A Retrospective Propensity-Matched Cohort Study of Intravenous Versus Oral Iron Formulations for Management of Iron Deficiency Anemia in Pregnancy.

Abstract

Anemia in pregnancy detrimentally impacts maternal and fetal health. Previous research has demonstrated faster and more robust hemoglobin (Hb) increases with intravenous (IV) iron when compared to oral iron. We aimed to characterize additional clinical impacts of IV iron and, by exploring multiple iron formulations, this study seeks to provide a comprehensive analysis of the effects, safety, and patient response to both treatment options. A retrospective propensity-matched cohort analysis was performed using a large database (TriNetX Research Network) from January 2000 to November 2025. We identified pregnant patients aged ≥18 years with iron deficiency anemia (IDA) in the second trimester with ferritin <30 ng/mL and hemoglobin <11 g/dL, constructing two cohorts: (1) patients treated with IV iron and (2) patients treated with oral iron within 2 months of their anemia diagnosis. Propensity score matching was performed by age, demographics, overweight and obesity, type 2 diabetes, lipid disorders, hypertension, heart failure, chronic ischemic heart disease, hypothyroidism, chronic kidney disease, gastro-esophageal reflux disease, high-risk pregnancy, neoplasms, nicotine dependence, alcohol use disorder, other substance use disorder, and pretreatment Hb grouped by <6.5 g/dL, 6.5 to 7.9 g/dL, 8 to 9.9 g/dL, and 10 to 10.9 g/dL. Primary outcomes were blood transfusions, maternal mortality, preeclampsia, cesarean section (CS), and preterm labor. Secondary outcomes were an adverse outcome composite (gastritis,nausea/vomiting or anaphylactic shock), Hb, and ferritin in the 3 months after treatment. Subgroup analysis of IV iron users (excluding iron sucrose) versus oral iron users was performed. There were 1693 postmatch patients per cohort. IV iron was associated with lower risk for preterm labor (7.7% vs 10.04%, risk ratio [RR] 0.77 [0.62-0.96]) and CS (18.67% vs 22.15%, RR 0.84 [0.74-0.96]) and higher posttreatment Hb (10.6 vs 9.7, adj. P = .0001) and ferritin (138 vs 39, adj. P = .0001). There was no difference in other outcome measures. There were 914 postmatch patients per cohort in the subgroup analysis. IV iron (excluding iron sucrose) was again associated with decreased risk of preterm labor (5.25% vs 9.30%, RR 0.57 [0.40-0.80]), higher Hb (10.7 vs 9.8, adj. P = .0001) and ferritin (175 vs 42, adj. P = .0001). All other outcomes were not significant. This study evaluates the differential effects of IV compared with oral iron formulations in a large cohort of matched pregnant patients. Compared to oral iron, IV iron may be preferable for increasing Hb, resolving IDA, and reducing maternal complications.