: Maintaining the hemoglobin of extremely low birth weight infants at these restrictive rather than liberal transfusion thresholds did not result in a statistically significant difference in combined death or severe adverse neurodevelopmental outcome.

Unlabelled: Infantile pyknocytosis (IP) is a rare hematological entity of newborns. It is a form of hemolytic anemia with unusual red cell morphology: the red blood cells are distorted, irregular, and small with many projections. Spontaneous resolution usually occurs by 4-6months of age., Observation: We describe the clinical features and biological parameters of 5 cases of IP. The first symptoms were always early jaundice, which required phototherapy. Anemia was severe in all babies and red blood cell transfusion was needed., Conclusion: IP is a rare cause of neonatal anemia whose diagnosis is based on a careful peripheral blood smear examination. In our study, anemia was severe and required red blood cell transfusion. Ethnic specificity and familial occurrence are reported in our experience.

Red blood cell (RBC) transfusions are administered to neonates and premature infants using poorly defined indications that may result in unintentional adverse consequences. Blood products are often manipulated to limit potential adverse events, and meet the unique needs of neonates with specific diagnoses. Selection of RBCs for small volume (5-20 mL/kg) transfusions and for massive transfusion, defined as extracorporeal bypass and exchange transfusions, are of particular concern to neonatologists. Mechanisms and therapeutic treatments to avoid transfusion are another area of significant investigation. RBCs collected in anticoagulant-additive solutions and administered in small aliquots to neonates over the shelf life of the product can decrease donor exposure and has supplanted the use of fresh RBCs where each transfusion resulted in a donor exposure. The safety of this practice has been documented and procedures established to aid transfusion services in ensuring that these products are available. Less well established are the indications for transfusion in this population; hemoglobin or hematocrit alone are insufficient indications unless clinical criteria (e.g. oxygen desaturation, apnea and bradycardia, poor weight gain) also augment the justification to transfuse. Comorbidities increase oxygen consumption demands in these infants and include bronchopulmonary dysplasia, rapid growth and cardiac dysfunction. Noninvasive methods or assays have been developed to measure tissue oxygenation; however, a true measure of peripheral oxygen offloading is needed to improve transfusion practice and determine the value of recombinant products that stimulate erythropoiesis. The development of such noninvasive methods is especially important since randomized, controlled clinical trials to support specific practices are often lacking, due at least in part, to the difficulty of performing such studies in tiny infants.

Since it was first cloned in 1985, the therapeutic potential of recombinant human erythropoietin in the neonatal hyporegenerative anaemias has been studied-the anaemia of prematurity and haemolytic disease of the newborn. Between 60% and 100% of preterm infants are transfused before three weeks of age, a large proportion receiving more than one transfusion. Blood transfusions are currently also the mainstay of treatment for the hyporegenerative anaemia encountered in neonates with Rhesus disease. Sometimes the situation is complicated by the religious beliefs of the parents. Blood transfusions are associated with numerous risks, from transmission of infection to local injury, and in an effort to minimize these risks Neonatologists have looked to recombinant erythropoietin. Despite an extensive number of studies, there is as yet no clear consensus as to whether the use of recombinant erythropoietin in Neonatal medicine minimizes the need for blood transfusions without risk to the neonate. In this article we review the evidence for and against the use of recombinant erythropoietin in Neonatal medicine.

In infants and children, elevated whole blood zinc protoporphyrin/heme (ZnPP/H) measures iron-deficient (ID) erythropoiesis. Because immature erythrocytes are less dense than mature erythrocytes, we hypothesized that the sensitivity of ZnPP/H is improved if measured in the least dense cells. Blood was collected from control suckling, mildly and severely ID suckling rats. Cord blood was collected after uncomplicated pregnancies (control), diabetic pregnancies (severe ID) and after pregnancies at-risk for iron deficiency (mild ID). ZnPP/H was measured before and after a two-step density centrifugation to obtain the lightest 6.25% of erythrocyte (top fraction). The difference between whole blood and top fraction was defined as DeltaZnPP/H. In rats, although the whole or top ZnPP/H differed by postnatal age, DeltaZnPP/H was greatest after the interval with least body iron accrual. In either rats or humans with mild ID, whole blood ZnPP/H was similar to, but DeltaZnPP/H was greater than controls. In rats and newborn humans, DeltaZnPP/H is more sensitive than whole blood ZnPP/H in identifying conditions associated with impaired erythrocyte iron delivery and may become a useful tool in measuring erythrocyte iron incorporation in early development.

