Anemia, which is characterised by a low blood haemoglobin concentration, is one of the main health issues in society. Worldwide, 32.4 million pregnant women have anaemia, according to the WHO. Iron deficiency anaemia is directly or indirectly responsible for about 591,000 perinatal deaths and 1,15,000 maternal fatalities. Anemia is generally caused by iron deficiency in 50% of cases. An estimated 3,26,000 maternal fatalities in India are attributable to IDA. Anemia in pregnancy is defined by the WHO as haemoglobin levels less than 11g/dL. Anemia can be classified as mild (haemoglobin 10–10.9 g/dL), moderate (haemoglobin 7–9.9 g/dL), severe (haemoglobin 4–6.9 g/dL), or extremely severe (haemoglobin 4 g/dL), according to the ICMR [1-3].

Iron deficiency anemia evolves through three stages. In the first stage depletion of storage iron occurs without affecting the red cell indices and hemoglobin synthesis. In stage two, both the indices change when iron supply to bone marrow is reduced (iron deficient erythropoiesis). In stage three, IDA develops due to insufficient supply of iron to sustain a normal hemoglobin concentration [4].

The FDA approved iron sucrose in November 2000. The molecular weight of iron sucrose, an iron hydroxide sucrose complex in water, ranges from 34,000 to 60,000 Daltons. Iron sucrose's advantages outweigh those of iron dextran, but they come with a longer hospital stay and the need for numerous infusions to reach the desired haemoglobin content. Rapid injection of iron sucrose also causes transferrin to become oversaturated, which can cause temporary unpleasant effects like nausea, vomiting, abdominal pain and hypotension [5].

Intravenous ferric carboxymaltose is a parenteral dextran free iron. FCM comprises a macromolecular iron hydroxide complex of polynuclear iron (III) hydroxide in a carbohydrate shell. FCM has a molecular weight of around 150,000 Daltons. In FCM, iron hydroxide is tightly bound within a carbohydrate shell which causes gradual release of iron in the body, thus avoiding acute toxicity and allowing large amounts of iron to be delivered. This results in a wider therapeutic window. Whereas in-case of less stable complexes, there is rapid release of iron which causes high level of transferrin saturation and increase in non-transferrin bound iron (NTBI) which is toxic to the body [5].

The present study was aimed to compare the Change in the Mean Packed Cell Volume after Intravenous Ferric Carboxymaltose and Iron Sucrose in the treatment of Iron Deficiency Anemia in Pregnancy.

Aims and Objectives

To compare the Change in the Mean Packed Cell Volume after Intravenous Ferric Carboxymaltose and Iron Sucrose in the treatment of Iron Deficiency Anemia in Pregnancy.

This study was carried out in the Department of Obstetrics and Gynecology, Kamla Nehru State Hospital for Mother and Child, Indira Gandhi Medical College, after approval from hospital ethical committee, from 1st June 2019 to 31st May 2020 for a period of one year.

Study Design

Prospective study.

Study Population

The study included 86 antenatal women with iron deficiency anemia.

Inclusion Criteria

• Gestational age 12 to 36 weeks 

• Hemoglobin 7 – 9.9 g/dL 

• Microcytic hypochromic anemia on peripheral blood smear

Exclusion Criteria

• Gestational age <12 weeks or >36 weeks

• Prior history of blood transfusion

• Anemia not caused by iron deficiency 

• History of disease associated with iron overload (thalassemia, hemochromatosis).

• Known hypersensitivity to parenteral iron.

• Chronic renal /hepatic or cardiovascular disease.

• Not consenting

Methodology

This was a hospital based randomized prospective interventional study. Enrolled women after fulfilling the inclusion and exclusion criteria were randomly assigned into two equal groups. Randomization in 1:1 ratio was carried out by computer generated simple random tables.

• Group A received intravenous FCM

• Group B received intravenous iron sucrose

The sample size was calculated by taking confidence interval as 95%, power of the study as 80% and mean difference of Hb to be detected between the two groups as 0.5 g/dL. The sample size was calculated using Epi software.

• The final sample size was 86

• 43 subjects received intravenous FCM in Group A

• 43 subjects received intravenous iron sucrose in Group B

Demographic data like age, educational qualification, socioeconomic status were recorded. Detailed menstrual, obstetrics and dietary history was taken from all the subjects.

