Parenteral dextran free iron is available intravenously as ferric carboxymaltose. A polynuclear iron (III) hydroxide complex in a carbohydrate shell makes up the macromolecular iron hydroxide complex in FCM. The molecular weight of FCM is approximately 150,000 daltons. In FCM, iron hydroxide is firmly bonded inside of a carbohydrate shell, causing progressive release of iron in the body while preventing acute toxicity and enabling the delivery of huge amounts of iron. Consequently, the therapeutic window is widened. In contrast, when fewer stable complexes are present, iron is released quickly, leading to high levels of transferrin saturation and an increase in non-transferrin bound iron (NTBI), which is harmful to the body.^(1-2)

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. ^(2-3)

FCM has better safety and tolerability compared to other parenteral iron. This is because FCM does not cross react with dextran antibodies and does not provoke oxidative stress reactions²⁴. FCM does not cross placental barrier in an in vitro dual perfusion model. The highest non-lethal dose of FCM was at least 5 times higher than that for iron sucrose. 1000 mg dose of FCM can be administered safely over 15 minutes. ^(4-5)

The present study was aimed to comparethe adverse effects after Intravenous Ferric Carboxymaltose and Iron Sucrose in the treatment of Iron Deficiency Anemia in Pregnancy.

AIMS AND OBJECTIVES:

To compare the adverse effects 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 1^st June 2019 to 31^st 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 was recorded. Detailed menstrual, obstetrics and dietary history was taken from all the subjects. 

Parameters used for the diagnosis of iron deficiency anemia was were:

• Complete blood count ­­-

• Hemoglobin 

• Packed cell volume 

• Peripheral blood smear with reticulocyte count

• Serum iron 

• Serum ferritin 

• Total iron binding capacity 

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.

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.

Statistical Analysis:

Data was entered in Microsoft Excel spread sheet 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.

A prospective study comparing theadverse effects after Intravenous Ferric Carboxymaltose and Iron Sucrose in the treatment of Iron Deficiency Anemia in Pregnancy was 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.). 1^st June 2019 to 31^st 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.

Figure 1: 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 1: 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 2: Distribution of Side Effect in Group A and B

Out of 43 subjects in group A, only 2 subjects (4.7%) developed local adverse effects in the form of pain at injection site. There were no systemic adverse effects observed in this group. Out of 43 subjects in group B, local adverse effects were noted in 3 subjects (7%). 1 subject complained of pain at injection site and rest of the 2 subjects complained of rashes. In group B, 2 subjects (4.7%) developed systemic adverse effects in the form of nausea and headache.

Antenatal women with moderate anemia were included in our study. In the present study the subjects after treatment with intravenous ferric carboxymaltose and iron sucrose were followed up at 2 and 4 weeks. Safety of both the iron preparations were assessed by observation of local and systemic adverse effects following infusion. 

In the present study out of 43 subjects in group A, 4.7% developed local adverse reactions and none of the subjects developed systemic reactions. Whereas in group B out of 43 subjects, 7% developed local adverse effects and 4.7% developed systemic adverse reactions. When both the groups were compared to assess the safety profile, subjects treated with ferric carboxymaltose developed less adverse effects as compared to those treated with iron sucrose and the difference was statistically significant (p<0.05). ⁽⁶⁾ reported no adverse effects in FCM group, whereas 2% of subjects had local adverse effects and 4% developed systemic effects in ISC group. ⁽⁷⁾ reported local adverse reactions in 6% of patients in FCM group and 8% of patients in ISC group. There were no systemic adverse reactions in either group making the safety of FCM and ISC comparable (p value 1.00). Similarly ⁽⁸⁾ reported no significant difference in the safety profile in FCM and ISC group. Our study observed better outcomes with ferric carboxymaltose compared with iron sucrose in terms of systemic and local adverse events.

Thus, it was observed that ferric carboxymaltose has a better safety profile and less adverse reactions as compared to iron sucrose.

Conflict of Interest: No

Funding: No funding sources

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