Objective: Determination of factors related to the need for transfusion in premature infants., Design: Descriptive., Method: The need for transfusion in premature infants was determined in 2 academic centres: University Medical Center Utrecht and Leiden University Medical Center, The Netherlands. The data had been acquired in another study. The factors under study were: hospital, pregnancy duration, birth weight, gender, time of clamping of the umbilical cord, total volume of blood sampled for diagnostic purposes, number of days of mechanical ventilation, total duration of admission and duration of the admission to the Neonatal Intensive care unit. Both hospitals followed the national interdisciplinary practice guideline 'Blood transfusion'., Results: The total volume ofsampled blood for diagnosis, the duration of the mechanical ventilation and the admission period were related to a greater need for transfusion. On the other hand, the chance of transfusions diminished with longer pregnancy duration or increased birth weight. The difference in need for blood transfusion between both centres was significant. The total volume of transfused erythrocytes showed a strong correlation with the volume sampled for diagnostic procedures., Conclusion: Anaemia in neonates is strongly related to the amount of blood taken for diagnostic procedures. Alternatives for blood transfusions in premature infants, and consequently for the reduction of the number of donors per child, are to be sought in delayed clamping of the umbilical cord, use of erythropoietin and use ofautologous umbilical cord blood.

Objective: To evaluate the fetal, neonatal, and long-term prognosis of massive fetomaternal hemorrhage (20 mL or more)., Methods: This series includes all patients with Kleihauer test values of 40 per 10,000 or higher over an 8-year period at two university hospitals. We examined obstetric, neonatal, and subsequent outcome data for the children., Results: During the study period, 48 patients had massive fetomaternal hemorrhage (crude incidence 1.1 per 1,000; corrected incidence for Rh-negative women 4.6 per 1,000). Six fetal deaths were observed, representing 1.6% of all fetal deaths during the period. Nine newborns (18.7%) were transferred to neonatal intensive care unit (NICU) and five (10.4%) had transfusions. Fetomaternal hemorrhages of 20 mL/kg or more significantly increased the risk of fetal death, induced preterm delivery, transfer to NICU, and neonatal anemia requiring transfusion. Long-term follow-up was not associated with neurological sequelae (0%, 95% confidence interval 0.0-11.6%)., Conclusion: When the transfused volume equals or exceeds 20 mL/kg, massive fetomaternal hemorrhage may lead to severe prenatal or neonatal complications., Level of Evidence: III.

Aim: 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., Methods: 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., Results: 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., Conclusion: 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.

Objective: To study the effects of recombinant human erythropoietin (rHuEpo) in preterm newborns (PTNs) with serious infectious diseases., Methods: A not randomized case-control study was carried out in 34 preterm newborns with diagnosis of serious infectious pathologies, gestational age up to 35 weeks, birth weight less than 1500 g and clinical stability. Newborns selected for treatment with rHuEpo received 400 U/kg erythropoietin ss, subcutaneously twice a week. Oral iron supplementation was initiated when the levels of serum ferritin were lower than 60 mcg/l. The study was continued for six weeks or until the patient was discharged from the hospital. Erythropoiesis, granulopoiesis, thrombocytopoiesis, the need for transfusions and the occurrence of new episodes of infectious disease were analyzed., Results: In the treated group there was a significant increase in the number of reticulocytes, although there was no statistically significant difference between the groups with regard to the number or volume of transfusions. There was no significant difference in neutrophils and platelet values., Conclusion: The use of rHuEpo, 800 U/kg/week, in PTNs with infectious diseases was effective in inducing erythropoiesis, without significant changes in the number of neutrophils or platelets. This strategy, and the accurate control of the blood collected for laboratory exams, may be beneficial for prevention of the anemia in PTNs with serious infectious diseases.

Aim: The aim of the present study is to define criteria for erythropoietin therapy of hyporegeneratory anemia in premature newborns according to hemoglobin (Hb) and hematocrit (Hct) concentration, and reticulocyte count (Ret)., Materials and Methods: The prospective study includes two groups of 20 newborns with anemia of prematurity, body weight at birth below 1500 grams and gestation age below 33 gestation week. The newborns in the first group have been treated with beta-erythropoietin for four weeks--750-1000 E/kg weekly dose, divided q48h. Hb, Hct and Ret have been monitored and compared with that of control group newborns. The therapy of newborns in the control group consisted of blood transfusions., Results: The hematological parameters in the newborns from the first group have been increased permanently after the first week of therapy, with Ret being most sensitive to the therapy. In the second group of newborns, due to blood transfusions, transient increase of Hb and Hct, and decrease of Ret have been observed in next days after the blood transfusions., Conclusions: The erythropoietin therapy of hyporegeneratory anemia in preterm newborns leads to rise in Hb, Hct and Ret. The therapy with blood transfusions suppresses erythropoiesis. This leads to decrease in Ret and transient rise in Hb, Hct and erythrocytes. That's why each blood transfusion leads to another one.

