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A pilot study on effect of intravenous iron sucrose on oxidative stress and antioxidant status of pregnant women with iron deficiency anemia
*Corresponding author: Sathiyapriya Viswanathan, Department of Biochemistry, ACS Medical College and Hospital, Chennai, Tamil Nadu, India. vvspriya@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Rameshkumar S, Viswanathan S, Jagadeesan AR, Dhanunjaya Y. A pilot study on effect of intravenous iron sucrose on oxidative stress and antioxidant status of pregnant women with iron deficiency anemia. Indian J Med Sci 2023;75:9-11.
Abstract
Objectives:
Iron deficiency anemia (IDA) is the most common nutritional deficiency among pregnant women in India. Iron can be supplemented orally or intravenously to treat IDA. Intravenous supplementation of iron can be risky as there is more possibility for the production of free iron in circulation. The role of free iron in the generation of free radicals and thereby oxidative stress is well known. The present study tends to evaluate oxidative stress and antioxidant status of intravenous iron sucrose treated pregnant women.
Materials and Methods:
This prospective study was conducted in ACS Medical College and Hospital, Chennai. Twenty pregnant women with moderate IDA (Hb: 7–9.9 g/dl) were included in the present study. Blood samples were collected before and after the treatment with intravenous iron sucrose to measure antioxidants such as reduced glutathione, catalase and superoxide dismutase, and lipid peroxidation marker such as malondialdehyde.
Results:
In the present study, plasma malondialdehyde levels were increased significantly after the treatment with intravenous iron sucrose. No significant alterations were observed in the levels of reduced glutathione and activities of catalase and superoxide dismutase.
Conclusion:
In the present study, intravenous iron sucrose infusion was associated with oxidative stress as evidenced by increased lipid peroxidation in antenatal women with IDA. Hence, treatment with antioxidants during iron infusions can be considered.
Keywords
Anemia
Antioxidants
Intravenous iron-sucrose
Oxidative stress
Pregnancy
INTRODUCTION
Iron deficiency anemia (IDA) is the most common nutritional deficiency among pregnant women. According to the WHO, the prevalence of IDA is about 38% among pregnant women.[1] In India, the prevalence is around 84%.[2] About half of the maternal deaths globally occur due to anemia in South Asian countries and India contributes to about 80% of this mortality ratio.[3] The main causative factors for iron deficiency during pregnancy are poor intake and low bioavailability. IDA is classified based on hemoglobin levels as mild (10–10.9 g %), moderate (7–9.9 g %), severe (4–6.9 g %), and very severe (<4 g %) (Good clinical practice 2011). The first line of treatment for mild IDA in pregnancy is oral iron therapy. However, in the case of moderate and severe anemia, it requires longer treatment duration and compliance issue also occurs. For moderate anemia, better treatment modality will be parenteral iron therapy.[4]
Various parenteral (intravenous and intramuscular) iron preparations are available in the market such as iron dextran, iron sucrose, iron sorbitol, and iron citrate of which iron sucrose has been reported to be safe and effective during pregnancy.[4] Intravenous iron-sucrose appears to be a treatment of choice with no serious side effects which is indicated in the rapid correction of anemia in pregnancy or restoring maternal iron stores because the total iron stores can be administered within a short period of time.[5] Therefore, intravenous iron sucrose transfusion is an effective treatment strategy for pregnant women with severe anemia during late pregnancy and in patients non-compliant to oral therapy.
Both iron overload and iron deficiency could promote the generation of free radicals and result in cellular damage.[6] The iron-transporting protein and transferrin are normally kept at around 30% of iron saturation to ensure that no free iron is available to catalyze the formation of dangerous radicals such as OH ion. High percentage transferrin saturation was found to be associated with the presence of non-transferrin-bound, potentially redox-active iron.[7] Redox-active iron, potent pro-oxidant levels were increased in hemodialysis patients on intravenous iron sucrose therapy.[8] Although intravenous iron is effective in correcting anemia during pregnancy, its consequence on the oxidative stress status of pregnant women is not known. Hence, the present study aims at determining the oxidative stress and antioxidant status of iron-deficient pregnant women on intravenous iron sucrose therapy.
MATERIALS AND METHODS
The present study is a prospective study conducted in the Department of Biochemistry in collaboration with Department of Obstetrics and Gynecology in ACS Medical College and Hospital, Chennai. About 20 pregnant women with moderate anemia (Hb: 7–9.9 g/dl) were included in the present study. Pregnant women having gestational diabetes mellitus, heart diseases, liver and renal disorders, peptic ulcer, allergy, asthma, inflammation, and anemia due to causes other than iron deficiency were excluded from the present study.