Parameters used for the diagnosis of iron deficiency anemia was Packed cell volume (Table 1). In both the groups, these investigations were done prior to infusion and at 2 and 4 weeks post infusion.

Group A: Ferric Carboxymaltose (FCM)

The subjects included in this group received single dose of 1000 mg intravenous FCM. 1000 mg FCM was diluted in 250 mL of normal saline and was transfused over a period of 30 minutes.

Group B: Iron Sucrose (ISC)

The total required dose of iron sucrose was calculated by using formula:

Total iron deficit (mg) = Pre pregnancy body weight (kg) × (Target Hb – Actual Hb) × 2.4 + Depot iron (mg)

Target Hb = 11 g/dL

Depot Hb = 15 mg/kg if body weight <35 Kg and 500 mg if body weight >35 Kg

Intravenous iron sucrose was given in a dose of 200 mg diluted in 200mL of normal saline over a period of 30 minutes on alternate days until required dose was administered.

Table 1: Parameters used for the Diagnosis of Iron Deficiency Anemia Was Packed Cell Volume

All the subjects included in the study were administered antihelminthic therapy with tablet albendazole 400mg first dose followed by repeat dose after 14 days.

In both the groups the general condition of the patient, blood pressure and pulse rate was examined every 5 minutes during transfusion and fetal heart rate was checked before and after transfusion. Both the groups were observed for adverse reactions for 4 hours post infusion.

Outcomes were assessed by measuring Packed Cell Volume2 and 4 weeks post infusion. The rise in Packed Cell Volume was assessed at 2 and 4 weeks post infusion in both the groups and compared at 4 weeks with respect to the baseline estimate.

Complete blood count measurements were done by an automated blood analyser machine, model MSTM 39S.

Statistical Analysis

Data was entered in Microsoft Excel spreadsheet and analysed using Epi Info Software version 7.2.2. Descriptive statistics were presented as proportions and their 95% confidence interval for qualitative variables whereas for quantitative variables means and their standard deviation were calculated. Independent student’s T- test was used for comparison of change in variables between the two groups. A two sided p-value <0.005 was considered statistically significant.

Observations

A prospective study comparing Change in the Mean Packed Cell Volume after Intravenous Ferric Carboxymaltose and Iron Sucrose in the treatment of Iron Deficiency Anemia in Pregnancywas conducted in the Department of Obstetrics and Gynaecology, Kamla Nehru State Hospital for Mother and Child (KNSH for M&C), Shimla, Himachal Pradesh with effect from (w.e.f.). 1st June 2019 to 31st May 2020.

In our study 86 antenatal women fulfilling the inclusion criteria were taken and divided into two equal groups. Group A was labelled for those study participants who received single dose of intravenous ferric carboxymaltose whereas group B were those study participants who received iron sucrose in multiple doses (Table 2).

Table 2: Comparison of Socio-Demographic Variables in Both Groups

In group A, there were 2 participants in 18 - 20 years of age group, 21 participants in 21 - 25 age group, 15 participants in 26 - 30 age group and 5 participants in 31 - 35 age group. In group B, there were 6 participants in 18 - 20 years’ age group, 18 participants in 21 - 25 years of age group, 14 participants in 26-30 age group, 4 participants in 31 - 35 age group and 1 participant in 35 - 40 age group. It was observed that maximum subjects were in the age group of 21-25 years in both the groups.

In group A, 9 participants were in the period of gestation between 21 to 25+6 weeks, 18 participants between 26 to 30+6 weeks and 16 participants between 31 to 36 weeks. In group B, 5 participants were in the period of gestation 21 to 25+6 weeks, 22 participants between 26 to 30+6 weeks and 16 participants between 31 to 36 weeks. In our study 41.9% of the subjects in group A and 51.2% of the subjects in group B were between the period of gestation 26 to 30+6 weeks.

Among parity distribution, 65.1% belonged to multigravida and 34.9% belonged to primigravida in group A. Whereas 60.5% belonged to multigravida and 39.5% belonged to primigravida in group B. 

In group A, only 1 participant belonged to class I, 3 participants belonged to class II, 32 participants belonged to class III, 6 participants belonged to class IV while 1 participant belonged to class V. In group B, 3 participants each belonged to class I and II, 30 participants belonged to class III, 6 participants belonged to class IV whereas only 1 participant belonged to class V. It was observed that maximum subjects in both the groups belonged to class III (lower middle class) according to modified Kuppuswamy scale (74.4% in group A and 69.8% in group B).

