Treatment Response and Effectiveness of Intravenous Ferric Carboxymaltose Versus Oral Iron in Postpartum Iron Deficiency Anaemia

Open Access

Abstract

Background: Iron deficiency anaemia (IDA) affects up to 50% of postpartum women globally, leading to fatigue, cognitive impairment, and delayed recovery. Oral iron, the standard treatment, often results in poor compliance and slow recovery due to gastrointestinal side effects. Ferric carboxymaltose (FCM), an intravenous iron formulation, has emerged as an alternative, offering rapid haemoglobin improvement and a favourable safety profile with single-dose administration. However, limited data exist on FCM's efficacy specifically in postpartum women. Objective: To compare the effectiveness of intravenous ferric carboxymaltose with oral iron in the treatment of iron deficiency anaemia in women after childbirth. Methods & Materials: This randomized controlled trial (RCT) was conducted in the Department of Obstetrics and Gynecology, Institute of Child and Mother Health (ICMH), Matuail, Dhaka. The sampling method was random selection based on patient availability. Data were collected from women aged 18-35 years. Patients diagnosed with postpartum iron deficiency anaemia, confirmed by haemoglobin (Hb) levels <10 g/dL and serum ferritin levels below 30 ng/mL, were included. Group I (n=38) received a single dose of intravenous FCM, while Group II (n=38) received oral iron. The outcomes of FCM and oral iron in treating postpartum IDA were compared between the groups. Descriptive and inferential analyses were performed using SPSS v26, with a p-value <0.05 considered statistically significant. Results: FCM group demonstrated a significantly greater increase in haemoglobin levels compared to the oral iron group. At baseline, haemoglobin levels were similar (8.45 g/dL vs. 8.57 g/dL). By the 2nd week, haemoglobin increased to 10.29 g/dL in the FCM group compared to 9.48 g/dL in the oral group, and by the 6th week, haemoglobin levels reached 12.65 g/dL in the FCM group and 11.92 g/dL in the oral iron group (p<0.001). Ferritin levels also increased significantly higher in the FCM group (225.02 ng/mL vs. 144.23 ng/mL at 2 weeks), and while they declined by the 6th week, they remained higher than in the oral iron group (134.71 ng/mL vs. 101.23 ng/mL). The failure to achieve target haemoglobin levels was lower in the FCM group (5.3% vs. 23.7%), with an odds ratio (OR) of 5.58, indicating a significantly higher failure rate in the oral iron group (p=0.022). Conclusion: Intravenous ferric carboxymaltose is more effective than oral iron in the management of postpartum iron deficiency anaemia. Outdoor Medical Officer, Department of Obstetrics and Gynaecology, Rangpur Medical College Hospital, Rangpur, Bangladesh aparnacb11@gmail.com (ORCID: 0009-0009-9979-9919) Professor and Head, Department of Obstetrics & Gynaecology, Institute of Child and Mother Health, Matuail, Dhaka, Bangladesh Associate Professor, Department of Obstetrics and Gynaecology, Institute of Child and Mother Health, Matuail, Dhaka, Bangladesh Assistant Surgeon, Department of Obstetrics and Gynaecology, Charbadam Union Health Centre, Ramgoti, Lakshmipur, Chattogram, Bangladesh Lecturer, Department of Obstetrics and Gynaecology, Naogaon Medical College, Naogaon, Bangladesh Emergency Medical Officer (EMO), Department of Obstetrics and Gynaecology, Upazila Health Complex, Paba, Rajshahi, Bangladesh Junior Consultant, Department of Anesthesiology, Pirganj Health Complex, Rangpur, Bangladesh INTRODUCTION Iron deficiency anaemia (IDA) remains one of the most common complications of the postpartum period, arising from a reduction in red blood cell mass that lowers the blood's oxygen-carrying capacity and can compromise maternal recovery and well-being.[1] Reported rates of postpartum anaemia (PPA) vary considerably between settings, from roughly 50% to 80% of women in different populations,[2,3] and even within a single country the range can be striking; in India, prevalence has been documented from 26.5% in rural coastal Karnataka to as high as 94.6% in rural Rajasthan, against a national average near 65%.[4] Postpartum IDA is usually confirmed through a full blood count together with serum ferritin and, where available, soluble transferrin receptor, which remain reliable markers of iron status in the weeks after delivery.[5] By convention, PPA is diagnosed when haemoglobin (Hb) falls below 120 g/L, with levels under 100 g/L regarded as clinically significant; Hb typically reaches its lowest point around 48 hours postpartum, reflecting the combined effect of delivery-related blood loss and pre-existing iron deficiency.[6] The World Health Organization defines postpartum anaemia more narrowly, as an Hb below 10 g/dL during this period.