Objective: Erythropoietin (EPO) is commonly used in very low birth weight neonates to minimize blood transfusions during hospitalization. Data are limited comparing the use of EPO along with a restricted transfusion schedule versus a restricted transfusion schedule alone. We compared the effects of a restricted transfusion schedule with EPO versus a restricted transfusion schedule alone during two consecutive 6-month periods., Methods: In period I, infants born at <30 weeks gestational age (GA) or <1,500 g birth weight (BW) were treated prophylactically for six weeks with EPO 1,000 U/kg/wk in three divided doses and blood transfusions were given using a restricted transfusion schedule. This was the called the EPO Group. In period II, a restricted transfusion schedule was utilized, but EPO was not administered. This constituted the No EPO Group. No other changes in clinical practice were introduced in either period., Results: There were 30 neonates in the EPO Group and 20 in the No EPO Group. There were no significant differences in sex, race, mean birth weight (1,074 +/- 283 versus 965 +/- 330 g), mean gestational age (28.9 +/- 2.96 versus 27.8 +/- 2.86 wks), 5 minute Apgar score (7.8 +/- 1.2 versus 7.6 +/- 1.1), or mean hematocrit (48.2% +/- 6.05 versus 48.6% +/- 6.31) at admission. There were no significant differences in the total number of transfusions between the two periods. In the EPO Group, 8/30 patients received 27 transfusions. Six transfusions violated guidelines based on hematocrit level. EPO was discontinued in three infants secondary to treatment-related neutropenia. There were two deaths unassociated with EPO treatment. Excluding deaths, 6 patients received 16 transfusions. In the No EPO Group, 8/20 patients received 13 transfusions. Two transfusions violated guidelines based on hematocrit. There were three deaths and one patient transfer. Excluding these four patients, 6 infants received 11 transfusions (P < or = 1.) Among survivors, there were no significant differences in mean total length of stay (49.3 +/- 22.7 versus 53.2 +/- 26.4 d), mean discharge weight (2,144 +/- 405 versus 2,358 +/- 458 g), or average weight gain/d (20.7 +/- 5.44 versus 22.6 +/- 6.81 g), between the two groups respectively, nor were there significant differences when all babies were included in the analysis. There was a significant difference in mean hematocrit at discharge, respectively, (38.3% +/- 6.84 versus 31.4% +/- 6.26; P = 0.003) in survivors., Conclusions: A restricted transfusion schedule without EPO use was associated with lower mean hematocrit at discharge, but not with an increased frequency of transfusions, nor significant differences in length of stay, discharge weight, or average daily weight gain. A restricted transfusion schedule alone avoided side effects and costs associated with EPO. Indications for transfusion and what constitutes appropriate levels of hemoglobin still require clinical investigation, including long-term clinical outcomes.

