losartan-potassium and Developmental-Disabilities

Hypoxic ischemic encephalopathy (HIE) is one of the leading causes of neonatal mortality in developing countries and leads to some form of neuro-developmental disability in latter part of life.. The aim of this study is to evaluate the role of erythropoietin (EPO) in neuroprotection for term newborn having HIE.. The literature search was done for various trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, Web of science, Scopus, Index Copernicus, and other database.. A total of nine studies fulfilled inclusion criteria. EPO has shown to cause reduction in death and disability, better long-term neuro-developmental outcome, improvement in EEG, and reduction in risk of cerebral palsy.. EPO treatment has neuroprotective effects against moderate/severe HIE and improves long-term behavioral neurological developments in neonates.

Topics: Asphyxia Neonatorum; Cerebral Palsy; Developmental Disabilities; Erythropoietin; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Neuroprotective Agents; Randomized Controlled Trials as Topic; Term Birth; Treatment Outcome

Recombinant human erythropoietin (rhEPO) is a promising pharmacological agent for neuroprotection in neonates.. To investigate whether prophylactic rhEPO administration in very preterm infants improves neurodevelopmental outcomes in a meta-analysis of randomized controlled trials (RCTs).. Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched in December 2016 and complemented by other sources.. RCTs investigating the use of rhEPO in preterm infants versus a control group were selected if they were published in a peer-reviewed journal and reported neurodevelopmental outcomes at 18 to 24 months' corrected age.. Data extraction and analysis followed the standard methods of the Cochrane Neonatal Review Group. The primary outcome was the number of infants with a Mental Developmental Index (MDI) <70 on the Bayley Scales of Infant Development. Secondary outcomes included a Psychomotor Development Index <70, cerebral palsy, visual impairment, and hearing impairment.. Four RCTs, comprising 1133 infants, were included in the meta-analysis. Prophylactic rhEPO administration reduced the incidence of children with an MDI <70, with an odds ratio (95% confidence interval) of 0.51 (0.31-0.81),. Prophylactic rhEPO improved the cognitive development of very preterm infants, as assessed by the MDI at a corrected age of 18 to 24 months, without affecting other neurodevelopmental outcomes. Current and future RCTs should investigate optimal dosing and timing of prophylactic rhEPO and plan for long-term neurodevelopmental follow-up.

Topics: Cognition Disorders; Developmental Disabilities; Erythropoietin; Humans; Infant; Infant, Extremely Premature; Infant, Newborn; Neuroprotection; Randomized Controlled Trials as Topic; Recombinant Proteins

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

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

Neonatal brain injury caused by extreme prematurity remains a great challenge for prevention. Erythropoietin (EPO) has shown neuroprotective effects in a series of neonatal experimental models and recent clinical trials of premature infants. In this meta-analysis of seven clinical trials, EPO was associated with a highly reproducible reduction in the risk of neurodevelopmental disability in preterm infants. However, there was no difference in the risk for morbidity, cerebral palsy, visual deficit, severe hearing deficit, necrotizing enterocolitis, intracranial hemorrhage and patent ductus arteriosus. The use of EPO, to some extent, is associated with reduction in neurodevelopmental disability in preterm infants. More double blind randomized controlled trials are needed to establish the best therapeutic approach for neuroprotection in preterm infants.

Topics: Brain Diseases; Developmental Disabilities; Erythropoietin; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Neuroprotective Agents; Randomized Controlled Trials as Topic

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

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

Recently, almost all kinds of general anesthetics currently used in human clinical anesthesia, have been shown to exert neurodegenerative effects such as apoptosis of neuronal cells during the rapid synaptogenesis of immature mammalian brains, and later neurocognitive impairment. There are several drugs or strategies to reduce this phenomenon such as alpha(2) agonist, xenon, melatonin, lithium, hypothermia and erythropoietin, but their safety and efficacy should be investigated much further. Some human studies have shown that surgery under general anesthesia in infancy is one of the risk factors of the impairment of neurocognitive function, but others including Dutch twin study have shown that it is not. Larger-sized prospective randomized studies in human such as SAFEKIDS (http://www.iars.org/safekids/) to ascertain if current clinical practice of general anesthesia impairs neurocognitive development of human neonates and infants, are expected. They will also clarify what kind of anesthetics and anesthetic strategies may be the risk factors of neurocognitive impairment in human neonates and infants.

