|Year : 2015 | Volume
| Issue : 2 | Page : 86-90
Study of efficacy of intravenous iron sucrose in patients with moderate iron deficiency anemia in pregnancy
Shrish Vijaykumar Raut1, Parag Anand Biniwale2
1 Department of Enteric Viruses, National Institute of Virology, Pune, Maharashtra, India
2 Department of Gynaecology, Kamala Nehru Municipal Hospital, Dr. Patankar Nursing Home, Pune, Maharashtra, India
|Date of Web Publication||4-Aug-2015|
Shrish Vijaykumar Raut
1079, Shukrawar Peth, Yashodhan, Pune - 411 002, Maharashtra
Source of Support: Dr. Patankar Medical Foundation’s Dr. Patankar Nursing Home, Pune., Conflict of Interest: None declared.
Introduction: Iron deficiency continues to be one of the most prevalent single nutrient deficiencies in the world. In the case of pregnant population, treatment of iron deficiency anemia efficiently would lead to a considerable reduction in the risk factors affecting maternal and fetal outcome.
Materials and Methods: In this retrospective, case control study; the data of pregnant women who have received uniform dose of Intravenous and oral therapy for proven moderate iron deficiency anemia in the second trimester were studied for efficacy and safety parameters. The hemoglobin levels before and after initiating treatment in both groups were compared.
Results and Conclusions: Intravenous and oral; both the treatments were associated with increment in hemoglobin but this rise was significantly more in the intravenous group than in oral. Comparing participants with low pretreatment hemoglobin among both groups, participants in the intravenous group were better benefited than oral due to respective treatment. Further it is found that hemoglobin increment is inversely proportional to the pretreatment hemoglobin irrespective of route of administration. Also intravenous iron is better tolerated compared to oral iron. So it can be concluded that intravenous iron therapy is much effective in correcting iron deficiency anemia in pregnancy than oral iron therapy.
Keywords: Anemia, iron deficiency, iron sucrose
|How to cite this article:|
Raut SV, Biniwale PA. Study of efficacy of intravenous iron sucrose in patients with moderate iron deficiency anemia in pregnancy. J Med Nutr Nutraceut 2015;4:86-90
|How to cite this URL:|
Raut SV, Biniwale PA. Study of efficacy of intravenous iron sucrose in patients with moderate iron deficiency anemia in pregnancy. J Med Nutr Nutraceut [serial online] 2015 [cited 2017 Nov 20];4:86-90. Available from: http://www.jmnn.org/text.asp?2015/4/2/86/162173
| Introduction|| |
Anemia affects nearly half of all pregnant women in the world. Among these pregnant women, 52% are in developing countries compared with 23% in the developed world. Iron deficiency continues to be one of the most prevalent single nutrient deficiencies in the world. Interventions are often designed to prevent the decrease in hemoglobin and decline in iron stores associated with pregnancy. Available data from India and elsewhere indicate that maternal morbidity rates are higher in women with hemoglobin below 8 g%. They are more susceptible to infections and recovery from infections may be prolonged. They may not be able to bear blood loss prior to or during labor and may succumb to infections more readily. Substantial proportions of maternal deaths are due to antepartum and postpartum hemorrhage. Also pregnancy induced hypertension and sepsis occur in women with moderate anemia. In view of the fetal and maternal risks associated with iron deficiency anemia, it is obvious that treating anemia efficiently would lead to a considerable reduction in the risk factors affecting maternal and fetal outcome. Indian data indicate that maternal morbidity rates are higher in women with hemoglobin below 8 g%. Also maternal mortality shows a steep increase when maternal hemoglobin falls below 5 g%. It has also been stated that anemia directly causes 20% of maternal deaths and indirectly accounts for another 20% of maternal deaths in India. So it is that segment of moderate iron deficiency anemia which is required to be treated vigorously in second trimester itself.
| Objectives|| |
- To study efficacy and safety of intravenous iron sucrose in correcting hemoglobin in pregnant women
- To compare effectiveness of intravenous iron sucrose over oral iron preparation of iron ascorbate in correcting Iron deficiency anemia of pregnancy.
| Materials and Methods|| |
The procedures followed during the study were in accordance with the ethical standards of the Institutional Ethics committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000. Institutional Ethics Committee approval was taken before initiating the study.