Background: Hematocrit falls after birth in preterm infants due to physiological factors and blood letting. Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anemia., Primary Objective: To assess the effectiveness and safety of early initiation of EPO (initiated before eight days after birth) in reducing red blood cell transfusions in preterm and/or low birth weight infants., Secondary Objectives: Subgroup analyses of low (< 500 IU/kg/week) and high (> 500 IU/kg/week) doses of EPO and, within these subgroups, analyses of the use of low (< 5 mg/kg/day) and high (> 5 mg/kg/day) doses of supplemental iron, in reducing red blood cell transfusions in these infants., Search Strategy: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, EMBASE, CINAHL, abstracts from scientific meetings published in Pediatric Research and reference lists of identified trials and reviews were searched in November 2005. No language restrictions were applied., Selection Criteria: Randomised or quasi-randomized controlled trials of early initiation of EPO treatment (started before 8 days of age) vs. placebo or no intervention in preterm (< 37 weeks) and/or low birth weight (< 2500 g) neonates. For inclusion, the studies needed to provide information on at least one outcome of interest., Data Collection and Analysis: Data were abstracted by the two authors on pre-tested data collection forms. Data were entered by one review author (AO) and checked for accuracy by the other (SA). Data were analysed using RevMan 4.2.8. The statistical methods included 'typical' relative risk (RR), risk difference (RD), number needed to treat to benefit (NNTB) and needed to treat to harm (NNTH) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes reported with their 95% confidence intervals (CI). A fixed effects model was used for meta-analyses. Heterogeneity tests, including the I(-)squared (I(2)) statistic, were performed to assess the appropriateness of pooling the data., Main Results: Twenty-three studies enrolling 2074 preterm infants in 18 countries were included in the review. All studies except one applied transfusion guidelines. The quality of the trials varied. Most trials were of small sample size. Only one study clearly stated that infants were excluded if they had received red blood cell transfusion prior to study entry (Arif 2005). A total of 16 studies, including 1825 infants reported on the primary outcome of "use of one or more red cell transfusions". The summary estimates were significant [typical RR; 0.80 (95% CI 0.75, 0.86); typical RD; -0.13 (95% CI -0.17, -0.09); typical NNTB; 8 (95% CI 6, 11)]. There was statistically significant heterogeneity [for RR (p< 0.004), I(2) = 56.7%; for RD (p = 0.003), I(2 ) = 56.0%]. Similar results were obtained in secondary analyses based on different combinations of high doses of EPO and high and low iron supplementation. There were insufficient data to draw conclusions for low doses EPO in combination with high or low dose of iron. Two studies (n = 188) reported a significant reduction in the number of donors to whom the infant was exposed [typical WMD; -0.63 (95% CI -1.07, -0.19)]. A significant reduction in the total volume (ml/kg) of blood transfused per infant [typical WMD; -6 ml (95% CI -1, -11)] and in the number of transfusions per infant [typical WMD -0.27 (95% CI -0.12, -0.42 )] was noted. There was a significant increase in the risk of stage > 3 retinopathy of prematurity (ROP) in the EPO group [typical RR; 1.71 (95% CI 1.15, 2.54); typical RD; 0.05 (95% CI 0.01, 0.09); NNTH; 20 (95% CI 11, 100)]. The non-significant results for ROP (any stage reported) showed a similar trend. The increased risk for ROP may be associated with use of higher doses of supplemental of iron in the EPO group than in the control group. The rates for mortality, sepsis, intraventricular haemorrhage, periventricular leukomalacia, necrotizing enterocolitis, bronchopulmonary dysplasia, neutropenia, hypertension, length of hospital stay or long-term neurodevelopmental outcomes were not significantly change by the administration of EPO., Authors' Conclusions: Early administration of EPO reduces the use one or more red blood cell transfusions, the volume of red blood cells transfused, and the number of donors and transfusions the infant is exposed to following study entry. The small reductions are of limited clinical importance. Any donor exposure is likely not avoided as most studies included infants, who had received red cell transfusions prior to trial entry. There was a significant increase in the rate of ROP (stage >3). Animal data and observational studies in humans support a possible association between treatment with EPO and the development of ROP. EPO does not significantly decrease or increase any of the other important neonatal adverse outcomes including mortality. The incidence of ROP should be ascertained in the studies that have already been conducted but did not report on this outcome. Any ongoing research should deal with the issue of ROP and evaluate the current clinical practice that will limit donor exposure through satellite units. Research efforts should focus on limiting donor exposure (to as few donors as possible) during the first few days of life in sick neonates, when red blood cell transfusions are most likely to be required and cannot be prevented by early (or late) EPO treatment. Due to the limited benefits and the increased risk of ROP, early administration of EPO is not recommended.

Objective: 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., Study Design: 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

The authors aimed to test the hypothesis that blood transfusions depress hematopoiesis in healthy infants with anemia of prematurity (AOP). They also set out to find markers that predict recovery from AOP. Thirty-nine premature babies underwent weekly and post-transfusion measurements of hemoglobin concentrations, reticulocyte counts (RCC), and erythropoietin levels (EPO). RCC and EPO dropped significantly 7 days after a blood transfusion but had normalized after 14 days. Elevated RCC or EPO levels were not predictive of an increase in hemoglobin. Postnatal HbFg/dL was higher in babies who had received transfusions. The authors conclude that blood transfusions depress erythropoiesis in infants with AOP and stimulate HbF synthesis but this effect is not sustained. Reticulocyte counts and erythropoietin levels are unhelpful in predicting recovery from AOP.

Background: The aim of this study was to detect and investigate the clinical effects of antineutrophil antibodies in neonates who had received a blood transfusion or exchange transfusion., Methods: Venous blood samples were drawn from 34 neonates at pretransfusion (sample 0), immediately after transfusion (sample 1), 2-3 weeks (sample 2) and 8-12 weeks (sample 3) after transfusion. Ten healthy neonates were in the control group. Antineutrophil antibodies were detected using flow cytometric assay., Results: Antineutrophil antibody was detected in the sera of 20 (58.8%) neonates in the study group. Of these 20 neonates, nine had antineutrophil antibodies in serum samples 0, 1 and 2, which were probably due to the passive transfer of maternal antibodies. Nine neonates had antineutrophil antibodies in serum samples 1 and 2, which were probably due to neutrophil antibodies being present in the donor's blood. In two neonates, antineutrophil antibodies were not detected in samples 0 and 1, but appeared in sample 2, which were probably actively produced by the neonates. All of the antineutrophil antibodies disappeared in the serum samples, except in one neonate. Only one preterm newborn developed neutropenia, which resolved spontaneously in a week. The presence of antineutrophil antibody in transfused neonates was significantly higher than in non-transfused neonates., Conclusions: The presence of neutrophil specific antibodies in transfused neonates is not rare and antineutrophil antibodies may be found more often in transfused neonates compared to non-transfused neonates. The clinical significance of those antibodies needs to be assessed since they are transient and their clinical effects are not evident.

