Comparison of oral iron replacement formulations for anemia in pregnancies with non-severe hemoglobinopathies

Abstract

Non-severe hemoglobinopathies (H) in pregnancy often predispose patients to development of anemia requiring increased iron requirements. While ferrous sulfate remains a commonly chosen preparation, there remains uncertainty. This study sought to determine which iron formulation proved most effective for pregnant patients with non-severe hemoglobinopathies. We conducted a multi-center, prospective observational study from 7/2021 to 7/2022 and included all pregnant women with H diagnosed with anemia requiring iron supplementation between 24 0/7 through 36 6/7 weeks-gestation. Patients with any H were together compared with a control group of otherwise uncomplicated pregnancies. Iron formulations of twice-daily PO ferrous sulfate 325mg, ferrous gluconate 324mg, and ferrous bisglycinate 28mg were included as covariates. Medication choice was determined by physician preference, with supplementation being initiated uniformly in patients with hemoglobin < 10.0 g/dL or symptomatic. The primary outcomes included refractory anemia requiring either IV iron or blood transfusion, as a discrete event, and treatment effectiveness defined as an increase of at least 1.0 g/dL over a 2-3 week period. The study included 313 patients diagnosed with anemia requiring supplementation, with 151 patients with H pregnancies. Overall, patients who were given ferrous bisglycinate had higher rates of compliance (98% versus 74%, p = 0.02) and treatment effectiveness (81.3% v. 68.4%, p=0.04). Among H patients, patients taking ferrous sulfate had higher rates of needing IV supplementation (17.3% versus 8.5%, p = < 0.001). Among uncomplicated pregnancies, patients taking ferrous gluconate had higher compliance rates (p = 0.01), and ferrous bisglycinate having a higher rate of treatment effectiveness (p = 0.003). When adjusting for confounding factors these differences remained significant. Alternative formulations of iron supplementation such as ferrous gluconate or ferrous bisglycine may be more effective options in managing anemia in both uncomplicated and H pregnancies.