Topics: Adrenergic alpha-2 Receptor Agonists; Anesthesia, General; Anesthetics, General; Animals; Apoptosis; Brain; Developmental Disabilities; Erythropoietin; Humans; Hypothermia, Induced; Infant; Infant, Newborn; Melatonin; Neurons; Xenon

Topics: Child Development; Child, Preschool; Developmental Disabilities; Double-Blind Method; Erythropoietin; Follow-Up Studies; Humans; Infant, Newborn; Infant, Premature; Neurodevelopmental Disorders; Neuroprotective Agents; Treatment Outcome

Very preterm infants are at risk of developing encephalopathy of prematurity and long-term neurodevelopmental delay. Erythropoietin treatment is neuroprotective in animal experimental and human clinical studies.. To determine whether prophylactic early high-dose recombinant human erythropoietin (rhEPO) in preterm infants improves neurodevelopmental outcome at 2 years' corrected age.. Preterm infants born between 26 weeks 0 days' and 31 weeks 6 days' gestation were enrolled in a randomized, double-blind, placebo-controlled, multicenter trial in Switzerland between 2005 and 2012. Neurodevelopmental assessments at age 2 years were completed in 2014.. Participants were randomly assigned to receive either rhEPO (3000 IU/kg) or placebo (isotonic saline, 0.9%) intravenously within 3 hours, at 12 to 18 hours, and at 36 to 42 hours after birth.. Primary outcome was cognitive development assessed with the Mental Development Index (MDI; norm, 100 [SD, 15]; higher values indicate better function) of the Bayley Scales of Infant Development, second edition (BSID-II) at 2 years corrected age. The minimal clinically important difference between groups was 5 points (0.3 SD). Secondary outcomes were motor development (assessed with the Psychomotor Development Index), cerebral palsy, hearing or visual impairment, and anthropometric growth parameters.. Among 448 preterm infants randomized (mean gestational age, 29.0 [range, 26.0-30.9] weeks; 264 [59%] female; mean birth weight, 1210 [range, 490-2290] g), 228 were randomized to rhEPO and 220 to placebo. Neurodevelopmental outcome data were available for 365 (81%) at a mean age of 23.6 months. In an intention-to-treat analysis, mean MDI was not statistically significantly different between the rhEPO group (93.5 [SD, 16.0] [95% CI, 91.2 to 95.8]) and the placebo group (94.5 [SD, 17.8] [95% CI, 90.8 to 98.5]) (difference, -1.0 [95% CI, -4.5 to 2.5]; P = .56). No differences were found between groups in the secondary outcomes.. Among very preterm infants who received prophylactic early high-dose rhEPO for neuroprotection, compared with infants who received placebo, there were no statistically significant differences in neurodevelopmental outcomes at 2 years. Follow-up for cognitive and physical problems that may not become evident until later in life is required.. clinicaltrials.gov Identifier: NCT00413946.

Topics: Child Development; Child, Preschool; Developmental Disabilities; Double-Blind Method; Drug Administration Schedule; Erythropoietin; Female; Humans; Infant, Newborn; Infant, Premature; Intention to Treat Analysis; Male; Neurodevelopmental Disorders; Neuroprotective Agents; Recombinant Proteins; Treatment Outcome

To investigate the safety and short term outcome of high dose recombinant human erythropoietin (rhEpo) given shortly after birth and subsequently over the first 2 days for neuroprotection to very preterm infants.. Randomized, double masked phase II trial. Preterm infants (gestational age 26 0/7-31 6/7 weeks) were given rhEpo (nt = 229; 3000 U/kg body weight) or NaCl 0.9% (nc = 214) intravenously at 3, 12-18, and 36-42 hours after birth.. There were no relevant differences between the groups for short-term outcomes such as mortality, retinopathy of prematurity, intraventricular hemorrhage, sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia. At day 7-10, we found significantly higher hematocrit values, reticulocyte, and white blood cell counts, and a lower platelet count in the rhEpo group.. Early high-dose rhEpo administration to very premature infants is safe and causes no excess in mortality or major adverse events.. ClinicalTrials.gov: NCT00413946.

