Clinical Outcomes Related to the Gastrointestinal Trophic Effects of Erythropoietin in Preterm Neonates: A Systematic Review and Meta-Analysis

Ananthan, Anitha; Balasubramanian, Hari; Rao, Shripada; Patole, Sanjay

doi:10.1093/advances/nmy005

Cited by 15 publications

(8 citation statements)

References 72 publications

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“…The meta‐analysis showed no significant effect of rEPO on the incidence of ≥stage II NEC and mortality, while the subgroup analysis indicated that subcutaneous rEPO could increase the risk of ROP. The results of our data are consistent with the previous meta‐analysis that focused on the gastrointestinal trophic effects of rEPO 42 . To our knowledge, this is the first meta‐analysis of RCTs of rEPO in preterm neonates that focused on respiratory outcomes (e.g., BPD and oxygen dependence days) related to short‐ and long‐term adverse morbidities.…”

Section: Discussionsupporting

confidence: 90%

“…The results of our data are consistent with the previous meta-analysis that focused on the gastrointestinal trophic effects of rEPO. 42 To our knowledge, this is the first metaanalysis of RCTs of rEPO in preterm neonates that focused on respiratory outcomes (e.g., BPD and oxygen dependence days) related to short-and long-term adverse morbidities.…”

Section: Discussionmentioning

confidence: 97%

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Erythropoietin for preventing bronchopulmonary dysplasia in preterm infants: A systematic review and meta‐analysis

Zhang

Hao

et al. 2022

Pediatric Pulmonology

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Background: Recombinant erythropoietin (rEPO) has erythropoiesis and anti-inflammatory properties that might help reduce lung injury in preterm infants.Objective: To conduct a systematic review and meta-analysis to evaluate the possible role of rEPO in altering the risk of bronchopulmonary dysplasia (BPD).Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were searched to identify randomized controlled trials (RCTs) that evaluated the effects of rEPO for the prevention of BPD in preterm infants.Results: Fourteen studies (3199 infants) were included. Our results could not demonstrate a significant effect of rEPO on the incidence of BPD36 (risk ratio[RR]: 0.97, 95% confidence interval [CI]: 0.87-1.09, p = 0.63, I 2 = 0, 12 RCTs, high-quality evidence), BPD28 (RR: 1.28, 95% CI: 0.91-1.79, p = 0.15, I 2 = 17%, three RCTs, low-quality evidence) and oxygen dependence days. The test for subgroup analysis by administration route of rEPO showed similar outcomes above. Some of the included trials reported a significant effect of intravenous rEPO on reduction of sepsis (RR: 0.82, 95% CI: 0.70-0.96, p = 0.01, I 2 = 0, high-quality evidence) and any stage necrotizing enterocolitis (NEC) (RR: 0.75, 95% CI: 0.59-0.94, p = 0.01, I 2 = 0, moderate-quality evidence). The incidence of mortality and stage II or higher NEC was comparable in rEPO and control infants. Conclusion:Our results suggest that rEPO does not affect the risk of developing BPD in preterm infants. Adequately powered RCTs are required to further confirm these findings.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 97%

Erythropoietin for preventing bronchopulmonary dysplasia in preterm infants: A systematic review and meta‐analysis

Zhang

Hao

et al. 2022

Pediatric Pulmonology

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“…Due to EPO's effects on the production of red blood cells, it has been used clinically since 1990 to treat anemia of prematurity [109,110]. The use of EPO reduces the need for blood transfusions in premature infants.…”

Section: Clinical Studies On Neonatal Hypoxic-ischemic Encephalopathymentioning

confidence: 99%

“…This suggests that the dose of EPO may be important (see also below). In a recent meta-analysis by Fischer et al [146] of four randomized control trials, including Natalucci et al [110], the neurodevelopmental outcome was analyzed for 547 placebo-treated and 574 r-Hu-EPO-treated premature infants (mainly aged 27 to 30 weeks-of-gestation at birth). The results indicated that prophylactic r-Hu-EPO significantly improved cognitive development and had no significant effect on other neurodevelopmental outcomes at a corrected age of 18 to 24 months.…”

