Intravenous Iron Sucrose versus Intramuscular Iron Sorbitol in management of iron deficiency anemia during pregnancy

INTRODUCTION

Reduced hemoglobin levels, red-cell count, or packed-cell volume are characteristics of anemia. According to World Health Organization (WHO) guidelines, 11 g/dL is considered the mean minimum tolerable hemoglobin level during gestation.¹

Anemia in gestation is defined by the Centers for Disease Control (CDC) as hemoglobin lower than 11 g/dl (Hematocrit: Hct < 33%) in the first and third trimesters and lower than 10.5 g/dl (Hct < 32%) in the 2nd trimester.²

The most widespread nutritional issue in the world is iron insufficiency, which is pandemic in many underdeveloped nations. Up to 50% of cases are caused by inadequate iron consumption, making it the most prevalent dietary deficit in the industrialized world. The incidence of IDA rises in gestation because of the increasing need for iron. In the underdeveloped world, this affects up to 52% of pregnant women.³

Both the mother's and the fetus's health are significantly impacted by anemia. It hinders the fetus's ability to get oxygen via the placenta and interferes with its normal intrauterine development, which may result in miscarriage and neonatal fatalities. Preterm birth rates (28.2%), preeclampsia (31.2%), and maternal sepsis are all up due to anemia.⁴

40–60% of maternal mortalities from heart failure, bleeding, infection, and pre-eclampsia are directly or indirectly attributable to iron deficiency anemia.⁵

In areas where anemia incidence is more than 40% in women and adolescents, the WHO established a worldwide guideline in 2016 suggesting daily oral iron intake (60mg iron) for 12 weeks. The WHO's position is based on the assumption that women who are iron deficient experience advantages from iron supplements, and that iron deficiency accounts for around 50% of anemia in low-income countries.⁶

Recent national recommendations include the tried-and-true intramuscular iron sorbitol citric acid combination as one of the first-line medications for managing mild IDA during pregnancy. This medication's main drawbacks are injection site discomfort and swelling, quick clearance necessitating greater dosages, and the necessity for frequent injections, all of which contribute to low compliance and high dropout rates. ⁷ Therefore, we need an iron treatment that is relatively recent and has superior effectiveness, less side effects, quick action, and better compliance. ⁸

Recent alternative strategies, such as parenterally administered iron sucrose, promise to be more effective because it slows the release of elemental iron from the complex, reduces renal excretion, speeds up the replenishment of iron stores, increases the availability of iron for erythropoiesis and, consequently, causes a rapid increase in hemoglobin, and is safe because of its low allergic impact and organ toxicity.⁹

The goal of the research was to assess the effectiveness and safety of intramuscular iron sorbitol citric acid complex and intravenous iron sucrose in treating iron deficiency anemia (IDA) in pregnancy.

PATIENTS AND METHODS

This study is randomized controlled research that was carried out on 100 pregnant ladies. They were recruited from Obstetrics and Gynecology clinics during the period from July 2021 till December 2021. This research was done at Kafr El Sheikh General Hospital and the Department of Obstetrics and Gynecology at Al-Azhar University's Faculty of Medicine.

Ethical and legal consideration: Approval of ethical committee was obtained as well as written consent was signed from all cases before participation in this study.

Sample size: The sample size was determined utilizing Epi Info STATCALC while taking into account the following presumptions: An odds ratio of 1.115 was derived using a- 95 percent two-sided confidence level, an 80 percent power, and a 5 percent error. In developing nations, IDA prevalence ranges from 35 to 75 percent (on average 56 percent).⁷

From the Epi-Info output, 86 was the ultimate maximum sample size. In order to account for potential drop-off cases during follow-up, the sample size was raised to 100 cases.

Inclusion criteria: Age between 21 and 35, Singleton gestation, and IDA diagnosed between 14 and 28 weeks with hemoglobin levels of 7-9 g/dL.

Exclusion criteria: the existence of anemia due to conditions other than iron insufficiency (such as thalassemia, folate insufficiency anemia, vitamin B12 insufficiency, etc.), multiple pregnancies, the existence of clinical or laboratory findings of hepatic, renal, or hematological abnormalities, cardiovascular disorders, renal malfunction, infections like malaria, hook worm infestation, and schistosomiasis, people who are known to be hypersensitive to iron preparations, instances with anti-partum hemorrhage (APH), pregnancy-induced hypertension, hemoglobin values  9 gm/dl, gestation age 32 weeks, recent blood transfusion, and G6PD deficiency or anti-partum hemorrhage (APH), pregnancy-induced hypertension(PIH), or a past of any hemorrhage propensity or gestation complications.

Intervention(s)

All cases were subjected to the followings:

Detailed history including personal history and past history, obstertric history history of last menstrual period (LMP), any previous contraceptive method medical and surgical history, Clinical examination: Body Mass Index (BMI) for mothers was computed, Symptoms and signs of anemia including pallor.