Red blood cell (RBC) transfusion guidelines are designed to maintain adequate tissue oxygenation by increasing blood oxygen-carrying capacity. However, since tissue oxygenation is not measured, RBC transfusion guidelines are mostly subjective. Clinical evidence of oxygen transport/consumption mismatches in infants is often unclear and confounded by multiple factors. Invasive hemoglobin measurements can contribute further to anemia if performed too frequently. Diffuse optical spectroscopy (DOS) is a noninvasive quantitative method to measure the tissue oxy, deoxy, and total hemoglobin concentrations (ctO2Hb, ctHb, ctTHb), as well as mixed arterial-venous tissue hemoglobin saturation (stO2). Our objective is to determine if DOS can assess changes in tissue oxygenation in very low birth weight (VLBW) infants undergoing RBC transfusions. DOS measurements of ctO2Hb and ctHb are performed on 10 VLBW infants before and within 24 h after RBC transfusion. Seven nontransfused infants are studied to evaluate hemodynamic variations independent of RBC transfusion. Tissue near-infrared absorption and scattering values are measured using a four-wavelength (690, 750, 810, and 830 nm) frequency-domain tissue oximeter (OxiplexTS, ISS, Champaign, Illinois). In transfused subjects, DOS demonstrates significant increases in ctO2Hb (48+/-13 versus 74+/-20 microM, p<0.002), ctTHb (87+/-17 versus 107+/-24 microM, p=0.004), and stO2 (54+/-8 versus 68+/-6%, p<0.004) post-transfusion. DOS measurements correlate with mean hemoglobin increases for all infants (r=0.83, p<0.0001). No significant DOS changes occurred in the nontransfused group. Calculations of the differential path length for these transfused subjects show high variability (approximately 20%). DOS may serve as a noninvasive bedside tool to assess tissue oxygenation in infants and provide a functionally based transfusion trigger.

Objective: 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., Study Design: 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., Results: 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., Conclusions: 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.

Erythropoietin (Epo) is frequently administered to premature infants to stimulate erythropoiesis. There is evidence from studies in animals and healthy adults that Epo also interacts with thrombopoiesis and platelet function. This study investigates the effect of Epo therapy on platelet reactivity, peripheral platelet counts and thiazole orange-positive (TO+) platelets in extremely low birth weight (ELBW) infants. In a randomised-controlled trial, ELBW infants with a birth weight < or =800 g and a gestational age < or =32 weeks were either randomised to a group receiving Epo during the first weeks of life or to a control group. Our results show that thrombin receptor-activating peptide (TRAP-6) -induced expression of P-selectin increased significantly during the first two weeks of Epo treatment. With the exception of week five, the number of TO+ platelets was significantly higher during the first eight weeks in Epo-treated infants compared to controls. The increase of TO+ platelets was not paralleled by an increase in total platelet count. We can conclude that Epo therapy has a short-lasting effect on platelet reactivity toTRAP-6 in ELBW infants during the first two weeks of life. Furthermore, Epo therapy is associated with an increase in the number of TO+ platelets compared to controls.

Objective: Transfusion practices for neonates are controversial and based on limited scientific information. We examined the use of the plethysmographic volume pulse to assess anemia., Design: We used near-infrared photoplethysmography (NIRP) to investigate signal strength parameters as area under the curve (AUC) and the first derivate of the amplitude (flux) in anemic infants before and after elective transfusion., Setting: Tertiary intensive care unit., Patients: Thirty-four neonates on day 25+/-15 of life with a pretransfusion hemoglobin level of 8+/-0.9 g/dl. Four infants were excluded for incomplete data., Interventions: Transfusion of 10 ml packed red cells per kilogram body weight, Measurements and Results: The volume pulse signal was obtained with a sensor attached to the sole of the foot. After transfusion we found a significant decrease in number of bradycardia episodes per hour (0.35 vs. 0.16) and episodes of pulse oximeter desaturation less than 85% per hour (1.8 vs. 1.3) and a significant increase in daily weight gain (12+/-7 vs. 20+/-18 g), but neither of the microcirculatory parameters changed significantly (AUC 102+/-38 vs. 101+/-44; flux 435+/-160 vs. 405+/-120)., Conclusions: Even though infants were transfused at very low levels of hemoglobin with significant clinical effects, microcirculation assessed by NIRP seemed not be affected. Infrared photoplethysmographs present flow not only in the nutritive capillaries but mainly in the subpapillary plexus at a greater depth. This thermoregulatory flow seems not be affected by blood transfusions of anemic infants.