Dosage of iron sucrose
The dose of total iron sucrose to be administered was calculated and rounded up to the nearest multiple of 100 mg.
Total dose = weight in kg × (target Hb in g/L–Actual Hb in g/L) × 0.24 + 500 mg. The calculated dose of iron sucrose complex was administered as 200 mg in 100 ml 0.9% sodium chloride intravenously over 20–30 min. This was given on alternate days with a maximum of 600 mg/week up to the total dose. Oral administration of iron was excluded during this period. Target hemoglobin was 120g/L.[9]
Blood collection
After taking informed consent from the patients, about 2 ml each of blood was collected in EDTA coated tubes before and after administration of intravenous iron sucrose. The following biochemical analyses were carried out. Hemoglobin content of the blood was analyzed using ERBA H 360 cell count analyzer and the erythrocyte reduced glutathione[10] catalase,[11] superoxide dismutase,[12] and malondialdehyde[13] were determined by standard procedures.
Statistical analysis
Results were analyzed by SPSS version 16.0. Student’s paired t-test was used to assess the significance of difference before and after the treatment. All results were presented as mean ± SD. P <0.05 was considered significant.
RESULTS
Patients’ baseline characteristics
A total of 20 pregnant anemic women took part in the present study. The baseline characteristics such as age of the participants, hemoglobin levels, and average gestational period of the participants are shown in [Table 1].
| Parameter | Variables |
|---|---|
| Age (Years) | 26.4±4.3 |
| Gestational period (weeks) | 28.5±4.5 |
| Hemoglobin (g/dl) | 9±0.9 |
Oxidative stress and antioxidant status of the antenatal women before and after intravenous iron sucrose treatment are shown in [Table 2]. There was no significant difference in the levels of glutathione before and after the treatment with I.V. iron sucrose. Catalase activities were not significantly different before and after the treatment.
| Parameters | Before treatment (n=20) |
After treatment (n=20) |
|---|---|---|
| Glutathione (mg/g Hb) | 1.49±0.37 | 1.44±0.36 |
| Catalase (U/ml) | 15.03±4.64 | 15.58±5.00 |
| SOD (U/ml) | 9489±1020 | 9181±993 |
| MDA (nmoles/ml) | 8.86±1.89 | 10.49±0.3.24* |
Superoxide dismutase activity shown before and after the treatment (with intravenous iron sucrose) was not significant. There was a statistically significant increase in malondialdehye (MDA) values after the treatment with intravenous iron.
DISCUSSION
In the present study, we did not find any significant difference in the levels of blood glutathione after infusion compared with basal level, that is, before infusion. An intravenous iron infusion did not alter the reduced glutathione to oxidized glutathione ratio in anemic patients up to 6 h in contrast to healthy volunteers where the above mentioned ratio is decreased.[14] This may explain why glutathione is not altered in our study.
In the present study, plasma levels of MDA, an end product of lipid peroxidation, were significantly elevated after intravenous iron sucrose infusion. According to a study done by Zager et al., various iron preparations including iron sucrose increased lipid peroxide levels in cell culture. The authors also revealed that the cell viability was least with iron sucrose compared with other preparations.[15] Increased MDA levels were demonstrated in dialysis patients treated with intravenous iron sucrose.[16] In addition to this, Roob et al. demonstrated the generation of MDA, and its peaking after 30 min of the start of an intravenous iron sucrose infusion. They also illustrated a rapid increase in redox-active iron a mediator of oxidative stress after infusion.[8]
A randomized and controlled trial showed that the effect of iron supplementation during the third trimester of pregnancy on iron status and lipid peroxidation and this study supported the hypothesis that high doses of iron might induce lipid peroxidation.[17] Excess iron intake has deleterious effects due to induction of direct intestinal damage, oxidative stress, cell toxicity, endothelial dysfunction, or growth of pathogens.[18,19]
In the present study, the antioxidant enzymes catalase and superoxide dismutase were not altered significantly, this may be due to immediate sample collection. Being enzymes, the regulatory mechanism has to be activated which may take more time. The present study was conducted with smaller sample size. Studying oxidative stress, in larger populations and, for longer duration (start of infusion and end of infusion), will provide more insight.
CONCLUSION
In the present study, intravenous iron sucrose infusion was associated with oxidative stress as evidenced by increased lipid peroxidation in antenatal women with IDA. Further study with more number of samples may help us to understand the role of intravenous iron sucrose on oxidative stress and antioxidant status.
Acknowledgment
This study was carried out under STS program of ICMR. The authors wish to thank ICMR for providing an opportunity to conduct this study.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent.
Conflicts of interest
There are no conflicts of interest.
Financial support and sponsorship
Indian Council of Medical Research Short Term Studentship.
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