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Meta-Analysis
. 2020 Feb 11;2(2):CD004865.
doi: 10.1002/14651858.CD004865.pub4.

Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants

Sanjay M Aher  1 , Arne Ohlsson  2
Affiliations
Meta-Analysis

Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants

Sanjay M Aher et al. Cochrane Database Syst Rev. .

Abstract

Background: Low plasma levels of erythropoietin (EPO) in preterm infants provide a rationale for the use of EPO to prevent or treat anaemia.

Objectives: To assess the effectiveness and safety of early versus late initiation of EPO in reducing red blood cell (RBC) transfusions in preterm and/or low birth weight (LBW) infants.

Search methods: The standard search of the Cochrane Neonatal Review Group (CNRG) was performed in 2006 and updated in 2009. Updated search in September 2009 as follows: The Cochrane Library, MEDLINE (search via PubMed), CINAHL and EMBASE were searched from 2005 to September 2009. The searches were repeated in March 2012. The Pediatric Academic Societies' Annual meetings were searched electronically from 2000 to 2012 at Abstracts2ViewTM as were clinical trials registries (clinicaltrials.gov; controlled-trials.com; and who.int/ictrp).

Selection criteria: Randomised or quasi-randomised controlled trials enrolling preterm or LBW infants less than eight days of age.

Intervention: Early initiation of EPO (initiated at less than eight days of age) versus late initiation of EPO (initiated at eight to 28 days of age).

Data collection and analysis: The standard methods of the CNRG were followed. Weighted treatment effects included typical risk ratio (RR), typical risk difference (RD), number needed to treat to benefit (NNTB), number needed to treat to harm (NNTH) and mean difference (MD), all with 95% confidence intervals (CI). A fixed-effect model was used for meta-analyses and heterogeneity was evaluated using the I-squared (I2) test.

Main results: No new trials were identified in March of 2012. Two high quality randomised double-blind controlled studies enrolling 262 infants were identified. A non-significant reduction in the 'Use of one or more RBC transfusions' [two studies 262 infants; typical RR 0.91 (95% CI 0.78 to 1.06); typical RD -0.07 (95% CI -0.18 to 0.04; I2 = 0% for both RR and RD] favouring early EPO was noted. Early EPO administration resulted in a non-significant reduction in the "number of transfusions per infant" compared with late EPO [typical MD - 0.32 (95% CI -0.92 to 0.29)]. There was no significant reduction in total volume of blood transfused per infant or in the number of donors to whom the infant was exposed. Early EPO led to a significant increase in the risk of retinopathy of prematurity (ROP) (all stages) [two studies, 191 infants; typical RR 1.40 (95% CI 1.05 to 1.86); typical RD 0.16 (95% CI 0.03 to 0.29); NNTH 6 (95% CI 3 to 33)]. There was high heterogeneity for this outcome (I2 = 86% for RR and 81% for RD). Both studies (191 infants) reported on ROP stage > 3. No statistically significant increase in risk was noted [typical RR 1.56 (95% CI 0.71 to 3.41); typical RD 0.05 (-0.04 to 0.14)] There was no heterogeneity for this outcome (0% for both RR and RD). No other important favourable or adverse neonatal outcomes or side effects were reported.

Authors' conclusions: The use of early EPO did not significantly reduce the 'Use of one or more RBC transfusions' or the 'Number of transfusions per infant" compared with late EPO administration. The finding of a statistically significant increased risk of ROP (any grade) and a similar trend for ROP stage > 3 with early EPO treatment is of great concern.

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Conflict of interest statement

None known.

Figures

1
1
Forest plot of comparison: 1 Early (0‐7 days) vs. late (8‐28 days) initiation of EPO, outcome: 1.1 Use of one or more red blood cell transfusions.
2
2
Forest plot of comparison: 1 Early (0‐7 days) vs. late (8‐28 days) initiation of EPO, outcome: 1.6 Retinopathy of prematurity (all stages).
1.1
1.1. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 1 Use of one or more red blood cell transfusions.
1.2
1.2. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 2 Total volume of red blood cells transfused per infant.
1.3
1.3. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 3 Number of red blood cell transfusions per infant.
1.4
1.4. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 4 Number of donors the infant was exposed to.
1.5
1.5. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 5 Mortality during initial hospital stay (all causes).
1.6
1.6. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 6 Retinopathy of prematurity (all stages).
1.7
1.7. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 7 Retinopathy of prematurity (stage >/= 3).
1.8
1.8. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 8 NEC.
1.9
1.9. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 9 IVH.
1.10
1.10. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 10 PVL.
1.11
1.11. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 11 BPD (oxygen at 36 weeks).
1.12
1.12. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 12 Sudden infant death after discharge.
1.13
1.13. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 13 Weight gain (grams) during the study period (from entry to exit from study).
1.14
1.14. Analysis
Comparison 1 Early (0‐7 days) versus late (8‐28 days) initiation of EPO, Outcome 14 Thrombocytosis (platelet count > 500 x 10 9/L).
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References

References to studies included in this review

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Aher 2004
    1. Aher SM, Ohlsson A. Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database of Systematic Reviews 2004, Issue 3. [DOI: 10.1002/14651858.CD004865.pub2] - DOI
Aher 2006
    1. Aher SM, Ohlsson A. Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database of Systematic Reviews 2006, Issue 3. [DOI: 10.1002/14651858.CD004865.pub2] - DOI - PubMed

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