Intravenous vs Oral Iron for Treating Iron Deficiency Anemia in Pregnancy: A Systematic Review and Meta-Analysis.

Importance: Although treatment of iron deficiency anemia (IDA) during pregnancy is recommended to improve pregnancy outcomes, the optimal route of iron therapy has not been determined. Objective: To update a systematic review and meta-analysis of the comparative association of intravenous (IV) vs oral iron for treating IDA with maternal and neonatal outcomes. Data Sources: This systematic review and meta-analysis updated a previous review from 2018 by searching Embase, Scopus, Ovid MEDLINE, the Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from February 17, 2018, through May 6, 2025, for randomized clinical trials (RCTs) comparing IV and oral iron to treat IDA in pregnancy. Raw data were abstracted from published studies. Study Selection: Titles and abstracts identified through the search strategy were independently screened by 2 reviewers, and full-text articles were obtained for studies deemed eligible. All full-text RCTs that were included compared any formulations of IV iron with oral iron for the treatment of IDA in pregnancy. Studies that enrolled nonpregnant women, lacked a comparison group, or used observational designs were excluded. Data Extraction and Synthesis: Two reviewers independently extracted data and assessed study quality. Main Outcomes and Measures: Primary outcomes were maternal hemoglobin and ferritin levels at childbirth. Secondary outcomes included blood transfusion, medication reactions, and neonatal outcomes. Pooled weighted mean differences (WMDs) and relative risks (RRs) with 95% CIs were calculated. Prespecified stratified analyses examined whether results differed by pretreatment hemoglobin level (≤9 g/dL vs >9 g/dL). Results: Ten new RCTs were identified and 1 RCT in the original meta-analysis was retracted, for a total of 29 RCTs including 11 771 unique participants. Compared with oral iron, IV iron therapy was associated with higher mean levels of maternal hemoglobin (WMD in 15 studies, 0.59 g/dL [95% CI, 0.31-0.87 g/dL]) and maternal ferritin (WMD in 8 studies, 50.93 ng/mL [95% CI, 33.56-68.29 ng/mL]) and neonatal ferritin (WMD in 8 studies, 21.38 ng/mL [95% CI, 5.50-37.25 ng/mL]) at delivery and a 37% lower rate of blood transfusion during delivery hospitalization (RR in 14 studies, 0.63 [95% CI, 0.49-0.82]), particularly among those with pretreatment hemoglobin level of 9 g/dL or less (RR in 6 studies, 0.58 [95% CI, 0.45-0.76]). No serious adverse events were reported. IV iron therapy was associated with a 43% lower rate of mild adverse effects (RR in 31 studies, 0.56 [95% CI, 0.41-0.76]). Conclusions and Relevance: In this systematic review and meta-analysis of 29 RCTs, compared with oral iron, IV iron for treating IDA in pregnancy was associated with improved maternal hematologic parameters and neonatal iron stores and reduced rates of blood transfusion and mild adverse effects without increasing serious adverse effects. These findings may support a greater role for IV iron in the treatment of IDA in pregnancy.