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

Background: Intravenous iron is increasingly being used in clinical practice to treat iron deficiency and anaemia. However, its effect on important safety outcomes, such as infection, remains uncertain. We systematically reviewed the risk of infection associated with administration of intravenous iron when compared with oral iron or no iron.  Methods: We searched for MEDLINE, EMBASE, CENTRAL and the Transfusion Evidence Library from 1966 to Jan 5, 2021 randomised controlled trials (RCTs) comparing intravenous iron with oral iron or no iron across all patient populations. Two reviewers independently extracted data, assessed risk of bias and graded the certainty of the evidence. A narrative synthesis was performed to characterize the reporting of infection. The primary outcome was risk of developing an infection. Data synthesis: A total of 154 RCTs (32,920 participants) were included in the main analysis.  Intravenous iron was associated with an increased risk of infection (Risk Ratio [RR] 1·17, 95% CI 1·04-1.31, I2=37%, moderate certainty) when compared with oral iron or no iron. Intravenous iron was associated with higher haemoglobin concentrations (Mean Difference 0·57 g/dL, 95% CI 0·50-0·64, 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: Intravenous iron administration is associated with an increased risk of infection. There was considerable variation in infection reporting between the included studies which may limit our understanding of the true nature and extent of this risk. Healthcare providers should recognise that the benefits of treating anaemia and reducing transfusion requirements may need to be balanced against the risk of developing infection. Well-designed studies, using standardized definitions of infection, are required. Registration Details: This study is registered with PROSPERO (CRD2018096023). Funding Information: NIHR Doctoral Research Fellowship (NIHR-DRF-2017-10-094). Declaration of Interests: AS (Shah) is currently supported by a National Institute for Health Research Doctoral Research Fellowship (NIHR-DRF-2017-10-094). Outside of this work, Prof Acheson’s research department has received grant support from Syner-Med (UK), Vifor Pharma (Switzerland) and Pharmacosmos A/S (Denmark). He has received honoraria and travel support for consulting or lecturing from Ethicon Endosurgery (UK), Johnson and Johnson Ltd (UK), Olympus (UK) and Vifor Pharma (Switzerland). All other authors have nothing to declare.