losartan-potassium and Birth-Weight

Recombinant human erythropoietin (rhEPO) lost its role in minimizing red blood cell transfusion in very preterm infants after it had been associated with severe retinopathy of prematurity (ROP). Previous systematic reviews did not stratify ROP by gestation and birth weight (BW).. The aim of this study was to investigate the effect of early prophylactic rhEPO on ROP in a stratified meta-analysis of randomized controlled trials (RCTs).. The databases EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched in January 2022 and complemented by citation searching. RCTs comparing early rhEPO treatment with no treatment or placebo were selected if they were published in a peer-reviewed journal and reported ROP outcomes. Previously unpublished data were requested from the study authors to allow stratified analyses by gestational age (GA) and BW. Data were extracted and analyzed using the standard methods of the Cochrane Neonatal Review Group. Pre-specified outcomes were "ROP stage ≥3" (primary outcome) and "any ROP.". Fourteen RCTs, comprising 2,040 infants of <29 weeks of GA, were included for meta-analysis. Data syntheses showed no effects of rhEPO on ROP stage ≥3 or on any ROP, neither in infants of <29 weeks GA, nor in infants of <1,000 g BW, nor in any GA strata. The risk ratio (95% confidence interval) for ROP stage ≥3 in infants of <29 weeks of GA was 1.13 (0.84, 1.53), p = 0.41 (quality of evidence: moderate).. The present meta-analysis detected no effects of early rhEPO on ROP in any comparison, but most stratified analyses were limited by low statistical power.

Topics: Anemia, Neonatal; Birth Weight; Erythropoietin; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Retinopathy of Prematurity; Risk Factors

Red blood cell (RBC) transfusion is a common and lifesaving therapy for anemic neonates and infants, particularly among those born prematurely or undergoing surgery. However, evidence-based indications for when to administer RBCs and adverse effects of RBC transfusion on important outcomes including necrotizing enterocolitis, survival, and long-term neurodevelopmental impairment remain uncertain. In addition, blood-banking practices for preterm and term neonates and infants have been largely developed using studies from older children and adults. Use of and refinements in emerging technologies and advances in biomarker discovery and neonatal-specific RBC transfusion databases may allow clinicians to better define and tailor RBC transfusion needs and practices to individual neonates. Decreasing the need for RBC transfusion and developing neonatal-specific approaches in the preparation of donor RBCs have potential for reducing resource utilization and cost, improving outcomes, and assuring blood safety. Finally, large donor-recipient-linked cohort studies can provide data to better understand the balance of the risks and benefits of RBC transfusion in neonates. These studies may also guide the translation of new research into best practices that can rapidly be integrated into routine care. This review highlights key opportunities in transfusion medicine and neonatology for improving the preparation and transfusion of RBCs into neonates and infants. We focus on timely, currently addressable knowledge gaps that can increase the safety and efficacy of preterm and term neonatal and infant RBC transfusion practices.

Topics: Age Factors; Anemia; Birth Weight; Blood Banks; Clinical Trials as Topic; Erythrocyte Transfusion; Erythrocytes; Erythropoietin; Hematology; Humans; Infant, Newborn; Infant, Premature; Research Design; Time Factors; Treatment Outcome

Twin studies have long been recognized for their value in learning about the aetiology of disease and specifically for their potential for separating genetic effects from environmental effects. The recent upsurge of interest in life-course epidemiology and the study of developmental influences on later health has provided a new impetus to study twins as a source of unique insights. Twins are of special interest because they provide naturally matched pairs where the confounding effects of a large number of potentially causal factors (such as maternal nutrition or gestation length) may be removed by comparisons between twins who share them. The traditional tool of epidemiological 'risk factor analysis' is the regression model, but it is not straightforward to transfer standard regression methods to twin data, because the analysis needs to reflect the paired structure of the data, which induces correlation between twins. This paper reviews the use of more specialized regression methods for twin data, based on generalized least squares or linear mixed models, and explains the relationship between these methods and the commonly used approach of analysing within-twin-pair difference values. Methods and issues of interpretation are illustrated using an example from a recent study of the association between birth weight and cord blood erythropoietin. We focus on the analysis of continuous outcome measures but review additional complexities that arise with binary outcomes. We recommend the use of a general model that includes separate regression coefficients for within-twin-pair and between-pair effects, and provide guidelines for the interpretation of estimates obtained under this model.

Topics: Birth Weight; Data Interpretation, Statistical; Erythropoietin; Guidelines as Topic; Humans; Least-Squares Analysis; Likelihood Functions; Linear Models; Regression Analysis; Twin Studies as Topic

Topics: Anemia, Hemolytic; Anemia, Neonatal; Bilirubin; Birth Weight; Blood Group Antigens; Diet; Erythrocytes; Erythrocytes, Abnormal; Erythropoiesis; Erythropoietin; Folic Acid Deficiency; Gestational Age; Hemoglobinometry; Hemorrhage; Humans; Immunization; Infant; Infant, Newborn; Isoantigens; Kinetics; Rh-Hr Blood-Group System; Thalassemia; Vitamin E Deficiency

Acute kidney injury (AKI) and disordered fluid balance are common in premature neonates; a positive fluid balance dilutes serum creatinine, and a negative fluid balance concentrates serum creatinine, both of which complicate AKI diagnosis. Correcting serum creatinine for fluid balance may improve diagnosis and increase diagnostic accuracy for AKI.. To determine whether correcting serum creatinine for fluid balance would identify additional neonates with AKI and alter the association of AKI with short-term and long-term outcomes.. This study was a post hoc cohort analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3, randomized clinical trial of erythropoietin, conducted at 19 academic centers and 30 neonatal intensive care units in the US from December 2013 to September 2016. Participants included extremely premature neonates born at less than 28 weeks of gestation. Data analysis was conducted in December 2022.. Diagnosis of fluid-corrected AKI during the first 14 postnatal days, calculated using fluid-corrected serum creatinine (defined as serum creatinine multiplied by fluid balance [calculated as percentage change from birth weight] divided by total body water [estimated 80% of birth weight]).. The primary outcome was invasive mechanical ventilation on postnatal day 14. Secondary outcomes included death, hospital length of stay, and severe bronchopulmonary dysplasia (BPD). Categorical variables were analyzed by proportional differences with the χ2 test or Fisher exact test. The t test and Wilcoxon rank sums test were used to compare continuous and ordinal variables, respectively. Odds ratios (ORs) and 95% CIs for the association of exposure with outcomes of interest were estimated using unconditional logistic regression models.. A total of 923 premature neonates (479 boys [51.9%]; median [IQR] birth weight, 801 [668-940] g) were included, of whom 215 (23.3%) received a diagnosis of AKI using uncorrected serum creatinine. After fluid balance correction, 13 neonates with AKI were reclassified as not having fluid-corrected AKI, and 111 neonates previously without AKI were reclassified as having fluid-corrected AKI (ie, unveiled AKI). Therefore, fluid-corrected AKI was diagnosed in 313 neonates (33.9%). Neonates with unveiled AKI were similar in clinical characteristics to those with AKI whose diagnoses were made with uncorrected serum creatinine. Compared with those without AKI, neonates with unveiled AKI were more likely to require ventilation (81 neonates [75.0%] vs 254 neonates [44.3%] and have longer hospital stays (median [IQR], 102 [84-124] days vs 90 [71-110] days). In multivariable analysis, a diagnosis of fluid-corrected AKI was associated with increased odds of adverse clinical outcomes, including ventilation (adjusted OR, 2.23; 95% CI, 1.56-3.18) and severe BPD (adjusted OR, 2.05; 95% CI, 1.15-3.64).. In this post hoc cohort study of premature neonates, fluid correction increased the number of premature neonates with a diagnosis of AKI and was associated with increased odds of adverse clinical outcomes, including ventilation and BPD. Failing to correct serum creatinine for fluid balance underestimates the prevalence and impact of AKI in premature neonates. Future studies should consider correcting AKI for fluid balance.. ClinicalTrials.gov Identifier: NCT01378273.

Topics: Acute Kidney Injury; Birth Weight; Bronchopulmonary Dysplasia; Cohort Studies; Creatinine; Erythropoietin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Neuroprotection; Retrospective Studies

To assess effects of iron supplementation, 66 mg elemental iron daily as ferrous fumarate, on iron status markers during normal pregnancies.. Randomized, double-blind, placebo-controlled study of 119 women (62 iron-, 57 placebo -treated) and their newborns. Hemoglobin (Hb), serum (S)-ferritin, S-transferrin saturation percentage (TSAT) and S-erythropoietin (S-EPO) were measured at 14-18, 24-27 weeks of gestation, prepartum, 1 and 8 weeks postpartum.. From 24-27 weeks gestation to 8 weeks postpartum, the iron group had higher Hb, S-ferritin and TSAT than the placebo group; prepartum, 11% had iron deficiency (ID) and 0% iron deficiency anemia (IDA) in the iron group, vs 60% and 18% in the placebo group; 8 weeks postpartum 1.6% in the iron group had ID and 1.6% IDA vs 14% and 7% in the placebo group. S-EPO levels in the iron group were lower than in the placebo group (p < 0.001). Mothers prepartum S-EPO values were correlated to newborns cord S-EPO values (p < 0.001). Newborns to iron treated mothers had higher cord S-ferritin levels than those to placebo treated mothers (p = 0.02). Newborn girls had higher cord S-ferritin levels than boys (p < 0.01). There was no impact of iron supplementation on the length of gestation, placental weight, or newborns birth weight. Birth weight was correlated only with mothers' body weight, length of gestation and placental weight.. Iron supplementation had a "positive" impact on iron status and Hb both during pregnancy and postpartum, with a low frequency of ID/IDA and also a "positive" influence on newborns iron status.