Section: Effects Of Epo In Clinical Trials For Preterm Infantsmentioning

confidence: 99%

Treatment of Neonatal Hypoxic-Ischemic Encephalopathy with Erythropoietin Alone, and Erythropoietin Combined with Hypothermia: History, Current Status, and Future Research

Oorschot

Sizemore

Amer

2020

IJMS

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Perinatal hypoxic-ischemic encephalopathy (HIE) remains a major cause of morbidity and mortality. Moderate hypothermia (33.5 °C) is currently the sole established standard treatment. However, there are a large number of infants for whom this therapy is ineffective. This inspired global research to find neuroprotectants to potentiate the effect of moderate hypothermia. Here we examine erythropoietin (EPO) as a prominent candidate. Neonatal animal studies show that immediate, as well as delayed, treatment with EPO post-injury, can be neuroprotective and/or neurorestorative. The observed improvements of EPO therapy were generally not to the level of control uninjured animals, however. This suggested that combining EPO treatment with an adjunct therapeutic strategy should be researched. Treatment with EPO plus hypothermia led to less cerebral palsy in a non-human primate model of perinatal asphyxia, leading to clinical trials. A recent Phase II clinical trial on neonatal infants with HIE reported better 12-month motor outcomes for treatment with EPO plus hypothermia compared to hypothermia alone. Hence, the effectiveness of combined treatment with moderate hypothermia and EPO for neonatal HIE currently looks promising. The outcomes of two current clinical trials on neurological outcomes at 18–24 months-of-age, and at older ages, are now required. Further research on the optimal dose, onset, and duration of treatment with EPO, and critical consideration of the effect of injury severity and of gender, are also required.

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“…The effects of EPO were studied in a meta-analysis, in which no effect was found on NEC incidence (RR 0.62 (95% CI 0.15-2.59) [230]. Also in two more recent small RCTs, no effect was found of enteral EPO administration on NEC incidence [231,232].…”

Section: Hormone Growth Factor or Vitamin-based Feeding Interventionsmentioning

confidence: 99%

Enteral Feeding Interventions in the Prevention of Necrotizing Enterocolitis: A Systematic Review of Experimental and Clinical Studies

et al. 2021

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Necrotizing enterocolitis (NEC), which is characterized by severe intestinal inflammation and in advanced stages necrosis, is a gastrointestinal emergency in the neonate with high mortality and morbidity. Despite advancing medical care, effective prevention strategies remain sparse. Factors contributing to the complex pathogenesis of NEC include immaturity of the intestinal immune defense, barrier function, motility and local circulatory regulation and abnormal microbial colonization. Interestingly, enteral feeding is regarded as an important modifiable factor influencing NEC pathogenesis. Moreover, breast milk, which forms the currently most effective prevention strategy, contains many bioactive components that are known to support neonatal immune development and promote healthy gut colonization. This systematic review describes the effect of different enteral feeding interventions on the prevention of NEC incidence and severity and the effect on pathophysiological mechanisms of NEC, in both experimental NEC models and clinical NEC. Besides, pathophysiological mechanisms involved in human NEC development are briefly described to give context for the findings of altered pathophysiological mechanisms of NEC by enteral feeding interventions.

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Clinical Outcomes Related to the Gastrointestinal Trophic Effects of Erythropoietin in Preterm Neonates: A Systematic Review and Meta-Analysis

Cited by 15 publications

References 72 publications

Erythropoietin for preventing bronchopulmonary dysplasia in preterm infants: A systematic review and meta‐analysis

Erythropoietin for preventing bronchopulmonary dysplasia in preterm infants: A systematic review and meta‐analysis

Treatment of Neonatal Hypoxic-Ischemic Encephalopathy with Erythropoietin Alone, and Erythropoietin Combined with Hypothermia: History, Current Status, and Future Research

Enteral Feeding Interventions in the Prevention of Necrotizing Enterocolitis: A Systematic Review of Experimental and Clinical Studies

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