Advancing Neonatal Outcomes: Erythropoietin in Preterm Care

Abstract

Background:
Preterm birth remains a significant global health challenge, contributing to high rates of neonatal mortality and long-term neurodevelopmental impairment. Despite advancements in neonatal intensive care, effective pharmacologic strategies for neuroprotection in preterm infants are limited. Recombinant human erythropoietin (rhEPO), traditionally used for anemia of prematurity, has shown potential neuroprotective effects due to its anti-apoptotic, anti-inflammatory, and neurotrophic properties.

Objective:
To systematically review the current evidence from randomized controlled trials (RCTs) and meta-analyses on the efficacy and safety of erythropoietin in improving neurodevelopmental outcomes in preterm neonates.

Methods:
A comprehensive literature search was conducted across PubMed and Frontiers databases for RCTs and meta-analyses published between 2020 and 2024. Inclusion criteria were English-language studies assessing neurodevelopmental outcomes following rhEPO therapy in preterm infants. Studies lacking full-text access, non-RCT design, case reports, or involving non-preterm populations were excluded. Data extraction focused on sample size, rhEPO dosage, administration protocols, and primary neurodevelopmental outcomes.

Key Results:
Among six included studies (four RCTs, one meta-analysis, one post hoc analysis), findings varied significantly. High-dose rhEPO administered early in life did not reduce the risk of severe neurodevelopmental impairment or death at two or five years of age in large trials. However, in selected subgroups, such as preterm infants with intraventricular hemorrhage, low-dose rhEPO showed significant improvements in combined outcomes of mortality and neurological disability. Cognitive gains associated with iron supplementation in rhEPO-treated infants were noted but not conclusively linked to rhEPO alone.

Conclusion:
Current evidence does not uniformly support rhEPO as an effective neuroprotective agent for the broader preterm population. While selective benefit is noted in high-risk groups, heterogeneity in study designs and outcomes limits generalizability. Further multicenter trials with standardized protocols and long-term follow-up are essential.