Topics: Anemia, Iron-Deficiency; Birth Weight; Denmark; Dietary Supplements; Erythropoietin; Female; Ferritins; Hemoglobins; Humans; Infant, Newborn; Iron; Iron Deficiencies; Male; Placenta; Postpartum Period; Pregnancy

Intraventricular hemorrhage (IVH) is a major cause of neonatal morbidity and mortality in preterm infants without a specific medical treatment to date.. To assess the safety and short-term outcomes of high-dose erythropoietin in preterm infants with IVH.. Between April 1, 2014, and August 3, 2018, a randomized double-blind clinical trial enrolled 121 preterm infants (gestational age <32 weeks or birth weight <1500 g) aged 8 or less days with moderate to severe IVH identified by cerebral ultrasonography from 8 Swiss and Austrian tertiary neonatal units. Statistical analyses were performed between October 1, 2019, and September 12, 2022.. Infants received intravenous high-dose erythropoietin (2000 units/kg body weight) or placebo at 4 time points between weeks 1 and 4 of life.. Secondary outcomes included (1) mortality and morbidity rates and (2) brain magnetic resonance imaging findings at term-equivalent age (TEA). The primary outcome was the composite intelligence quotient at 5 years of age (not available before 2023).. Sixty infants (48% male [n = 29]) were randomly assigned to receive erythropoietin, and 61 infants (61% male [n = 37]) were randomly assigned to receive placebo. The median birth weight was 832 g (IQR, 687-990 g) in the erythropoietin group and 870 g (IQR, 680-1110 g) in the placebo group. Median gestation was 26.1 weeks (IQR, 24.8-27.3 weeks) in the erythropoietin group and 27.0 weeks (24.9-28.1 weeks) in the placebo group. The 2 groups had similar baseline characteristics and morbidities. Up to TEA, 10 newborns died (16.7%) in the erythropoietin group, and 5 newborns (8.2%) died in the placebo group (adjusted odds ratio, 2.24 [95% CI, 0.74-7.66]; P = .15). Infants receiving erythropoietin had higher mean hematocrit levels. Conventional magnetic resonance imaging at TEA for 100 infants showed no significant differences in global or regional brain injury scores.. This preliminary report of a randomized clinical trial found no evidence that high-dose erythropoietin in preterm infants with IVH affects brain injury scores on conventional magnetic resonance imaging at TEA. Higher mortality in the erythropoietin group was not significant but should be reassessed based on future results from similar trials.. ClinicalTrials.gov Identifier: NCT02076373.

Topics: Birth Weight; Brain Injuries; Cerebral Hemorrhage; Child, Preschool; Erythropoietin; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; 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

To evaluate the efficacy and safety of repeated low-dose human recombinant erythropoietin (rhEPO) in the improvement of neurological outcomes in very preterm infants.. A total of 800 infants of ≤32-week gestational age who had been in an intensive care unit within 72 hours after birth were included in the trial between January 2009 and June 2013. Preterm infants were randomly assigned to receive rhEPO (500IU/kg; n = 366) or placebo (n = 377) intravenously within 72 hours after birth and then once every other day for 2 weeks. The primary outcome was death or moderate to severe neurological disability assessed at 18 months of corrected age.. Death and moderate/severe neurological disability occurred in 91 of 338 very preterm infants (26.9%) in the placebo group and in 43 of 330 very preterm infants (13.0%) in the rhEPO treatment group (relative risk [RR] = 0.40, 95% confidence interval [CI] = 0.27-0.59, p < 0.001) at 18 months of corrected age. The rate of moderate/severe neurological disability in the rhEPO group (22 of 309, 7.1%) was significantly lower compared to the placebo group (57 of 304, 18.8%; RR = 0.32, 95% CI = 0.19-0.55, p < 0.001), and no excess adverse events were observed.. Repeated low-dose rhEPO treatment reduced the risk of long-term neurological disability in very preterm infants with no obvious adverse effects. Ann Neurol 2016;80:24-34.

Topics: Birth Weight; Disability Evaluation; Erythropoietin; Female; Gestational Age; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature; Male; Mortality; Recombinant Proteins

To evaluate the value of third trimester ultrasound (estimated fetal weight, cheek-to-cheek diameter, sectional Wharton's jelly area, sectional areas and fractional volumes in extremities) to predict birth weight and cord biochemical markers at birth (leptin, insulin, c-peptide, IGF1, erythropoietin and ferritin) in diabetic pregnancies.. Prospective study in 49 patients with gestational diabetes. An ultrasound was performed between 32 and 34 weeks. Clinical data were collected, and a blood sample was obtained from cord after birth. ROC curve models were evaluated for 75(th) and 90(th) birth weight percentile. Univariate and multivariate models were used to assess the association between ultrasound and neonatal outcomes.. Sectional areas and fractional volumes showed significant differences and highest AUC values for predicting birth weight. A significant association was found for extremities measurements with total birth weight and its percentile. The only marker which showed a significant association to estimated fetal weight was erythropoietin. Sectional areas and fractional volumes related to cord leptin, erythropoietin, insulin and c-peptide.. Sectional areas and fractional volumes improve the predictive value of estimated fetal weight in diabetic pregnancies. They also show a predictive association to biochemical changes in cord (leptin, insulin and erythropoietin) related to increased adiposity and risk of fetal hypoxia. © 2015 John Wiley & Sons, Ltd.

Topics: Adult; Birth Weight; Body Fat Distribution; C-Peptide; Diabetes, Gestational; Erythropoietin; Female; Fetal Blood; Humans; Insulin; Leptin; Pregnancy; Prospective Studies; Ultrasonography, Prenatal

The aim of this study was to compare two neuroprotective strategies to supportive care in the treatment of perinatal asphyxia.. A total of 67 term newborns with perinatal asphyxia were included and randomized into three groups: one group received supportive treatment; another group received a single dose of 40 mg/kg phenobarbital; and the third received three daily doses of 1000 IU/kg erythropoietin. The following parameters were analyzed: gestational age, birthweight, Apgar scores, cord blood pH, total serum antioxidant status (TAS), superoxide dismutase (SOD), glutathione peroxidase (GPx) and malondialdehyde (MDA). The newborns were included in the follow-up program and examined up to 18 months of age.. TAS was higher in the erythropoietin group than in the other groups. SOD and GPx were lower for infants treated with phenobarbital or erythropoietin compared to control infants. MDA was lower in the erythropoietin group compared to the other groups, although the difference was not statistically significant (P > 0.05). The mortality rate was lower in the phenobarbital and erythropoietin groups (both 4.6%) than in the control group (17.4%). Long-term neurologic follow up showed a high incidence of sequelae in the control group compared to the phenobarbital and erythropoietin groups. Follow-up results were better in the phenobarbital group than in the erythropoietin group for motor and cognitive function at 3 and 6 months and worse for expressive language. At 18 months, however, the differences between these two groups were not significant.. High-dose phenobarbital or erythropoietin along with supportive treatment has a positive influence on the outcome of newborns with perinatal asphyxia. Phenobarbital has the advantage of low cost and simplicity.

Topics: Asphyxia Neonatorum; Birth Weight; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Gestational Age; Hematinics; Humans; Hypnotics and Sedatives; Infant, Newborn; Injections, Intravenous; Injections, Subcutaneous; Male; Oxidative Stress; Phenobarbital; Prospective Studies; Recombinant Proteins; Treatment Outcome

Darbepoetin can be administered either intravenously (i.v.) or subcutaneously (s.c.). However, no information is available regarding pharmacokinetics and pharmacodynamics following its i.v. administration to neonates.. We administered a single i.v. dose (4 microg/kg) of darbepoetin to 10 neonates who had a hemoglobin < or =10.5 g/dl. Blood was obtained for immature reticulocyte fraction (IRF) and absolute reticulocyte count (ARC), before and 48 h following the dose. Blood was also drawn for pharmacokinetic analysis once before and at four pre-set intervals after dosing.. The study subjects ranged from 704 to 3025 g (median, 1128 g) birth weight, and were 26.0-40.0 weeks (median, 29.2 weeks) gestation at delivery. When the darbepoetin dose was given, ages ranged from 3 to 28 days (median, 8.5 days) with a hemoglobin of 9.8 +/- 0.7 g/dl (mean +/- s.d.). Doses were administered by i.v. infusion over 4 h. No adverse effects of the infusions were detected. The half-life of darbepoetin (t (1/2)) was 10.1 h (range 9.0-22.7 h), the volume of distribution was 0.77 l/kg (range 0.18-3.05 l/kg) and the clearance was 52.8 ml/h/kg (range 22.4-158.0 ml/h/kg). In the preterm neonates, there was no significant correlation between gestational age, or age at darbepoetin administration, and pharmacokinetic parameters. However, in the term and near-term neonates, volume of distribution correlated significantly with both gestational and age at darbepoetin administration (P < 0.05). Forty-eight hours after dosing, the IRFs and ARCs were elevated in six subjects and not in four. Those with predosing reticulocyte counts >200,000/microl did not have an increase in reticulocytes by 48 h (P < 0.05).. Darbepoetin administered i.v. to neonates had a shorter t (1/2), a larger volume of distribution and more rapid clearance than reported in children. We observed a significantly shorter t (1/2) and a less consistent rise in IRF and ARC after i.v. dosing than we previously reported following 4 microg/kg administered SC.

