Efficacy

Pregnancy The rationale for iron supplementation during pregnancy in developing countries is based on a combination of considerations including the high prevalence of anemia in pregnancy (the majority of which is probably associated with iron deficiency), carefully conducted trials that show that consuming iron tablets during pregnancy improves maternal iron status, the higher maternal mortality risks associated with severe anemia, and the postulated risks of iron deficiency in pregnancy (i.e., increased risk of fatigue, cardiovascular stress, impaired resistance to infection, and poor tolerance to heavy blood loss and surgical interventions at delivery) and for fetal development. Although evidence supports the efficacy of iron supplementation in improving the iron status of pregnant women, no trials have examined the impact of iron supplementation on maternal mortality in severely anemic women. Also, there is a lack of causal evidence from controlled studies linking mild-to-moderate iron-deficiency anemia - which is much more prevalent than severe anemia - with an increased risk of low birth weight, preterm delivery, or obstetrical or perinatal complications.

Infancy Iron supplementation in infants is sometimes advised to prevent iron deficiency, even in populations with a relatively low prevalence of iron-deficiency anemia. The US Institute of Medicine, for example, recommends iron drops for exclusively breast-fed infants between 4 and 6 months of age. There is ample evidence from well-designed and controlled studies to show that iron supplementation in infancy significantly improves hemoglobin and ferritin levels, and studies are currently investigating the impact of iron supplementation on dimensions of cognitive development. The benefits and risks of infant iron supplementation, however, remain controversial, particularly in iron-replete children. This is because, although iron is an essential nutrient for adequate infant growth, immune function, and development, it may also contribute to a greater risk of infection if the excess iron increases a pathogen's access to free iron for its own growth and reproduction. Some studies have reported a higher prevalence of diarrhea in iron-supplemented infants, which calls into question the appropriateness of existing hemoglobin and ferritin cut-offs for defining true deficiency in infants and points to the need to clarify the cut-off issue in order to determine an appropriate age for starting iron supplementation.

Low-birth-weight infants Low-birth-weight infants are born with low iron stores and have higher iron requirements for growth. Their iron needs cannot be met from breast milk alone, and, therefore, they are a priority target for iron supplementation.

Preschooler and school-age children Several, but not all, placebo-controlled supplementation trials have demonstrated that iron supplements improve hemoglobin concentrations in preschoolers in developing countries, and there is substantial evidence that iron supplementation of anemic children improves their school performance and verbal and other skills.

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