In group A all the subjects were having normal BMI (between 18.5 - 24.9 kg/ m2). Whereas in group B, only 1 subject was underweight (BMI < 18.5 kg/m2) and rest of the subjects were having normal BMI (Table 3).

Table 3: Dose of Ferric Carboxymaltose and Iron Sucrose

All the subjects included in group A received a single dose of 1000 mg FCM. Out of 43 participants in group B, 25.6% received dose of ISC between 801 - 850 mg. The mean dose of ISC was 831.26 mg (Table 4).

Table 4: Change in Packed Cell Volume (PCV) in Group A and B

In group A, the mean value of baseline packed cell volume was found to be 25.6 % while in group B, the mean value of baseline packed cell volume was found to be 25.26%. The baseline means packed cell volume (p value = 0.505) was comparable in group A and B. The mean value in packed cell volume at 2 weeks of follow up was 33.64 % in FCM group and 31.02 % in ISC group. At 4 weeks post infusion the mean packed cell volume was 37.11% in FCM group whereas it was 34.17% in ISC group.

At both the follow up visits the increase in packed cell volume was higher in FCM group compared to ISC group which was statistically significant. (p <0.001) (Table 5).

Table 5: Independent T-Test for Comparison Between Two Groups

In the stage of iron deficient erythropoiesis, there is fall in hemoglobin levels with low serum iron and serum ferritin but at this stage packed cell volume remains unchanged. The stage of iron deficiency anemia is associated with a fall in packed cell volume.

All the subjects in our study had decreased levels of packed cell volume (25.6 % in group A and 25.2% in group B). The rise in PCV at 4 weeks from the baseline was 11.4% in group A and 8.9% in group B. The difference in increase in PCV levels in group A and B was statistically significant (p-value <0.001). Similar observations were made by Garg et al. [6], who showed a greater rise in packed cell volume in FCM group compared to ISC group (4.8% and 4.2% respectively).

Singh S et al. [7], also reported a significant rise in PCV in FCM group compared to ISC group (6.57% versus 5.6%). While in comparison to these studies, our study observed a higher rise in packed cell volume in subjects treated with ferric carboxymaltose (11.4% in the present study versus 6.57% [7] and 4.8% [6].

The present study concluded that at both the follow up visits the increase in packed cell volume was higher in FCM group compared to ISC group which was statistically significant. (p<0.001).

1. Stevens, G.A. et al. “Global, regional and national trends in hemoglobin concentration and prevalence of total and severe anemia in children and pregnant and non-pregnant women for 1995–2011: A systematic analysis of population-representative data.” The Lancet Global Health, vol. 1, no. 1, July 2013, pp. e16–e25.

2. “FOGSI general clinical practice recommendations: management of iron deficiency anaemia in pregnancy”. 2016. Available at: http://www.fogsi.org/wp-content/uploads/2016/05/The-evidence-base_IDA-Pregnancy-24-May-2016-Clean.pdf

3. Indian Council of Medical Research: Evaluation of Nutritional Anaemia Prophylaxis Program, Task Force Study. New Delhi, 1989. Available at: https://www.icmr.nic.in/sites/default/files/icmr_bulletins/bufeb00.pdf

4. Ezzati, M. et al. “Comparative quantification of health risks: Global and regional burden of disease attributable to selected major risk factors”. World Health Organization, 2004.

5. Suchdev, P.S. et al. “Assessment of iron status in settings of inflammation: challenges and potential approaches.” The American Journal of Clinical Nutrition, vol. 106, suppl. 6, December 2017, pp. 1626S–1633S.

6. Garg, R. et al. “Iron carboxymaltose: A safe and effective molecule to combat anaemia in pregnancy.” International Journal of Current Research and Academic Review, vol. 4, no. 2, February 2016, pp. 124–130.

7. Singh, S. et al. “Comparing the safety and efficacy of intravenous iron sucrose and intravenous ferric carboxymaltose in treating postpartum anemia.” International Journal of Reproduction, Contraception, Obstetrics and Gynecology, vol. 5, no. 5, May 2016, pp. 1451–1457.