Consequences of Iron Deficiency and Iron Deficiency Anemia

Iron deficiency anemia has been implicated in adverse pregnancy outcomes, maternal and infant mortality, cognitive dysfunction and developmental delays in infants and children, and compromised physical capacity in children and adults. However, data to support causal relationships with some of these outcomes is limited, and the extent to which outcomes are associated with iron deficiency specifically or more generally with anemia regardless of the etiology is the subject of debate.

A variety of observational studies demonstrate an association of maternal hemoglobin concentrations during pregnancy with birth weight, the likelihood of low birth weight and preterm birth, and perinatal mortality, such that adverse pregnancy outcomes are associated in a 'U-shaped' manner with the lowest and highest maternal hemoglobin concentrations. Anemia during pregnancy may not be specific to iron deficiency, and randomized trials utilizing a strict placebo to firmly establish a causal link between iron status per se and adverse pregnancy outcomes are rare because of ethical concerns about denying women iron supplements during pregnancy. However, two randomized trials, one conducted in a developed country and the other in a developing country, have shown a positive impact of iron supplementation during pregnancy on birth weight. In the developed country study, control women with evidence of compromised iron stores were offered iron supplements at 28 weeks of gestation after 8 weeks of randomized iron supplementation. In the developing country study, the control group received supplemental vitamin A and the intervention group received folic acid in addition to iron.

Mortality among pregnant women and infants and children also increases with severe anemia. However, most data showing this relationship are observational and clinic based. Anemia in such circumstances is unlikely to be attributable to iron deficiency alone; furthermore, the degree to which mild to moderate anemia influences mortality outcomes is not well established.

Iron deficiency and iron deficiency anemia have been associated with impaired cognitive development and functioning. These effects of iron deficiency may be mediated in part by the deprivation of functional iron in brain tissue, and the impact of iron deprivation may vary depending on its timing in relation to critical stages of brain development. Iron interventions in anemic school-age children generally result in improved school performance. The results of iron interventions in infants and preschool-age children are less clear, perhaps in part because cognition is more difficult to measure in this age group.

Studies have shown a negative impact of iron deficiency anemia on work productivity among adult male and female workers in settings requiring both strenuous labor (rubber plantation) and less intensive efforts (factory work). The impact of iron deficiency anemia on performance may be mediated by a reduction in the oxygen-carrying capacity of blood associated with low hemoglobin concentration and by a reduction in muscle tissue oxidative capacity related to reductions in myoglobin and effects on iron-containing proteins involved in cellular respiration.

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