Topics: Birth Weight; Darbepoetin alfa; Erythropoietin; Female; Gestational Age; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Infusions, Intravenous; Intensive Care Units, Neonatal; Male; Premature Birth; Reticulocyte Count

In this study, it is hypothesized that a planned increase in the dose of recombinant human erythropoietin (rh-EPO) can prevent transfusion in very low birth weight infants. Two different regimens of rh-EPO were administrated, one consisting in increasing dosage up to 5000 U/kg/wk, according to the individual reticulocytes response, and the second in a standard therapy of 1250 U/kg/wk. Fifty-one infants participated. Despite a significant higher reticulocytosis, the study was prematurely terminated due to the results of an interim analysis showing that transfusion was not avoided by increasing the rh-EPO. No significant differences were found between the two regimens concerning transfusion rate, volume transfused, gain in weight, and adverse effects. Progressive titration of rh-EPO to improve the biological response does not leave premature infants free of transfusion.

Topics: Birth Weight; Dose-Response Relationship, Drug; Double-Blind Method; Erythropoietin; Female; Hematologic Tests; Humans; Infant; Male; Recombinant Proteins; Reticulocyte Count; Reticulocytes; Reticulocytosis; Retrospective Studies; Survival Analysis; Transfusion Reaction; Treatment Outcome

To investigate the toxic effect of tobacco smoke on the fetus, we measured in cord blood the concentrations of alpha-fetoprotein (AFP), the principal serum protein in early ontogenic development, and erythropoietin (EPO), as an index of chronic fetal hypoxia. A total of 103 consecutively enrolled term newborns of smoking mothers and 103 term infants of nonsmoking parents were studied. The mean +/- SD AFP concentrations in the newborns of the mothers who smoked 1-50, 5-50, and 10-50 cigarettes/day were 86.4 +/- 88.9, 96.3 +/- 91.9 and 118.7 +/- 103.7 ng/ml, respectively. The difference of all three groups from the control neonates (57.7 +/- 37.2) was significant. The EPO concentrations in the newborns of the mothers who smoked 1-50 (53.9 +/- 64.6 mU/ml) and 5-50 (56.3 +/- 68.5) cigarettes/day were significantly greater than in the control neonates (29.5 +/- 16.1). In the newborns of the smoking mothers there was a significant positive correlation between AFP concentrations and number of cigarettes smoked per day, and a negative correlation between AFP and birth weight or length. There was no correlation between AFP and EPO concentrations, as well as between EPO and birth weight, length or number of cigarettes smoked per day.. The absence of a correlation between erythropoietin and birth weight or length and the negative correlations between alpha-fetoprotein and these anthropometric parameters suggest that the intra-uterine growth retardation caused by maternal smoking is not due to tissue hypoxia, but that both growth retardation and elevated alpha-fetoprotein result from the direct or indirect toxic effect of a factor(s) present in tobacco smoke.

Topics: alpha-Fetoproteins; Analysis of Variance; Birth Weight; Body Height; Embryonic and Fetal Development; Erythropoietin; Female; Fetal Blood; Fetal Growth Retardation; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Reference Values; Smoking

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

Topics: Birth Weight; Erythropoietin; Female; Growth; Hematocrit; Hemoglobins; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Injections, Subcutaneous; Milk Proteins; Milk, Human; Recombinant Proteins

High-dose human recombinant erythropoietin (rEPO) is a promising potential neuroprotective treatment in preterm and full-term neonates with hypoxic-ischemic encephalopathy (HIE). There are limited data on the pharmacokinetics of high-dose rEPO in neonates. We examined the effects of body weight, gestation age, global asphyxia, cerebral ischemia, hypothermia and exogenous rEPO on the pharmacokinetics of high-dose rEPO in fetal sheep. Near-term fetal sheep on gestation day 129 (0.87 gestation) (full term 147 days) received sham-ischemia (

Topics: Animals; Asphyxia Neonatorum; Birth Weight; Body Weight; Combined Modality Therapy; Dose-Response Relationship, Drug; Embryonic Development; Erythropoietin; Female; Fetus; Gestational Age; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Infusions, Intravenous; Injections, Intravenous; Models, Biological; Neuroprotective Agents; Recombinant Proteins; Sheep; Species Specificity

Iron stores at birth are essential to meet iron needs during the first 4-6 months of life. The present study aimed to investigate iron stores in normal birth weight, healthy, term neonates. Umbilical cord blood samples were collected from apparently normal singleton vaginal deliveries (n=854). Subjects were screened and excluded if C-reactive protein (CRP) > 5 mg/l or α1-acid glycoprotein (AGP) > 1 g/l, preterm (<37 complete weeks), term < 2500g or term > 4000g. In total, 762 samples were included in the study. Serum ferritin, soluble transferrin receptor (sTfR), hepcidin, and erythropoietin (EPO) were measured in umbilical cord blood samples; total body iron (TBI) (mg/kg) was calculated using sTfR and ferritin concentrations. A total of 19.8% newborns were iron deficient (ferritin 35 μg/l) and an additional 46.6% had insufficient iron stores (ferritin < 76 μg/l). There was a positive association between serum ferritin and sTfR, hepcidin, and EPO. Gestational age was positively associated with ferritin, sTfR, EPO, and hepcidin. In conclusion, we demonstrate a high prevalence of insufficient iron stores in a Chinese birth cohort. The value of cord sTfR and TBI in the assessment of iron status in the newborn is questionable, and reference ranges need to be established.

Topics: Adult; Biomarkers; Birth Weight; C-Reactive Protein; Cordocentesis; Erythropoietin; Female; Ferritins; Fetal Blood; Gestational Age; Hepcidins; Humans; Infant, Newborn; Inflammation; Inflammation Mediators; Iron; Iron Deficiencies; Orosomucoid; Pregnancy; Receptors, Transferrin

Topics: Birth Weight; Erythrocyte Transfusion; Erythropoietin; Humans; Infant; Infant, Extremely Low Birth Weight; Infant, Newborn; Infant, Very Low Birth Weight

Hepcidin, an iron-regulatory hormone, plays a key role in preventing iron overload. Few studies have investigated the regulation of hepcidin in low-birth-weight (LBW) infants who are vulnerable to iron imbalance.. To identify perinatal factors associated with serum hepcidin levels in LBW infants.. Ninety-two LBW infants with a median gestational age (GA) of 32.6 weeks and birth weight of 1,587 g were prospectively enrolled. Serum hepcidin-25 (Hep25) levels were measured from umbilical cord blood using liquid chromatography-tandem mass spectrometry. The relationship between Hep25 levels and prematurity or other possible hepcidin-regulatory factors was evaluated.. The median Hep25 level was 7.3 ng/mL (interquartile range: 2.85-16.38). log(Hep25) correlated with birth weight (r = 0.229, p = 0.028), log(interleukin-6 [IL-6]) (r = 0.408, p < 0.001), log(erythropoietin) (r = -0.302, p = 0.004), transferrin saturation (r = 0.29, p = 0.005), soluble transferrin receptor (r = -0.500, p < 0.001), and log(ferritin) (r = 0.696, p < 0.001). Serum iron and hemoglobin levels did not correlate with log(Hep25). Hep25 levels were higher among infants with chorioamnionitis and infants born vaginally and lower among infants born to mothers with pregnancy-induced hypertension than among infants without the respective characteristics. Stepwise multiple linear regression analysis confirmed the significant association of log(Hep25) with GA, log(IL-6), log(erythropoietin), and soluble transferrin receptor.. Among LBW infants, GA, IL-6, erythropoietin, and soluble transferrin receptor were associated with Hep25 levels. Therefore, prematurity, inflammation, hypoxia, and erythropoietic activity may be important perinatal factors that affect hepcidin levels.

Topics: Adult; Biomarkers; Birth Weight; Chromatography, Liquid; Erythropoietin; Female; Fetal Blood; Gestational Age; Hepcidins; Humans; Infant, Low Birth Weight; Infant, Newborn; Interleukin-6; Male; Prospective Studies; Receptors, Transferrin; Tandem Mass Spectrometry

The substantial risk of iron overload is not routinely monitored in most of the neonatal intensive care units (NICUs) in Japan; however, blood transfusion is an essential strategy for successfully treating preterm low-birth-weight infants.. The aim of this study was to investigate the iron status and clinical features of infants with a birth weight of <1,500 g, i.e. very-low-birth-weight infants (VLBWIs).. This prospective observational study enrolled 176 (82.6%) patients from a total of 213 VLBWIs admitted to our NICU from 2009 to 2014. Clinical information was collected including maternal records and infant morbidity and treatment. Management strategies including enteral iron supplementation, erythropoietin administration and blood transfusion were allowed according to the consensus in Japan. The hematological status was surveyed from birth to 12 postnatal weeks of age. The iron status was determined according to serum iron, unbound iron-binding capacity and serum ferritin. The definition of hyperferritinemia was set as a value of ≥500 ng/ml.. Twenty-four (13.6%) infants displayed hyperferritinemia. A multiple logistic analysis selected 3 associated factors of hyperferritinemia: surgical ligation for patent ductus arteriosus, sepsis and moderate or severe states of bronchopulmonary dysplasia. We also verified that the value of ferritin was significantly correlated with those of aspartate transaminase, creatine kinase and C-reactive protein according to a multilinear regression analysis. After excluding the ferritin data of these outliers, we did not observe any factors associated with hyperferritinemia.. Hyperferritinemia might be associated with oxygen radical diseases and susceptibility to infection.

