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ORIGINAL ARTICLE
Year : 2020  |  Volume : 64  |  Issue : 2  |  Page : 168-172  

Effectiveness of intravenous ferric carboxymaltose in improving hemoglobin level among postpartum women with moderate-to-severe anemia at a secondary care hospital in Faridabad, Haryana – An interventional study


1 Professor and Head, Center for Community Medicine, All India Institute of Medical Sciences, New Delhi, India
2 Associate Professor, Center for Community Medicine, All India Institute of Medical Sciences, New Delhi, India
3 Assistant Professor, Department of Community and Family Medicine, All India Institute of Medical Sciences, Kalyani, West Bengal, India
4 Associate Professor, Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
5 Additional Professor, Center for Community Medicine, All India Institute of Medical Sciences, New Delhi, India

Date of Submission21-Feb-2019
Date of Decision11-May-2019
Date of Acceptance15-Apr-2020
Date of Web Publication16-Jun-2020

Correspondence Address:
Ravneet Kaur
Centre for Community Medicine, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijph.IJPH_85_19

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   Abstract 


Background: Postpartum anemia is associated with postpartum anxiety, depression, poor cognitive interaction, and delayed infant development. Oral iron is the currently recommended therapy but is associated with gastrointestinal complaints and poor compliance. Parenteral iron dextran may cause serious side effects, whereas iron sucrose requires repeated visits. Intravenous ferric carboxymaltose (FCM) is given as an infusion in a single setting, which is logistically convenient both to patients and health system. It can be particularly beneficial for postpartum women who are usually discharged from health facility 48 h after delivery. Objectives: The objectives of this study were to estimate the change in mean hemoglobin (Hb) level 6 weeks after administration of intravenous FCM and to document any adverse events following administration among postpartum women. Methods: A prospective, interventional follow-up study was conducted from August to December 2018. One hundred eligible postpartum women with Hb level of 5–9.9 g/dl were administered a calculated dose of intravenous FCM based on Ganzoni's formula with Hb target of 12 g/dl. Hb and serum ferritin were measured at baseline and at 6 weeks after FCM infusion and compared for mean increase. Results: There was a significant increase in Hb and serum ferritin levels after administration of FCM. The mean (95% confidence interval) increase in the Hb and serum ferritin after 6 weeks was 4.2 (3.9–4.5) g/dl and 137.3 (113.6–161.0) ng/ml, respectively. No major adverse events were reported. Conclusion: Administration of FCM was safe and effective in the treatment of moderate-to-severe anemia among postpartum women.

Keywords: Anemia, ferric carboxymaltose, hemoglobin, parenteral, postpartum


How to cite this article:
Kant S, Kaur R, Ahamed F, Singh A, Malhotra S, Kumar R. Effectiveness of intravenous ferric carboxymaltose in improving hemoglobin level among postpartum women with moderate-to-severe anemia at a secondary care hospital in Faridabad, Haryana – An interventional study. Indian J Public Health 2020;64:168-72

How to cite this URL:
Kant S, Kaur R, Ahamed F, Singh A, Malhotra S, Kumar R. Effectiveness of intravenous ferric carboxymaltose in improving hemoglobin level among postpartum women with moderate-to-severe anemia at a secondary care hospital in Faridabad, Haryana – An interventional study. Indian J Public Health [serial online] 2020 [cited 2020 Jul 13];64:168-72. Available from: http://www.ijph.in/text.asp?2020/64/2/168/286824




   Introduction Top


Postpartum period is defined as the period beginning just after childbirth throughout the subsequent 6 weeks. The burden of anemia among postpartum women is high. The World Health Organization has defined postpartum anemia (PPA) as hemoglobin (Hb) of <10 g/dl during the postpartum period.[1] The prevalence of PPA reported by different studies varies from 50% to 75%.[2],[3] PPA has been associated with postpartum stress, depression, anxiety, poor cognitive interaction, and delayed infant development.[4]

PPA is mostly left untreated, as for many women, goal is achieved temporarily in the form of delivery. Many of these women may again become pregnant with inadequate body iron reserves, leading to adverse maternal and fetal outcomes. Oral iron therapy is currently the recommended treatment for PPA.[5] However, the effectiveness of oral iron is limited due to gastrointestinal complaints and consequent poor compliance by the patients.

