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Meta-Analysis
. 2021 Nov 1;4(11):e2133935.
doi: 10.1001/jamanetworkopen.2021.33935.

Risk of Infection Associated With Administration of Intravenous Iron: A Systematic Review and Meta-analysis

Akshay A Shah  1   2   3 , Killian Donovan  3 , Claire Seeley  4 , Edward A Dickson  5   6 , Antony J R Palmer  7 , Carolyn Doree  8 , Susan Brunskill  8 , Jack Reid  9 , Austin G Acheson  5   6 , Anita Sugavanam  9 , Edward Litton  10 , Simon J Stanworth  1   2   8   11
Affiliations
Meta-Analysis

Risk of Infection Associated With Administration of Intravenous Iron: A Systematic Review and Meta-analysis

Akshay A Shah et al. JAMA Netw Open. .

Erratum in

  • Errors in Data.
    [No authors listed] [No authors listed] JAMA Netw Open. 2022 Jan 4;5(1):e2146637. doi: 10.1001/jamanetworkopen.2021.46637. JAMA Netw Open. 2022. PMID: 35015070 Free PMC article. No abstract available.
  • Error in Data.
    [No authors listed] [No authors listed] JAMA Netw Open. 2024 Dec 2;7(12):e2454479. doi: 10.1001/jamanetworkopen.2024.54479. JAMA Netw Open. 2024. PMID: 39652353 Free PMC article. No abstract available.
  • Correction to Meta-Analysis to Acknowledge Retracted Study.
    [No authors listed] [No authors listed] JAMA Netw Open. 2025 Jan 2;8(1):e250887. doi: 10.1001/jamanetworkopen.2025.0887. JAMA Netw Open. 2025. PMID: 39869341 Free PMC article. No abstract available.

Abstract

Importance: Intravenous iron is recommended by many clinical guidelines based largely on its effectiveness in reducing anemia. However, the association with important safety outcomes, such as infection, remains uncertain.

Objective: To examine the risk of infection associated with intravenous iron compared with oral iron or no iron.

Data sources: Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials (RCTs) from 1966 to January 31, 2021. Ongoing trials were sought from ClinicalTrials.gov, CENTRAL, and the World Health Organization International Clinical Trials Search Registry Platform.

Study selection: Pairs of reviewers identified RCTs that compared intravenous iron with oral iron or no iron across all patient populations, excluding healthy volunteers. Nonrandomized studies published since January 1, 2007, were also included. A total of 312 full-text articles were assessed for eligibility.

Data extraction and synthesis: Data extraction and risk of bias assessments were performed according to the Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) and Cochrane recommendations, and the quality of evidence was assessed using the GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach. Two reviewers extracted data independently. A random-effects model was used to synthesize data from RCTs. A narrative synthesis was performed to characterize the reporting of infection.

Main outcomes and measures: The primary outcome was risk of infection. Secondary outcomes included mortality, hospital length of stay, and changes in hemoglobin and red blood cell transfusion requirements. Measures of association were reported as risk ratios (RRs) or mean differences.

Results: A total of 154 RCTs (32 920 participants) were included in the main analysis. Intravenous iron was associated with an increased risk of infection when compared with oral iron or no iron (RR, 1.17; 95% CI, 1.04-1.31; I2 = 37%; moderate certainty of evidence). Intravenous iron also was associated with an increase in hemoglobin (mean difference, 0.57 g/dL; 95% CI, 0.50-0.64 g/dL; I2 = 94%) and a reduction in the risk of requiring a red blood cell transfusion (RR, 0.93; 95% CI, 0.76-0.89; I2 = 15%) when compared with oral iron or no iron. There was no evidence of an effect on mortality or hospital length of stay.

Conclusions and relevance: In this large systematic review and meta-analysis, intravenous iron was associated with an increased risk of infection. Well-designed studies, using standardized definitions of infection, are required to understand the balance between this risk and the potential benefits.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Acheson reported receiving grant support from Syner-Med (UK), Vifor Pharma (Switzerland), and Pharmacosmos A/S (Denmark) and honoraria and travel support for consulting or lecturing from Ethicon Endosurgery (UK), Johnson and Johnson Ltd (UK), Olympus (UK), and Vifor Pharma (Switzerland) outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Selection of Studies in the Systematic Review
NRSs indicates nonrandomized studies; RCTs, randomized clinical trials.
Figure 2.
Figure 2.. Association Between Risk of Infection and Intravenous Iron When Compared With Oral Iron
The risk ratios were calculated using a random-effects model with Mantel-Haenszel weighting. The size of the data markers indicates the weight of the study. Error bars indicate 95% CIs. Orange indicates unclear risk of bias; blue, low risk of bias; and grey, high risk of bias.
Figure 3.
Figure 3.. Association Between Risk of Infection and Intravenous Iron When Compared With No Iron
The size of the data markers indicates the weight of the study. Error bars indicate 95% CIs. Orange indicates unclear risk of bias; blue, low risk of bias; and grey, high risk of bias.
See this image and copyright information in PMC

Comment in

References

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