Is it time to rethink oral iron first in pregnancy anemia?

Clinical takeaway: For pregnant patients with iron-deficiency anemia, particularly those with more severe anemia, IV iron may offer meaningful advantages over oral iron, including lower transfusion risk and better maternal and neonatal iron stores. These findings add to growing evidence that current treatment guidelines may warrant reconsideration.

Iron-deficiency anemia affects roughly one-third of pregnancies worldwide and is associated with adverse maternal and neonatal outcomes. While oral iron remains the recommended first-line treatment in most guidelines, its gastrointestinal adverse effects and limited absorption can compromise effectiveness.

In a systematic review and meta-analysis published in JAMA Network Open, investigators pooled data from 29 randomized trials involving 11,771 pregnant individuals with iron-deficiency anemia who received either IV or oral iron therapy. Compared with oral iron, IV iron was associated with higher maternal hemoglobin levels at delivery (about 0.6 g/dL higher on average) and substantially higher maternal ferritin levels, indicating improved iron repletion. Neonatal ferritin levels were also higher among infants whose mothers received IV iron.

Perhaps most clinically relevant, IV iron was linked to a 37% lower risk of blood transfusion during delivery hospitalization. The benefit appeared even greater among patients with more severe anemia at baseline (hemoglobin ≤9 g/dL), who experienced a roughly 42% reduction in transfusion risk. IV iron also produced higher hemoglobin and ferritin levels within 4 to 6 weeks of treatment.

Safety findings favored IV therapy as well. No serious adverse reactions were reported in the trials that tracked these events, and overall mild adverse effects were 44% less common with IV iron. Gastrointestinal adverse effects, a common reason for poor adherence to oral iron, were reduced by nearly 90% with IV treatment.

The authors concluded that their findings “support a greater role for IV iron therapy in clinical guidelines recommending optimal treatment of [iron-deficiency anemia] in pregnancy, particularly among those with severe anemia.”

In an accompanying editorial, Drs. Michael Auerbach and Helain Landy argued that the results “put into question” current recommendations that reserve IV iron for patients who cannot tolerate or do not respond to oral therapy. They noted that continuing to favor a less effective treatment with frequent gastrointestinal adverse effects “when a superior alternative exists” warrants reassessment of current practice.

Source: Sales SK, Rajprohat S, Simon L, et al. (2026 Sep 23) JAMA Netw Open. Intravenous vs Oral Iron for Treating Iron Deficiency Anemia in Pregnancy: A Systematic Review and Meta-Analysis