Intravenous and Oral Iron Strategies for Iron-Deficiency Anemia in Pregnancy: A Systematic Review of Randomized Controlled Trials From a Hematology Perspective

Iron-deficiency anemia is the most common hematologic disorder in pregnancy. Slow iron repletion, poor gastrointestinal tolerance, and late presentation during gestation often limit the effectiveness of oral ferrous salts, which remain the traditional first-line treatment. Intravenous iron offers faster iron delivery, but its role in routine antenatal care remains uncertain, particularly regarding its long-term safety and cost-effectiveness compared to traditional oral iron treatments. This qualitative systematic review included 10 randomized controlled trials published within the last decade that enrolled pregnant women with iron-deficiency anemia or persistent iron deficiency (defined, where applicable, as ferritin <30 μg/L after approximately four weeks of oral iron therapy) and compared intravenous iron with oral iron or one intravenous formulation with another. Across the included trials, intravenous iron generally produced more rapid ferritin replenishment and, in many studies, a faster rise in hemoglobin than oral therapy. Oral ferrous preparations were associated with more gastrointestinal adverse effects; for example, in one study, gastrointestinal treatment-related events were reported in more women receiving oral ferrous sulfate versus those receiving ferric carboxymaltose. In another trial, nausea/vomiting occurred in greater number of oral-iron recipients versus intravenous ones, while constipation and epigastric discomfort were reported only in the oral group. By contrast, serious intravenous treatment-related events were uncommon in the larger trials.​ ​Smaller and medium-sized trials generally favored parenteral iron for hematologic recovery, but the largest pragmatic studies from India, Malawi, and Nigeria showed that biochemical superiority did not consistently translate into lower rates of late-pregnancy anemia or improved major maternal and neonatal outcomes. One head-to-head intravenous trial also suggested practical and hematologic advantages of ferric carboxymaltose over iron sucrose. From a hematology perspective, intravenous iron appears most useful when rapid restoration of iron stores is needed, when adherence to oral therapy is doubtful, or when little time remains before delivery. Future trials should standardize ferritin-based diagnostic criteria, clearly distinguish hematologic from obstetric endpoints, and better define which patients are most likely to derive clinically meaningful benefit from parenteral iron.