Iron prophylaxis in pregnancy: Intravenous route versus oral route

doi:10.1016/j.ejogrb.2009.03.006

European Journal of Obstetrics & Gynecology and Reproductive Biology

Volume 144, Issue 2, June 2009, Pages 135-139

https://doi.org/10.1016/j.ejogrb.2009.03.006 Get rights and content

Abstract

Objective

To assess and compare the efficacy and safety of two and three doses of intravenous iron sucrose with daily oral ferrous sulphate in the prophylaxis of iron deficiency anaemia in pregnant women.

Study design

260 women with singleton pregnancy who met inclusion criteria and who gave informed consent were randomised between the 21st and 24th week into either the intravenous iron group or the oral iron group. Of 130 women in the intravenous iron group, 75 women received two doses of 200 mg iron sucrose and 55 three doses of 200 mg iron sucrose. The first dose was administered between the 21st and 24th gestational weeks, the second between the 28th and 32nd and the third between the 35th and 37th. The women of the oral group were given oral tablets of 80 mg ferrous sulphate daily, beginning on the day of study enrolment and stopping on the day of delivery.

Results

There was a non-significant trend to a higher frequency of responders (haemoglobin ≥ 11 g/dl) in the intravenous iron group (75 vs. 80%). There was a significant difference of repleted iron stores before delivery (ferritin > 50 μg/l) in the group with three intravenous iron doses in comparison to the oral iron group (49 vs. 14%; p < 0.001). No differences were observed in regard to maternal and perinatal outcomes.

Conclusions

There was no clinically significant difference in the haematological, maternal and foetal outcomes in the parenteral route of iron prophylaxis in pregnant women.

Introduction

Anaemia is the most common medical disorder in pregnancy. Over 90% of anaemia is due to red-cell iron deficiency associated with depleted stores and deficient iron intake [1]. Anaemia leads to an increased length of hospitalisation, and to an increased risk of blood transfusion during the peripartum and postpartum period, and so increases the risk of transmission of infectious diseases in countries with insufficient transfusion programmes [2], [3]. In previous studies it was shown that haemoglobin (Hb) levels under 9.0 g/dl are related to adverse maternal and neonatal outcomes as preterm delivery and low birthweight [4], [5], [6], [7].

Systematic iron prophylaxis during pregnancy has been debated [8], [9], [10]. The first choice in the prophylaxis of iron deficiency anaemia for almost all women is oral iron replacement because of its effectiveness, safety, and low cost. But long-term oral prophylaxis can produce side effects, in particular on the digestion [11]. Coupled with digestive side effects and with the attention needed for daily self-dosing, poor compliance often results. However, Milman et al. showed that a supplement of 80 mg of ferrous iron or less does not have documented side effects [12]. On the other hand, although iron absorption may be adequate in healthy, iron-replete women, it is far below the iron requirement of iron-depleted or iron-deficient pregnant women [11], [13]. In addition, even women who respond well to oral supplementation require a period of months to reach target Hb.

Section snippets

Study design and randomisation

The study, conducted between 2003 and 2005, was an open, randomised, active-controlled, phase IV, single-centre clinical trial carried out at the Department of Obstetrics, Zurich University Hospital, Switzerland. The aim was to assess and compare the efficacy and safety of two and three doses of intravenous iron sucrose with daily oral ferrous sulphate in the prophylaxis of iron deficiency anaemia in pregnant women. The study was approved by the Human Research Ethics Committee at the Women's

Results

Of 130 women allocated to intravenous iron prophylaxis, 20 women were excluded from analysis due to lost to follow-up or discontinued prophylaxis. In the oral group, 11/130 women were excluded. The final analysis was performed on 229 women. The demographic and clinical characteristics of the study group are shown in Table 1. There was no difference between these groups according to age, gravidity, parity, BMI and blood pressure.