Currently, three parenteral iron preparations are available for use in India – iron dextran, iron sucrose, and ferric carboxymaltose (FCM). The use of iron dextran is limited due to high rate of side effects, including life-threatening anaphylactoid reactions. Treatment with iron sucrose involves repeated visits, as a patient may require three to four doses. For patients with Hb <7 g/dl, blood transfusion remains a treatment of last resort, but there is a risk of transfusion reactions. Moreover, facilities for blood transfusion may not be available at many health facilities.

Intravenous FCM is given as intravenous IV infusion in a single setting. Studies have already demonstrated that FCM is more effective than iron dextran and comparable results with iron sucrose preparation.[6],[7] A recent meta-analysis reported that following treatment with intravenous FCM, the mean Hb change from baseline increased steadily over weeks 1–6, with a mean increase of about 3 g/dl by week 6 and sustained at that level to week 12. This increase is substantially more than the anticipated rise by intake through oral iron.[8] Moreover, FCM offers an advantage in terms of required dose that can be administered over a single visit as in contrast to other intravenous iron preparations.

In India, postpartum women usually are discharged from health facility 48 h after delivery. This window can be used as an opportunity to treat PPA by administration of a single dose of FCM. Thus, it will be of immense value to the health systems as it will warrant less visits of the patients for taking complete doses and thus logistically will be convenient both to the patients and health-care professionals. FCM use has been approved for clinical use in India and found to be safe to administer. However, limited evidence exists currently from secondary care centers about the use of FCM for moderate or severe anemia among postpartum women.[7],[9],[10],[11]

The study was done to estimate the change in mean Hb level 6 weeks after intravenous administration of FCM and to document any adverse events following administration of FCM among postpartum women with Hb level of 5–9.9 g/dl who delivered at a subdistrict hospital (SDH) in Haryana, India.


   Materials and Methods Top


Study setting and study population

The study was conducted in the maternity ward of a SDH in Haryana state, India. SDH, Ballabgarh, was a 50-bedded secondary care hospital. Every year, more than 4,000 deliveries were conducted at this health facility. As a part of routine care, Hb level of all women admitted for delivery was recorded at the time of admission and after delivery. In accordance with the guidelines of the Government of India, women were discharged 48 h after delivery, and those having anemia were provided appropriate treatment.

The study was carried out from August 2018 to December 2018.

Study design

This was a prospective, interventional follow-up study involving postpartum women with moderate and severe anemia (Hb level between 5.0 and 9.9 g/dl). Consecutive sampling strategy was adopted for recruitment of women in postpartum period.

Inclusion and exclusion criteria

All postpartum women with Hb level of 5–9.9 g/dl, who delivered a live baby through normal vaginal route, were included in the study. We excluded women who were known to be suffering from renal or hepatic impairment, had Hb level <5 g/dl, were known to be allergic to iron formulations, had received any form of parenteral iron or blood transfusion during the current pregnancy, or were suffering from any chronic/systemic illness or blood disorders.

Sample size

Assuming a standard deviation of mean change of hemoglobin of 1.2 g/dl,[11] power of 95%, level of significance of 5%, nonresponce rate of 20%, and to detect 0.5 g/dl difference in the outcome (Hb) variable, the minimum required sample was 90 participant using the formula:



Assuming other possible factors such as wastage of stored sample for long storage period and inability to draw adequate sample during follow-up, we recruited 100 postpartum women for this study.