This review evaluates the potential of delayed cord-clamping for improving iron status and reducing anaemia in term infants and for increasing the risk of polycythaemia and hyperbilirubinaemia. We applied a strict search protocol to identify controlled trials of early vs late cord-clamping. Four trials from developing and four from industrialised countries were finally assessed. Two of the four studies from developing countries found a significant difference in infant haemoglobin levels at 2-3 months of age in favour of delayed cord-clamping. This difference was more marked when mothers were anaemic. Three of four studies from industrialised countries showed a significant difference in haematocrit levels in favour of delayed clamping. Although meta-analysis showed an increased risk for hyperbilirubinaemia of 12%, no studies reported the need to apply phototherapy or perform exchange transfusion. We conclude that delayed cord-clamping in term infants, especially those with anaemic mothers, increases haemoglobin concentration in infants at 2-3 months of age and reduces the risk of anaemia, without an associated increased risk of perinatal complications. In developing countries where fetal anaemia is common, the advantages of delayed cord-clamping might be especially beneficial.

Unlabelled: Anaemia of prematurity (AOP) is caused by a deficiency of erythropoietin, which stimulates differentiation, and growth of erythroid progenitors. The previous standard of therapy of AOP was erythrocyte transfusions. Following successful clinical trials using recombinant human eryrthropoietin (rHuEpo) to treat adults, the rHuEpo has been used to prevent and treat anaemia in preterm infants. The aim of the study was to evaluate the influence of rHuEpo treatment on parameters of the erythrocytic system in peripheral blood, iron concentration, and unsaturated iron bind capacity (UIBC), as well as on erythrocyte transfusion requirements, in preterm infants with AOP, having no infection and not receiving oxygen support. Twenty-four children with AOP, that were hospitalized during one year, with no signs of infection and without any form of oxygen therapy, were investigated. The rHuEpo was administered subcutaneously 700 U/kg/week, in two doses. Infants: also received oral iron. The percentage of children with AOP treated by supplementary transfusions was compared in two one-year periods, before and after the introduction of rHuEpo therapy. In over 50% of children, satisfactory improvement of erythrocytic picture was achieved after administration of 4-7 doses of rHuEpo. In the year prior to the introduction of rHuEpo therapy, 91% of children with AOP required supplementary red cells transfusions, while only 13% when rHuEpo was applied., Conclusions: The rHuEpo is the drug of choice in the treatment of anaemia of prematurity. Therapeutic use of rHuEpo markedly diminished quantity of supplementary transfusions in children with AOP.

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

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.

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., (Copyright 2001 by W.B. Saunders Company)

Objective: To assess whether a high intake of oral iron would increase the effect of recombinant human erythropoietin (rHuEPO) on hemoglobin synthesis., Methods: 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., Results: 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)., Conclusion: 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.

Background: Anemia is common among very low birth weight newborns and requires frequent blood transfusions. Erythropoietin was been reported to be useful in the prevention of this anemia., Aim: To assess the benefits of early (before the third week of life) Human recombinant Erythropoietin (r-EPO) administration to reduce the requirement of blood transfusions in very low birth weight newborns., Patients and Methods: Sixty newborns under 1500 g of birthweight were randomly assigned to receive r-EPO (n = 29) or placebo (n = 31) three times per week, during four weeks. Packed red cell volume and reticulocyte counts were measured weekly. Serum erythropoietin was measured prior to eighth dose. Transfusion requirements were recorded., Results: r-EPO reduced transfusions from 1.41 +/- 1.1 to 0.69 +/- 1 transfusions/newborns (p < 0.001). At the fourth week of treatment, reticulocyte count was 14.8 +/- 7 and 6.4 +/- 4.9% in the active treatment group and placebo group respectively (p < 0.001)., Conclusions: r-EPO reduces the requirement of transfusions in low birth weight infants.

Objective: 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., Methods: 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)., Results: 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., Conclusions: 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.

Objective: To assess management and outcome of pregnancies with anti-Kell in the West Midlands in the UK over 13 years., Design: A retrospective review of casenotes., Setting: A regional referral clinic for red cell alloimmune disease and fetal medicine unit at a university hospital., Population: Sixty-five pregnancies were identified in 52 Kell-sensitised women with Kell positive partners from the records of the Birmingham Blood Transfusion Centre., Methods: Information from the casenotes was entered on a database and comparisons were made using the SPSS for Windows statistics package., Main Outcome Measures: Mode of sensitisation, degree of fetal or neonatal anaemia, need for transfusion, gestation at delivery, birthweight and pregnancy outcome., Results: Alloimmunisation was transfusion-related in 29 pregnancies and pregnancy-induced in 33. The cause could not be identified in three cases. There were 22 proven Kell positive fetuses, of which 18 were affected, in which alloimmunisation was pregnancy-related in 12 cases and transfusion-related in five. Antibody titres and amniotic fluid OD450 were not helpful in management. Severe or very severe disease occurred in 50% of the affected pregnancies (9/18). There was no difference in pregnancy outcome between transfusion or pregnancy induced sensitisation., Conclusions: Anti-Kell alloimmunisation is an uncommon cause of serious anaemia in a significant proportion of affected pregnancies. There appears to be no difference between that caused by pregnancy or transfusion. Estimation of fetal haemoglobin concentration by cordocentesis is recommended, as antibody titres and amniocentesis are not helpful.