Topics: Bronchopulmonary Dysplasia; Developmental Disabilities; Dose-Response Relationship, Drug; Double-Blind Method; Enterocolitis, Necrotizing; Erythropoietin; Europe; Hematocrit; Humans; Hypoxia-Ischemia, Brain; Infant, Newborn; Infant, Premature; Intracranial Hemorrhages; Leukocyte Count; Leukomalacia, Periventricular; Neuroprotective Agents; Platelet Count; Recombinant Proteins; Reticulocyte Count; Retinopathy of Prematurity; Sepsis

We previously reported decreased transfusions and donor exposures in preterm infants randomized to Darbepoetin (Darbe) or erythropoietin (Epo) compared with placebo. As these erythropoiesis-stimulating agents (ESAs) have shown promise as neuroprotective agents, we hypothesized improved neurodevelopmental outcomes at 18 to 22 months among infants randomized to receive ESAs.. We performed a randomized, masked, multicenter study comparing Darbe (10 μg/kg, 1×/week subcutaneously), Epo (400 U/kg, 3×/week subcutaneously), and placebo (sham dosing 3×/week) given through 35 weeks' postconceptual age, with transfusions administered according to a standardized protocol. Surviving infants were evaluated at 18 to 22 months' corrected age using the Bayley Scales of Infant Development III. The primary outcome was composite cognitive score. Assessments of object permanence, anthropometrics, cerebral palsy, vision, and hearing were performed.. Of the original 102 infants (946 ± 196 g, 27.7 ± 1.8 weeks' gestation), 80 (29 Epo, 27 Darbe, 24 placebo) returned for follow-up. The 3 groups were comparable for age at testing, birth weight, and gestational age. After adjustment for gender, analysis of covariance revealed significantly higher cognitive scores among Darbe (96.2 ± 7.3; mean ± SD) and Epo recipients (97.9 ± 14.3) compared with placebo recipients (88.7 ± 13.5; P = .01 vs ESA recipients) as was object permanence (P = .05). No ESA recipients had cerebral palsy, compared with 5 in the placebo group (P < .001). No differences among groups were found in visual or hearing impairment.. Infants randomized to receive ESAs had better cognitive outcomes, compared with placebo recipients, at 18 to 22 months. Darbe and Epo may prove beneficial in improving long-term cognitive outcomes of preterm infants.

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

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

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

The purpose of this study was to evaluate the efficacy and safety of erythropoietin in neonatal hypoxic-ischemic encephalopathy (HIE), by using a randomized, prospective study design.. A total of 167 term infants with moderate/severe HIE were assigned randomly to receive either erythropoietin (N = 83) or conventional treatment (N = 84). Recombinant human erythropoietin, at either 300 U/kg (N = 52) or 500 U/kg (N = 31), was administered every other day for 2 weeks, starting <48 hours after birth. The primary outcome was death or disability. Neurodevelopmental outcomes were assessed at 18 months of age.. Complete outcome data were available for 153 infants. Nine patients dropped out during treatment, and 5 patients were lost to follow-up monitoring. Death or moderate/severe disability occurred for 35 (43.8%) of 80 infants in the control group and 18 (24.6%) of 73 infants in the erythropoietin group (P = .017) at 18 months. The primary outcomes were not different between the 2 erythropoietin doses. Subgroup analyses indicated that erythropoietin improved long-term outcomes only for infants with moderate HIE (P = .001) and not those with severe HIE (P = .227). No negative hematopoietic side effects were observed.. Repeated, low-dose, recombinant human erythropoietin treatment reduced the risk of disability for infants with moderate HIE, without apparent side effects.

Topics: Asphyxia Neonatorum; Brain Damage, Chronic; China; Developmental Disabilities; Disability Evaluation; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Follow-Up Studies; Humans; Hypoxia-Ischemia, Brain; Infant; Infant, Newborn; Infusions, Intravenous; Injections, Subcutaneous; Intensive Care Units, Neonatal; Male; Neurologic Examination; Prospective Studies; Psychomotor Disorders; Recombinant Proteins