[7] In developing countries, the high burden of PPA reflects an overlapping set of causes: antenatal iron deficiency, blood loss at delivery, and infections such as malaria and intestinal parasites.[8,9,10] Haemoglobinopathies and the broader effects of poor socioeconomic conditions, inadequate nutrition, limited education, weak antenatal care, and delivery complications add further to this burden.[11] Young maternal age, postpartum haemorrhage, and poor adherence to antenatal iron and folic acid supplementation add further to this risk.[12] The consequences extend well beyond laboratory values. Reduced oxygen delivery produces palpitations, dizziness, fatigue, and breathlessness that interfere with daily functioning, and PPA has been linked to postpartum depression, chronic fatigue, and cognitive impairment that can affect maternal-infant bonding.[13,14,15] Untreated anaemia has also been associated with shorter breastfeeding duration, low infant birth weight, developmental delay, and a greater risk of infection and haemorrhage during recovery.[13,14,15] Oral iron, typically ferrous sulfate, gluconate, or fumarate, has long been the first-line treatment because it is inexpensive and simple to administer,[16] but gastrointestinal side effects such as nausea, constipation, and abdominal discomfort frequently undermine adherence, particularly in women already coping with the physical demands of the postpartum period.[17] Absorption itself is inconsistent, reduced by calcium, tannins, and phytates and by conditions such as coeliac disease, while vitamin C improves uptake; the prolonged courses needed to rebuild iron stores are also difficult to sustain where follow-up care is limited.[18] Intravenous ferric carboxymaltose (FCM) has emerged as an alternative for women who cannot tolerate or do not respond adequately to oral therapy. By bypassing the gut, FCM allows rapid, single-infusion replenishment of iron stores with a generally favourable safety profile.[19] A growing body of trial evidence indicates that FCM raises haemoglobin more quickly than oral iron.[20,21,22] It has also been reported to cause fewer gastrointestinal side effects and to be better tolerated overall.[1,23,24] These advantages appear to translate into improved adherence and higher patient satisfaction across settings.[25] Given how widespread PPA remains, especially across low- and middle-income settings, FCM holds real promise for improving maternal recovery, yet comparative data specific to postpartum women are still limited, and questions around cost-effectiveness and longer-term maternal and neonatal outcomes remain largely unanswered.[1] This study was therefore designed to compare the effectiveness of intravenous FCM with oral iron in treating iron deficiency anaemia among women following childbirth. METHODS & MATERIALS This randomized controlled trial was conducted in the Department of Obstetrics and Gynecology, Institute of Child and Mother Health (ICMH), Matuail, Dhaka, over a 12-month period from July 2023 to June 2024. The study population comprised women diagnosed with iron deficiency anaemia (IDA) immediately after childbirth who attended the in-patient department of Obstetrics and Gynecology at ICMH; the interventional group (Group I) received intravenous ferric carboxymaltose (FCM), while the control group (Group II) received oral iron, with participants selected by simple random sampling based on availability. Sample size was calculated using the formula for comparison of two means (zα = 2.58 at the 1% level of significance, zβ = 1.64 at 95% power), with mean haemoglobin and standard deviation values for the two groups drawn from a previous study, giving 38 participants per group, for a total of 76. Dependent variables were haemoglobin and serum ferritin at baseline, 2 weeks, and 6 weeks, achievement of target haemoglobin, and treatment side effects; independent variables were age, education, occupation, monthly income, parity, and baseline BMI. Postpartum anaemia was defined as a haemoglobin concentration below 10 g/dL with ferritin below 30 ng/mL within the first week after childbirth, the postpartum period as the 42 days following delivery of the placenta, and BMI (weight in kilograms divided by height in metres squared) as underweight (<18.5 kg/m²), normal (18.5-24.9 kg/m²), or overweight (25.0-29.9 kg/m²). FCM was administered intravenously according to the manufacturer's recommendations based on haemoglobin and bodyweight: participants under 35 kg received 500 mg as a single dose, those 35 kg to under 70 kg received 1500 mg in two doses at least 7 days apart, and those 70 kg or above received 2000 mg in two doses at least 7 days apart, subject to