Topics: Birth Weight; Bronchopulmonary Dysplasia; C-Reactive Protein; Ductus Arteriosus, Patent; Erythropoietin; Female; Ferritins; Gestational Age; Humans; Infant, Newborn; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Iron Metabolism Disorders; Iron Overload; Japan; Logistic Models; Male; Multivariate Analysis; Prospective Studies; Sepsis

Little is known about anemia and iron status in US newborns because screening for anemia is typically not undertaken until 1 y of age. This study was undertaken to characterize and identify determinants of iron status in newborns born to pregnant adolescents.. Pregnant adolescents (≤ 18 y, n = 193) were followed from ≥ 12 wk gestation until delivery. Hemoglobin, ferritin, soluble transferrin receptor, serum iron, hepcidin, erythropoietin (EPO), IL-6, and C-reactive protein were assessed in maternal and cord blood.. At birth, 21% of the neonates were anemic (Hb < 13.0 g/dl) and 25% had low iron stores (ferritin < 76 µg/l). Cord serum ferritin concentrations were not significantly associated with gestational age (GA) at birth across the range of 37-42 wk. Neonates born to mothers with ferritin < 12 µg/l had significantly lower ferritin (P = 0.003) compared to their counterparts. Hepcidin and IL-6 were significantly (P < 0.05) higher in neonates born to mothers with longer durations of active labor.. Given the importance of the iron stores at birth on maintenance of iron homeostasis over early infancy, additional screening of iron status at birth is warranted among those born to this high risk obstetric population.

Topics: Adolescent; Anemia; Birth Weight; Black or African American; C-Reactive Protein; Erythropoietin; Female; Ferritins; Fetal Blood; Gestational Age; Hepcidins; Humans; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Interleukin-6; Iron; Labor, Obstetric; Pregnancy; Pregnancy in Adolescence; Prevalence; Receptors, Transferrin; White People

To determine if there is any difference in amniotic fluid erythropoietin (EPO) concentration between fetuses small for gestational age (SGA) and appropriate for gestational age (AGA), and between the constitutionally small (CSF) and growth-restricted (GRF) fetuses.. EPO concentrations in the amniotic fluid samples were determined by EpoELISA test in 38 pregnancies with SGA and 15 pregnancies with AGA fetuses. In the SGA group we measured Ponderal index (PI) and skin-fold thickness (SFT). If PI and/or SFT were below 10th percentile the neonate was GRF. If both PI and SFT were above 10th percentile the neonate was CSF.. Higher levels of EPO were detected in the SGA in comparison to the AGA fetuses (p < 0.01). EPO concentration was higher in GRF compared to CSF (p < 0.05). The EPO cut-off level between SGA and AGA was 6.81 IU/L (sensitivity 92.3%; specificity 73.3%), and between GRF and CSF was 9.8 IU/L (sensitivity 81%; specificity 80%).. The preliminary results of this study suggest that amniotic fluid erythropoietin concentration is elevated in growth-restricted fetuses and could potentially be used for distinction between growth restricted and constitutionally small fetuses. Confirmation of these results on a larger group of pregnant women is needed.

Topics: Adult; Amniotic Fluid; Biomarkers; Birth Weight; Case-Control Studies; Diagnosis, Differential; Erythropoietin; Female; Fetal Growth Retardation; Humans; Infant, Small for Gestational Age; Pregnancy; Prenatal Diagnosis; Somatotypes; Young Adult

Preterm very-low-birth-weight (VLBW) infants weighing <1.5 kg at birth develop anemia, often requiring multiple red blood cell transfusions (RBCTx). Because laboratory blood loss is a primary cause of anemia leading to RBCTx in VLBW infants, our purpose was to simulate the extent to which RBCTx can be reduced or eliminated by reducing laboratory blood loss in combination with pharmacodynamically optimized erythropoietin (Epo) treatment.. Twenty-six VLBW ventilated infants receiving RBCTx were studied during the first month of life. RBCTx simulations were based on previously published RBCTx criteria and data-driven Epo pharmacodynamic optimization of literature-derived RBC life span and blood volume data corrected for phlebotomy loss.. Simulated pharmacodynamic optimization of Epo administration and reduction in phlebotomy by ≥ 55% predicted a complete elimination of RBCTx in 1.0-1.5 kg infants. In infants <1.0 kg with 100% reduction in simulated phlebotomy and optimized Epo administration, a 45% reduction in RBCTx was predicted. The mean blood volume drawn from all infants was 63 ml/kg: 33% required for analysis and 67% discarded.. When reduced laboratory blood loss and optimized Epo treatment are combined, marked reductions in RBCTx in ventilated VLBW infants were predicted, particularly among those with birth weights >1.0 kg.

Topics: Anemia; Birth Weight; Blood Volume; Computer Simulation; Erythrocyte Transfusion; Erythropoietin; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Phlebotomy; Time Factors; Transfusion Reaction

Hereditary Spherocytosis (HS) is a common haemolytic anaemia in which 75% of cases are autosomal dominant. As most newborns with HS have a family history of disease, haematologists often see these infants before their physiologic haemoglobin nadir, which is exaggerated in comparison with healthy infants. The objective of this study was to evaluate the frequency of implementation and cost of erythropoietin-stimulating agents (EPO) versus transfusion in infants with HS at a single paediatric programme. In the last decade, only 15% of infants with HS at our centre have been treated with EPO, which costs twice that of a single transfusion and EPO treated infants did not always avoid transfusion. Infrequent prescription of EPO therapy to infants with HS at our centre may be related to the incomplete data supporting its use.

Topics: Birth Weight; Erythrocyte Transfusion; Erythropoietin; Female; Gestational Age; Hematinics; Humans; Infant; Infant, Newborn; Male; Severity of Illness Index; Spherocytosis, Hereditary; Treatment Outcome

Exogenous human erythropoietin (EPO) artificially synthesised through recombinant DNA technology (rHuEPO) is currently used as a substitute for blood transfusion in preterm and low birth weight neonates. The objective of this study is to determine whether the use of rHuEPO is associated with an increased severity of retinopathy of prematurity (ROP) in preterm neonates.. This retrospective review studies neonates who were admitted to a tertiary perinatal unit and screened for ROP during the 10-year period from January 2003 to December 2012.. : During the 10-year period, 688 preterm neonates underwent ROP screening, with 198 identified as having ROP. The incidence of stage 1 ROP was 51.5% (102/198), followed by 35.9% (71/198) for stage 2, and 12.6% (25/198) for stage 3 and greater. Plus disease was seen in 14 neonates (7.1%). Treatment (laser photocoagulation) was administered in 64% of neonates (16/25) with stage 3 of the disease and above because of progression to threshold ROP. Twenty-six (13%) of the neonates received rHuEPO treatment. There were no statistically significant differences in birth weight (910.4 vs 885 g; P=0.71), gestational age (26.5 vs 25.8 weeks; P=0.09), and duration of ventilation (512 vs 501.4 h; P=0.92) between neonates who did not receive rHuEPO compared with those who were treated with rHuEPO. Multivariate regression analysis showed that the use of EPO was associated with increased severity of ROP.. EPO therapy appears to increase the risk of development and worsening of ROP.

Topics: Anemia, Neonatal; Birth Weight; Epoetin Alfa; Erythropoietin; Female; Gestational Age; Hematinics; Humans; Infant, Newborn; Infant, Premature; Laser Coagulation; Male; Recombinant Proteins; Retinopathy of Prematurity; Retrospective Studies; Risk Factors; Severity of Illness Index

This study aims to investigate the incidence and the relative risk factors of retinopathy of prematurity (ROP) and posterior-ROP (P-ROP): ROP in Zone I and posterior Zone II, as well as to analyze the occurrence of surgical treatment of ROP and to evaluate the short term outcome of the disease in Italy.. It is a prospective multicenter observational study; all infants with a birth weight (BW) ≤ 750 g and/or a gestational age (GA) ≤27 weeks born between January 1st 2008 and December 31st 2009 in 25 III level Italian neonatal intensive care units were eligible for the study.. 421 infants were examined: 265 (62.9%) developed ROP and 102 (24.2%) P-ROP.. P-ROP is the most aggressive type of ROP. It associates with lower GA and sepsis. Obstetricians and Neonatologists must focus on the reduction of severe preterm births and on the prevention of neonatal early and late onset sepsis in order to reduce the incidence of P-ROP.

Topics: Birth Weight; Erythropoietin; Female; Gestational Age; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Intracranial Hemorrhages; Italy; Laser Therapy; Male; Multivariate Analysis; Prospective Studies; Retinopathy of Prematurity; Sepsis

Very preterm infants commonly develop anemia requiring multiple red blood cell transfusions (RBCTx). This is in part attributable to heavy laboratory phlebotomy loss. Quantification of the extent to which laboratory blood loss contributes to anemia sufficient to prompt RBCTx has not been examined.. Twenty-six preterm infants weighing less than 1500 g at birth requiring ventilator support who received one or more RBCTx were intensively studied during the first month of life. Hemoglobin (Hb) loss via laboratory blood loss and RBC senescence and Hb gain from RBCTx were precisely accounted for in a Hb mass balance mathematical model developed to assess the impact of phlebotomy on RBCTx when restrictive RBCTx criteria were applied.. Study subjects had a birth weight of 880 ± 240 g (mean ± SD) and a Hb level of 14.4 ± 2.4 g/dL at birth and received 3.81 ± 2.15 RBCTx during the study period. Modeling indicated that even with the total elimination of laboratory phlebotomy loss, a reduction of 41% to 48% in RBCTx was achievable.. The present modeling results indicate that while phlebotomy reduction can significantly decrease the number of RBCTx administered to preterm infants, total elimination of all RBCTx will likely require other approaches, for example, stimulation of erythropoiesis with erythropoiesis-stimulating agents.