Study tools

A self-designed, semi-structured questionnaire was used to collect sociodemographic information of study participants. Hb was measured using a digital hemoglobinometer –HemoCue 201+ (HemoCue AB-Hb photometer; Angelholm, Sweden) method from capillary blood. The distal and lateral parts of the middle finger were pricked following aseptic procedures. The first drop was discarded. The second drop of blood was collected on microcuvette. Hb level was measured following standard methodology as prescribed by the manufacturer. A single person (nurse in-charge) was responsible for estimation of Hb. Hb level was measured at baseline, i.e., at the time of recruitment, and again at end line, i.e., 6 weeks after FCM infusion.

Collection of blood specimen

Five milliliters of venous blood from the cubital fossa was collected (3 mL and 2 mL in two plain vials) under strict aseptic precautions from each study participant for estimation of Liver Function Test/Kidney Function Test (LFT/KFT) and serum ferritin. Three milliliters of venous blood was collected from each participant at the end line for estimation of serum ferritin.

Calculation of dose of iron requirement

The total dose of iron requirement was calculated using Ganzoni's formula, i.e., total iron requirement (in mg) = Body weight (in kg) × (Target Hb − Actual Hb in g/dl) × 2.4 + Iron stores. Target Hb was set at 12 g/dl and allowance for iron stores as 500 mg.

Ferric carboxymaltose administration

FCM (Orofer FCM; Emcure Pharmaceuticals Ltd., Pune, India) was administered as an intravenous infusion of 500–1000 mg dose based on requirement with 100 ml of 0.9% normal saline solution over 15 min. The dose was administered by a trained staff nurse under the supervision of a physician. All lifesaving equipment were available to deal with any unexpected severe adverse reaction.

Follow-up

The study participants were followed up after 6 weeks of administration of FCM for estimation of change of Hb and serum ferritin levels. They were called over phone to come to SDH, Ballabgarh, for follow-up investigations. Venous blood was collected for the estimation of serum ferritin at baseline (before administering calculated dose of FCM) and end line (6 weeks after FCM infusion).

Laboratory tests

Serum ferritin level was measured by enhanced chemiluminescent assay with the help of Access-2 (Beckman Coulter Machine). Periodic calibration of study tools was done.

Quality assurance

Hb estimation was done by HemoCue 201+. Quality control was run after every 30 samples checked. Serum ferritin was estimated in the Laboratory of the Department of Biochemistry in AIIMS, New Delhi. This laboratory has strict internal quality assurance in place.

Ethics

Ethical approval was obtained from the Institutional Ethics Committee, AIIMS, New Delhi (Vide Letter Reference No. IEC-138/06.04.2018, RP-26/2018). Informed written consent was taken from each study participant after reading and explaining the participant information sheet to them in the local language. The study was registered prospectively in the Clinical Trials Registry-India (CTRI) ref. CTRI/2018/06/014432.

Statistical analysis

Data were entered in Microsoft Excel, and analysis was done using STATA version 11 (Stata Corp LLC 4905, Lakeway Drive College Station, Texas USA). Continuous data were expressed in mean (SD) and categorical data were expressed in frequencies and percentages. The Shapiro–Wilk test was applied to test for normality of data. The Wilcoxon signed-rank test was applied to test for significance for nonnormal data. A paired t- test was applied for Hb. P <0.05 was considered statistically significant.


   Results Top


One hundred postpartum women were recruited in the study initially. Four postpartum women did not return for follow-up visit scheduled at 6 weeks after FCM administration resulting in attrition rate of 4%. Paired (baseline and end line) measurements for Hb and ferritin were available for 96 postpartum women.

Sociodemographic and other baseline characteristics of postpartum women

The mean (SD) age of the postpartum women was 24.1 (3.1) years. The mean (SD) period of gestation at the time of delivery was 274.3 (17.2) days. Almost one-third (36.5%) of the postpartum women were primipara. One-fourth (25.0%) of newborns had birth weight of <2500 g (low birth weight). Most of the postpartum women (63.5%) had normal body mass index [Table 1].
Table 1: Distribution of study participants by socio-demographic and other baseline characteristics (n=96)

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Dosage requirement of ferric carboxymaltose

The mean (SD) requirement of FCM was 909.3 (97.6) mg of elemental iron.