Chronic anemia is very frequent in very low birth weight (VLBW) infants. Lowered red cells life span, hemolysis, low production of erythropoietin, phlebotomies, excessive body growth are its most important causes. A reduction of the number of transfusions to babies with chronic anemia was obtained through r-HuEpo. A serie accounting for 89 newborns < 1500 g (18 < 1000 g) with a mean weight of 1069 g (+/- 238) in whom early treatment with r-HuEpo was performed (from 9.55 +/- 3.04 day), 300 UI three times a week s.c., is presented. Therapy with r-HuEpo was carried out for 6 weeks, or until the baby weighed 1800 g. During the treatment, each baby received iron, folic acid, multivitaminic supplements. Patients were monitored with red blood cells count, comprehensive of reticolocytes, ipochromic cells (Ipo-cells), content of hemoglobin of reticolocytes (CHr), each week. Iron, ferritine and transferrine were obtained only twice a month, as they required further blood sampling. 10.1% neonates received transfusions: the percentage of transfused VLBW infants was much higher (55.5%) before than after the introduction of r-HuEpo (p = 0.0002). 33.3% extremely low birth weight (ELBW) infants required transfusions (vs 95.5% in pre r-HuEpo period) (p < 0.0001). Our results confirm the importance of Ipo-cells and CHr to monitor early alterations of iron cellular employment.

Objective: 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., Patients and Methods: 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., Results: 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., Conclusions: 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.

Objectives: Very low birth weight (< 1500 g) infants frequently require packed red blood cell transfusions, and transfusion rates vary among neonatal intensive care units (NICUs). We analyzed transfusions and compared outcomes among NICUs., Study Design: In a 6-site prospective study, we abstracted all newborns weighing < 1500 g (total = 825) born between October 1994 and September 1995. Transfusion frequency and volume and phlebotomy number were analyzed by site and adjusted for birth weight and illness severity. We compared rates of intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, growth, and length of stay between the high and low transfuser NICUs., Results: Sites differed significantly in mean birth weight, illness severity, number of transfusions, pretransfusion hematocrit, blood draws, and donor number. Multivariate adjustment for these risks showed that the highest transfusing NICU transfused an additional 24 cc/kg per baby during the first 14 days and 47 cc/kg per baby after 15 days, relative to the lowest transfusing NICU. The presence of arterial catheters increased the frequency of blood transfusions. The rates of intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia were not higher in the 2 lowest transfusing NICUs, nor were there differences in 28-day weight gain or length of stay., Conclusions: Major differences in transfusion practices for very low birth weight infants exist among NICUs. Because clinical outcomes were no different in lower transfuser NICUs, it is likely that transfusion and phlebotomy guidelines could result in fewer transfusions, fewer complications, and reduced cost.

To evaluate the quantitative aspects of the shift in production from fetal hemoglobin (HbF) to adult hemoglobin (HbA), the HbF and HbA mass were estimated in a preterm infant (gestational age 29 weeks) for 22 weeks after an exchange transfusion the second day of life, leading to an initial HbA% of 100. Up until the estimated time of delivery, the HbA mass declined continuously, at a rate corresponding to a survival time of the transfused HbA erythrocytes of 100 days, and the rise in total hemoglobin mass could be ascribed solely to a rise in the HbF mass. HbF% maximum was reached 3 weeks before HbF mass maximum, and, thus, the HbF% and HbA% time courses gave no basis for evaluation of the production/destruction balance of HbF and HbA erythrocytes. The applied quantitative approach seems to be a useful additional procedure for evaluating the switch from HbF to HbA production and for estimating HbA erythrocyte survival time in preterm infants.

Objective: To evaluate the efficacy and safety of recombinant human erythropoietin (rHuEPO) in very low birth weight infants with anemia of prematurity., Study Design: Thirty infants were randomly assigned to receive either rHuEPO (300 U/kg per dose) or placebo twice a week. Hematologic parameters, transfusion requirements, caloric intake, and growth were monitored., Results: The number and volume of erythrocyte transfusions were significantly lower in infants treated with rHuEPO. Serum ferritin levels, similar in both groups at study entry, fell and were significantly lower in rHuEPO-group infants at the completion of the study. An inverse correlation was observed between reticulocyte count and absolute neutrophil count both at entry and at completion of the study., Conclusion: Twice-a-week administration of rHuEPO significantly reduces the need for erythrocyte transfusion in very low birth weight infants in stable condition. A significant decrease in serum ferritin levels in infants receiving rHuEPO suggests the need to determine the optimal dose of iron supplementation in these infants.

