Safety and Effectiveness of Intravenous vs Oral Iron for Treatment of Anemia in the Prenatal and Postpartum Periods

How do the safety and effectiveness of intravenous (IV) iron compare with oral iron in the treatment of anemia in the prenatal and postpartum periods?

In the prenatal setting, treatment of iron deficiency anemia with IV iron rather than oral iron may slightly increase the hemoglobin level 3 to 6 weeks after treatment and around the time of birth¹; however, there is no significant effect on postpartum hemorrhage, need for blood transfusion, or rates of breast-feeding.¹ (Strength of Recommendation [SOR]: C, consensus, disease-oriented evidence, usual practice, expert opinion, or case series for studies of diagnosis, treatment, prevention, or screening.)

In the postpartum setting among patients with iron deficiency anemia, IV iron therapy is associated with increased treatment adherence, a slight reduction in fatigue in the first month, and lower risk of constipation compared with oral iron treatment.² (SOR: A, inconsistent or limited-quality patient-oriented evidence.)

Iron deficiency anemia is the most common micronutrient deficiency in the world, affecting approximately 12% to 20% of all pregnancies in North America.^3–5 It is associated with adverse maternal and infant outcomes, including maternal death, preterm labor, postpartum hemorrhage, and low birth weight.⁵ The authors of these Cochrane reviews sought to compare the safety and effectiveness of the two most common treatments for iron deficiency anemia in the prenatal and post-partum periods.^1,2

In the first review, the authors identified 13 randomized controlled trials (RCTs; N = 3,939) comparing IV with oral iron to treat iron deficiency anemia in pregnancy.¹ Participants were pregnant patients, mainly from India and Africa, who were diagnosed with iron deficiency anemia (ie, hemoglobin level less than 11 g/dL [110 g/L] or hematocrit less than 33%) at any stage of pregnancy. Patients with chronic disease that could affect baseline hemoglobin levels (eg, kidney disease, thalassemia) were excluded.

The analysis suggested that IV iron increased hemoglobin levels slightly more than oral iron (mean difference = 0.49; 95% CI, 0.28–0.69) when measured 3 to 6 weeks after treatment and likely reduced anemia status around birth (relative risk [RR] = 0.85; 95% CI, 0.77–0.93; four RCTs; n = 1,240; moderate-certainty evidence).¹ Receiving IV iron rather than oral iron during pregnancy decreased the likelihood that patients would have a hemoglobin level of less than 11 g/dL at the time of delivery (RR = 0.85; 95% CI, 0.77–0.93; number needed to treat [NNT] with IV rather than oral iron = 11; moderate-certainty evidence). In addition, giving IV vs oral iron during pregnancy decreased the likelihood that patients would have a hemoglobin level less than 11 g/dL 4 to 6 weeks postpartum (RR = 0.66; 95% CI, 0.59–0.73; NNT = 4; low-certainty evidence) or a hemoglobin level less than 7 g/dL (70 g/L) 6 weeks postpartum (RR = 0.16; 95% CI, 0.03–0.84; NNT = 59; very low-certainty evidence).

Antenatal treatment with IV iron is associated with a higher postpartum hemoglobin level compared with oral iron (mean difference = 0.54; 95% CI, 0.41–0.68; three RCTs; n = 1,950; low-certainty evidence), although there was no significant effect on postpartum hemorrhage, the need for blood transfusion, or breastfeeding rates.¹ None of the trials reported on maternal well-being. The reviewers noted that IV iron did not seem to increase the risk of adverse effects compared with oral iron for the specific adverse effects chosen for comparison (ie, risk of severe infection, prolonged hospital stay, admission to the intensive care unit); however, there was significant heterogeneity in the reporting of adverse effects across the trials, which limits confidence in this conclusion.