Topics: Anemia, Neonatal; Birth Weight; Blood Transfusion; Blood Volume; Blood Volume Determination; Computer Simulation; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Male; Models, Cardiovascular; Phlebotomy; Pregnancy

In spite of improvement in obstetrical care, pregnancy in women with type 1 diabetes mellitus is associated with increased perinatal morbidity and mortality. Hyperglycemia during pregnancy causes excessive fetal growth and chronic fetal hypoxia as reflected in increased erythropoietin (EPO) levels in amniotic fluid (AF).. We hypothesized that the degree of fetal hypoxia would correlate with fetal oxidative and nitrosative stress as evidenced ty the concentration of specific biomarkers in AF.. 19 pregnant women with type 1 or insulin-treated gestational diabetes mellitus were studied. AF samples were collected and processed for EPO, meta-tyrosine, nitro-tyrosine and 8-hydroxy-2-deoxiguanosine by chemiluminescent immunoassay and high-performance liquid chromatography coupled to tandem mass spectrometry methods, respectively.. The mean (SD) of the last HbA1c concentration before delivery was 7.7% (1.1). Median gestational age was 258 days (range 231-268). Birth weight was 3,868 ± 695 g with a z-score >2 SD in 47% of the cases. A significant correlation was found between the concentrations of AF EPO and meta-tyrosine/phenylalanine ratio (p < 0.001), nitro-tyrosine (p < 0.01) and 8-oxo-dG/2dG ratio (p < 0.001).. We confirmed that fetuses of type 1 diabetes or insulin-treated gestational diabetes pregnancies experience chronic hypoxia as reflected by increased EPO concentrations in AF near term. Moreover, EPO levels significantly correlated with the concentration of oxidative and nitrosative stress biomarkers in AF. This pro-oxidant status may predispose newborn infants to poor postnatal adaptation and early neonatal complications.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Amniocentesis; Amniotic Fluid; Biomarkers; Birth Weight; Chromatography, High Pressure Liquid; Chronic Disease; Deoxyguanosine; Diabetes Mellitus, Type 1; Diabetes, Gestational; Erythropoietin; Female; Fetal Hypoxia; Gestational Age; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Immunoassay; Infant, Newborn; Insulin; Male; Nitrosation; Oxidative Stress; Pilot Projects; Pregnancy; Pregnancy in Diabetics; Tandem Mass Spectrometry; Tyrosine; Young Adult

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

Despite advances in clinical care, the incidence of bronchopulmonary dysplasia (BPD) remains high in premature infants. Erythropoietin (EPO) is used for the treatment of anemia of prematurity (AOP) to decrease blood transfusion needs. EPO has been shown to mobilize circulating endothelial progenitor cells and to enhance lung repair in animal models.. To determine whether EPO treatment for AOP was associated with a reduced incidence of BPD in premature infants.. This retrospective study was performed on all live-born neonates with birth weights from 500 to 1,500 g and gestational age (GA) from 22 to 32 weeks admitted from 1994 to 2002. Infants who received EPO and those who did not receive EPO were compared for incidence of BPD and other morbidities.. Of 478 patients, 297 received EPO before 36 weeks' postmenstrual age (group 1) and 181 did not receive EPO (group 2). Group 1 was of similar birth weight but lower GA than group 2. The incidence of BPD was lower in group 1 than group 2 (26 vs. 36%, p = 0.03); after adjusting for significant risk factors, the adjusted odds ratio for BPD was 0.50 (95% CI 0.32, 0.79), p = 0.0028. The BPD rate was much lower when EPO was initiated before 4 weeks of age (16%) as compared to later initiation (44%).. This study shows an association between EPO treatment and reduced incidence of BPD in preterm infants, particularly when EPO treatment was initiated within the first 4 weeks of life.

Topics: Birth Weight; Bronchopulmonary Dysplasia; California; Erythropoietin; Female; Gestational Age; Humans; Incidence; Infant; Infant, Extremely Low Birth Weight; Infant, Extremely Premature; Infant, Newborn; Injections, Subcutaneous; Male; Oxygen; Retrospective Studies; Treatment Outcome

Despite the common occurrence of anemia in very low birth weight (VLBW) infants, the erythropoiesis and Hb production rates and their relationship to plasma erythropoietin (EPO) concentrations remain unknown in these subjects. To determine these quantities, all blood removed by phlebotomy and administered by red blood cell (RBC) transfusion over the first 30 days of life was recorded in 14 ventilated VLBW infants born at 24 to 28 weeks of gestation. Discarded blood from frequent clinically ordered laboratory blood samples was used to construct plasma EPO, Hb, and RBC concentration-time profiles for each infant. A pharmacodynamic Hb mass balance model that accounted for the dynamic hematological conditions experienced by these infants was simultaneously fitted to the plasma EPO, Hb, and RBC concentrations from each individual subject, while accounting for subject growth. Based on the model estimates, an average of 4.69 g of Hb was produced over the first 30 days of life, compared with 5.97 g removed by phlebotomies and 12.3 g administered by transfusions. These high transfusion amounts were consistent with a relatively short RBC life span and rapidly expanding blood volume with infant growth. The estimated mean body weight-scaled Hb production rate dropped nearly 3-fold after birth to 0.144 g/day x (kg)(3/4). Although only estimated in a subset of the subjects, the mean plasma EPO EC(50) of 28.5 mU/ml and maximal Hb production rate (E(max)) indicated that a severalfold increase in Hb production rate could be achieved with only a modest increase in plasma EPO concentrations.

Topics: Birth Weight; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Female; Gestational Age; Hemoglobins; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Male; Models, Biological; Phlebotomy; Respiration, Artificial

Recombinant human erythropoietin (rhEPO) is used for the treatment of anemia of prematurity. However, it has also been found to have properties similar to vascular endothelial growth factor (VEGF), the major angiogenic factor implicated in the pathogenesis of retinopathy of prematurity (ROP). We sought to determine whether rhEPO is an independent risk factor for the development of ROP.. Data were analyzed from 264 infants admitted to the Loma Linda University Children's Hospital neonatal intensive care unit in 1994 and 2002. The data included demographic characteristics, incidence of major morbidities, rhEPO treatment, number of red blood cell transfusions received, and incidence and severity of ROP. A multiple logistic regression model was used to determine the relation of the studied risk factors to the incidence (any stage) and severity (threshold ROP requiring cryotherapy or laser photocoagulation) of ROP.. The risk of developing ROP increased among infants who received >20 doses of rhEPO was higher compared with those who received < or =20 doses (OR, 3.53; 95% CI, 1.59, 7.85). These infants were also more likely to require laser photocoagulation (OR, 4.31; 95% CI, 1.99, 9.33). The age at which rhEPO was started was also a significant risk factor, with those starting rhEPO after 20 days of age having almost fourfold the risk of ROP compared with those starting it on or before 20 days of age (OR, 3.57; 95% CI, 1.59, 8.03).. rhEPO was found to be a significant independent risk factor for the development of ROP.

Topics: Age Factors; Anemia, Neonatal; Birth Weight; California; Dose-Response Relationship, Drug; Erythropoietin; Follow-Up Studies; Humans; Incidence; Infant, Newborn; Models, Statistical; Prognosis; Recombinant Proteins; Regression Analysis; Retinopathy of Prematurity; Retrospective Studies; Risk Factors

To evaluate the frequency and severity of retinopathy of prematurity in extremely low-birth-weight (ELBW) infants who received recombinant human erythropoietin (rHuEPO), and to compare the frequency of blood cell transfusions these infants required with a matched control group who did not receive rHuEPO.. Retrospective cohort analysis.. Level III neonatal intensive care unit in a large academic medical center.. One hundred thirty-eight ELBW infants who received rHuEPO and 138 ELBW infants who did not (control group) but who were matched by birth weight, gestational age, sex, and year of birth and who survived to the first ophthalmologic examination.. The rHuEPO was started before the 8th day of life in 115 (83%) of the 138 infants. Stages III-V retinopathy of prematurity occurred with similar frequency in both groups of infants (rHuEPO group 19% [26 infants] vs control group 20% [27 infants], p>0.05). Infants in the rHuEPO group received fewer transfusions on average during their hospitalization compared with those in the control group (4.2 vs 6.1 transfusions, p<0.01).. Use of rHuEPO for prevention or treatment of anemia of prematurity in ELBW infants does not increase the frequency of severe retinopathy of prematurity and reduces the number of transfusions.

Topics: Anemia, Neonatal; Birth Weight; Blood Transfusion; Cohort Studies; Erythropoietin; Female; Gestational Age; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Male; Pregnancy; Pregnancy Outcome; Recombinant Proteins; Retinopathy of Prematurity; Retrospective Studies; Risk Assessment

To determine the effects of maternal diabetes on fetal iron status using serum transferrin receptors (STfR) and their ratio to ferritin (TfR-F index) in cord blood.. Iron, ferritin, erythropoietin, STfR and haemoglobin concentration were measured and TfR-F index calculated in 97 maternal/cord blood pairs. Forty-nine women had type 1 diabetes (diagnosed before pregnancy) and these were compared with forty-eight non- diabetic controls. The women with type 1 diabetes were recruited consecutively from attendance at the joint antenatal endocrine clinic while the control group of women was recruited from consecutive attendance at the remaining antenatal clinics.. The infants of the diabetic women had significantly lower levels of ferritin (47 vs 169 mug/l; p<0.01) and higher STfR (17.4 vs 12.9 mg/l; p<0.01) and TfR-F index (10.4 vs 5.8; p<0.01) than controls. They were also significantly more acidotic at birth (7.25 vs 7.30; p<0.01), were born at an earlier gestation (36.7 vs 39.7 weeks; p<0.01) and had higher z Scores for weight (0.53 vs 0.02; p = 0.016).. Maternal diabetes causes depletion of fetal iron stores and is associated with higher fetal iron demands as indicated by higher STfR level and TfR-F index in cord blood.

