Intravenous iron versus blood transfusion for postpartum anemia: a systematic review and meta-analysis

Abstract

Background: Intravenous iron (IV-iron) is used as an alternative to, or alongside, red blood cell transfusion (RBC-T) to treat more severe postpartum anemia (PPA), although optimal treatment options remain unclear. No previous systematic reviews have examined IV-iron and RBC-T, including patient-reported outcomes and hematological responses.

Methods: A systematic review and meta-analysis of randomized trials comparing IV-iron and RBC-T with each other, oral iron, no treatment, and placebo for the treatment of PPA. Key inclusion criteria were PPA (hemoglobin < 12 g/dL) and IV-iron or RBC-T as interventions. Key exclusion criteria were antenatal IV-iron or RBC-T. Fatigue was the primary outcome. Secondary outcomes included hemoglobin and ferritin concentrations, and adverse events. From 27th August 2020 to 26th September 2022, databases, registries, and hand searches identified studies. A fixed-effect meta-analysis was undertaken using RevMan (5.4) software. The quality of the studies and the evidence was assessed using the Cochrane Risk of Bias table, and Grading of Recommendations, Assessment, Development, and Evaluation. This review is registered with the Prospective Register of Systematic Reviews (CRD42020201115).

Results: Twenty studies and 4196 participants were included: 1834 assigned IV-iron, 1771 assigned oral iron, 330 assigned RBC-T, and 261 assigned non-intervention. Six studies reported the primary outcome of fatigue (1251 participants). Only studies of IV-iron vs. oral iron (15 studies) were available for meta-analysis. Of these, three reported on fatigue using different scales; two were available for meta-analysis. There was a significant reduction in fatigue with IV-iron compared to oral iron (standardized mean difference - 0.40, 95% confidence interval (CI) - 0.62, - 0.18, I² = 0%). The direction of effect also favored IV-iron for hemoglobin (mean difference (MD) 0.54 g/dL, 95% confidence interval (CI) 0.47, 0.61, I² = 91%), ferritin, (MD 58.07 mcg/L, 95% CI 55.74, 60.41, I² = 99%), and total adverse events (risk-ratio 0.63, 95% CI 0.52, 0.77, I² = 84%). The overall quality of the evidence was low-moderate.

Discussion: For all outcomes, the evidence for RBC-T, compared to IV-iron, non-intervention, or dose effects of RBC-T is very limited. Further research is needed to determine whether RBC-T or IV-iron for the treatment of PPA is superior for fatigue and hematological outcomes.

Keywords: Adverse drug reaction; Anemia; Erythrocyte transfusion; Fatigue; Ferric compounds; Hematinics; Intravenous infusion; Iron; Iron deficiency; Puerperal disorders.

Fig. 1

PRISMA flowchart including searches of databases, registers, and other methods

Fig. 2

Risk of bias assessment for included studies

Fig. 3

Forest plot for comparison of IV-iron vs. oral iron: fatigue

Fig. 4

Forest plot for comparison of IV-iron vs. oral iron: Hb concentration longest follow-up (g/dL)

Fig. 5

Forest plot for comparison of IV-iron vs. oral iron: ferritin concentration longest follow-up (mcg/L)