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

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

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

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

Erythropoietin therapy is effective in decreasing transfusions to varying degrees in preterm infants. Recent animal studies using erythropoietin doses to achieve serum concentrations > 1000 mU/mL report neuroprotective effects. We evaluated the relationship between erythropoietin concentrations and neurodevelopmental outcome in extremely low birth weight infants.. Preterm infants who weighed < or = 1000 g at birth were randomly assigned to erythropoietin (400 U/kg 3 times per week) or placebo/control. Therapy was initiated by 4 days after birth and continued through the 35th postmenstrual week. All infants received supplemental parenteral and enteral iron. Peak serum erythropoietin concentrations were obtained every 2 weeks. Follow-up evaluation included anthropometric measurements, Bayley scales of mental and psychomotor development, neurologic examination, and determination of overall neurodevelopmental impairment. Data were collected at 18 to 22 months' corrected age by certified examiners who were masked to the treatment group. Analyses were performed to identify correlations between erythropoietin concentrations and outcomes.. Sixteen extremely low birth weight infants were enrolled; 1 infant died at 2 weeks (placebo/control), and 15 had erythropoietin concentrations measured (7 erythropoietin, 8 placebo/control). Peak erythropoietin concentrations were significantly different between groups during the study (erythropoietin: 2027 +/- 1464 mU/mL; placebo/control: 26 +/- 11 mU/mL). Before follow-up, 3 infants died (1 erythropoietin, 2 placebo/control), and 12 were available for follow-up (6 erythropoietin, 6 placebo/control). At 18 to 22 months' follow-up, none of the erythropoietin recipients and 2 of the placebo/control infants had Mental Development Index scores < 70. Erythropoietin recipients had Mental Development Index scores of 96 +/- 11, and placebo/control infants had Mental Development Index scores of 78 +/- 7. Psychomotor Development Index scores were similar between groups (87 +/- 13 vs 80 +/- 7). There were no differences between groups with respect to anthropometric measurements. Two of 6 infants in the erythropoietin group and 4 of 6 infants in the placebo/control group had some form of neurodevelopmental impairment. Posthoc analysis showed that infants with erythropoietin concentrations > or = 500 mU/mL had higher Mental Development Index scores than infants with erythropoietin concentrations < 500 mU/mL.. Erythropoietin concentrations did not correlate with Psychomotor Development Index or overall incidence of neurodevelopmental impairment; however, infants with elevated erythropoietin concentrations had higher Mental Development Index scores than those with lower erythropoietin concentrations. Close follow-up of infants who are enrolled in large, multicenter, high-dose erythropoietin studies is required to determine whether a correlation exists between elevated erythropoietin concentrations and improved neurodevelopmental outcome.

Topics: Blood Transfusion; Child Development; Cognition Disorders; Developmental Disabilities; Erythropoietin; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Very Low Birth Weight; Male; Predictive Value of Tests; Psychomotor Disorders

Hypoxic-ischemic (HI) injury to the developing brain remains a major cause of morbidity. To date, few therapeutic strategies could provide complete neuroprotection. Erythropoietin (EPO) has been shown to be beneficial in several models of neonatal HI. This study examines the effect of treatment with erythropoietin on postnatal day 2 (P2) rats introduced with HI injury.. Rats at P2 were randomized into four groups: sham, bilateral carotid artery occlusion (BCAO), BCAO + early EPO, and BCAO + late EPO groups. Pups in each group were injected with either saline or EPO (5000U/kg) intraperitoneally once at immediately (early) or 48h (late) after HI induction. Body weight was assessed at P2 before and day 7 after HI. Mortality Rate was assessed at 24h, 48h and 72h after HI and brain water content was assessed at 72h. Brain weight and expression of myelin basic protein (MBP) were assessed at day 7 and day 14. At day 31 to 35 following HI insult, neurological behavior function was assessed via Morris water maze (MWM) test.. HI cause significant higher mortality in male than in female (P=0.0445). Among the surviving animal, HI affect significantly the body growth, brain growth, MBP expression, and neurological behavior. EPO treatments at both early and late time points significantly benefit the rats in injury recovery, in which they promoted weight gains, reduced brain edema, as well as improved spatial learning ability and memory.. We demonstrated a single dose of EPO at 5000U/kg immediately or 48h after HI injury had significant benefit for the P2 rats in injury recovery, and there was no adverse effect associated with either EPO treatment.

Topics: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Body Weight; Brain Edema; Developmental Disabilities; Disease Models, Animal; Erythropoietin; Hypoxia-Ischemia, Brain; Maze Learning; Myelin Basic Protein; Neuroprotective Agents; Rats; Rats, Sprague-Dawley

Topics: Developmental Disabilities; Erythropoietin; Humans; Infant, Premature; Neuroprotective Agents

Preterm infants are at risk for neurodevelopmental sequelae even in absence of major cerebral lesions. The hypothesis that Human Recombinant Erythropoietin (rEpo) could improve the neurodevelopmental outcome in risk neonates has raised the highest interest in recent years.. A group of preterm neonates born at a gestational age ≤ 30 weeks and free from major cerebral lesions or major visual impairment, were included in the study if they had a complete neurologic evaluation for at least 24 months of postmenstrual age. They were assigned to group I in the case they had been treated with rEpo or group II if untreated. The aim was to evaluate whether rEpo, given at the high cumulative doses utilized for hematologic purposes, is able to improve the neurodevelopmental outcome in preterm infants born at a gestational age ≤ 30 weeks. A group of 104 preterm neonates were studied: 59 neonates who received rEpo for 6.9 ± 2.4 weeks at a median cumulative dose of 6300 UI/Kg (6337 ± 2434 UI/Kg), starting at a median age of 4 days and 45 neonates who were born in the period preceding the routine use of rEpo. The neurodevelopmental quotient at 24 month postmenstrual age was assessed utilizing the Griffiths' Mental Developmental Scales.. Our results failed to show any difference in the Developmental Quotient at 24 month. Bronchopulmonary dysplasia, minor intraventricular hemorrhages and blood transfusions were the clinical features significantly related to the Developmental Quotient.. Our results do not support the hypothesis that rEpo, administered with the schedule utilized for hematologic purposes, improve the neurodevelopmental outcome of preterm neonates, at least those preterm infants free from major impairments.

