Erythropoietin monotherapy for neuroprotection after neonatal encephalopathy in low-to-middle income countries: a systematic review and meta-analysis

Abstract

Objective We examined whether erythropoietin monotherapy improves neurodevelopmental outcomes in near-term and term infants with neonatal encephalopathy (NE) in low-middle income countries (LMICs). Methods We searched Pubmed, Embase, and Web of Science databases to identify studies that used erythropoietin (1500–12,500 units/kg/dose) or a derivative to treat NE. Results Five studies, with a total of 348 infants in LMICs, were retrieved. However, only three of the five studies met the primary outcome of death or neuro-disability at 18 months of age or later. Erythropoietin reduced the risk of death (during the neonatal period and at follow-up) or neuro-disability at 18 months or later (p < 0.05). Death or neuro-disability occurred in 27.6% of the erythropoietin group and 49.7% of the comparison group (risk ratio 0.56 (95% CI: 0.42–0.75)). Conclusion The pooled data suggest that erythropoietin monotherapy may improve outcomes after NE in LMICs where therapeutic hypothermia is not available.

Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh

“…Future research exploring the origins and timing of birth-related brain injury might help to develop effective neuroprotective interventions. Neuroregenerative therapies such as erythropoietin 31 might be more effective in these settings than therapies with an acute neuroprotective effect alone.…”

Lack of Neuroprotection with a Single Intravenous Infusion of Human Amnion Epithelial Cells after Severe Hypoxia–Ischemia in Near-Term Fetal Sheep

“…Hypoxia–ischemia (HI) before, during or around the time of birth is the primary cause of hypoxic–ischemic encephalopathy (HIE), which occurs in approximately 2/1000 live births in high resource settings and approximately 26/1000 live births in low resource settings [ 1 ], and is associated with a high rate of mortality and morbidity in survivors, including lifelong physical and mental disabilities [ 2 , 3 ]. Therapeutic hypothermia (TH) is now established as a neuroprotective treatment for term infants with moderate to severe HIE in high resource settings [ 4 , 5 ].…”

Need for more evidence in the prevention and management of perinatal asphyxia and neonatal encephalopathy in low and middle-income countries: A call for action

“…Given the sub-acute nature of brain injury in LMICs [ 5 ], it is likely that drugs with neuroregenerative properties are more effective than acute neuroprotective therapies, until the underlying mechanisms are known. A recent systematic review of five small studies of erythropoietin monotherapy in LMICs, involving 348 neonates from tertiary neonatal intensive care units, showed a significant reduction in death or disability (RR 0.56; 95 % CI, 0.42–0.75), when administered within 24 h after birth [ 72 ]. Erythropoietin monotherapy needs to be evaluated in well designed and adequately powered randomized control trials in LMICs before clinical use, irrespective of the results of high-income country erythropoietin trials where erythropoietin is evaluated as an adjunct to cooling therapy, particularly as cerebral iron depletion may negate the effects of erythropoietin neuroprotection.…”