All the patients attending Antenatal care OPD between June 2010 and February 2012 were screened retrospectively with the help of inclusion and exclusion criteria as follows.
- Age 20 to 35 years
- Singleton pregnancy completing 20 weeks of gestation
- Anemia as per definition of World Health Organization, hemoglobin between 8 to 10 g/dL or hematocrit of <30%
- Iron deficiency anemia profile shows decreased serum iron (could be lower side of normal) with raised total iron binding capacity
- Patients who received three doses of intravenous iron sucrose 200 mg each on alternate day were included in the intravenous iron therapy group
- Patients who received tablet ferrous ascorbate with 100 mg elemental iron single tablet daily for 8 weeks were included in the oral iron therapy group.
- Serum ferritin >15 mcg/L
- Underlying disease such as hypertension, gestational diabetes mellitus, heart disease, peptic ulcer, etc
- History of antepartum hemorrhage likely to recur, for example placenta previa
- Thalassemia disease detected by hemoglobin high performance liquid chromatography (Hb HPLC), for example B thalassemia major
- History of bleeding tendency or blood transfusions.
The data about change in hemoglobin were recorded after average period 8 weeks in both the groups. The hemoglobin levels before (pretreatment) and after (posttreatment) initiating treatment were compared. For the intravenous group, no test dose was given and any adverse reactions were monitored over an hour following the dose of Iron sucrose. The data were retrospectively analyzed for any of the immediate, early, and late adverse drug reactions reported in both groups.
The data of total 200 participants were considered for the study, 100 from each group; intravenous and oral. This study did not calculate the optimal dose of iron sucrose required by each woman based on her pretreatment hemoglobin. The response to a uniform dose over a range of pretreatment hemoglobin was studied.
- Hemoglobin estimation of intravenous blood by fully automated cell counter Nihon Kohden
- Iron deficiency anemia profile which includes serum iron, serum total iron binding capacity and serum ferritin with the chemiluminescence method by using fully automated ADVIA Centaur
- Estimation of Hemoglobinopathies by the high performance liquid chromatography technique.
The “t test of difference between two means” was used as a test of significance with 95% confidence interval. The software Statistical Program for Social Sciences (SPSS) version number 17 was used for data analysis.
| Results|| |
The mean increment in hemoglobin among the intravenous group was 1.6 g% and that of oral therapy was 0.87 g%. This increment was seen after approximate duration of 8 weeks. Combined mean of both oral and intravenous treatment groups was 56.75 days with standard deviation (SD) 4.26. The mean duration of treatment in the intravenous group was 56.41 days (SD = 2.72) and that among the oral group was 57.10 days (SD 3.29). The difference between mean duration of treatment among both groups was statistically not significant (P = 0.108); indicating that both treatments were administered for almost equal duration of days.
The pretreatment mean hemoglobin among both groups was 9.16 (SD = 0.56 for intravenous and 0.59 for oral). So there was no significant difference (P = 0.961) between pretreatment mean hemoglobin in both groups. In fact the means are coinciding on normal distribution curve indicating that samples were randomly distributed in both groups.
Intragroup comparison between pretreatment and posttreatment showed that both treatments; intravenous and oral, were associated with increment in hemoglobin which is statistically highly significant (P < 0.001)*.
Among the post treatment values, mean hemoglobin in the intravenous group was 10.76 g% (SD = 0.62) and that among the oral group was 10.03 g% (SD = 0.61). This difference was statistically highly significant (P < 0.001)*. The posttreatment mean hemoglobin was more in the intravenous group than oral indicating that hemoglobin rise was better in the intravenous group compared to the oral group.
Further participants in both pre and posttreatment groups of intravenous and oral were classified according to grades of hemoglobin concentration as shown in [Table 1].
|Table 1: Distribution of patients with respect to hemoglobin levels at pretreatment and posttreatment with respect to groups|
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It was found that, among the intravenous category, out of 16 individuals of grade 1 hemoglobin (8 to 8.5 g%), 11participants (68.75%) were shifted to grade 5 hemoglobin (10 g% or more). On the contrary among oral category, out of 24 individuals of grade 1 hemoglobin, only one participant (4.17%) was transferred to grade 5 hemoglobin (10 g% or more).