Changes in levels of hemoglobin and serum ferritin

The mean (SD) Hb at baseline and 6 weeks after administration of FCM was 8.5 (1.1) g/dl and 12.6 (1.3) g/dl, respectively. The mean (95% confidence interval [CI]) increase in the Hb level 6 weeks after administration of FCM was 4.2 (3.9–4.5) g/dl. This increase in Hb level was statistically significant (P < 0.001) [Table 2].
Table 2: Change in hemoglobin and ferritin after administration of ferric carboxymaltose (n=96)

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The mean (SD) ferritin at baseline and 6 weeks after administration of FCM was 15.8 (17.2) ng/ml and 153.0 (121.3) ng/ml, respectively. The mean (95% CI) increase in the serum ferritin level 6 weeks after administration of FCM was 137.3 (113.6–161.0) ng/ml (P < 0.001) [Table 2].

More than two-third (68.4%) of the anemic postpartum women became nonanemic (Hb ≥12 g/dl) 6 weeks after FCM administration. The quantum of mean increase in Hb was inversely related with baseline Hb level, i.e., improvement in Hb level was maximum among postpartum women with severe anemia (Hb <7 g/dl) at baseline. The improvement of Hb among postpartum women with severe anemia was 6.4 g/dl (95% CI: 5.8–7.0 g/dl) 6 weeks after administration of FCM [Table 3].
Table 3: Change in mean hemoglobin level by baseline hemoglobin level category

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Adverse effects of ferric carboxymaltose

Nine postpartum women (9.4%) developed mild side effects. Mild itching over injection site was the most common side effect (n = 7), followed by mild palpitation (n = 1) and perception of increased body heat (n = 1). Symptoms subsided with antiallergic medication. No severe adverse effect was identified warranting to stop FCM transfusion in these women.


   Discussion Top


To summarize, the mean (95% CI) increase in Hb level was 4.1 (3.8–4.5) g/dl 6 weeks following FCM administration among postpartum women who had moderate-to-severe anemia (Hb: 5–9.9 g/dl). During the same period, the mean (95% CI) increase in serum ferritin level was 164.7 (119.8–209.5) ng/ml. Both the changes were statistically significant (P < 0.01).

Our findings are consistent with the findings of other published studies across the world where reported increase of Hb ranged from 2.4 to 4.4 g/dl, 4–6 weeks after FCM therapy.[9-11,12] The lowest Hb rise of 2.4 g/dl was reported by Seid et al.,[12] 4 weeks after the FCM therapy, where 606 postpartum women received single-dose FCM (15 mg/kg body weight). Difference in study settings and follow-up interval were the possible reasons behind this finding. The finding of our study is almost similar to the study by Rathod et al., where 100 postpartum women were given FCM using Ganzoni's formula. The reported rise in Hb was 4.4 g/dl at 6 weeks after FCM therapy.[9] Standard methodology and strict quality control measures were undertaken in Hb estimation. Thus, the measurements were reliable and valid. HemoCue 201 + instrument was used for the measurement of Hb. The choice of HemoCue was based on the fact that it required less training and gave rapid results as it had shorter turn-around time and also that turbidity was corrected due to the measurement of two wavelengths. HemoCue has been reported to be highly sensitive (94%) and specific (95%) with capillary blood when compared with gold standard (cyanmethemoglobin) method.[13] A single trained staff nurse carried out Hb estimation using fresh microcuvettes on each day. Hence, chance of misclassification of category of anemia at the time of enrollment was minimized. We believe that residual error, if any, is likely to be small and thus does not seriously threaten the internal validity of the findings. Moreover, the residual error is likely to remain constant both during baseline and end line measurements. Therefore, the difference in mean Hb level observed between these two measurements is unlikely to get affected. We had an adequate sample size; this resulted in a precise estimate with a narrow 95% CI limits.