Topics: Birth Weight; Diabetes Mellitus, Type 1; Erythropoietin; Female; Ferritins; Fetal Blood; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Iron; Maternal-Fetal Exchange; Pregnancy; Pregnancy in Diabetics; Receptors, Transferrin

Anemia is prevalent among pregnant adolescents, but few data exist on biochemical indicators of iron status in this group. We hypothesized that among an at-risk population of African-American, pregnant adolescents, the degree of iron depletion and deficiency would be marked, and that iron deficiency anemia would comprise the majority of the observed anemia. To examine this, blood samples were collected from 80 girls (< or =18 y old) attending an inner city maternity clinic, 23 of whom were studied longitudinally in the 2nd and 3rd trimesters depending on contact at the clinic. Sample sizes for the biomarkers varied according to the blood volume available at the time the assays were completed. Descriptive statistics were applied to characterize iron status, and multivariate regression and logistic analyses were used to identify significant determinants of iron status. Depleted iron stores (ferritin < or = 15 microg/L) were indicated for 25% (n = 44) and 61% (n = 59) of adolescents during the 2nd and 3rd trimesters, respectively. Serum folate (39.3 +/- 15.4 nmol/L, n = 60), RBC folate (2378 +/- 971 nmol/L, n = 60), and serum vitamin B-12 concentrations (313 +/- 163 pmol/L, n = 60) were within normal ranges. Adolescents with serum transferrin receptor:serum ferritin ratios (R:F ratio) > 300 during the 2nd trimester were 12.5 times (95% CI 2.83, 55.25) more likely to be classified with iron deficiency anemia during the 3rd trimester (P = 0.0002) than those with lower ratios. Estimates of body iron were lower in those tested after wk 26 of gestation (P < 0.0001), and reserves were depleted in 5.0% vs. 31.3% of the 2nd (n = 40) and 3rd (n = 48) trimester cohorts, respectively. In conclusion, iron-deficiency anemia was prevalent among these pregnant minority adolescents. Targeted screening and interventions to improve diet and compliance with prenatal iron supplementation are warranted for this at-risk group.

Topics: Adolescent; Anemia, Iron-Deficiency; Birth Weight; Black or African American; Body Mass Index; Erythropoietin; Female; Ferritins; Folic Acid; Gestational Age; Hemoglobins; Humans; Iron; Iron Deficiencies; Leptin; Pregnancy; Pregnancy Complications; Pregnancy in Adolescence; Regression Analysis; Transferrin; Vitamin B 12; Weight Gain

Animal and human studies demonstrated elevated erythropoietin (EPO) levels in response to intrauterine hypoxic events. Other studies documented an association between fetal hypoxia and elevated nucleated red blood cell (NRBC) counts and have speculated that it is the elevation of EPO that results in an increase in NRBC counts. Thus, the purpose of our study was to determine the correlation between EPO levels and NRBC counts in the human fetus.. Data were collected prospectively between April and July of 2003. Term singleton pregnancies were eligible to participate in the study. Umbilical cord blood was collected immediately after birth for determination of fetal EPO levels and NRBC counts.. Forty pregnancies formed the study population. The mean gestational age at delivery was 39.5 +/- 1.2 weeks (+/-SD) and the mean birth weight was 3500 +/- 372 g. The median EPO (mU/mL) was 34 (range 13-427). The median NRBC/100 white blood cells was 10 (range 0-150). A simple regression analysis indicated that NRBC counts are significantly and positively correlated with EPO (P=.0004, R(2)=0.287).. Our results suggest a significant association between EPO and NRBC counts in term singleton fetuses. These results support the hypothesis that fetal NRBC and EPO are interrelated. However, the relatively low R(2) indicates that there are other (yet to be determined) hypoxia-derived mediators that result in an elevation of fetal NRBC counts.

Topics: Adult; Biomarkers; Birth Weight; Erythroblasts; Erythrocyte Count; Erythropoietin; Female; Fetal Blood; Fetal Hypoxia; Humans; Infant, Newborn; Postpartum Period; Predictive Value of Tests; Pregnancy; Probability; Prospective Studies; Regression Analysis; Sampling Studies; Sensitivity and Specificity

In this study we investigated whether chronic fetal hypoxia, as indicated by amniotic fluid erythropoietin levels, is associated with perinatal morbidity in type 1 diabetic pregnancies.. A total of 331 women with type 1 diabetes had at least one childbirth between 1995 and 2000. The amniotic fluid erythropoietin concentration was measured in 156 diabetic singleton pregnancies at a median time of 1 day before Caesarean section without labour contractions and in 19 healthy control subjects at Caesarean section.. The median amniotic fluid erythropoietin level was 14.0 mU/ml (range 2.0-1975.0) in diabetic pregnancies and 6.3 mU/ml (range 1.7-13.7) in controls (p<0.0001). Of the 156 diabetic patients, 21 (13.5%) had amniotic fluid erythropoietin levels higher than 63.0 mU/ml. Amniotic fluid erythropoietin levels correlated negatively with umbilical artery pH (r=-0.49, p<0.0001) and pO2 (r=-0.62, p<0.0001) at birth and neonatal lowest blood glucose level (r=-0.47, p<0.0001). Positive correlations were found between amniotic fluid erythropoietin levels and umbilical artery pCO2 (r=0.49, p<0.0001) and last maternal HbA1c (r=0.43, p<0.0001). Furthermore, a U-shaped correlation was demonstrated between amniotic fluid erythropoietin levels and birthweight z score (z score below -0.6 SD units: r=-0.63, p=0.0007; z score above +1.0 SD units: r=0.32, p=0.0014). Neonatal hypoglycaemia, hypertrophic cardiomyopathy and admission to the neonatal intensive care unit occurred significantly more often in cases with high amniotic fluid erythropoietin levels (>63.0 mU/ml) than in those with normal levels. Multivariate logistic regression analysis revealed that amniotic fluid erythropoietin was the only variable independently related to low umbilical artery pH (<7.21; p<0.0001) and neonatal hypoglycaemia (p=0.002). Low umbilical artery pO2 (<15.0 mm Hg) was explained by amniotic fluid erythropoietin (p<0.0001) and birthweight z score (p=0.004).. Antenatal high amniotic fluid erythropoietin levels can identify type 1 diabetic pregnancies at increased risk of severe perinatal complications.

Topics: Adult; Amniotic Fluid; Biomarkers; Birth Weight; Blood Glucose; Cesarean Section; Erythropoietin; Female; Fetal Diseases; Gestational Age; Humans; Infant, Newborn; Infant, Newborn, Diseases; Maternal Age; Morbidity; Pregnancy; Pregnancy in Diabetics; Umbilical Arteries

The purpose of this study was to examine whether fetal leptin concentration correlates with severity of chronic or subchronic fetal hypoxia as indicated by increased fetal concentrations of erythropoietin in fetuses of mothers with Type I (insulin dependent) diabetes mellitus.. We measured leptin and erythropoietin concentrations in cord plasma and amniotic fluid with radioimmunoassay in 25 pregnancies (gestational age 37.2 +/- 1.0 weeks). Fetuses with amniotic fluid erythropoietin over 22.5 mU/ml were classified as hypoxic (n = 9) and those with amniotic fluid erythropoietin below 22.5 mU/ml (n = 16) as non-hypoxic.. The hypoxic fetuses had significantly higher cord leptin concentrations than non-hypoxic fetuses (median 36.8; range, 12.5-135.1 vs median 16.2; range, 3.7-52.2 micrograms/l), (p = 0.0066). Cord plasma leptin (n = 25) correlated directly with amniotic fluid erythropoietin (r = 0.727, p = 0.0001), with cord plasma erythropoietin (r = 0.644, p = 0.0005) and with the maternal last trimester HbA1C (r = 0.612, p = 0.0019) and negatively with cord artery pO2 (r = -0.440, p = 0.032), and pH (r = -0.414, p = 0.040).. Fetal leptin concentrations increased concomitantly with erythropoietin during chronic or subchronic hypoxia. This phenomenon could indicate a role for leptin in fetal adaptation to hypoxia.

Topics: Amniotic Fluid; Birth Weight; Body Constitution; Diabetes Mellitus, Type 1; Erythropoietin; Female; Fetal Blood; Fetal Hypoxia; Gestational Age; Glycated Hemoglobin; Humans; Infant, Newborn; Leptin; Male; Pregnancy; Pregnancy in Diabetics; Reference Values; Regression Analysis

We sought to determine whether umbilical cord plasma erythropoietin levels were different in deliveries complicated by meconium passage and to determine whether this response is influenced by gestational age.. Fetal erythropoietin levels were measured in 203 appropriately grown neonates at 37 to 43 weeks of gestation; among those, 70 had passed meconium.. Meconium passage in the entire population was associated with elevated fetal erythropoietin levels (68 vs 31 mIU/mL; P <.001). Cord blood gases, pH, base deficit, and PO (2), as well as the 1- and 5-minute Apgar scores, were not different between the meconium and no-meconium groups. Gestational age and birth weights were significantly higher in the meconium group. Stepwise multiple regression analysis with meconium and gestational age used as the independent variables showed both meconium and gestational age to be independently associated with fetal erythropoietin levels (r = 0.356, F = 14.5; meconium, P <.001; gestational age, P <.01).. These results suggest that meconium passage can be associated with chronic fetal hypoxia as demonstrated by elevated fetal erythropoietin levels, independent of gestational age.

