Treatments for iron-deficiency anaemia in pregnancy
Although the best method of treating anaemia has not been clarified in this review, in theory oral treatment is the most feasible option, and therefore it is likely to remain the most widely used approach. Intravenous iron administration was associated with a higher risk of venous thrombosis than intramuscular administration.
RHL Commentary by Walraven G
1. EVIDENCE SUMMARY
This review examines the effectiveness on maternal and neonatal morbidity and mortality, haematological parameters and side-effects of different treatments for iron-deficiency anaemia in pregnancy. Hundred-and-one trials of treatment for this condition were identified. Seventeen of these, involving 2578 women in total, met the reviewers' inclusion criteria. Most of the remaining trials were excluded because they were not truly randomized or had other methodological shortcomings.
The review was complicated by the lack of common definitions of iron-deficiency anaemia, lack of agreement on the tests to be used in diagnosing the condition and the cut-off points for diagnosing iron-deficiency in pregnancy, especially in the presence of other causes of anaemia and a co-existing infection. Few of the studies assessed clinical outcomes, and these randomized controlled trials (RCTs) were too small to estimate important clinical effects.
In one trial (n=125) conducted in West Java, Indonesia, oral iron supplementation for anaemia in pregnancy was compared with a placebo (1). This trial showed a reduction in anaemia and higher mean haemoglobin and serum ferritin levels in the iron supplementation group. The addition of vitamin A to iron supplementation improved the results of the therapy. Unfortunately, the study evaluated the outcome at the end of treatment during the second trimester of pregnancy, and not at term (or at least the third trimester), which would have been more appropriate.
Comparison of different treatments showed that intravenous (IV) iron administration was associated with a higher risk of venous thrombosis than intramuscular (IM) administration, but the IM route resulted in pain at the injection site more frequently. Skin coloration was more frequently observed in people receiving IM iron-dextran compared with IM iron-sorbitol. As expected, women taking oral iron preparations complained of nausea and constipation more frequently than those receiving IV preparations. Pooled estimates (two RCTs, 137 women) for haemoglobin levels at four weeks favoured IV iron treatments compared with oral iron (2,3).
On the basis of this review, no recommendation can be made regarding how to treat iron-deficiency anaemia in pregnancy.
Both the search strategy and the strategy for extracting the data were appropriate.
2. RELEVANCE TO UNDER-RESOURCED SETTINGS
2.1. Magnitude of the problem
The prevalence of anaemia in pregnancy (haemoglobin below 11 g/dL) in many developing countries is high, with reported rates of 35–75% (4). A United Nations expert panel considered severe anaemia (<7 g/dL) an associated cause in up to half of maternal deaths worldwide (5). At least half of all anaemia cases have been attributed to iron deficiency (6). In many developing countries endemic problems such as malaria and helminth infections, together with the problem of poor nutrition make anaemia one of the most common pathologies in pregnancy.
2.2. Feasibility of the intervention
In order to identify anaemia in pregnancy, an accurate method for measuring haemoglobin levels is needed. Many clinics in developing countries, especially those in sub-Saharan Africa, rely only on conjunctival inspection. The WHO Colour Scale might still be useful, especially at the primary health care level as a screening tool despite observed limitations in accuracy (7, 8). The routine measurement of serum ferritin—a better indicator of body iron stores than haemoglobin concentration—is unrealistic for most of the low-income countries.
Although the best method of treating anaemia has not been clarified in this review, oral treatment is in theory the most feasible and therefore likely to remain the most widely used. The side-effects of oral iron administration or women’s dislike of the tablets owing to smell or taste have often been blamed for treatment failure, although a literature review found that side-effects accounted for only 10% of non-compliance. Rather, in most cases, women did not take their tablets because they never received them or received inadequate quantities (9).
Mostly anecdotal evidence suggests that IV and IM iron administration is associated with allergic reactions and allergic shock. Compared with IM iron sucrose, IV iron sucrose significantly increased haematological indices, but it is unclear what the effects are on maternal and neonatal morbidity. In addition, there is uncertainty whether IV iron sucrose may increase the incidence of serious adverse effects such as venous thromosis, which were frequent in the studies (9/41; 22%). The use of non-sterile injection equipment and blood transfusion are associated with the risk of transmission of parasites and viruses such as HIV and hepatitis.