The haematological data before delivery are shown in Table 2. There

Discussion

The present study is the first to evaluate the efficacy and safety of intravenous iron sucrose in the prophylaxis of iron deficiency anaemia during pregnancy. On the basis of our results, there is no clinically significant benefit for the parenteral route in iron prophylaxis of anaemia. Stimulation of erythropoiesis as evidenced by an increase in haemoglobin and haematocrit was observed in subjects of the intravenous iron as well as of the oral iron group. Serum ferritin, which is the best

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Cited by (42)

Safety and effectiveness of intravenous iron sucrose versus standard oral iron therapy in pregnant women with moderate-to-severe anaemia in India: a multicentre, open-label, phase 3, randomised, controlled trial
2019, The Lancet Global Health
Citation Excerpt :
Evidence on the effect of intravenous iron sucrose on improvement in haemoglobin concentration is conflicting. Although a large body of evidence demonstrates significant improvement in haemoglobin concentration (ranging from 2 g/dL to 3 g/dL) 4–6 weeks after the start of therapy with both intravenous and oral therapy,27–29 others have shown no significant increase with intravenous therapy.13,21,30,31 The conflicting results could be due to small sample sizes (n=75–270) and high average baseline haemoglobin concentration (8–10 g/dL).
Intravenous iron sucrose is a promising therapy for increasing haemoglobin concentration; however, its effect on clinical outcomes in pregnancy is not yet established. We aimed to assess the safety and clinical effectiveness of intravenous iron sucrose (intervention) versus standard oral iron (control) therapy in the treatment of women with moderate-to-severe iron deficiency anaemia in pregnancy.
We did a multicentre, open-label, phase 3, randomised, controlled trial at four government medical colleges in India. Pregnant women, aged 18 years or older, at 20–28 weeks of gestation with a haemoglobin concentration of 5–8 g/dL, or at 29–32 weeks of gestation with a haemoglobin concentration of 5–9 g/dL, were randomly assigned (1:1) to receive intravenous iron sucrose (dose was calculated using a formula based on bodyweight and haemoglobin deficit) or standard oral iron therapy (100 mg elemental iron twice daily). Logistic regression was used to compare the primary maternal composite outcome consisting of potentially life-threatening conditions during peripartum and postpartum periods (postpartum haemorrhage, the need for blood transfusion during and after delivery, puerperal sepsis, shock, prolonged hospital stay [>3 days following vaginal delivery and >7 days after lower segment caesarean section], and intensive care unit admission or referral to higher centres) adjusted for site and severity of anaemia. The primary outcome was analysed in a modified intention-to-treat population, which excluded participants who refused to participate after randomisation, those who were lost to follow-up, and those whose outcome data were missing. Safety was assessed in both modified intention-to-treat and as-treated populations. The data safety monitoring board recommended stopping the trial after the first interim analysis because of futility (conditional power 1·14% under the null effects, 3·0% under the continued effects, and 44·83% under hypothesised effects). This trial is registered with the Clinical Trial Registry of India, CTRI/2012/05/002626.
Between Jan 31, 2014, and July 31, 2017, 2018 women were enrolled, and 999 were randomly assigned to the intravenous iron sucrose group and 1019 to the standard therapy group. The primary maternal composite outcome was reported in 89 (9%) of 958 patients in the intravenous iron sucrose group and in 95 (10%) of 976 patients in the standard therapy group (adjusted odds ratio 0·95, 95% CI 0·70–1·29). 16 (2%) of 958 women in the intravenous iron sucrose group and 13 (1%) of 976 women in the standard therapy group had serious maternal adverse events. Serious fetal and neonatal adverse events were reported by 39 (4%) of 961 women in the intravenous iron sucrose group and 45 (5%) of 982 women in the standard therapy group. At 6 weeks post-randomisation, minor side-effects were reported by 117 (16%) of 737 women in the intravenous iron sucrose group versus 155 (21%) of 721 women in the standard therapy group. None of the serious adverse events was found to be related to the trial procedures or the interventions as per the causality assessment made by the trial investigators, ethics committees, and regulatory body.
The study was stopped due to futility. There is insufficient evidence to show the effectiveness of intravenous iron sucrose in reducing clinical outcomes compared with standard oral iron therapy in pregnant women with moderate-to-severe anaemia.
WHO, India.
How I treat anemia in pregnancy: Iron, cobalamin, and folate
2017, Blood
Citation Excerpt :
