Efficacy and safety of high and low dose recombinant human erythropoietin on neurodevelopment of premature infants

Abstract

Background: To evaluate the effect of recombinant human erythropoietin (rhEPO) in nervous system of premature infants including different dosage. Methods: The multiple databases like Pubmed, Embase, Cochrane databases and China National Knowledge Database were used to search for the relevant studies, and full-text articles involved in the evaluation on effect of rhEPO for neurodevelopment among premature infants. Review Manager 5.2 was adopted to estimate the effects of the results among selected articles. Forest plots, sensitivity analysis and bias analysis for the articles included were also conducted. Results: Finally, 10 eligible studies were eventually satisfied the included criteria. The results showed that rhEPO was much higher than placebo group in composite cognitive score (MD = 5.89, 95% confidential interval {CI} [1.95, 9.82], P = .003; I 2 = 89%), there was no significant difference between rhEPO and placebo groups (RR = 0.93, 95% CI [0.60, 1.43], P = .74; I 2 = 51%) and no difference in neurodevelopmental impairment between rhEPO and placebo was insignificant (RR = 0.55 95% CI [0.30, 1.02], P = .06). Composite cognitive score in high dose rhEPO was much higher than placebo group (MD = 10.39, 95% CI [8.84, 11.93], P < .0001, I 2 = 0%) and low dose rhEPO also had higher composite cognitive score than placebo group (MD = 2.58, 95% CI [0.80, 4.37], P = .004, I 2 = 11%). Limited publication bias was observed in this study. Conclusion: Recombinant human erythropoietin might be a promotor for neurodevelopment among premature infants with limited adverse events.

Can Erythropoietin Reduce Hypoxemic Neurological Damages in Neonates With Congenital Heart Defects?

“…EPO administration to improve oxygen delivery and treat anemia in infants have been proposed by several studies, sometimes together with iron administration (Kling, 2020). A very recent meta-analysis confirmed the efficacy and safety of rhEPO in preterm infants (Qin and Qin, 2021). Some of the white matter neurological damages in such patients are quite similar to the ones observed in preterm infants (Wintermark et al, 2015), The studies investigating neurological effects of EPO in preterms might be suggestive of its potential neuroprotective effect too.…”

Neurodevelopmental outcomes of preterm infants

“…Previous studies reported that rhEPO improves the cognitive development of VP but not EP infants. Moreover, there was no significant effect on any secondary outcome, such as psychomotor development, cerebral palsy, or severe visual or hearing impairment [52][53][54][55] . The effects of prebiotic and probiotic supplementation and micro-(zinc, iodine) or macronutrient (amino acid) supplementation on the neurodevelopment of A c c e p t e d A r t i c l e preterm infants have been studied, but the evidence remains insufficient 56-60) .…”