Overview of Interventions for Controlling Iron Deficiency Anemia

Iron Supplements in Context

A varied array of interventions exist that are designed to prevent and correct iron deficiency anemia. These include dietary improvement, fortification of foods with iron, iron supplementation, and other public health measures, such as helminth control. All of these approaches improve iron status in some contexts. The appropriate use of iron supplements will be an important part of anemia control programs in almost all contexts, but supplements should be viewed as one of several tools in the battle against iron deficiency anemia.

In many populations, the amount of iron absorbed from the diet is not sufficient to meet many individuals' requirements. This is especially likely to be true during infancy and pregnancy, when physiological iron requirements are the highest. If the amount of absorbable iron in the diet cannot be immediately improved, iron supplementation will be a necessary component of programs to control iron deficiency anemia. This will almost always be the case for children 6-24 months of age and pregnant women.

The priority among target groups for iron supplementation is based on the likelihood of both iron deficiency and the public health benefits resulting from its control. Pregnant and postpartum women and children 6-24 months of age are the priority target groups for both reasons. Where anemia is very prevalent, supplementation would also benefit women of reproductive age, preschool children, school-age children, and adolescents, and this might be a reasonable strategy. In these target groups, the decision to supplement will likely depend most on feasibility, which might be highest in a daycare or school setting for children and adolescents or in a workplace setting for women.

Iron supplements are essential for the rapid treatment of severe iron deficiency anemia in all sex and age groups. With proper training, health workers can assess very low hemoglobin levels or extreme pallor with reasonable sensitivity and high specificity. Where severe anemia is relatively common (prevalence 2 % or more of a population group), its detection and treatment in primary care facilities is necessary to prevent morbidity and mortality from severe anemia.

A daily protocol of iron supplementation is recommended for treatment and prevention in the priority target groups. Numerous studies have evaluated whether the frequency of iron supplementation can be reduced from daily to twice or once per week without compromising the efficacy of supplementation. The efficacy of once- or twice-weekly supplementation in school-age children, adolescents, and nonpregnant women is promising, and the operational efficiency of intermittent dosing regimens is being evaluated. While research is ongoing to evaluate these regimens in different population groups, the current recommendation remains daily supplementation for young children and pregnant women.

The dosage for iron supplementation in mass programs is unchanged from previous recommendations, except that the pregnancy dose has been reduced to 60 mg/day. Because the efficiency of absorption of iron increases as iron deficiency anemia becomes more severe, this dose should provide adequate supplemental iron to women who do not have clinically severe anemia if it is given for an adequate duration. However, if the duration of supplementation during pregnancy is short, a higher dose (120 mg/day) is recommended.

Supplementation with 400 µg of folic acid around the time of conception significantly reduces the incidence of neural tube defects, a group of severe birth defects. Folate supplementation begun after the first trimester of pregnancy is too late to prevent birth defects. A daily dose of 400 µg folic acid is a safe and healthy intake for women during pregnancy and lactation but is more than the amount required to produce an optimal hemoglobin response in pregnant women. Nevertheless, if iron supplements containing 400 µg folic acid are available, their use in supplementation programs is recommended. If such supplements are not available, the currently available iron supplement containing 250 µg folic acid should be used until higher folate formulations can be obtained.

Food-based Interventions

Fortification of suitable food vehicles with absorbable forms of iron is a highly desirable approach to controlling iron deficiency. If a fortifiable food exists that is consumed by many people at risk of iron deficiency, fortification is likely to be the most cost-effective component of its control. Therefore, some fortification activity, either planning or implementation, is a recommended part of programs in all contexts.

There are many possible strategies for iron fortification. One approach is to fortify a staple food that is consumed in significant quantities by most of the population. Fortification of wheat flour with iron is technically relatively simple and this has been successfully implemented in several countries in the Caribbean, South America, North America, and Great Britain. Another approach is to fortify a widely consumed condiment. Fish sauce, curry powder, salt, and sugar have all been successfully fortified with iron. In South America, both dried and liquid milk and milk products such as yogurt have been fortified with iron. Fortified infant foods are an especially important component of iron deficiency anemia control in children receiving complementary foods. Fortified complementary foods have been shown to be effective in preventing infant iron deficiency anemia in the United States and Latin America.

The amount of iron absorbed from the diet is highly dependent on the composition of the diet, namely, the quantities of substances that enhance or inhibit dietary iron absorption. Tea and coffee inhibit iron absorption when consumed with a meal or shortly after a meal. Heme food sources, predominately red meats, contain highly absorbable iron and promote the absorption of iron from other less bioavailable food sources. Vitamin C (ascorbic acid) is also a powerful enhancer of iron absorption from nonmeat foods when consumed with a meal. The size of the vitamin C effect on iron absorption increases with the quantity of vitamin C in the meal. Unfortunately, foods rich in vitamin C tend to be seasonally available, and both meat and vitamin C-rich foods tend to be expensive in less-developed countries. Germination and fermentation of cereals and legumes improve the bioavailability of iron by reducing the content of phytate, a substance in food that inhibits iron absorption. Although much is known about factors that enhance or inhibit iron absorption, the amount of change in iron absorption that can be achieved through dietary improvements accessible to poor populations remains in question. Dietary improvement becomes more feasible as economic means and dietary diversity increase.

