Iron deficiency anemia during pregnancy is associated with an increased risk of low birth weight, preterm birth, maternal and perinatal mortality and poor Apgar score. Furthermore, iron deficiency anemia in pregnancy may predispose to postpartum iron deficiency anemia [1-3].

Intravenous iron preparations like iron sucrose is available for the treatment of iron deficiency anemia. Parenteral iron provides replenishment of iron stores without gastrointestinal side effects. Parenteral iron can be used in second and third trimester and during the postpartum period [4].

Iron sucrose was FDA approved in November 2000. Iron sucrose is an iron hydroxide sucrose complex in water with a molecular weight of 34,000-60,000 daltons. The drawbacks of iron dextran are overcome by iron sucrose but it’s disadvantage includes multiple infusions to achieve the target hemoglobin concentration and thus prolonged hospital stay. Rapid administration of iron sucrose also leads to over saturation of transferrin leading to transient adverse events in the form of nausea, vomiting, abdominal pain and hypotension [5].

The present study was aimed to evaluate the efficacy and safety ofIntravenous Iron Sucrose in the treatment of iron deficiency anemia in pregnancy.

Aims and Objectives

To assess the efficacy and safety of intravenous 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 43 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 prospective study. Enrolled women after fulfilling the inclusion and exclusion criteria were given intravenous iron sucrose. 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 were (Table 1):

Table 1: Clinical and Laboratory Parameters Assessed for Diagnosing Iron Deficiency Anemia in the Study Population

• Complete blood count

• Hemoglobin 

• Packed cell volume 

• Peripheral blood smear with reticulocyte count

• Serum iron 

• Serum ferritin 

Total iron binding capacity.

These investigations were done prior to infusion and at 2 and 4 weeks post infusion.

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 200 mL 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 400 mg first dose followed by repeat dose after 14 days.

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. Subjects were observed for adverse reactions for 4 hours post infusion.

Outcomes were assessed by measuring complete blood count including hemoglobin and packed cell volume, peripheral blood smear along with reticulocyte count, serum iron, serum ferritin and total iron binding capacity values 2 and 4 weeks post infusion.

The rise in these parameters were assessed at 2 and 4 weeks post infusion. These outcome parameters were also compared at 4 weeks with respect to the baseline estimates.

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

For performing peripheral smear, blood slides were stained with Giemsa stain. The stock solution of giemsa stain was prepared by mixing 0.15g of giemsa powder in 12.5ml of glycerine and 12.5 ml of methyl alcohol. Before use one volume of stock solution was dissolved in nine volume of buffered water (1:9). The blood smears were fixed with methanol for 2-5 minutes. The fixed films were then transferred to jars containing giemsa stain and allowed to stand for 7-15 minutes after which the slides were washed and air dried and examined under oil emersion lens of microscope.

For measuring reticulocyte count, staining was done with brilliant cresyl blue followed by examination under 100X magnification of objective lens.

Measurement of serum iron was done by TPTZ-NO DEPROTEINIZATION method.

Measurement of serum ferritin was done by Chemiluminescent Microarticle Immunoassay (CMIA).

Statistical Analysis

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

A prospective study to evaluate the efficacy and safety of 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 43 antenatal women fulfilling the inclusion criteria were taken and given iron sucrose in multiple doses.

In our study, 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 (Table 2).

Table 2: Distribution according to Age and Socio Economic Status

According to distribution of subjects according to socioeconomic status calculated by modified Kuppuswamy scale 2019, in our study, 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 belonged to class III (lower middle class) according to modified Kuppuswamy scale (69.8%).

In our study, 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. So, in our study, 51.2% of the subjects were between the period of gestation 26 to 30+6 weeks. In our study, 60.5% belonged to multigravida and 39.5% belonged to primigravida. In the present study, only 1 subject was underweight (BMI <18.5 kg/m²) and rest of the subjects were having normal BMI (Table 3).

Table 3: Distribution according to POG, Parity and BMI

Out of 43 participants, 25.6% received dose of ISC between 801-850 mg. The mean dose of ISC was 831.26 mg (Table 4).

Table 4: Dose of Iron Sucrose

The mean value of baseline hemoglobin, reticulocyte count, packed cell volume, serum iron, serum ferritin and total iron binding capacity was found to be 8.36 g/dL, 0.74%, 25.26%, 36.17 ug/dL, 10.514 ng/dL and 493.460 ug/dL respectively. The mean value of hemoglobin, reticulocyte count, packed cell volume, serum iron, serum ferritin and total iron binding capacity at two weeks post infusion was found to be 10.03 g/dL, 2.228%, 31.021%, 92.758 ug/dL, 116.114 ng/dL and 410.61 ug/dL respectively. The mean value of haemoglobin, reticulocyte count, packed cell volume, serum iron, serum ferritin and total iron binding capacity at four weeks was found to be 11.002 g/dL, 2.507%, 34.17%, 111.03 ug/dL, 96.367 ng/dL and 380.540 ug/dL respectively (Table 5).

Table 5: Comparison of Variables at Baseline, 2 Weeks and 4 Weeks

These variables were compared at four weeks with respect to the baseline estimates. There was a very strong evidence against null hypothesis and there was significant difference in all the parametersat four weeks (p<0.001) (Table 6).

Table 6: Difference in the Variables from Baseline to 4 Weeks

Out of 43 subjects, 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. About 2 subjects (4.7%) developed systemic adverse effects in the form of nausea and headache (Table 7).

