ArticlePediatrics2012
Erythropoietin for neuroprotection in neonatal encephalopathy: safety and pharmacokinetics.
Article in Pediatrics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01913340 (Neonatal Erythropoietin And Therapeutic Hypothermia Outcomes Study), which is not on this map. Cited by 96 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neonatal Erythropoietin And Therapeutic Hypothermia Outcomes Study
Who cites it
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 201 citations in OpenAlex.
- Stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants.The Cochrane database of systematic reviews · 2020Pooled it
- On target dosing: erythropoietin exposure in neonates with hypoxic-ischemic encephalopathy in the HEAL trial.Pediatric research · 2025Trial
- Brain Injury Outcomes after Adjuvant Erythropoietin Neuroprotection for Moderate or Severe Neonatal Hypoxic-Ischemic Encephalopathy: A Report from the HEAL Trial.Developmental neuroscience · 2024Trial
- Risk of seizures in neonates with hypoxic-ischemic encephalopathy receiving hypothermia plus erythropoietin or placebo.Pediatric research · 2023Trial
- Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns.The New England journal of medicine · 2022Trial
- Target-mediated disposition population pharmacokinetics model of erythropoietin in premature neonates following multiple intravenous and subcutaneous dosing regimens.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2019Trial
- High-dose erythropoietin population pharmacokinetics in neonates with hypoxic-ischemic encephalopathy receiving hypothermia.Pediatric research · 2017Trial
- Erythropoietin monotherapy in perinatal asphyxia with moderate to severe encephalopathy: a randomized placebo-controlled trial.Journal of perinatology : official journal of the California Perinatal Association · 2017Trial
- Recombinant human erythropoietin improves neurological outcomes in very preterm infants.Annals of neurology · 2016Trial
- Preschool Assessment of Preterm Infants Treated With Darbepoetin and Erythropoietin.Pediatrics · 2016Trial
- Population Pharmacokinetics of Darbepoetin Alfa in Conjunction with Hypothermia for the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy.Clinical pharmacokinetics · 2015Trial
- Darbepoetin administration to neonates undergoing cooling for encephalopathy: a safety and pharmacokinetic trial.Pediatric research · 2015Trial
- Pharmacokinetics and Brain Distribution of a Purine-Derived Neuroprotective Agent after Intranasal Administration in Neonatal Rats with Hypoxic-Ischemic Brain Injury.Pharmaceutical research · 2026Article
- Neuroprotective properties of erythropoietin (Epo) and its receptor (EpoR) in open spinal dysraphism (OSD): an investigation of EpoR expression in a rat OSD model, along with in vitro studies on the neuroprotective effects of Epo on rat spinal cord-derived neural progenitor cells.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2025Article
- Pharmacological Therapies for Consequences of Perinatal Hypoxic-Ischemic Brain Injury: Where Are We Now?International journal of molecular sciences · 2025Review
- Review
- Neonatal encephalopathy due to suspected hypoxic ischemic encephalopathy: pathophysiology, current, and emerging treatments.World journal of pediatrics : WJP · 2024Review
- Early Postnatal Administration of Erythropoietin and Its Association with Neurodevelopmental Outcomes and Incidence of Intraventricular Hemorrhage and Hypoxic-Ischemic Encephalopathy: A Four-Week Observational Study.Pediatric reports · 2024Article
- Advances in Therapies to Treat Neonatal Hypoxic-Ischemic Encephalopathy.Journal of clinical medicine · 2023Review
- A narrative review on treatment strategies for neonatal hypoxic ischemic encephalopathy.Translational pediatrics · 2023Review
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
objectiveTo determine the safety and pharmacokinetics of erythropoietin (Epo) given in conjunction with hypothermia for hypoxic-ischemic encephalopathy (HIE). We hypothesized that high dose Epo would produce plasma concentrations that are neuroprotective in animal studies (ie, maximum concentration = 6000-10000 U/L; area under the curve = 117000-140000 U*h/L).
methodsIn this multicenter, open-label, dose-escalation, phase I study, we enrolled 24 newborns undergoing hypothermia for HIE. All patients had decreased consciousness and acidosis (pH < 7.00 or base deficit ≥ 12), 10-minute Apgar score ≤ 5, or ongoing resuscitation at 10 minutes. Patients received 1 of 4 Epo doses intravenously: 250 (N = 3), 500 (N = 6), 1000 (N = 7), or 2500 U/kg per dose (N = 8). We gave up to 6 doses every 48 hours starting at <24 hours of age and performed pharmacokinetic and safety analyses.
resultsPatients received mean 4.8 ± 1.2 Epo doses. Although Epo followed nonlinear pharmacokinetics, excessive accumulation did not occur during multiple dosing. At 500, 1000, and 2500 U/kg Epo, half-life was 7.2, 15.0, and 18.7 hours; maximum concentration was 7046, 13780, and 33316 U/L, and total Epo exposure (area under the curve) was 50306, 131054, and 328002 U*h/L, respectively. Drug clearance at a given dose was slower than reported in uncooled preterm infants. No deaths or serious adverse effects were seen.
conclusionsEpo 1000 U/kg per dose intravenously given in conjunction with hypothermia is well tolerated and produces plasma concentrations that are neuroprotective in animals. A large efficacy trial is needed to determine whether Epo add-on therapy further improves outcome in infants undergoing hypothermia for HIE.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.