ArticlePloS one2015
Elevated endogenous erythropoietin concentrations are associated with increased risk of brain damage in extremely preterm neonates.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02745990 (Recombinant Human Erythropoietin Improve Neurodevelopmental Outcomes in Extremely Preterm Infants), which is not on this map. Cited by 21 papers.
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.
Recombinant Human Erythropoietin Improve Neurodevelopmental Outcomes in Extremely Preterm Infants
Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Trial
- Trial
- Elucidating the Pivotal Neuroprotective Mechanisms and Therapeutic Variants of Erythropoietin in Neonatal Brain Injury.Current topics in medicinal chemistry · 2025Review
- Cytokine dysregulation in children with severe neurological impairment correlates with significant clinical outcomes.Frontiers in pediatrics · 2025Article
- Chronic Inflammation Offers Hints About Viable Therapeutic Targets for Preeclampsia and Potentially Related Offspring Sequelae.International journal of molecular sciences · 2024Review
- Retinopathy of prematurity and neurodevelopmental outcomes in preterm infants: A systematic review and meta-analysis.Frontiers in pediatrics · 2023Review
- Early Biomarkers of Hypoxia and Inflammation and Two-Year Neurodevelopmental Outcomes in the Preterm Erythropoietin Neuroprotection (PENUT) Trial.EBioMedicine · 2021Article
- Endogenous erythropoietin concentrations and association with retinopathy of prematurity and brain injury in preterm infants.PloS one · 2021Article
- Inflammatory predictors of neurobehavior in very preterm infants.Early human development · 2020Article
- Cytokine dysregulation persists in childhood post Neonatal Encephalopathy.BMC neurology · 2020Article
- An Integrative Review of Cytokine/Chemokine Predictors of Neurodevelopment in Preterm Infants.Biological research for nursing · 2019Review
- The biological embedding of neonatal stress exposure: A conceptual model describing the mechanisms of stress-induced neurodevelopmental impairment in preterm infants.Research in nursing & health · 2019Article
- Among Children Born Extremely Preterm a Higher Level of Circulating Neurotrophins Is Associated with Lower Risk of Cognitive Impairment at School Age.The Journal of pediatrics · 2018Observational
- The complex aetiology of cerebral palsy.Nature reviews. Neurology · 2018Review
- Neonatal systemic inflammation and the risk of low scores on measures of reading and mathematics achievement at age 10 years among children born extremely preterm.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2018Article
- Circulating biomarkers in extremely preterm infants associated with ultrasound indicators of brain damage.European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society · 2018Observational
- Chorioamnionitis, neuroinflammation, and injury: timing is key in the preterm ovine fetus.Journal of neuroinflammation · 2018Article
- Systemic Inflammation during the First Postnatal Month and the Risk of Attention Deficit Hyperactivity Disorder Characteristics among 10 year-old Children Born Extremely Preterm.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017Observational
- Early predictors of neonatal intraventricular hemorrhage.Electronic physician · 2017Article
- Regeneration in the nervous system with erythropoietin.Frontiers in bioscience (Landmark edition) · 2016Review
Corrections and comments
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Authors and funding
12 authors at 9 institutions in 3 countries.
Funding
Abstract
backgroundWe sought to determine, in very preterm infants, whether elevated perinatal erythropoietin (EPO) concentrations are associated with increased risks of indicators of brain damage, and whether this risk differs by the co-occurrence or absence of intermittent or sustained systemic inflammation (ISSI).
methodsProtein concentrations were measured in blood collected from 786 infants born before the 28th week of gestation. EPO was measured on postnatal day 14, and 25 inflammation-related proteins were measured weekly during the first 2 postnatal weeks. We defined ISSI as a concentration in the top quartile of each of 25 inflammation-related proteins on two separate days a week apart. Hypererythropoietinemia (hyperEPO) was defined as the highest quartile for gestational age on postnatal day 14. Using logistic regression and multinomial logistic regression models, we compared risks of brain damage among neonates with hyperEPO only, ISSI only, and hyperEPO+ISSI, to those who had neither hyperEPO nor ISSI, adjusting for gestational age.
resultsNewborns with hyperEPO, regardless of ISSI, were more than twice as likely as those without to have very low (< 55) Mental (OR 2.3; 95% CI 1.5-3.5) and/or Psychomotor (OR 2.4; 95% CI 1.6-3.7) Development Indices (MDI, PDI), and microcephaly at age two years (OR 2.4; 95%CI 1.5-3.8). Newborns with both hyperEPO and ISSI had significantly increased risks of ventriculomegaly, hemiparetic cerebral palsy, microcephaly, and MDI and PDI < 55 (ORs ranged from 2.2-6.3), but not hypoechoic lesions or other forms of cerebral palsy, relative to newborns with neither hyperEPO nor ISSI.
conclusionhyperEPO, regardless of ISSI, is associated with elevated risks of very low MDI and PDI, and microcephaly, but not with any form of cerebral palsy. Children with both hyperEPO and ISSI are at higher risk than others of very low MDI and PDI, ventriculomegaly, hemiparetic cerebral palsy, and microcephaly.
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