Table 7: Distribution of Side Effects

The present study was conducted with the objective to evaluate the efficacy and safety of Intravenous Iron Sucrose in the treatment of iron deficiency anemia in pregnancy. 

In the present study maximum subjects were in age group 21-25 years. Similar distribution of age was reported by Agrawal et al. [6]and Saini et al. [7].

In the present study 60.5% were multigravida. Mahajan et al. [8], Khan et al. [9] also showed that iron deficiency anemia is more common in multigravida. Less inter pregnancy interval leading to depleted iron stores, poor nutrition due to economical burden can be factors contributing to higher prevalence of iron deficiency anemia among multigravida.

Patel et al. [10], observed higher prevalence of iron deficiency anemia in lower socioeconomic class. In our study maximum subjects belonged to lower middle class according to modified Kuppuswamy scale. Our study is consistent with the study done by Mahajan et al. [8]. Therefore our study also suggests that lower socioeconomic status is a predisposing factor for the development of iron deficiency anemia.

Antenatal women with moderate anemia were included in our study. The baseline hemoglobin was 8.36 g/dL in subjects. Metgud et al. [11], also included subjects with moderate anemia and the baseline hemoglobin was 8.8 g/dL in ISC group. Naqash et al. [12], included subjects with severe anemia and the mean value of baseline hemoglobin was 7.6 g/dL.

The earliest response to treatment incase of iron deficiency anemia is reticulocytosis. Piva et al. [13] observed a rise in reticulocyte count by fifth day post intravenous iron transfusion. In our study patients had reticulocytosis on treatment follow up.

In the present study the subjects after treatment were followed up at 2 and 4 weeks. At 2 weeks post infusion the mean hemoglobin was 10.03 g/dL. Mean hemoglobin at 4 weeks was 11.02 g/dL. The change in hemoglobin at 2 and 4 weeks was statistically significant (p value <0.001). In study conducted by Mahajan et al. [8], the subjects when followed up at 2 weeks showed statistically significant increase in hemoglobin. Similar observations were made at 4 weeks of follow up in hemoglobin and was found to be statistically significant (p value <0.001). Verma et al. [14], also reported a significant rise in hemoglobin at 2 and 4 weeks of treatment with iron sucrose. Whereas Naqash et al. [12] followed up patients at 4 weeks only and found a significant rise in hemoglobin levels in subjects treated with iron sucrose. 

In the present study the rise in hemoglobin at 2 weeks was 1.67 g/dL. Mahajan et al. [8], reported that the rise in hemoglobin at 2 weeks with p value <0.05. Verma et al. [14], also reported a significant rise in hemoglobin. Swetha et al. [15], also observed that rise in hemoglobin at 2 weeks follow up.

Our study showed a significant rise in hemoglobin in subjects with iron sucrose. The rise in hemoglobin from the baseline at 4 weeks was 2.6 g/dL in subjects who received iron sucrose. Metgud et al. [11], also observed that the rise in hemoglobin. Naqash et al. [12], reported that the rise in hemoglobin at 4 weeks.

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 (25.2%). The rise in PCV at 4 weeks from the baseline was 8.9%. Similar observations were made by Garg et al. [16] who showed a greater rise in packed cell volume (4.2%). Singh et al. [17] also reported a significant rise in PCV. While in comparison to these studies, our study observed a higher rise in packed cell volume in subjects 6.57 and 4.8% [16].

Over 90% of iron deficiency anemia is associated with depleted iron stores. Insufficient supply of iron causes inability to sustain a normal hemoglobin concentration, therefore iron deficiency anemia develops. In our study all the subjects had low serum iron before the start of treatment and baseline value of serum iron was 36.1 ug/dL. The rise in serum iron at 4 weeks was 74.86 ug/dL which was observed to be of statistical significance. Whereas Naqash et al. [12] followed up patients at 4 weeks only and documented a significant rise in serum iron in subjects treated with iron sucrose. 

Body iron stores are determined by serum ferritin levels. Serum ferritin levels <12 ng/mL is diagnostic of iron deficiency anemia. In the present study baseline value of serum ferritin was 10.5 ng/mL. The rise in serum ferritin at 4 weeks was 85.8 ng/mL in subjects treated with iron sucrose. Khan et al. [9], observed a significant rise in serum ferritin in ISC group at 4 weeks of treatment. Mahajan et al. [8] also reported a significant rise in serum ferritin in ISC group. However Jose et al. [18] followed up patients up to 12 weeks post infusion and found that iron sucrose produced similar replenishment of iron stores. 

Iron deficiency anemia is characterized by increase in total iron binding capacity. On follow up at 4 weeks the fall in TIBC was 112.92 ug/dL. Naqash et al. [12] reported a statistically significant fall in TIBC in subjects treated with iron sucrose. Whereas Jose et al. [18] followed up patients at 3 weeks post infusion and found non-significant fall in TIBC in ISC group.

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, 7% developed local adverse effects and 4.7% developed systemic adverse reactions. Agrawal et al. [6] reported that 2% of subjects had local adverse effects and 4% developed systemic effects in ISC group. Patel [10] reported local adverse reactions in 8% of patients in ISC group but there were no systemic adverse reactions.

Parenteral iron preparations like iron sucrose are preferred in subjects who experience side effects after oral iron treatment, are non-compliant to oral iron or due to malabsorption. The present study concluded that intravenous iron sucrose is efficacious in replenishment of iron stores in a short duration of time and improvement of hemoglobin levels and had good safety profile.

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