RELATION BETWEEN MATERNAL ANEMIA AND IRON DEFICIENCY

Anemia as an undesirable health outcome
In maternal anemia and iron deficiency, the anemia itself is often regarded as an adverse outcome. Evidence is strong that in most undeveloped and in many developed countries, iron deficiency is the main cause of anemia in women and that iron supplementation under trial conditions prevents or corrects the anemia (3). In other words, there is evidence of a benefit or efficacy associated with iron supplementation. Consequently, large-scale iron supplementation programs during pregnancy are a common practice, although evidence of supplementation effectiveness has not been impressive (3, 4). The key argument supporting anemia as an outcome measure is related to the fact that red blood cells contain hemoglobin, which is an essential component of the respiratory system for oxygen transport. Any substantial reduction in red blood cells and hemoglobin reflects a reduced capacity of oxygen transport to tissue. Such a reduction in oxygen transport can be regarded as an adverse health outcome; thus, iron deficiency has a definite effect on health because of anemia (evidence of deficiency).

Anemia as a predictor of reproductive outcomes
In looking at pregnancy-related or reproductive outcomes, there has been a change from regarding anemia as an undesirable health outcome to regarding it as a predictor or cause of other adverse outcomes, ie, maternal and fetal mortality, preterm birth, and low birth weight. Two interesting issues have emerged from this change in perspective. One issue is that the association between mild-to-moderate anemia and other adverse reproductive outcomes is weak (evidence of risk only). Some studies found an association between anemia and adverse pregnancy outcomes, whereas other studies did not show a significant association (2). Additionally, the positive association observed in several epidemiologic studies does not establish a causal relation without the support of a plausible biological mechanism (5). Direct evidence showing that a reduction in anemia will lead to fewer adverse birth outcomes (evidence of benefit) is lacking. This leads to the question, Why provide iron supplementation if there is no evidence of beneficial reproductive outcomes? (2).

A second issue, which emerged from some of the same epidemiologic studies that found an association between anemia and a greater risk of poor birth outcomes, is that high hemoglobin values are significantly associated with poor birth outcomes (evidence of risk) (6–9). These observations raised the issue of whether we should be concerned about high hemoglobin concentrations during pregnancy. If higher than normal hemoglobin concentrations lead to poor birth outcomes, then a related question is, Should we be concerned about iron supplementation during pregnancy, given that iron supplementation can increase the hemoglobin concentration of some women? These issues are discussed below.

In examining the evidence related to high and low hemoglobin concentrations, it is important to evaluate the meaning of hemoglobin concentration. Is hemoglobin concentration a predictor or risk factor for poor pregnancy outcomes as used in epidemiologic studies (a potential cause), or is it a physiologic variable that can be regarded as an outcome in itself (a consequence)?