European Journal of Cardiovascular Medicine

Iron deficiency anemia (IDA) is the most common nutritional deficiency worldwide, affecting nearly 1.5 billion individuals, with pregnant women constituting one of the most vulnerable groups [1,2]. The global prevalence of anemia in pregnancy is estimated to exceed 50% in low- and middle-income countries, contributing significantly to maternal and perinatal morbidity [3].

During pregnancy, iron requirements increase substantially to support maternal erythropoiesis, placental development, and fetal growth [4]. Failure to meet these requirements results in iron deficiency (ID) and IDA, which have been linked to adverse outcomes such as preterm labor, fetal growth restriction, postpartum hemorrhage, increased need for blood transfusion, and impaired neurodevelopmental outcomes in offspring [5–7].

Although oral iron supplementation remains the first-line therapy for mild anemia, its effectiveness is often limited by poor gastrointestinal absorption, dose-dependent adverse effects, and low compliance rates, which may reach up to 50% [8,9]. Intravenous iron therapy is therefore recommended for women with moderate to severe anemia, intolerance to oral iron, or when rapid correction is clinically indicated [10].

Ferric carboxymaltose (FCM) is a dextran-free intravenous iron formulation that allows administration of high doses (up to 1000 mg per infusion) over a short duration with minimal risk of hypersensitivity reactions [11]. Several studies and systematic reviews have demonstrated the superiority of FCM over oral iron and iron sucrose in terms of hemoglobin response, replenishment of iron stores, and patient compliance [12–15].

However, data focusing on comprehensive red cell indices—particularly mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH)—remain limited. These indices are critical markers of iron-restricted erythropoiesis and hematological recovery.

This study aims to evaluate the safety and efficacy of ferric carboxymaltose in pregnant women with moderate iron deficiency anemia, with detailed assessment of changes in hemoglobin, serum ferritin, MCV, and MCH, and to compare these findings with existing literature.

Study Design and Setting A prospective interventional study was conducted, between December 2024 and December 2025, in the department of General Medicine and department of obstetrics and gynaecology at Government Medical college Handwara, Jammu and Kashmir, India. Participants Pregnant women aged ≥20 years, between 14 weeks and 28 weeks’ gestation, diagnosed with iron deficiency anemia, with: 1. Serum ferritin <15 µg/L 2. Moderate anemia (Hb 7–9.9 g/dL) in pregnancy as defined by World Health Organisation (WHO) 3. Microcytic hypochromic indices (MCV <80 fl, MCH <27 pg) were included after informed consent. Exclusion Criteria 1. Severe anemia (Hb <7 g/dL) 2. Non-iron deficiency anemia 3. Known hypersensitivity to intravenous iron 4. Chronic renal and hepatic disorders 5. Hemoglobinopathies Intervention Ferric carboxy maltose (Revofer®) was used for the study as it is available free of cost to patients in the Government hospitals of Jammu and Kashmir. Ferric carboxymaltose (Revofer®) dose was calculated according to body weight and hemoglobin deficit using Ganzoni formula (Total iron deficit (mg)=Body weight (kg)×[Target Hb (g/dL)−Actual Hb (g/dL)]×2.4+Iron stores (mg)). Ferric carboxymaltose was administered intravenously in 100 ml Normal saline over 15 minutes and only a maximum of 1000 mg per week was given. Doses >1000 mg were divided into two infusions one week apart. Outcome Measures Primary outcomes: • Change in hemoglobin, serum ferritin, MCV, and MCH at 6 and 12 weeks. Secondary outcomes: •Adverse events related to ferric carboxymaltose infusion. Statistical Analysis Data were analyzed using SPSS version 20.0. Continuous variables were expressed as mean ± standard deviation (SD), and categorical variables as frequencies and percentages. Changes in hematological parameters (hemoglobin, serum ferritin, mean corpuscular volume, and mean corpuscular hemoglobin) from baseline to 6 and 12 weeks were analyzed using paired sample t-tests. A p-value <0.05 was considered statistically significant. Safety outcomes were assessed descriptively.

In this study 120 patients were enrolled. The mean maternal age of the study participants was 25.2 ± 4.6 years, and the mean gestational age was 20.1 ± 3.2 weeks. The average body mass index (BMI) was 26.1 ± 3.9 kg/m². At baseline, participants had a mean hemoglobin level of 8.02 ± 0.55 g/dL, indicating moderate anemia. Iron stores were markedly depleted, with a mean serum ferritin level of 9.8 ± 2.5 µg/L. Red cell indices showed microcytic anemia, with a mean corpuscular volume (MCV) of 71.8 ± 3.6 fL and a mean corpuscular hemoglobin (MCH) of 23.7 ± 1.8 pg. Baseline characteristics of the study population are shown in table 1.