Topics: Apgar Score; Birth Weight; Erythropoietin; Female; Fetal Blood; Fetal Hypoxia; Gestational Age; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Logistic Models; Meconium; Odds Ratio; Oxygen; Pregnancy; Regression Analysis

The estimation of cord blood erythropoietin in subjects with pre-eclampsia and eclampsia.. Erythropoietin was measured, using ELISA, in the cord blood of infants born to 83 mothers with pre-eclampsia, and 7 with eclampsia. Another 90 subjects with no evidence of pre-eclampsia or eclampsia were taken as control subjects. Maternal parity, gestational age, blood pressures, 24-h urine protein and Apgar scores of the infants delivered were also noted.. Cord blood erythropoietin levels were statistically significantly higher (P<0.001) in infants born to mothers with pre-eclampsia and eclampsia. There was a significant positive correlation (P<0.01) between cord blood erythropoietin levels and maternal blood pressure (systolic and diastolic) and albuminuria. A negative correlation (P<0.01) was observed with the birth weights of infants.. Pre-eclampsia and eclampsia are associated with higher levels of cord blood erythropoietin.

Topics: Adult; Albuminuria; Apgar Score; Biomarkers; Birth Weight; Blood Pressure; Case-Control Studies; Eclampsia; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Female; Fetal Blood; Gravidity; Humans; Hydrogen-Ion Concentration; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Uric Acid

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 purpose of this study was to investigate the placental passage of erythropoietin in a placental perfusion model ex vivo.. In an open system 18 placentas were perfused on both the maternal and the fetal side. Erythropoietin and a reference substance were added to either the maternal or fetal perfusion medium. In the first series of experiments, radiolabeled erythropoietin was added to the perfusion medium in four different concentrations to help determine the transfer rate of erythropoietin. Based on the results of these experiments unlabeled erythropoietin was added to the perfusate in three different concentrations. Radiolabeled erythropoietin was used in addition to erythropoietin because measuring radioactivity in a gamma counter is less expensive than measuring by immunoassay.. Accumulation of radioactivity in the venous portion of the fetal circuit was only 3.21% of the activity added to the maternal circuit. No evidence of transfer of erythropoietin to the contralateral compartment was noted, regardless of whether the test substance was added maternally or fetally. These results were independent of the concentration used. The reference compound antipyrine showed a mean transfer rate of 27.9%, which is in keeping with previous results.. There is no transport of erythropoietin across fetal membranes. This finding is particularly remarkable in view of results published recently indicating the placenta as a site of erythropoietin production. The lack of its transport across the human placenta is most likely due to its high molecular weight.

Topics: Biological Transport; Birth Weight; Erythropoietin; Extraembryonic Membranes; Female; Humans; In Vitro Techniques; Iodine Radioisotopes; Maternal-Fetal Exchange; Molecular Weight; Placenta; Pregnancy; Pregnancy Trimester, Third; Time Factors

The aim of this study was to compare the neonatal nucleated red blood cell counts in preterm infants in the presence and absence of clinical and histologic chorioamnionitis while controlling for gestational age and birth weight percentile.. Nucleated red blood cell counts were obtained from preterm infants delivered after preterm labor or preterm premature rupture of membranes. Patients were divided on the basis of clinical and histologic chorioamnionitis. Nucleated red blood cell counts between groups were compared, and regression analysis controlling for gestational age and birth weight percentile was performed.. Of 359 patients, both measures of infection status were significantly associated with increased nucleated red blood cell counts. In the regression analysis histologic chorioamnionitis retained significance, whereas clinical chorioamnionitis did not.. Histologic chorioamnionitis produces an erythropoietic response in the fetus. Whether fetal erythropoiesis is a direct response to mediators of inflammation or whether it is the result of a rise in erythropoietin is unknown.

Topics: Birth Weight; Chorioamnionitis; Erythrocyte Count; Erythropoiesis; Erythropoietin; Female; Fetal Blood; Fetal Membranes, Premature Rupture; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Obstetric Labor, Premature; Pregnancy; Regression Analysis

Erythropoietin (EPO) levels were measured using an ELISA method in umbilical cord plasma from 68 appropriately grown neonates at 27 to 43 weeks of gestation (EGA). A consistent but small (5%) difference was found between the EPO levels in the umbilical artery (Ua), 21.0 +/- 2.5 mlU/mL (mean +/- SEM), and umbilical vein (Uv), 22.0 +/- 2.7 mlU/mL (p < 0.02, n = 30). Significant inverse correlations were found between Ua EPO levels and pO2 (r = -0.44, p < 0.002), pH (r = -0.68, p < 0.0001), as well as base deficit (r = -0.56, p < 0.0001). A significant correlation was found between EGA and Ua EPO from 27 to 43 weeks of gestation (r = 0.45, p < 0.001, n = 68). One and 5 minute Apgar scores did not correlate with EPO. These findings indicate that EPO correlates strongly with cord gas parameters and thus may serve as a clinically useful marker for both subacute fetal distress and chronic uteroplacental insufficiency.

Topics: Apgar Score; Birth Weight; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Fetal Blood; Gestational Age; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Oxygen; Reference Values

The need for red cell transfusions is reduced but not eliminated by recombinant human erythropoietin (rhEPO) in very low birthweight (VLBW) infants. To detect factors associated with the decision to transfuse VLBW infants during rhEPO treatment and to explain rhEPO 'non-responders', the subgroup of those 120 VLBW infants who were treated with rhEPO 750 IU/kg per week in the second European Multicentre rhEPO Trial was evaluated. Sixty (50%) infants received at least one transfusion during erythropoietin treatment. Transfusion was frequent in infants with extremely low birthweight (79% for 750-999 g), low gestational age (70% for < or = 28 weeks), low initial haematocrit or low initial reticulocyte count (61% for haematocrit < or = 0.48 and reticulocytes < or = 9%, respectively). Considerable differences among centres were found for sampling blood loss, iron supply, and transfusion rate, which ranged from 13% to 73% and was related to the volume of diagnostic blood loss (19% vs 80% for blood loss < 1 vs > or = 1 ml/kg per day). The prognostic variables birthweight, initial haematocrit, and gestational age were found to be most predictive for transfusion. To improve rhEPO response in VLBW infants, there is a need to minimise diagnostic blood loss, to prevent iron deficiency, and to develop rational criteria for transfusion in preterm infants.

Topics: Birth Weight; Erythrocyte Transfusion; Erythropoietin; Female; Gestational Age; Hematocrit; Hematologic Tests; Humans; Infant; Infant, Newborn; Infant, Very Low Birth Weight; Male; Multivariate Analysis; Prognosis; Recombinant Proteins; Risk Factors; Treatment Outcome

In this study we determine the erythropoietin levels and hematocrit in 22 women with preterm labor, 21 with insulin-dependent diabetes, 22 with preeclampsia, and 20 with normal gestation. The erythropoietin level was higher in the preeclamptic group than in the diabetic group compared with the normal and premature groups. There were no hypoxic fetuses. From this study, we found that the mechanism of increased erythropoietin levels in neonates can be different from fetal hypoxia. Further studies are needed on this subject.

Topics: Adult; Birth Weight; Diabetes Mellitus, Type 1; Erythropoietin; Female; Fetal Blood; Humans; Obstetric Labor, Premature; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Prospective Studies

To evaluate the kinetics of erythropoietin (EPO) production and address the pathogenesis of anemia of prematurity, we measured EPO levels in infants during the first year of life.. Using a radioimmunoassay, serum EPO levels were measured in 97 infants classified into three groups according to weight: group A, n = 40, < 1,500 g; group B, n = 19, 1,500-2,499 g; and group C, n = 38, > or = 2,500 g.. The serum EPO level ranged widely during the early neonatal period from days 0 to 6 (group A, < 5 to 307 mU/ml; group B, 10-340 mU/ml; and group C, 9-108 mU/ml). EPO reached its lowest level (< 20 mU/ml) between days 7 and 50 in all groups. The hemoglobin concentration reached its nadir between days 51 and 150 in all groups, with the lowest concentration observed in low birth weight infants. In contrast, the EPO level during the anemic phase was approximately 20 mU/ml and was independent of birth weight. A negative correlation between serum EPO level and hemoglobin concentration was observed only in group C (r = -0.54, p < 0.05). The negative slope of the regression equation in group C exceeded that of groups A and B (p < 0.05). When the relationship between EPO and Hb was evaluated over periods of 7-50 days, 51-100 days, and > 101 days, respectively, we noted a significant correlation between values on days 7 and 50 in group A (r = -0.53, p < 0.05) and between days 51 and 100 in group B (r = -0.76, p < 0.05).. These data suggest the appreciable EPO production in premature infants, but its insufficient response to the depressed hemoglobin level, implying the need to administer exogenous EPO to infants with anemia of prematurity.

