SynthesisEuropean journal of pediatrics2022
Early erythropoietin for preventing necrotizing enterocolitis in preterm neonates - an updated meta-analysis.
Synthesis in European journal of pediatrics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed, 3 syntheses or guidelines pooled it, 11 citations in OpenAlex.
- Association of anemia and necrotizing enterocolitis in neonates: Systematic review and meta-analysis of transfusion thresholds, erythropoietin trials, and observational studies.Journal of neonatal-perinatal medicine · 2026Pooled it
- Early erythropoiesis-stimulating agents in preterm or low-birthweight infants.The Cochrane database of systematic reviews · 2026Pooled it
- Comparative efficacy of different single drugs to prevent necrotizing enterocolitis in preterm infants: an update systematic review and network meta-analysis.Frontiers in nutrition · 2024Pooled it
- Development of an electrochemiluminescence assay to measure serum darbepoetin concentration in extremely preterm infants.Bioanalysis · 2025Article
- The microbiome's hidden influence: preclinical insights into inflammatory responses in necrotizing enterocolitis.Seminars in immunopathology · 2025Review
- Breastfeeding and Future Cardiovascular, Kidney, and Metabolic Health-A Narrative Review.Nutrients · 2025Review
- Evolutionary bridges: how factors present in amniotic fluid and human milk help mature the gut.Journal of perinatology : official journal of the California Perinatal Association · 2024Review
- The Role of Erythropoietin in Preventing Anemia in the Premature Neonate.Children (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous systematic reviews suggest reduction in necrotizing enterocolitis (NEC) among preterm infants supplemented with erythropoietin (EPO). We aimed to update our 2018 systematic review in this field considering the evidence accumulated over the last 3 years. Randomized controlled trials (RCTs) reporting the effect of early EPO supplementation vs placebo/no EPO supplementation on any stage NEC in preterm infants were included. Fixed effect model was used for meta-analysis. Trial sequential analysis (TSA) was conducted to verify the effects of EPO on NEC after accounting for repeated significance testing. A total of 22 RCTs (n = 5359) were included, of which six were new (n = 2541 additional preterm infants) in comparison to our previous systematic review. EPO significantly decreased the risk of any stage NEC (232/2669 (8.7%) vs 313/2690 (11.6%); RR: 0·76; TSA adjusted 95% CI (0·64, 0·90); p = 0·0008, number needed to treat (NNT) = 34). The risk of definite NEC (≥ Stage II) was also significantly reduced by EPO administration (105/2219 (4.7%) vs 141/2246 (6.3%); RR: 0.77; 95% CI (0.61, 0.98); p = 0.03, NNT: 62). However, the results for definite NEC were no longer significant on sensitivity analyses that included (a) only double-blind RCTs and (b) only prospectively registered trials. The quality of evidence was deemed moderate-to-low for the reported outcomes.
conclusionThere is moderate to low-quality evidence that early prophylactic EPO reduces any stage and ≥ Stage II NEC in preterm neonates. Prospectively registered, adequately powered, double-blind RCTs are required to confirm these findings. WHAT IS KNOWN: • Experimental studies have shown that erythropoietin (EPO) has gastrointestinal trophic effects. • Systematic reviews have shown that early treatment with EPO may decrease the risk of gut injury in preterm or low birth weight infants. WHAT IS NEW: • Early EPO supplementation significantly reduced the incidence of any stage NEC and definite NEC in preterm infants < 34 weeks of gestation. • EPO had no significant effect on definite NEC in the analyses that included only double-blinded and prospectively registered RCTs. How might it impact clinical practice in the foreseeable future? • Early prophylactic EPO can be recommended for NEC prevention if its benefits are consistently demonstrated in adequately powered randomized trials with a low risk of bias.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.