Baseline characteristics of the study population (Table 1)

Following treatment with ferric carboxymaltose (FCM), there was a significant improvement in all hematological parameters (Table 2). Mean hemoglobin levels increased significantly from 8.02 ± 0.55 g/dL at baseline to 13.8 ± 0.6 g/dL at 6 weeks, and remained high at 12.9 ± 0.5 g/Dl at 12 weeks (p < 0.001). Serum ferritin levels showed a marked rise from 9.8 ± 2.5 µg/L at baseline to 136.2 ± 18.4 µg/L at 6 weeks, with sustained levels of 124.6 ± 16.9 µg/L at 12 weeks (p < 0.001).

Similarly, red cell indices improved significantly after treatment. The mean MCV increased from 71.8 ± 3.6 fL at baseline to 90.4 ± 3.0 fL at 6 weeks, and 89.9 ± 3.1 fL at 12 weeks (p < 0.01). The mean MCH also rose significantly from 23.7 ± 1.8 pg at baseline to 29.8 ± 1.5 pg at 6 weeks and 30.1 ± 1.6 pg at 12 weeks (p < 0.01).

Hematological Response to Ferrous carboxymaltose (Table 2)

These findings demonstrate a significant and sustained hematological response to ferric carboxymaltose therapy.

No serious anaphylactic reactions were reported. Minor infusion-site discomfort and itching occurred in 3% and 1.6% of the participants respectively, and resolved spontaneously.

This study demonstrates that intravenous ferric carboxymaltose is highly effective in correcting moderate iron deficiency anemia during pregnancy, with rapid and sustained improvement in hemoglobin, iron stores, and red cell indices.

The observed mean hemoglobin rise of approximately 5.8 g/dL at 6 weeks is consistent with findings reported by Obaid et al. [12], Froessler et al. [16], and Breymann et al. [17], all of whom documented significantly faster hemoglobin correction with FCM compared to oral iron or iron sucrose. The sustained hemoglobin levels at 12 weeks suggest durable erythropoietic response and adequate iron bioavailability.

Importantly, this study highlights significant normalization of Mean Corpuscular Volume (MCV) and Mean Corpuscular Hemoglobin (MCH), reflecting correction of microcytosis and hypochromia—hallmarks of iron-restricted erythropoiesis. Similar improvements in red cell indices were reported in randomized trials by Jose et al. and Christoph et al., where FCM demonstrated superior restoration of erythrocyte morphology compared to iron sucrose [18,19]. These findings reinforce that hemoglobin alone may underestimate hematologic recovery if iron stores and red cell indices are not concurrently evaluated.

The marked increase in serum ferritin observed in our cohort mirrors results from multiple studies and systematic reviews, including Palaniappan et al. [15], which emphasized the superior iron-repletion capacity of FCM. Sustained ferritin levels at 12 weeks indicate replenishment of iron stores, reducing the likelihood of relapse later in pregnancy or postpartum.

From a safety perspective, the absence of serious adverse reactions aligns with the established safety profile of FCM reported across large trials and meta-analyses [11,14,20]. The dextran-free formulation eliminates the risk of anti-dextran mediated anaphylaxis, a major limitation of older iron preparations.

The clinical implications are substantial. Rapid anemia correction reduces the risk of peripartum transfusion, postpartum anemia, and associated maternal fatigue, and may contribute to improved neonatal outcomes, as suggested in prior literature [6,7,17]. Similar results could be expected in severe iron deficiency anemia in pregnant women, however, a similar study can be done including such cohort of patients to look for the actual benefit.

Limitations

This was a single-arm study without a comparator group. Randomized controlled trials comparing FCM with other intravenous iron formulations in similar populations would further strengthen evidence.

Ferric carboxymaltose is a safe, well-tolerated, and highly effective treatment for iron deficiency anemia with moderate anemia during pregnancy. It provides rapid normalization of hemoglobin, replenishment of iron stores, and significant improvement in red cell indices, supporting its role as a preferred intravenous iron therapy when rapid correction is required. Acknowledgment The authors sincerely acknowledge the dedication and invaluable support of the nursing staff of the Departments of General Medicine and Obstetrics and Gynaecology for administering ferric carboxymaltose as per protocol and for diligently monitoring patients for adverse drug reactions. Financial support and sponsorship Nil Conflicts of interest There was no conflict of interest.

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