IV iron is superior to oral iron in achieving a sustained Hb response, reducing the need for packed RBC transfusions and improving quality of life for chronic heart failure,43 inflammatory bowel disease,44 chronic kidney diseases and hemodialysis,45 and cancer-related anemia.46 Several authors have reported that parenteral iron therapy in pregnancy and postpartum is associated with a more rapid increase in Hb and/or better replenishment of iron stores than is oral therapy.18,47-54 Patient 1 had Crohn ileitis, a history of menorrhagia, and may have started the pregnancy with suboptimal iron stores.
Anemia of pregnancy, an important risk factor for fetal and maternal morbidity, is considered a global health problem, affecting almost 50% of pregnant women. In this article, diagnosis and management of iron, cobalamin, and folate deficiencies, the most frequent causes of anemia in pregnancy, are discussed. Three clinical cases are considered. Iron deficiency is the most common cause. Laboratory tests defining iron deficiency, the recognition of developmental delays and cognitive abnormalities in iron-deficient neonates, and literature addressing the efficacy and safety of IV iron in pregnancy are reviewed. An algorithm is proposed to help clinicians diagnose and treat iron deficiency, recommending oral iron in the first trimester and IV iron later. Association of folate deficiency with neural tube defects and impact of fortification programs are discussed. With increased obesity and bariatric surgery rates, prevalence of cobalamin deficiency in pregnancy is rising. Low maternal cobalamin may be associated with fetal growth retardation, fetal insulin resistance, and excess adiposity. The importance of treating cobalamin deficiency in pregnancy is considered. A case of malarial anemia emphasizes the complex relationship between iron deficiency, iron treatment, and malaria infection in endemic areas; the heightened impact of combined etiologies on anemia severity is highlighted.
The safety of intravenous iron preparations: Systematic review and meta-analysis
2015, Mayo Clinic Proceedings
Citation Excerpt :
The literature search identified 5326 publications; of them, 164 were potentially eligible publications on IV iron therapy. A total of 103 trials16,24-125 published from January 1, 1966, through December 31, 2013, fulfilled the inclusion criteria (Figure). Pooled together, 10,390 patients treated with IV iron were compared with 4044 patients treated with oral iron, 1329 treated with no iron, 3335 treated with placebo, and 155 treated with IM iron.
To amass all available evidence regarding the safety of intravenous (IV) iron preparations to provide a true balance of efficacy and safety.
Systematic review and meta-analysis of all randomized clinical trials comparing IV iron to another comparator. All electronic databases until January 1, 2014, were reviewed. Primary outcome was occurrence of severe adverse events (SAEs). Secondary outcomes included all-cause mortality and other adverse events (AEs). Subgroup analysis was performed on the basis of type of IV iron, comparator, treated condition, and system involved.
A total of 103 trials published between 1965 through 2013 were included. A total of 10,390 patients were treated with IV iron compared with 4044 patients treated with oral iron, 1329 with no iron, 3335 with placebo, and 155 with intramuscular iron. There was no increased risk of SAEs with IV iron (relative risk [RR], 1.04; 95% CI, 0.93-1.17; I²=9%). Subgroup analysis revealed a decreased rate of SAEs when IV iron was used to treat heart failure (RR, 0.45; 95% CI, 0.29-0.70; I²=0%). Severe infusion reactions were more common with IV iron (RR, 2.47; 95% CI, 1.43-4.28; I²=0%). There was no increased risk of infections with IV iron. Gastrointestinal AEs were reduced with IV iron.
Intravenous iron therapy is not associated with an increased risk of SAEs or infections. Infusion reactions are more pronounced with IV iron.
Clinical outcome post treatment of anemia in pregnancy with intravenous versus oral iron therapy: a systematic review and meta-analysis
2024, Scientific Reports
Intravenous ferric derisomaltose versus oral iron for persistent iron deficient pregnant women: a randomised controlled trial
2023, Archives of Gynecology and Obstetrics
DIAGNOSIS OF ANEMIA AND THE PROPER MEDICATION FOR ITS MANAGEMENT IN POPULATION OF ALSAMAWAH CITY, IRAQ
2023, Community Practitioner

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^☆: Clinical trial registration: VEN-ZHPRO 2003 DR 4219. Trial title: Efficacy of intravenous Venofer^® compared with oral Tardyferon^® in the prophylaxis of iron deficiency anaemia in pregnant women: an open randomised study.

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Iron prophylaxis in pregnancy: Intravenous route versus oral route☆

Abstract

Objective

Study design

Results

Conclusions

Introduction

Section snippets

Study design and randomisation

Results

Discussion

Eur J Obstet Gynecol Reprod Biol

Am J Clin Nutr

Int J Gynaecol Obstet

Eur J Obstet Gynecol Reprod Biol

Int J Gynaecol Obstet

Am J Clin Nutr

Am J Clin Nutr