Similarly among the intravenous category, out of 22 individuals of grade 2 hemoglobin (8.5 to 9 g%), 16 participants (72.73%) were shifted to grade 5 hemoglobin (10 g% or more). On the contrary among the oral category, out of 17 individuals of grade 2 hemoglobin, only one participant (5.88%) transferred to grade 5 hemoglobin (10 g% or more). These observations show that intravenous iron therapy is more effective in correcting iron deficiency anemia in pregnancy than oral iron therapy probably because of bypassing of gastric mucosal barrier and replenishing Iron stores much faster than oral therapy.
When comparison is made between mean increment (posttreatment minus pretreatment) in hemoglobin in different pretreatment hemoglobin categories among both intravenous and oral groups, it was observed that low pretreatment hemoglobin has shown comparatively better increment while high pretreatment hemoglobin has shown comparatively low increment. And this trend is consistent in both intravenous and oral iron treatment see [Table 2]. This finding suggests that hemoglobin increment is inversely proportional to the pretreatment hemoglobin, irrespective of route of administration.
|Table 2: Mean change in hemoglobin with respect to the pretreatment hemoglobin groups|
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In the intravenous treatment group no serious adverse events were observed like anaphylaxis. Only two patients were reported pruritus at the site of administration.
In the oral group, five individuals reported taste perversion, 18 participants reported constipation and 19 individuals reported gastric upset. None of the individuals were suffered from a serious adverse event like anaphylaxis in both groups. So it appears from observations that intravenous iron is better tolerated than oral iron.
*P values are so small that for all practical purposes they are considered as less than 0.001.
| Discussion|| |
The highest and lowest posttreatment hemoglobin among the intravenous iron group is 11.8 g% and 8.9 g% respectively and those among the oral iron group is 11.8 g% and 8.8 g% respectively. The maximum increase observed in the intravenous group is 2.8 g% and minimum increment is 0.6 g%. The maximum increase observed in the oral group is 2.3 g% and minimum increment is 0.2 g%. The worse result of treatment seen is no change in hemoglobin posttreatment in the intravenous group and reduction of 0.5 g% in the case of oral group.
A randomized study of oral versus intravenous iron conducted in Tamil Nadu shows that the maximum increase in the oral group achieved was 1.3 g, and the worst result was reduction by 0.3 g. The maximum increase in the intravenous group achieved during that period was 3.6 g/dL and the least increase was 0.3 g/dL.
Intragroup comparison between pretreatment and posttreatment shows that both treatments, intravenous and oral, show increment in hemoglobin which is statistically significant (P < 0.001)*.
This shows both modalities of treatments show significant rise in hemoglobin. So both treatments are effective in correcting moderate iron deficiency anemia of pregnancy if treatments are started in the midtrimester (20th to 28th weeks in this study) of pregnancy.
The Cochrane review for Iron deficiency anemia in pregnancy shows that iron sucrose is effective in pregnancy and in the postpartum period in patients who do not respond to oral iron, who are noncompliant to oral iron. In both cases, according to the present data, the expected hemoglobin increase and time for therapy are predictable in responding patients.
There is significant rise in posttreatment mean hemoglobin in the intravenous group than in the oral group. (P < 0.001)* indicating that intravenous treatment increases hemoglobin more compared to the oral treatment group. These findings are consistent with results of the other studies.
The study conducted to compare between intravenous iron polymaltose complex and oral ferrous fumarate in the treatment of iron deficiency anemia in pregnancy shows that treatment with intravenous iron dextrin resulted in a significantly better level and rate of increase of hemoglobin (P < 0.001). Serum ferritin, which is the best indicator of iron stores, was significantly higher (P < 0.001) in the intravenous group. The results suggest that intravenous iron as a total dose infusion is able to replenish iron stores more efficiently, completely and at a faster rate than oral iron therapy, thus providing the fuel for stimulation of full erythopoiesis compared to oral iron.
Another study shows that the change in hemoglobin from baseline was significantly higher in the intravenous group than the oral group at each measurement taken at 14th and 28th day; the changes with respect to subsequent hemoglobin were significantly higher on the 14th (P = 0.004) and 28th (P = 0.031) days.
