Iron supplements taken one, two or three times a week for preventing anaemia and its consequences in menstruating women

Approximately one out of three non-pregnant women of reproductive age are anaemic worldwide. Although causes of anaemia are multiple, it very often results from sustained iron deficiency. Being anaemic makes women more likely to suffer infections and to have a diminished physical and work performance. If they become pregnant, they may also have a greater risk of having low birth weight babies and other complications during delivery.

Daily iron supplementation (sometimes combined with folic acid and other vitamins and minerals) for three months has traditionally been the standard practice to prevent or treat anaemia in women, but its use has been limited as it is frequently associated with side effects such as nausea, teeth staining or constipation. Intermittent supplementation (that is the consumption of supplements one, two or three times a week on non-consecutive days) has been proposed as an effective and safer alternative to daily supplementation. It has been suggested that intermittent regimens increase haemoglobin concentrations with fewer negative side effects and this may encourage women to adhere better to the intervention for a longer period. In this review we included studies examining the administration of intermittent iron supplements versus no intervention, a placebo or the same supplements given on a daily basis.

This review includes 21 randomised controlled trials involving 10,258 women. Although the quality across trials was variable, the findings suggest that women receiving intermittent supplementation with iron alone or in combination with folic acid or other nutrients were less likely to be anaemic and had higher haemoglobin and ferritin concentrations than those women who received no iron supplements or a placebo. However, intermittent supplementation was less effective than daily supplementation in preventing or controlling anaemia. Information on disease outcomes, adherence, side effects, economic productivity and work performance is scarce and the evidence about the effects of intermittent supplementation on them is unclear.

Overall, whether the supplements were given once or twice weekly, for less or more than three months, contained less or more than 60 mg of elemental iron per week, or to populations with different degrees of anaemia at baseline did not seem to affect the findings. Furthermore, the response did not differ in areas where malaria is frequent, although very few trials were conducted in these settings.

Authors' conclusions: 

Intermittent iron supplementation in menstruating women is a feasible intervention in settings where daily supplementation is likely to be unsuccessful or not possible. In comparison with daily supplementation, the provision of iron supplements intermittently is less effective in preventing or controlling anaemia. More information is needed on morbidity (including malaria outcomes), side effects, work performance, economic productivity, depression and adherence to the intervention.

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Background: 

Daily iron supplementation has been traditionally a standard practice for preventing and treating anaemia but its long term use has been limited as it has been associated with adverse side effects such as nausea, constipation and teeth staining. Intermittent iron supplementation has been suggested as an effective and safer alternative to daily iron supplementation for preventing and reducing anaemia at population level, especially in areas where this condition is highly prevalent.

Objectives: 

To assess the effects of intermittent oral iron supplementation, alone or in combination with other nutrients, on anaemia and its associated impairments in menstruating women, compared with no intervention, a placebo or daily supplementation.

Search strategy: 

We searched the following databases in May 2011: CENTRAL (The Cochrane Library 2011, Issue 2), MEDLINE (1948 to May Week 3, 2011), EMBASE (1980 to 2011 Week 20), CINAHL (1937 to current), POPLINE (all available years), Science Citation Index (1970 to 27 May 2011), BIOSIS Previews (1969 to current), and CPCI-S (1990 to 27 May 2011). On 7 July 2011 we searched all available years in the following databases: SCIELO, LILACS, IBECS and IMBIOMED, the Networked Digital Library of Theses and Dissertations, metaRegister and the WHO International Clinical Trials Registry Platform (ICTRP). We also contacted relevant organisations (on 11 October 2011) to identify ongoing and unpublished studies.

Selection criteria: 

Randomised and quasi-randomised trials with either individual or cluster randomisation. Participants were menstruating women, that is women beyond menarche and prior to menopause who were not pregnant or lactating and did not have a known condition that impeded the presence of menstrual periods. The intervention was the use of iron supplements intermittently (one, two or three times a week on non-consecutive days) compared with no intervention, a placebo, or the use of same supplements on a daily basis.

Data collection and analysis: 

Two review authors independently assessed the eligibility of studies against the inclusion criteria, extracted data from included studies, checked data entry for accuracy and assessed the risk of bias of the included studies.

Main results: 

We included 21 trials involving 10,258 women. Although the quality across trials was variable, the results consistently show that in comparison with no intervention or a placebo, intermittent iron supplementation (alone or with any other vitamins and minerals) reduces the risk of having anaemia (RR 0.73; 95% CI 0.56 to 0.95, 10 trials) and improves the concentration of haemoglobin (MD 4.58 g/L; 95% CI 2.56 to 6.59, 13 trials) and ferritin (MD 8.32 μg/L; 95% CI 4.97 to 11.66, six trials). However, in comparison with daily supplementation, women receiving supplements intermittently presented anaemia more frequently (RR 1.26; 95% CI 1.04 to 1.51, six trials), despite achieving similar haemoglobin concentrations on average (MD -0.15 g/L; 95% CI -2.20 to 1.91, eight trials).

Information on disease outcomes, adherence, side effects, economic productivity and work performance is scarce and the evidence about the effects of intermittent supplementation on them is unclear.

Overall, whether the supplements were given once or twice weekly, for less or more than three months, contained less or more than 60 mg of elemental iron per week, or to populations with different degrees of anaemia at baseline did not seem to affect the findings. Furthermore, the response did not differ in areas where malaria is frequent, although very few trials were conducted in these settings.

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