Response of reticulocyte and red blood cell indices to single-dose intravenous iron in pregnant women with moderate iron deficiency anemia: secondary analysis of the RAPIDIRON trial

BACKGROUND: Iron deficiency anemia in pregnancy is a significant health concern. Reticulocyte hemoglobin equivalent (Ret-He) and immature reticulocyte fraction (IRF) are emerging as early markers, yet their response to different iron therapies in pregnancy is underexplored. OBJECTIVE: To determine whether intravenous single-dose iron administration produces a more favorable effect on reticulocyte indices than oral iron therapy in anemic pregnant women. METHODS: This is a secondary analysis of the RAPIDIRON Trial, a multicenter, three-arm randomized controlled trial comparing ferric carboxymaltose (FCM), ferric derisomaltose (FDM) and standard oral ferrous sulfate. Reticulocyte hemoglobin equivalent (Ret-He), Immature Reticulocyte Fraction (IRF) and other red blood cell indices including Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin (MCH), Mean Corpuscular Hemoglobin Concentration (MCHC) were measured at baseline (12-16 weeks), mid-gestation (26-30 weeks) and 42 days postpartum. Cord blood indices were assessed at delivery. RESULTS: By 26-30 weeks of gestation, iron deficient anemic women receiving IV iron demonstrated significant improvements in all red cell indices when compared to those receiving oral iron. Specifically, MCV increased by 2.87 fL (95% CI, 2.41-3.33) in the IV FDM group and 3.02 fL (95% CI, 2.54-3.49) in the IV FCM group compared to oral iron. Similarly Ret-He levels were also significantly increased in IV FDM and FCM compared to oral iron (1.32 (1.02, 1.63) and 1.31 (1.01, 1.62) respectively. By 42 days postpartum, intergroup differences in Ret-He, IRF and other parameters were no longer statistically significant, indicating that hematologic parameters had converged across treatment arms, reflecting restoration of iron homeostasis and stabilization of erythropoiesis in all groups. CONCLUSION: Intravenous iron therapy produces a more rapid and pronounced improvement in maternal red cell and reticulocyte indices than oral iron in moderately anemic pregnant women. Ret-He and IRF are emerging as early and sensitive biomarkers of iron availability and erythropoietic activity, with potential clinical utility for early detection of treatment response and optimization of iron therapy in pregnancy.