Objectives: 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., Study Design: 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., Results: 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., Conclusions: Anemia of prematurity and BPD increase heart rate, cardiac output, stroke volume, and SF. These hemodynamic compensatory responses are normalized by transfusion.

In an attempt to stimulate erythrocyte production and thereby decrease the requirement for red blood transfusions, recombinant human erythropoietin (rHuEPO) was administered to 16 premature infants with birth weights less than 1000 g and to 18 with birth weights of 1000-1300 g; two corresponding groups, who did not receive rHuEPO, were used as control groups. The rHuEPO was administered subcutaneously in a dose of 300 IU/kg three times a week for 6-8 weeks. The erythropoietin decreased the red blood requirement in both groups of infants, and the increment of hemoglobin following rHuEPO administration was not statistically significant. No correlation was observed between gestational age, number of transfusions, and reticulocyte percentage. The effect of rHuEPO was higher in the group of infants with birth weights of 1000-1300 g than in those of less than 1000 g. No significant side effects were observed during rHuEPO administration.

Unlabelled: OBJECTIVE/STUDY DESIGN: After blood loss, production of erythropoietin in adults increases, which accelerates erythropoiesis and restores the erythroid mass. It is unclear whether preterm infants with large phlebotomy losses have a similar response. We therefore measured serum erythropoietin concentrations in 11 ill preterm infants (1057 +/- 167 gm) as their phlebotomy losses accumulated., Results: Before the first transfusion, erythropoietin concentrations were 68.9 +/- 36.2 mU/ml (range 0 to 205 mU/ml) at 5 ml/kg blood out, 17.4 +/- 8.9 mU/ml at 10 ml/kg, and 4.8 +/- 2.6 mU/ml at 15 ml/kg. Erythropoietin concentrations did not increase in any patients despite increasing phlebotomy losses., Conclusion: Serum erythropoietin concentrations in ill preterm infants do not increase in the face of significant blood loss. Although the mechanistic explanation for this failure is unclear, it likely contributes to the transfusion requirements of this population.

Objective: To determine whether intravenously administered iron supplements would improve the hematologic response to recombinant erythropoietin in stable preterm infants., Methods: 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)., Results: 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)., Conclusions: 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.

Background: Whether and when to transfuse in anemia of prematurity is highly controversial. Some authors suggest transfusions simply if the hemoglobin (Hb) level is below a defined normal range. Others propose the use of clinical or laboratory parameters in anemic patients to decide whether to transfuse or not., Hypothesis: A decreasing amount of circulating Hb should cause a compensatory increase in cardiac output (CO) and an increase in arterial serum lactate., Materials and Methods: In 56 anemic preterm infants (not in respiratory or hemodynamic failure) we analyzed CO after the first week of life using a Doppler sonographic method. At the same time serum lactate levels, Hb levels and oxygen saturation were registered. Nineteen of these patients were given transfusion when they demonstrated clinical signs of anemia by tachycardia > 180/min, tachypnea, retractions, apneas and centralization (group 2). The remaining 37 patients were not transfused (group 1). Serum lactate, CO, heart rate (HR), oxygen delivery, respiratory rate, capillary refill and Hb were analyzed in both groups and in group 2 before and 12-24 h after transfusion. Data between groups 1 and 2 and in group 2 before and after transfusion were compared., Results: In the 56 patients studied no linear correlation between Hb and CO or between Hb and serum lactate was found. Nor could any correlation be demonstrated between the other variables studied. Examining the subgroups separately, a negative linear correlation was demonstrated between serum lactate and oxygen delivery in group 2. No other significant correlations were detected. However, when the pre- and post-transfusion data were compared in group 2 (increase of Hb from 9.45 (SD 3.44) to 12.5 (SD 3.8) g/100 ml), the CO decreased from 281.3 (SD 162.6) to 224 (SD 95.7) ml/kg per min (p < 0.01) and serum lactate decreased significantly from 3.23 mmol/l (SD 2.07) before to 1.71 (SD 0.83) after transfusion. Oxygen delivery was 35.8 (+/- 0.19) ml/kg per min group 1, 27.8 (+/- 0.05) pre- and 43.4 (+/- 0.07) post-transfusion in group 2 (p < 0.01)., Conclusions: CO measurements and serum lactate levels add little information to the decision-making process for blood transfusions, as neither CO nor serum lactate levels correlate with HB levels in an otherwise asymptomatic population of preterm infants. In infants where the indication for blood transfusion is made based on traditionally accepted clinical criteria, serum lactate is an additional laboratory indicator of impaired oxygenation, as it correlates significantly with oxygen delivery. A significant lower oxygen delivery in patients in whom blood transfusion is indicated and an increase in oxygen induced by transfusion demonstrate the value of these criteria in identifying preterm infants who benefit from transfusion.

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.

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.