Investigations: Complete blood count (CBC): level of hemoglobin, Hematocrit (PCV), Median corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Median corpuscular hemoglobin concentration (MCHC).

Vitamine B12 and Folic acid

Serum Ferritin was measured by ELISA kits.

Randomization and allocation: 100 patients who met the requirements were randomly assigned using a computer-generated list of random numbers in such a manner that each patient had an equal chance of being in either of the two groups (1:1). Then, allocation into two equal groups as follows: Group A: contained 50 pregnant women who got intravenous iron sucrose therapy (Sacrofer IV). Group B: contained 50 pregnant women who got intramuscular iron sorbitol therapy (Haempower injection IM).

Interevention: Following thorough sensitivity testing in both groups, iron was administered. The Ganzoni Formula was used to determine the amount of iron needed in both groups, with the target hemoglobin set at 11 gm/dl: Total iron deficit (mg) = Body wt (kg) × {Target Hb - Actual Hb (gm/dl)} ×2.4+500 ¹⁰, In group A, up to the predicted dosage, iron sucrose was administered as 150 mg (3 ampules, each of 2.5 ml) in 100 ml of 0.9 percent normal saline infusion over 3 h every third day (Sacrofer IV).

In group B, Using the "Z" approach, daily intramuscular injections of 1.5 ml of iron sorbitol complex up to the estimated dosage were administered (Haempower injection IM). Every instance was watched for negative outcomes:

Follow up: After the course of therapy, the patients were told to make one visit on day 21. Both spontaneous complaints from patients and unfavorable effects that were detected were documented. Blood samples from both groups were taken for analysis in order to determine the efficacy parameters (serum ferritin, TIBC, median corpuscular volume, median corpuscular hemoglobin, median corpuscular hemoglobin concentration, median corpuscular volume, median corpuscular hemoglobin, PCV, and median hemoglobin level).

Statistical analysis: Using the SPSS software (Statistical Package for Social Science), version 26, the acquired data were processed and statistically evaluated. The Shapiro Walk test was performed to check the data for normal distribution. For both parametric and non-parametric variables, the student t test was employed to determine the variance between quantitative variables in two groups.

RESULTS

Student t test; *p is significant at <0.05

Table 1: Basic characteristics of the two investigated groups

Group A had an average age of 26.8 ±5.2 and group B 27.3± 5.3. Between the two study groups, there was no statistically substantial variation. The average BMI for group A was 25.1± 2.4 while for group B it was 25.4 ±2.3. Between the two study groups, there was no statistically substantial variation in BMI. (Table 1).

Fig. 1: Gestational age among the two studied groups

The median gestation ages for groups A and B were 20.9± 3.9 and 20.8± 4.2, respectively. Between the two study groups, there was no statistically substantial variation.

Chi square test; *p is significant at <0.05

Table 2: Abortion and previous surgery among the two studied groups

There were 84% and 80% had no history of abortion and 16% and 20% had previous history of abortion among group A and group B respectively. Regarding prior abortions, there was no statistical substantial variation between the two study groups. according prior surgery, there was no statistically substantial variation between the two study groups (Table 2).

Student t test; *p is substantial at <0.05

Table 3: Serum ferritin pretreatment among the two studied groups

according serum ferritin and TIBC pretreatment, there was no statistically substantial variation between the two study groups. (Table 3).

Student t test; *p is substantial at <0.05

Table 4: Comparison between the two groups according Hb, MCV, HCT, MCH, MCHC post treatment

Group A was statistically substantially greater than group B regarding Hb, MCV, HCT, MCH and MCHC post treatment (Table 4).

Student t test; *p is substantial at <0.05

Table 5: Comparison the two studied groups regarding serum ferritin post treatment.

Group A was statistically substantial higher regarding serum ferritin. Moreover, regarding post-treatment TIBC, there was no statistically substantial variation between the two study groups. (Table 5).

Student t test; *p is substantial at <0.05

Table 6: Comparison between lab results of the pre and post treatment among group A

Group A post treatment was statistically substantially higher than group A pre-treatment regarding Hb, MCV, HCT, MCH, MCHC and serum ferritin, however TIBC was statistically significantly lower in post-treatment compared to pre-treatment (Table 6).

Student t test; *p is substantial at <0.05

Table 7: Comparison between lab results of the pre and post treatment among group

Group B post treatment was statistically substantially higher than group B pre-treatment regarding Hb, HCT, MCH, MCHC and serum ferritin, however MCV was increased and TIBC was decreased post-treatment but without statistically significant difference (Table 7).

Fisher Exact test; *p is substantial at <0.05

Table 8: Adverse effect among the two studied groups

Anaphylactic reaction, constipation, diarrhea, local thrombophlebitis, myalgia, pain, and tachycardia & dyspnea were more prevalent in group A compared to group B but without statistically substantial difference. Moreover, fatigue, nausea, and upper GIT troubles were more prevalent in group B compared to group A but without statistically substantial difference. However, Brown pigmentation at site of injection was substantially more often in group B compared to group A (Table 8).