Cognitive Outcomes of Preterm Infants Randomized to Darbepoetin, Erythropoietin, or Placebo

Ohls, Robin K.; Kamath‐Rayne, Beena D.; Christensen, Robert D.; Wiedmeier, Susan E.; Rosenberg, Adam A.; Fuller, Janell; Lacy, Conra Backstrom; Roohi, Mahshid; Lambert, D K; Burnett, Jill; Pruckler, Barbara; Peceny, Hannah; Cannon, Daniel C.; Lowe, Jean

doi:10.1542/peds.2013-4307

Cited by 123 publications

(100 citation statements)

References 36 publications

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“…Based on those results from neonatal rodent brain injury models, clinical studies showed that high‐dose rhEPO (2,500–3,000U/kg) administered after birth was well tolerated in preterm and term infants14, 20, 33, 37, 42 and conferred neuroprotection 16, 36. In a previous study using low‐dose rhEPO to prevent anemia in preterm infants, it was observed that preterm infants with rhEPO treatment also had significant neurodevelopmental improvement 38. Another previous study using low‐dose rhEPO (250–400U/kg, 3 times a week for 6 weeks) to prevent anemia in premature infants of birth weight < 1,500g found that the neurodevelopmental outcome improvement was related to the total cumulative dose of rhEPO,46 suggesting that repeated low‐dose rhEPO treatment could be beneficial.…”

Section: Discussionmentioning

confidence: 99%

“…Recent experimental34, 35 and clinical17, 36, 37, 38 studies indicate that rhEPO is a promising candidate for very preterm infants with brain injury and that it improves neurodevelopment and reduces the risk of neurodevelopmental disability. However, the safe dose range, timing, and duration of rhEPO administration still require careful exploration and consideration.…”

Section: Discussionmentioning

confidence: 99%

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Recombinant human erythropoietin improves neurological outcomes in very preterm infants

Shi

Sun

et al. 2016

Annals of Neurology

115

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ObjectiveTo evaluate the efficacy and safety of repeated low‐dose human recombinant erythropoietin (rhEPO) in the improvement of neurological outcomes in very preterm infants.MethodsA 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.ResultsDeath 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.InterpretationRepeated 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

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Recombinant human erythropoietin improves neurological outcomes in very preterm infants

Shi

Sun

et al. 2016

Annals of Neurology

115

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“…58 Epo monotherapy, without hypothermia, may be useful for neonatal conditions other than HIE, such as perinatal stroke, 59 congenital heart disease, 60 and brain injury of prematurity. [61][62][63][64] This is the first clinical study of HIE that assesses biomarkers of efficacy to evaluate whether Epo provides additional neuroprotection to hypothermia. We found that Epo treatment was associated with significantly reduced severity of brain injury on MRI, specifically in the subcortical region (ie, the area that contains the basal ganglia, thalamus, and internal capsule).…”

Section: Sensitivity Analysesmentioning

confidence: 99%

High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial

Mathur²,

et al. 2016

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OBJECTIVE: To determine if multiple doses of erythropoietin (Epo) administered with hypothermia improve neuroradiographic and short-term outcomes of newborns with hypoxic-ischemic encephalopathy. METHODS:In a phase II double-blinded, placebo-controlled trial, we randomized newborns to receive Epo (1000 U/kg intravenously; n = 24) or placebo (n = 26) at 1, 2, 3, 5, and 7 days of age. All infants had moderate/severe encephalopathy; perinatal depression (10 minute Apgar <5, pH <7.00 or base deficit ≥15, or resuscitation at 10 minutes); and received hypothermia. Primary outcome was neurodevelopment at 12 months assessed by the Alberta Infant Motor Scale and Warner Initial Developmental Evaluation. Two independent observers rated MRI brain injury severity by using an established scoring system. RESULTS:The mean age at first study drug was 16.5 hours (SD, 5.9). Neonatal deaths did not significantly differ between Epo and placebo groups (8% vs 19%, P = .42). Brain MRI at mean 5.1 days (SD, 2.3) showed a lower global brain injury score in Epo-treated infants (median, 2 vs 11, P = .01). Moderate/severe brain injury (4% vs 44%, P = .002), subcortical (30% vs 68%, P = .02), and cerebellar injury (0% vs 20%, P = .05) were less frequent in the Epo than placebo group. At mean age 12.7 months (SD, 0.9), motor performance in Epotreated (n = 21) versus placebo-treated (n = 20) infants were as follows: Alberta Infant Motor Scale (53.2 vs 42.8, P = .03); Warner Initial Developmental Evaluation (28.6 vs 23.8, P = .05).CONCLUSIONS: High doses of Epo given with hypothermia for hypoxic-ischemic encephalopathy may result in less MRI brain injury and improved 1-year motor function.

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“…In a study, including preterm infants, it was observed that none of the surviving infants developed CP, while five in the placebo group did. 15 …”

Section: Drugsmentioning

confidence: 99%

Clinical neurorestorative progresses in cerebral palsy

Sharma¹,

Geng²,

Sane³

et al. 2017

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Cerebral palsy (CP), group of permanent nonprogressive clinical disorders in children, is caused by damage to the immature brain. Conventionally available treatments for CP are mainly targeted toward management of its symptoms. With the upcoming field of neurorestorative strategies, we are now able to repair the core brain damage in CP. There are various drugs, stem cells, etc, which have been implicated to have neurorestorative properties. Autologous bone marrow stem cells, umbilical cord stem cells, neural stem cells, and olfactory ensheathing cells have shown the safety and efficacy in preliminary studies. Here, we review the different medicines and cell types that have shown beneficial effects in clinical studies. We propose that combination strategies may be the future of neurorestoration.

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Cognitive Outcomes of Preterm Infants Randomized to Darbepoetin, Erythropoietin, or Placebo

Cited by 123 publications

References 36 publications

Recombinant human erythropoietin improves neurological outcomes in very preterm infants

Recombinant human erythropoietin improves neurological outcomes in very preterm infants

High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial

Clinical neurorestorative progresses in cerebral palsy

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