Iron deficiency anaemia, the late manifestation of chronic iron deficiency, is the most common nutrient deficiency among pregnant women (WHO 1992). Iron deficiency is caused by an insufficient supply of iron to the cells following depletion of the body's reserves (Viteri 1998). The main causes of iron deficiency are a diet poor in absorbable iron, an increased requirement for iron (e.g. pregnancy) or a loss of iron due to parasitic infections (Crompton 2002; INACG 2002b).

Although haemoglobin and haematocrit are commonly used to screen for iron deficiency, their low values are not specific to iron deficiency. Anaemia in pregnancy is diagnosed if haemoglobin (Hb) concentration is lower than 110 g/L during the first and third trimesters or lower than 105 g/L during the second trimester. Iron deficiency anaemia is defined as anaemia accompanied with depleted iron stores and signs of a compromised supply of iron to the tissues (WHO 2001). Iron deficiency can be identified using laboratory tests such as serum ferritin, serum iron, transferrin and transferrin receptors. However, these tests are often not readily available and have limitations in their interpretation in some settings and conditions. Each test does not correlate closely with one another because each reflects a different aspect of iron metabolism. The use of multiple indicators is useful for population‐based assessments of iron deficiency anaemia, when this is feasible.

The consequences of iron deficiency anaemia are serious and can include diminished intellectual and productive capacity (Hunt 2002) and possibly increased susceptibility to infections (Oppenheimer 2001). During pregnancy, low Hb levels, indicative of moderate (between 70 and 90 g/L) or severe anaemia (less than 70 g/L), are associated with maternal and child mortality and infectious diseases (INACG 2002a). Also, low Hb levels may be associated with low birthweight, heavier placentas and increased frequency of prematurity. Favourable pregnancy outcomes occur 30% to 45% less often in anaemic mothers, and their infants have less than one half of normal iron reserves. Iron deficiency affects adversely the cognitive performance and development and physical growth of these infants (WHO 2001). High haemoglobin levels (greater than 130 g/L) have also been associated with negative pregnancy outcomes (Hytten 1964; Hytten 1971; Murphy 1986; Scholl 1997).

The association between iron deficiency without anaemia and adverse perinatal outcomes is less clear. Some studies have shown an association between iron deficiency and preterm delivery and subsequent low birthweight, inadequate pregnancy weight gain, and decreased defences against infections (Garn 1981; Prema 1982; Kandoi 1991; Scholl 1992).

Interventions to control iron deficiency and iron deficiency anaemia include education, control of parasitic infections, improvement of sanitation, iron supplementation and iron fortification (INACG 1977). The amount of iron that can be absorbed from diet alone is insufficient to cover the increased iron requirements during pregnancy. Most women would need additional iron as well as sufficient iron stores to prevent iron deficiency (Bothwell 2000). Thus, direct iron supplementation has been extensively used in most low‐ and middle‐income countries as an intervention to combat iron deficiency and anaemia during pregnancy. It has been recommended that iron supplements also contain folic acid, an essential B‐vitamin. The rationale for this combination lies in the need of folic acid to cover the increased requirements of pregnancy, due to the rapidly dividing cells in the fetus and elevated urinary losses.

There is evidence to show that iron supplementation with or without folic acid during pregnancy results in a substantial reduction of women with haemoglobin levels less than 100 g/L in late pregnancy, at delivery and six weeks postpartum (Mahomed 2003a; Mahomed 2003b; Villar 2003). However, the impact of iron supplementation interventions under field conditions has been limited and its effectiveness questioned (Beaton 1999). The failure has been attributed to inadequate infrastructure and poor compliance (Mora 2002) although few studies have evaluated this issue adequately. It has been suggested that the problem may reside in the sole expectation of this intervention to improve haemoglobin concentration, rather than maternal or infant health (Beaton 2000).

International organizations have been advocating routine iron and folate supplementation for every pregnant woman in areas of high anaemia prevalence (Villar 1997; Beard 2000). While iron supplementation with or without folic acid has been used in a variety of doses and regimens, current recommendations include the provision of a daily dose of 60 mg of iron for pregnant, non‐anaemic women if supplementation for more than six months is possible and an increased dose of 120 mg of iron daily if the duration of supplementation is shorter or the women are anaemic (INACG 1998). This supplement should include 400 µg of folic acid or lower doses if this amount is not available.

Less frequent regimens of supplementation, such as weekly or fortnightly with iron alone or in conjunction with folic acid, have been evaluated in the last decade as a promising innovative regimen. The rationale is that taking iron less frequently increases compliance due to fewer side‐effects, particularly gastrointestinal effects (heartburn, nausea, vomiting, diarrhoea, or constipation). However, some authors have questioned this belief indicating that the main reason for the poor compliance with the programs is the unavailability of iron supplements for the targeted women (Galloway 1994). Recently, other potentially detrimental effects have been associated with excess iron intake (i.e. cell damage from the production of reactive oxygen species) and with higher levels of haemoglobin concentrations (Casanueva 2003).

This review will combine the two currently published Cochrane Reviews on iron and iron and folate supplementation that have clearly shown improvements on biochemical and haematological parameters, and evaluate the issues related to alternative doses and periodicity as well as the potential hazards of these interventions (Mahomed 2003a; Mahomed 2003c).