Topics: Anemia; Birth Weight; Erythrocyte Count; Erythropoietin; Female; Hemoglobins; Humans; Infant; Infant, Newborn; Infant, Premature; Male

To determine whether prophylactic treatment with recombinant human erythropoietin (rHuEPO) and iron would reduce the need for blood transfusions, we randomly assigned 22 premature infants with gestational ages less than or equal to 32 weeks and birth weights less than or equal to 1.75 kg to receive rHuEPO, 400 IU/kg three times a week, plus iron, 20 mg/wk intravenously, from the second day of life (11 infants), or no rHuEPO and no iron (11 infants). The two groups had similar birth weights and clinical variables. The treated infants required fewer blood transfusions (0.8 +/- 1.5 vs 3.1 +/- 2.1; p = 0.01) and less volume of packed erythrocytes (14.2 +/- 25.9 vs 48.4 +/- 34.0 ml/kg; p = 0.02). The amounts of blood sampled were not different (19.5 +/- 21.1 vs 27.8 +/- 19.1 ml/kg; p = 0.35). Reticulocyte and hematocrit values were higher in the treated group (4.46% +/- 0.8% vs 1.49% +/- 1.1% (p = 0.0001) and 48.1% +/- 7.3% vs 43.8% +/- 4.7% (p = 0.004), respectively). No side effects of either rHuEPO or intravenously administered iron were noted. These data indicate that rHuEPO, in combination with iron supplementation, is effective in reducing the need for blood transfusions in the premature infant. More information is needed on dosage, timing, and iron and vitamin supplementation.

Topics: Birth Weight; Blood Cell Count; Blood Transfusion; Erythrocyte Transfusion; Erythropoietin; Gestational Age; Hematocrit; Humans; Infant, Newborn; Infant, Premature; Injections, Intravenous; Injections, Subcutaneous; Iron; Recombinant Proteins; Reticulocytes

In the present study the antepartum relationship between maternal diabetic glucose control and fetal hypoxaemia was examined in 44 Type 1 (insulin-dependent) diabetic and 23 non-diabetic control pregnancies. Maternal HbA1C was used to assess maternal integrated blood glucose control while fetal metabolic control was evaluated by antepartum glucose, insulin, and C-peptide determinations in amniotic fluid at elective caesarean delivery. Fetal hypoxaemia was assessed indirectly by fetal umbilical vein plasma erythropoietin level at delivery. A prospectively developed statistical pathway model was used to examine the relationship of these variables. In applying forced stepwise multiple regression with this model, we observed in the diabetic subjects that mean maternal HbA1C during the last month of pregnancy correlated significantly with fetal umbilical venous erythropoietin at delivery (r = 0.57, p less than 0.001). Additional significant contributions to umbilical venous erythropoietin were found for amniotic fluid glucose and amniotic fluid insulin when these two independent variables were added in stepwise fashion (p less than 0.01). We conclude that in diabetic pregnancy, antepartum control of maternal hyperglycaemia is a significant factor associated with fetal hypoxaemia. We speculate that this effect is mediated through perturbations which accelerate fetal metabolism and which is expressed by amniotic fluid levels of glucose and insulin.

Topics: Amniotic Fluid; Biomarkers; Birth Weight; Blood Glucose; C-Peptide; Cesarean Section; Diabetes Mellitus, Type 1; Erythropoietin; Female; Fetal Blood; Glucose; Glycated Hemoglobin; Humans; Infant, Newborn; Insulin; Models, Biological; Pregnancy; Pregnancy in Diabetics; Prospective Studies; Reference Values; Regression Analysis; Umbilical Veins

Nonhuman primate models of gestational diabetes have produced fetopathies most similar to those of the human infant of the mother with gestational diabetes (IGDM). Fetal hyperglycemia, hyperinsulinemia, macrosomia, selective organomegaly, intrauterine death, and placental hyperplasia are hallmarks of the fetopathy of the IGDM. The chronic infusion of insulin into the fetus of a normal pregnant rhesus monkey results in fetal hyperinsulinemia with normal to low plasma metabolic substrate concentrations. Under these conditions, fetal hyperinsulinemia is sufficient to cause fetal growth and hormone changes observed in the human IGDM. Our studies provide evidence that the soft tissue hyperplasia in the fetal macrosomia syndromes in humans and nonhuman primates in which fetal hyperinsulinemia is observed is the direct result of that chronic in utero hyperinsulinemia.

Topics: Adipose Tissue; Amino Acids; Animals; Birth Weight; Blood Glucose; C-Peptide; Disease Models, Animal; Erythropoietin; Female; Fetal Blood; Fetal Hypoxia; Fetus; Glucagon; Hydrocortisone; Insulin; Macaca mulatta; Pregnancy; Pregnancy in Diabetics

On the basis that fetal levels of plasma erythropoietin (Ep) may reflect fetal oxygenation the primary purpose of the present study was to assess the relation between Ep measured in cord plasma at delivery and the intrapartum fetal heart rate (FHR) record. A scoring system for interpreting FHR recordings blindly was prospectively utilized in 41 selected human pregnancies during the 4 h immediately preceding birth. The correlation of the overall mean FHR score for each individual patient with cord plasma Ep was significant such that the highest Ep levels were observed in those infants with the most abnormal FHR scores. Furthermore, when the birthweights of the infants were adjusted for gestational age, sex, and birth order, birthweight centile was negatively correlated with cord plasma Ep. When both FHR score and birthweight were simultaneously correlated with cord plasma Ep using multiple regression, the combined effect of these two factors improved the association of either alone with both contributing approximately equally.

Topics: Birth Weight; Delivery, Obstetric; Erythropoietin; Female; Fetal Blood; Fetal Heart; Fetal Monitoring; Heart Rate; Humans; Hypoxia; Pregnancy; Prospective Studies

Since several hours of hypoxemia in fetal animals is sufficient to cause an increase in the plasma erythropoietin level and since labor may be associated with fetal hypoxemia, this study was undertaken to determine if erythropoietin levels in cord blood were higher in fetuses subjected to labor. Two groups of term (37 to 41 weeks) singleton pregnancies were compared: (1) those delivered by elective repeat cesarean section without prior labor (n = 18) and (2) those delivered vaginally (n = 23). Erythropoietin was measured by a radioimmunoassay in which a highly purified human erythropoietin (70,000 U/mg of protein) was used and which has a sensitivity limit of 4 to 5 mU/ml. The mean cord serum erythropoietin level was higher in pregnancies with labor (46 +/- 34 mU/ml, mean +/- SD) compared to those without (26 +/- 10, p less than 0.02). There were no differences between the two groups for maternal age, gestational age, birth weight, infant sex, or Apgar scores. No association of erythropoietin with either gestational age or sex was found. In 11 pregnancies without labor, comparisons were made among simultaneously obtained samples of umbilical arterial plasma, umbilical venous plasma, and mixed cord serum. Although there were no differences between umbilical arterial and umbilical venous plasma erythropoietin levels (21.3 +/- 9.3 versus 19.0 +/- 7.8 mU/ml), mixed cord serum was inexplicably higher (24.4 +/- 9.5 mU/ml, p less than 0.01). We concluded that in uncomplicated pregnancies the duration and intensity of labor are sufficient to cause an increase in the fetal erythropoietin level at delivery.

Topics: Adolescent; Adult; Apgar Score; Birth Weight; Erythropoietin; Female; Fetal Blood; Fetal Hypoxia; Humans; Infant, Newborn; Labor, Obstetric; Male; Pregnancy; Radioimmunoassay

We performed sequential studies in 45 premature infants (birth weights less than 1500 g) from 7 to 120 days of age to determine factors governing the erythropoietin response to a declining hemoglobin concentration. The hemoglobin level and the plasma erythropoietin showed a significant inverse correlation (r = 0.50, P less than 0.001), as did, even more strikingly, the plasma erythropoietin response and the infants' oxygen-unloading capacity (r = 0.55, P less than 0.001). In infants with "right-shifted" oxygen-hemoglobin dissociation curves (hemoglobin F less than 30 per cent) hemoglobin levels fell 2 to 3 g per deciliter lower than those in infants with "left-shifted" curves (hemoglobin F greater than 60 per cent) before comparable erythropoietin responses occurred. It appears that premature infants respond appropriately to alterations in oxygen unloading capacity and that the position of the oxygen-hemoglobin dissociation curve and not the hemoglobin concentration alone has a major role in modulated erythropoiesis.

Topics: Birth Weight; Erythropoietin; Female; Fetal Hemoglobin; Follow-Up Studies; Humans; Infant, Newborn; Infant, Premature; Male; Oxygen; Oxygen Consumption; Partial Pressure; Radioimmunoassay

Topics: Anemia, Neonatal; Biological Transport; Birth Weight; Cell Survival; Erythrocyte Count; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Folic Acid Deficiency; Hemoglobins; Humans; Infant Nutritional Physiological Phenomena; Infant, Newborn; Infant, Premature; Iron Deficiencies; Oxygen Consumption; Pregnancy; Reticulocytes; Vitamin B 12 Deficiency; Vitamin E Deficiency

Topics: Birth Weight; Carbon Radioisotopes; Erythropoietin; Female; Fetal Hemoglobin; Gestational Age; Hemoglobins; Humans; Infant, Newborn; Leucine; Placenta Diseases; Pregnancy

Topics: Birth Weight; Embryonic and Fetal Development; Erythrocyte Count; Erythropoietin; Female; Fetal Diseases; Gestational Age; Hematocrit; Humans; Hypoxia; Infant, Newborn; Infant, Premature; Pregnancy; Reticulocytes