Several possible mechanisms associate iron deficiency anemia with poor cognitive development in children. Compared to children without anemia, anemic children tend to move around and explore their environment less, which may lead to developmental delays (12). Conduction of auditory and optic nerve impulses to the brain has been found to be slower in children with iron deficiency anemia. Neurotransmitter synthesis may also be sensitive to iron deficiency (13).

Although most observational studies have found relationships between iron deficiency anemia in children and poor cognitive development, poor school achievement, and behavior problems, it is difficult to separate the effects of iron deficiency anemia from other types of deprivation in such studies.

 
Only one randomized controlled trial found a significant benefit of iron supplementation on indices of cognitive development in anemic children under the age of 2 years. Four randomized controlled trials found a significant benefit of iron supplementation on cognition and school achievement in children over 2 years of age, while two studies found no effect.

Lead toxicity

A number of epidemiological studies have found iron deficiency to be associated with increased intestinal absorption of and blood levels of lead in young children.

However, the use of iron supplementation in lead poisoning should be reserved for those individuals who are truly iron deficient or who experience long-lasting lead exposure, such as continued residence in lead-exposed housing (3, 14).

Pregnancy complications

Epidemiological studies provide strong evidence of an association between severe anemia in pregnant women and adverse pregnancy outcomes, such as low birth weight, premature birth, and maternal mortality. Iron deficiency can be a major contributory factor to severe anemia, but evidence that iron deficiency anemia is a causal factor in poor pregnancy outcomes is still lacking (15, 16).

Nevertheless, most experts consider the control of maternal anemia to be an important part of prenatal health care.

 
Elevated hemoglobin, especially in later pregnancy, is also associated with poor pregnancy outcomes, but there is no evidence that this association is related to high iron intakes or iron supplementation (16).

Impaired immune function

Sufficient iron is critical to several immune functions, including the differentiation and division of white blood cells (e.g., 'T lymphocytes') and the generation of highly reactive oxygen molecules by iron-dependent enzymes, which are used for killing pathogens (13). Despite the critical functions of iron in the immune response, the nature of the relationship between iron deficiency and susceptibility to infection, especially with respect to malaria, remains controversial. 

In vitro studies in cell culture and animal studies suggest that the survival of infectious agents that spend part of their life cycle within host cells, such as plasmodia (malaria) and mycobacteria (tuberculosis) may be enhanced by iron therapy; thus, high-dose iron supplementation of children residing in the tropics has been associated with increased risk of clinical malaria and other infections, such as pneumonia.

 
Controlled clinical studies are needed to determine the appropriate use of iron supplementation in regions where malaria is common, as well as in the presence of infectious diseases such as HIV, tuberculosis, and typhoid (17).