Single-dose Intravenous Iron Versus Oral Iron for Treatment of Maternal Iron Deficiency Anemia: A Randomized Clinical Trial

Maternal iron deficiency anemia (IDA) in pregnancy is a global concern because of its association with postpartum hemorrhage, low birth weight (LBW), preterm birth, and long-term childhood development. In 2025, the United Nations established a goal to reduce the prevalence of anemia by 50% in reproductive age women by 2025. However, strategies to address iron deficiency have been inadequate with hardly any change in the rate of anemia in pregnant women from 52% in 2000 to 48% in 2019. Most national and international guidelines recommend treating IDA with oral iron therapy. Yet, intravenous (IV) iron formulations have been shown to be more effective in improving hemoglobin (Hb) and iron stores with greater tolerability and adherence than oral iron. Evidence comparing IV and oral iron on perinatal outcomes have been limited. The aims of the current study were to assess whether single-dose IV iron administered in the second trimester was superior to oral iron and to evaluate IV iron and oral iron on the maternal outcome of nonanemic state (NAS). This was a 3-arm, semi-blinded, superiority randomized controlled trial conducted at 19 community and primary health care centers in 4 cities across India from March 15, 2021 to May 12, 2023. Included were women between the ages of 18 and 40 years, with singleton pregnancies who were diagnosed with moderate IDA (Hb: 7.0ro 9.9 g/dL) at 14 to 17 weeks of gestation. Excluded were those with any fetal anomaly, history of cardiovascular disease, known hemoglobinopathy, or any disease or condition contraindicated by the treatment. Participants were randomly assigned 1:1:1 to treatment with twice daily oral iron (60 mg), a single dose of IV ferric carboxymaltose (20 mg/kg body weight), or single dose of IV ferric derisomaltose (20 mg/kg body weight). The primary outcomes were LBW (<2500 g) assessed within 72 hours of delivery or NAS attainment (Hb: ≥11 g/DL) at 30 to 34 weeks’ or at delivery. The analysis included 1450 participants in the oral iron arm, 1462 in the ferric carboxymaltose arm, and 1456 in the ferric derisomaltose arm. The incidence of LBW was lowest in participants who received IV ferric carboxymaltose (25.2%) compared with oral iron (29.3%) and IV ferric derisomaltose (29.1%). The number needed to treat to prevent one case of LBW was 24.7 (97.55% CI, 12.6-529.5). The incidences of NAS achievement were 69.7% in the oral iron arm, 73.0% in the IV ferric carboxymaltose arm, and 73.1% in the IV ferric derisomaltose arm. The incidences of nonresponse to therapy, need for rescue therapy, use of predelivery transfusion, and use of supplemental, non-study iron were lower in both IV arms versus oral iron arm. Mean Hb values were higher in the IV arms than oral iron arm at follow-up visits between 20 and 34 weeks, but the difference was no longer present at delivery and 6 weeks postpartum. In conclusion, there were fewer cases of LBW without an increase in safety concerns with single-dose IV ferric carboxymaltose compared with oral iron. In addition, the rates of attaining NAS were similar, but the IV arms had reduced need for rescue therapy or predelivery transfusion. (Abstracted from Am J Obstet Gynecol. 2025;233:120.e1-18)