Replenishing iron stores is an important clinical consideration as reduced iron stores place the patient at high risk for reoccurrence of iron-deficiency anemia. The current study also demonstrated that FCM resulted in replenishment in iron stores significantly at 6 weeks of the study (mean [95% CI] serum ferritin rise: 164.7 [119.8–209.5]) ng/ml. This finding was consistent with the findings by Rathod et al. where the rise in levels of ferritin after 6 weeks of FCM administration was 142 ng/ml and 126 ng/ml, respectively.[9],[10]

Two-third of the women (68.4%) achieved the target Hb level of 12 g/dl at 6 weeks of FCM infusion. This finding highlighted that body iron stores were replenished. In Indian context, where short birth interval is common, restoration of body iron stores would be an important target to be achieved in terms of health of postpartum women.

We observed that the improvement in Hb level was highest (6.4 [95% CI: 5.8–7.1] g/dl) among the women with severe anemia (Hb: 5–6.9 g/dl). This finding was consistent with other studies done in India.[1],[6] In India, severe anemia (Hb <7 g/dl) among postpartum women is treated with blood transfusion. Blood transfusion treats the symptoms but does not eliminate the underlying cause of anemia. Moreover, blood transfusion is associated with risk of reaction and transmitting blood-borne infections. Moreover, facility for blood transfusion may not be available at all health facilities, and there is an ever-existing supply–demand gap that exists in terms of availability of blood.[14] Thus, FCM could be a useful modality in treatment of postpartum women with severe anemia (Hb 6.9–5 g/dl).

The observed side effects after FCM infusion were very mild in nature, and around 9% of postpartum women reported such side effects. Studies reported the incidence rate of side effects of 6%–11% following FCM therapy.[15],[16],[17] FCM has low immunogenic potential, and release of iron from the complex in bloodstream is low. Both the factors attribute to the less side effects caused by FCM in comparison to other iron preparations. Moreover, the current study found that a single dose of FCM could produce a significant increase in Hb and ferritin level. This has immense programmatic implications as inclusion of FCM in a national guideline for treating postpartum anemia would save resources and improve patients' compliance.

Erroneous rise in serum ferritin level can be seen during acute infection for which C-reactive protein is a proxy marker.[18] However, we could not find any reason that would support assumption of differential rate of infection at 2 time points. We did no collect data on socioeconomic characteristics and dietary pattern of the study participants.


   Conclusion Top


FCM administration was well-tolerated, safe, and effective in treating moderate-to-severe anemia among postpartum women attending a secondary level hospital in Haryana, India. It also improved iron stores in the form of serum ferritin with minimum side effects during postpartum period.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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World Health Organization. Haemoglobin Concentrations for the Diagnosis of Anaemia and Assessment of Severity. Vitamin and Mineral Nutrition Information System. Geneva: World Health Organization; 2011.  Back to cited text no. 1
    
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Hussain I, Bhoyroo J, Butcher A, Koch TA, He A, Bregman DB. Direct comparison of the safety and efficacy of ferric carboxymaltose versus Iron dextran in patients with iron deficiency anemia. Anemia 2013;2013:169107. Doi: 10.1155/2013/169107. Epub 2013. Available from: https://pubmed.ncbi.nlm.nih.gov/24069536/. [Last accessed on 2020 May 12].  Back to cited text no. 6
    
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Sharma N, Thiek JL, Natung T, Ahanthem SS. Comparative study of efficacy and safety of ferric carboxymaltose versus iron sucrose in post-partum Anaemia. J ObstetGynaecol India 2017;67:253-7.  Back to cited text no. 10
    
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Akhtar K, Sherwani RK, Rahman K, Hasan J, Shahid M. HemoCue photometer: A better alternative of hemoglobin estimation in blood donors? Indian J Hematol Blood Trans 2008;24:170-2.  Back to cited text no. 13
    
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Northrop-Clewes CA. Interpreting indicators of iron status during an acute phase response-lessons from malaria and human immunodeficiency virus. Ann Clin Biochem 2008;45:18-32.  Back to cited text no. 18
    



 
 
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