Topics: Anemia, Neonatal; Child Development; Developmental Disabilities; Dose-Response Relationship, Drug; Erythropoietin; Female; Follow-Up Studies; Humans; Infant, Newborn; Infant, Premature; Male; Neurologic Examination

Topics: Developmental Disabilities; Erythropoietin; Female; Humans; Infant, Extremely Low Birth Weight; Pregnancy; Pregnancy Outcome

Topics: Developmental Disabilities; Erythropoietin; Female; Humans; Infant, Extremely Low Birth Weight; Pregnancy; Pregnancy Outcome

To evaluate long-term outcomes of 60 extremely low birth weight (ELBW) infants treated with or without three injections of high-dose erythropoietin (Epo).. A retrospective analysis of anthropometric and neurodevelopmental outcome data comparing 30 ELBW infants enrolled in a phase I/II study examining the pharmacokinetics of high-dose Epo (500, 1000 and 2500 U/kg × 3 doses) administered to 30 concurrent controls.. Birth characteristics and growth from 4 to 36 months were similar for untreated and Epo-treated patients. Multiple linear regression analysis of neurodevelopmental follow-up scores from 17/25 Epo-treated and 18/26 control infants identified that Epo correlated with improvement of cognitive (R=0.22, P=0.044) and motor (R=0.15, P=0.026) scores. No negative long-term effects of Epo treatment were evident.. Retrospective analysis of the only available long-term follow-up data from ELBW infants given high-dose Epo treatment suggests that Epo treatment is safe and correlates with modest improvement of neurodevelopmental outcomes.

Topics: Brain Diseases; Cognition Disorders; Developmental Disabilities; Erythropoietin; Female; Humans; Infant, Extremely Low Birth Weight; Infant, Newborn; Pregnancy; Pregnancy Outcome; Retrospective Studies

Topics: Child Development; Developmental Disabilities; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Erythropoietin; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Premature; Male; Recombinant Proteins; Risk Assessment; Treatment Outcome; United States; United States Food and Drug Administration

We hypothesized that higher cumulative doses of recombinant erythropoietin (rEPO) for extremely preterm infants during the first 6 postnatal weeks would improve developmental outcomes, as evidenced in evaluations with the Bayley Scales of Infant Development-II Revised.. This was a retrospective cohort study with a data set for a group (N = 366) of infants of <1500 g and < or =30 weeks of gestation that was created initially to examine the association between rEPO treatment and retinopathy of prematurity. Infants who underwent developmental follow-up evaluations at corrected age of >12 months were included. The associations between rEPO doses and higher Bayley Scales of Infant Development Psychomotor Developmental Index and Mental Developmental Index (MDI) scores were estimated in multivariate linear regression analyses.. Eighty-two infants underwent developmental evaluations after 12 months. The median age of evaluation was 25 months. The median 6-week cumulative rEPO dose was 3750 U/kg. In multivariate analyses, Psychomotor Developmental Index (PDI) scores were associated with transfusions, female gender, birth weight, and 5-minute Apgar scores (R(2) = 0.39). MDI scores were associated with 6-week rEPO dose, female gender, prenatal steroid treatment for > or =48 hours, and breast milk feedings (R(2) = 0.40).. These findings identify a dose-response relationship between rEPO treatment and improved MDI scores. They are consistent with findings of adult studies and animal brain injury models and await confirmation.

Topics: Child Development; Child, Preschool; Cognition Disorders; Cohort Studies; Developmental Disabilities; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Follow-Up Studies; Gestational Age; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Linear Models; Male; Multivariate Analysis; Predictive Value of Tests; Pregnancy; Probability; Psychomotor Disorders; Recombinant Proteins; Retrospective Studies; Risk Assessment; Statistics, Nonparametric; Time Factors; Treatment Outcome