A randomized study of oral versus intravenous iron shows that women given intravenous iron, the 15 days followup 87 percentage showed an increase of hemoglobin levels with an average of 0.4 g/dL. In the 3 month followup there was an increase by 0.9 g/dL as an average with all patients showing an increase in hemoglobin levels.
In a study, there were 52 patients and 59 controls. The iron sucrose complex group achieved a significantly higher hemoglobin level (128.5+/6.6 g/L vs. 111.4+/12.4 g/L in the control group P < or = 0.001) in a shorter period (6.9+/1.8 weeks vs. 14.9+/3.1 weeks in the control group, P < or = 0.001).
Although when the intragroup comparison is made between pretreatment and posttreatment hemoglobin, both treatments are found to be effective. As there is significant rise in hemoglobin, posttreatment, in both intravenous and oral groups, considerations should be given to the following factors like:
- Compliance of the patient to the treatment
- Non responders to the oral Iron therapy or Iron intoleranc (probably macronutrients and other non iron micronutrient deficiencies, malabsorption syndrome, food habits reducing iron absorption from gastrointestinal tract and others reasons which are less likely associated with pregnancy, e.g., anemia related with chronic illness, malabsorption syndrome)
- Cost-effectiveness of the treatment modalities.
Compared with other studies it was found that intravenous iron significantly increased maternal hemoglobin at 4 weeks (one randomized controlled trial, 90 women; 95% CI 0.39-0.97) and at birth (one randomized controlled trial, 90 women; 95% CI 0.34-1.16) and increased the proportion of non anemic women those with hemoglobin level equal or greater than 11 g/dL (90 women; 95% CI 1.21 to 1.94).
When participants were classified according to graded hemoglobin levels, it was found that among participants with pretreatment low hemoglobin more participants in the intravenous group were transferred to high hemoglobin category compared to those with oral iron therapy.
When mean change in hemoglobin with respect to pretreatment hemoglobin for the intravenous and oral groups was studied, it was observed that hemoglobin increment is inversely proportional to the pretreatment hemoglobin irrespective of route of administration and mean increment in the intravenous group is twice that of the oral group.
These observations could be explained with the fact that iron disappearance from serum depends on the need for iron in the iron stores and iron utilizing tissues of the body. In gastric mucosa, curtain mechanism is working at cellular level which limits iron absorption from gut. Serum clearance of iron is expected to be more rapid in more iron-deficient patients compared to less iron-deficient patients or healthy individuals.
So it can be concluded that intravenous iron therapy is much effective in correcting iron deficiency anemia in pregnancy than oral iron therapy probably because of bypassing of gastric mucosal barrier and replenishing Iron stores much faster than oral therapy.
This study shows that intravenous iron is better tolerated compared to oral iron. Participants on oral iron therapy reported adverse events like gastric upset, constipation, and taste perversion. Compared with other studies there were also no reports of any adverse reactions with intravenous iron dextrin, whereas there were a considerable proportion of women on oral iron therapy who reported side effects.
Oral treatment increased constipation, compared with intravenous treatment (one randomized controlled trial, 100 women; 95% CI 0.00 to 0.61). No significant differences were found for constipation when intravenous iron was compared to controlled released iron.
Good tolerance to iron sucrose formulation is partly due to the low allergenic effect of the sucrose complex, partly due to slow release of elementary iron from complex. Accumulation of iron sucrose in parenchyma of organs is low compared with iron dextran or iron gluconate, while incorporation into the bone marrow for erythropoiesis is considerably faster.
| Conclusions|| |
- Intravenous and oral treatments are effective in correcting iron deficiency anemia of pregnancy if treatment started in the second trimester
- Intravenous iron therapy causes significant improvement in hemoglobin and is much effective in correcting iron deficiency anemia in pregnancy compared to oral treatment
- Intravenous iron is safe and effective option for pregnant women with iron deficiency anemia.
| Acknowledgment|| |
The authors sincerely thank the in charge of Dr. Patankar Medical Foundation’s Dr. Patankar Nursing Home, Pune for allowing us to conduct this study. We also acknowledge the Mr. Shrivallabh Sane for his contribution in statistical analysis with software.
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[Table 1], [Table 2]