a maximum single dose of 1000 mg and a weekly cumulative limit of 1000 mg. Participants in the oral iron group received two tablets of Ferrous Ascorbate (48 mg), Folic Acid (0.5 mg), and Zinc Sulfate (22.5 mg) twice daily, 30 minutes before meals, tea, or coffee, with instructions to take tablets with food if side effects developed. A semi-structured questionnaire with a consent form and data collection sheet was administered through 15-30 minute interviews, with data collected according to respondent availability. Following Institutional Review Board approval, 76 postpartum women aged 18-35 years who had delivered by caesarean section or vaginally were enrolled after giving written informed consent, and were allocated 1:1 to the two groups using a lottery system in which participants drew one of two coloured cards under supervision. Baseline sociodemographic, anthropometric, and obstetric data were recorded on standardised sheets, and each participant underwent clinical examination. After intravenous FCM, participants were monitored for at least 2 hours for immediate adverse reactions, including anaphylaxis, skin rash, dyspnoea, facial flushing, metallic taste, urticaria, hypotension, headache, chest pain, or tachycardia. All participants were followed up at 2 and 6 weeks, when haemoglobin and ferritin were reassessed and, for the oral iron group, adherence was checked by collecting returned blister packs; the primary outcome was change in haemoglobin from baseline to the 2- and 6-week follow-ups. Blood samples (5 mL) were drawn from the antecubital vein under aseptic precautions at each follow-up by trained laboratory technologists, with complete blood count performed on an Automated Celltac ES 5 Diff Hematology Analyzer (Nihon Kohden, Japan) and serum ferritin assessed alongside it. Statistical analysis was performed in SPSS v26 (SPSS Inc., Chicago, IL, USA): descriptive statistics were presented as frequencies, percentages, and mean ± SD; the ANOVA F-test compared baseline, 2-week, and 6-week haemoglobin and ferritin changes between groups; chi-square and Fisher's exact tests compared sociodemographic, BMI, parity, and adverse-effect distributions; and p<0.05 was considered significant. Of 98 women assessed for eligibility, 18 were excluded and 4 withdrew or could not be contacted before randomisation, leaving 76 women randomised 1:1 into the two groups, both of which completed their allocated intervention in full with no loss to follow-up or missing data. Confidentiality was maintained through signed informed consent, unique participant identification numbers for sample handling and reporting, and standard safety and privacy procedures; no placebo was used. Ethical clearance was obtained from the Institutional Review Board of ICMH, Matuail, Dhaka, and the concerned department. All participants gave informed written consent free of duress, were briefed on the study's purpose, risks, and benefits, and were assured of their right to withdraw at any time; given that only 5 mL of blood was drawn per participant, risk of complications was minimal, and any discomfort, mild pain, weakness, or vertigo was managed with reassurance and analgesics. Inclusion Criteria Women diagnosed with postpartum iron deficiency anaemia within the first week after delivery. Haemoglobin (Hb) levels between 7-9.9 g/dL. Serum ferritin levels <30 μg/L. Exclusion Criteria Severe anaemia (Hb <7 g/dL). Other types of anaemia, including sickle cell disease, thalassemia, or anaemia due to chronic liver or kidney disease. Recent blood transfusion or allergy to ferric carboxymaltose/parenteral iron. RESULTS The sociodemographic characteristics of postpartum anaemic patients treated with ferric carboxymaltose and oral iron were compared in Table I. There were no significant differences between the groups in terms of age distribution (p=0.387), educational qualifications (p=0.429), occupation (p=0.798), or monthly family income (p=0.883). The mean ages were similar, with 24.55 ± 3.17 years for the ferric carboxymaltose group and 24.79 ± 2.28 years for the oral iron group (p=0.710). Table I Categorization of the respondents according to their sociodemographic characteristics by group. Sociodemographic characteristics Ferric carboxymaltose (n=38) Oral iron (n=38) P-value 20 - 25 years 27 (71.1) 27 (71.1) 26 - 30 years 9 (23.7) 10 (26.3) 0.387 31 - 35 years 2 (5.3) 1 (2.6) Mean age ± SD 24.55 ± 3.17 24.79 ± 2.28 0.710 Primary education 9 (23.7) 5 (13.2) SSC 22 (57.9) 23 (60.5) 0.429 HSC and above 7 (18.4) 10 (26.3) Household work 28 (73.7) 27 (71.1) 0.798 Service holder 10 (26.3) 11 (28.9) Income ≤ 30,000 taka 4 (10.5) 5 (13.2) Income 31,000-50,000 taka 25 (65.8) 26 (68.4) 0.883 Income > 50,000 taka 9 (23.7) 7 (18.4)