- Diane E. Pappas, MD, JD
Iron deficiency anemia remains the most common nutritional deficiency in children in the United States. Rapid growth, insufficient dietary intake, and limited absorption of dietary iron combine to place children at increased risk for iron deficiency. Pallor, irritability, fatigue, and tachycardia are common manifestations of moderately severe anemia, but milder degrees may be clinically inapparent.
Evidence is increasing that iron deficiency that progresses to anemia can have significant long-term effects. Infants who have anemia score lower on tests of mental and motor development than those who do not. The severity and duration of anemia correlate with poorer test performance. However, short-term iron therapy or correction of anemia has not been shown to improve test scores. Diminished performance on tests of mental and motor development has been shown in 5-year-old children who suffered anemia as infants. Thus, cognitive deficits as a result of iron deficiency anemia at a critical period of development may be long-lasting or even irreversible.
Iron is critical for numerous biologic processes, including oxygen transport. Most iron in the body is found in hemoglobin. Iron necessary for growth and replacement of daily iron losses is supplied by the diet. Iron is transported in plasma by a specialized transport protein called transferrin. Iron stores are concentrated in the liver, bone marrow, and spleen in the form of ferritin, from which iron can be mobilized readily.
Hemoglobin concentrations are elevated at birth, but decrease over the first few months of life. The normal term infant is born with enough iron to last about 6 to 9 months. Not surprisingly, iron deficiency is most common at 10 to 15 months of age as the infant becomes dependent on dietary sources to replenish his or her iron supply. Iron deficiency progresses slowly through several stages. Initially iron stores are depleted, although red blood cell production continues. The red cell distribution width (RDW) appears to be the earliest detectable laboratory change. This is a measure of the variation in size of red blood cells and can be used to detect increased anisocytosis. RDW greater than 14.5% is consistent with iron deficiency anemia.
As iron stores are depleted further, serum ferritin levels decline. Serum ferritin is an accurate indicator of tissue iron stores. In iron deficiency, serum ferritin levels are less than 8 to 12 mcg/L. Ferritin levels are normal or increased during infection.
As iron deficiency continues, serum iron decreases to less than 30 mcg/dL. Serum iron is affected by many factors, including iron absorption, the iron available as a result of red blood cell destruction, and the size of iron stores. Diurnal variation of serum iron further complicates its usefulness as a screening test.
Total iron binding capacity (TIBC) measures the amount of iron that can bind to serum proteins. As iron stores are depleted, TIBC begins to increase. Transferrin saturation provides a measure of the iron available for hemoglobin synthesis. Hemoglobin synthesis is impaired at saturations of 10% to 15%.
Impairment of hemoglobin synthesis results in accumulation of free erythrocyte protoporphyrin (FEP). When iron is not available for hemoglobin synthesis, there is a build-up of precursor molecules that lack iron (protoporphyrins), which are incorporated into red blood cells. FEP is increased in lead poisoning, chronic disease, and iron deficiency. Lead poisoning produces very high levels of FEP.
As the hemoglobin concentration falls, the result is anemia. There are age-specific guidelines that define anemia; for a child of 6 to 24 months of age, a hemoglobin concentration of less than 11g/dL is considered anemic. Unfortunately, there is significant overlap between the hemoglobin levels of anemic and normal individuals, which results in both false-negative and false-positive results when hemoglobin is used as a screening test for iron deficiency anemia. The American Academy of Pediatrics currently recommends hemoglobin assessment at 9 months, 5 years, and 14 years to screen for iron deficiency.
When one or more of the previously noted laboratory tests suggests iron deficiency, a therapeutic trial of iron supplementation is one means of confirming the diagnosis. Oral iron salts are administered at a dose of 3 to 6 mg/kg per day of elemental iron. An increase of 1 g/dL or greater in the hemoglobin concentration after 1 month of iron therapy confirms the diagnosis. Recent infection may cause a decreased hemoglobin concentration that will rise spontaneously, making it impossible to determine if the improvement was due to iron therapy. Reticulocytosis becomes evident at 7 to 10 days after initiating therapy. Therapy should be continued for 2 to 3 months to replenish iron stores. Families also should be educated about diet.
Comment
The prevalence of iron deficiency anemia in early childhood has declined in all socio-economic groups in the United States due to improved nutrition. Previously a problem among infants younger than 1 year of age, iron deficiency anemia now is more common among toddlers. Inadequate iron in food that is introduced upon weaning and delayed weaning from the bottle are major contributors. Because cow milk contains little iron, replaces food with higher iron content, can inhibit iron absorption, and can cause occult intestinal bleeding, early introduction (younger than 1 year) of cow milk and large consumption (>24 oz) of it after the first year of life are risk factors for iron deficiency. Breast milk or iron-fortified formula is recommended until age 12 months. At 4 to 6 months of age, term infants require an additional source of iron in their diets, such as iron-fortified cereal. Boutry and Needlman (Pediatrics. 1996;98:1138–1142) found that a brief, three-component dietary history was a useful screening test for microcytic anemia among children ages 15 to 60 months. A history of dietary deficiency was defined as: 1) fewer than five servings each of meat, grains, vegetables, and fruit per week; 2) more than 16 oz of milk per day; or 3) daily intake of fatty snacks, sweets, or more than 16 oz of soft drink. This brief history correctly identified children at low risk for microcytic anemia 97% of the time.
Adolescence is another time of rapid growth and risk for iron deficiency. For males, the risk decreases after pubertal growth. For females, growth and menstruation cause greater iron needs. Although rates of iron deficiency anemia have decreased in young children, rates of anemia among low-income women during pregnancy are high and have not improved. Again, preventive counseling and screening are key. The American Academy of Pediatrics’ Pediatric Nutrition Handbook (3rd ed. Barness LA, ed. Elk Grove Village, Ill: American Academy of Pediatrics; 1993) and the recently published Centers for Disease Control and Prevention’s “Recommendations to prevent and control iron deficiency in the United States” (Morbid Mortal Week MMWR. 1998;47[No. RR-3]) are important resources for review.
- Copyright © 1998 by the American Academy of Pediatrics