2.3. Applicability of the results of the Cochrane Review
On the basis of this review no recommendation can be made regarding the treatment of iron-deficiency anaemia in pregnancy in developing countries and therefore the applicability of the results cannot be considered.
2.4. Implementation of the intervention
The need to avoid blood transfusions to treat severe anaemia makes the prevention and treatment of mild-to-moderate anaemia of utmost importance. The Cochrane Review on routine iron supplementation in pregnancy concludes that the available data from controlled trials provide evidence of an improvement in haematological indices in women receiving preventative iron supplementation, but also here there is not enough information available on clinical maternal and infant outcomes and this will need further assessment (10). Unpleasant side-effects of iron supplementation, inadequate availability of tablets, a misguided perception among health workers that anaemia is not a serious problem, and insufficient supplementation owing to late consultation for antenatal care are all obstacles to running a successful programme. The impact of community- or clinic-based supplementation can be improved by counselling on why, how, and when to take iron tablets and by supplying sufficient tablets in a timely manner (11).
The causes of anaemia will vary from region to region and these are in general, more or less documented. There is, however, a need for consensus on the cut-off points for mild, moderate, and severe iron-deficiency anaemia.
Good quality clinical trials need to be done urgently, especially to study interventions for severe iron-deficiency anaemia in pregnant women (haemoglobin levels less than < 7 g/dL without signs of imminent heart failure). In such trials different treatments and routes of administration should be compared for well-defined laboratory values, side-effects, and especially the effects on maternal and neonatal morbidity and mortality.
- Suharno D, West CE, Muhalil, Karyadi D, Hautvast JG. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. The lancet 1993;342:1325-1328.
- Al RA, Unlubilgin E, Kandemir O, Yalvac S, Cakir L, Haberal A. Intravenous versus oral iron for treatment of anemia in pregnancy: a randomized trial. Obstetrics & Gynecology 2005; 106: 1335-40.
- Bayoumeu F, Subiran-Buisset C, Baka NE, Legagneur H, Monnier-Barbarino P, Laxenaire MC. Iron therapy in iron-deficiency anemia in pregnancy : intravenous route versus oral route. American Journal of Obstetrics and Gynecology 2002; 186:518-22.
- World Health Organization. The prevalence of anaemia in women: a tabulation of available information. Geneva, WHO 1992; (WHO/MCH/MSM/92.2):119-124.
- Controlling iron deficiency. A report based on an Administrative Committee on Coordination/Subcommittee on Nutrition workshop. Nutrition-State-of-the-Art Series. Nutrition Policy Discussion Paper No 9. Geneva, United Nations. 1991.
- Van den Broek NR, Letsky EA, White SA, Shenkin A. Iron status in pregnant women: which measurements are valid. British Journal of Haematology 1998;103:817-824.
- World Health Organization. Haemoglobin colour scale: a practical answer to a vital need. WHO Department of blood safety and clinical technology, Geneva, 2001.
- Gies S, Brabin BJ, Yassin MA, Cuevas LE. Comparison of screening methods for anaemia in pregnant women in Awassa, Ethiopia. Tropical Medicine and International Health 2003;8:301-9.
- Galloway R, McGuire J. Determinants of compliance with iron supplementation: supplies, side effects, or psychology. Social science and medicine 1994;39:381-390.
- Pena-Rosas JP, Viteri FE. Effects of routine oral iron supplementation with or without folic acid for women during pregnancy (Cochrane Review). In: The Cochrane Database Syst Rev, 2006;3:CD004736.
- Menendez C, Todd J, Alonso PL et al . The effects of iron supplementation during pregnancy, given by traditional birth attendants, on the prevalence of anaemia and malaria. Transactions of the royal society of tropical medicine and hygiene 1994;88:590-593.
This document should be cited as: Walraven G. Treatments for iron-deficiency anaemia in pregnancy: RHL commentary (last revised: 20 June 2007). The WHO Reproductive Health Library; Geneva: World Health Organization.