Even where poverty limits dietary choices, some general nutrition education messages have benefits for controlling iron deficiency anemia. All nutrition education programs should promote and support exclusive breastfeeding for about 6 months followed by breastfeeding with appropriate complementary foods, including iron-rich or iron-fortified foods where possible, through the second year of life. Some breast-milk substitutes, especially cow milk, are prone to cause gastrointestinal bleeding in infants, which can cause iron deficiency anemia. Also, promoting adequate food intake in young children and pregnant women can ensure that total iron intake is high even though the percentage of iron absorbed from each meal (i.e., the iron bioavailability) remains low. Promoting adequate food intake in young children requires the development or promotion of low-viscosity, nutrient-dense foods for infants. Educational messages might include teaching mothers to feed 4-5 meals per day to young children and encouraging adequate food intake and weight gain in pregnancy.

Helminth Control

Where hookworm infection is endemic (prevalence 20-30% or higher) and anemia is very prevalent, hookworm infection is likely to be an important cause of anemia, especially moderate-to-severe anemia. Hookworms (Necator americanus and Ancylostoma duodenale) infect approximately 1 billion of the world's population, an estimated 44 million of whom are pregnant women. Hookworms cause intestinal blood loss by feeding on the intestinal mucosa. The amount of blood lost is directly proportional to the number of worms infecting the host. A moderate infection of hookworms approximately doubles the iron losses of a child or menstruating woman. At the population level, endemic hookworm infection contributes to the prevalence of anemia and has the greatest effect on the prevalence of moderate and severe anemia. The prevalence and intensity of hookworm infection increases with age, so that its effect is greatest on the iron status of school-age children, adolescents, and adults, including pregnant women.

In populations with endemic hookworm, anthelminthic therapy should be given presumptively to anyone with severe anemia, because treatment is safe and much less expensive than diagnosing hookworm infection. Anthelminthic treatment to school children without prior screening is currently recommended in the school setting and combined with iron-folate supplementation in antenatal care. School-based anthelminthic chemotherapy (deworming) alone may help prevent moderate-to-severe anemia in schoolchildren, but the most effective strategy for anemia control is to combine anthelminthic chemotherapy with iron supplementation. In antenatal care, anthelminthic therapy combined with iron and folate supplementation enhances the hemoglobin response to iron supplementation. Mebendazole, albendazole, levamisole, and pyrantel may all be safely administered to pregnant women after the first trimester.

Three schistosomes can cause anemia: Schistosoma mansoni and S. japonicum, which are intestinal parasites, and S. haematobium, which infects the bladder and urinary tract. Although all three forms can cause severe anemia, the role of S. haematobium (urinary schistosomiasis) as a cause of anemia in populations is more firmly established than that of intestinal schistosomiasis. The geographic distribution of endemic S. haematobium is limited to Africa and the Middle East. Hematuria can be detected by using reagent test strips (for example, Hemastix, Ames Laboratories, Elkhart, IN), and in severe infection, blood in urine can be observed visually (red, brown, or foggy urine). Urinary schistosomiasis is transmitted by swimming or wading in bodies of water that are habitats for infected snails. Infection is usually most prevalent and severe in children, older boys, and men, who are more likely to swim. Where urinary schistosomiasis is endemic, it should be considered in the treatment of severe anemia and in school-based anthelminthic chemotherapy programs. Praziquantel safely and effectively treats this infection.

Malaria Control

Plasmodium falciparum malaria causes a profound anemia during and after acute infection. The anemia is caused by hemolysis of red cells combined with suppression of erythropoiesis. Consequently, body iron is shifted from hemoglobin to storage forms. Whether malaria increases iron losses from the body is not fully understood but is unlikely. The increased red cell turnover may bring about folate deficiency, especially during pregnancy when folate requirements are already high. For these reasons, detecting and treating malaria are essential for treating severe anemia where P. falciparum malaria is endemic. Where P. falciparum malaria is endemic, the use of insecticide-impregnated bednets in communities decreases the prevalence of severe anemia in young children. Malaria prophylaxis during pregnancy may reduce the prevalence of anemia in first and second pregnancies and improve birth weight. Malaria prophylaxis has less benefit as a public health measure in multiparous women. Although malaria-related anemia is usually not primarily iron deficiency anemia, such distinctions are not important to primary health care providers and some recommendations about the use of antimalarial drugs are included in these guidelines.

Reproductive and Obstetric Interventions

Preventing adolescent pregnancies, reducing the total number of pregnancies, and increasing the time between pregnancies will also contribute to the control of iron deficiency anemia in women. Pregnancy creates a large demand for iron, which is needed to develop the fetus and placenta and to expand a woman's blood volume. Additional iron is lost with blood lost at delivery. When the iron demands of pregnancy are combined with the iron demands of adolescent growth, girls enter adulthood at great risk of iron deficiency. The postpartum period is a time of recuperation of iron status, as iron in additional red blood cells made during pregnancy becomes available. This is especially true during the period of full breastfeeding and lactational amenorrhea, because the iron cost of breastfeeding is typically less than the iron cost of regular menstruation. Thus, the promotion of exclusive breastfeeding for about 6 months followed by breastfeeding with complementary feeding into the second year of life will contribute to the control of iron deficiency anemia in women of reproductive age. When women have 2 or more years between pregnancies, they are more likely to enter the subsequent pregnancy with adequate iron status. However, these interventions alone will not be sufficient to control anemia where dietary iron deficiency persists.

Obstetrical practices can also contribute to the control of iron deficiency anemia in infants. More red blood cells are transferred from the placenta to the newly born infant if the umbilical cord is not clamped and ligated until it stops pulsating. By holding the infant on the mother's abdomen, continued blood flow to the infant is allowed without an excess risk of polycythemia (i.e., the baby getting too many blood cells). This increases the body iron content of the infant, which will help to prevent iron deficiency in later infancy.