Iron Deficiency Prevention in Infants and Toddlers
Today’s Dietitian
By Cindy Fitch, PhD, RD
Vol. 6, No. 12, p. 32

Iron deficiency in infants and toddlers is declining, but dietitians must still know how to advise parents on the best ways to keep their children’s diets iron-rich.

The prevalence of iron deficiency anemia in children has declined dramatically over the last three decades. Improvements in infant nutrition have resulted in an increased intake of readily available dietary iron. While this is a pediatric nutrition success story, the battle is not yet won. The goal for Healthy People 2010 is to reduce the prevalence of iron deficiency to 5% of children aged 1 to 2.1 Data from the National Health and Nutrition Examination Survey (NHANES) of 1999-2000 indicated that 7% of children aged 1 to 2 were iron-deficient.2 There is still room for improvement in iron status among young children.

The terms iron deficiency and anemia are sometimes used interchangeably, but they do not describe the same condition. In determining iron status, remember that iron is found in two main compartments in the body: functional iron and storage iron. Functional iron is present in all body cells and is necessary for oxygen transport and diffusion and electron transport for energy production. Storage iron denotes the body’s iron reserve. Iron deficiency can represent a continuum—from mild to severe iron depletion. In mild iron depletion, iron stores are decreased and the individual is at risk for iron deficiency if the body’s requirement for iron exceeds the amount available, but there are no known functional defects. Further iron depletion will lead to a reduction in iron for cellular processes. Eventually, the deficit in available iron will affect the synthesis of heme for red blood cells, leading to iron deficiency anemia.

Anemia is defined as a hemoglobin concentration below the fifth percentile for healthy people at a given age. It may be caused by iron deficiency or a deficiency of any number of other nutrients required for the synthesis of red blood cells. More commonly, it is caused by infection, inflammation, or mild hereditary traits such as thalassemia.

Measuring Iron Status
There is no single laboratory test that accurately reflects iron status, but it is possible to evaluate by using a combination of tests. The most commonly used tests include serum ferritin, transferrin saturation, erythrocyte protoporphyrin, mean corpuscular volume (MCV), red cell distribution width (RDW), and hemoglobin. Serum transferrin receptor is a test that is being used in research projects but is not widely used clinically at this time. Each test reflects a different aspect of iron metabolism:

• Serum ferritin. Serum ferritin concentration reflects iron stores in healthy people, and a low value is characteristic of iron depletion. However, conditions such as inflammation, infection, and chronic disease can elevate serum ferritin concentrations independent of iron status. Normal values don’t necessarily mean adequate iron stores.

• Transferrin saturation. Transferrin saturation refers to the degree to which transferrin, the iron-transport protein, is filled with iron and reflects the circulating iron available for the synthesis of heme. It is calculated from the measured concentrations of serum iron and iron-binding capacity. Serum iron has large diurnal fluctuations, and iron-binding capacity is dependent on adequate protein and energy availability, so either test alone is not useful. Using them together to calculate transferrin saturation compensates somewhat for their individual limitations but doesn’t differentiate between anemia due to iron deficiency or chronic disease.

• Erythrocyte protoporphyrin. As circulating iron is diminished, less iron is available for heme synthesis. This leads to an increase of protoporphyrin, the precursor to heme, in red blood cells. Erythrocyte protoporphyrin is also affected by environmental lead exposure and varies inversely with blood lead levels. This makes it a less effective laboratory test for assessment of iron status in toddlers because they are the age group most likely to be exposed to environmental lead.

• MCV. MCV indicates the average size of red blood cells. In iron deficiency, newly formed red blood cells are small (microcytic) and MCV will be low. In folate or B12 deficiency, the cells are large and MCV will be high. If iron and folate or B12 are inadequate, MCV can be normal because it measures the average size. MCV is also decreased during inflammation or in thalassemia.

• RDW. RDW is an index of the heterogeneity of the red blood cells. Elevated RDW indicates a greater difference in size among red blood cells and when seen with a low MCV is indicative of iron deficiency, whereas normal RDW with low MCV is indicative of thalassemia.

• Hemoglobin and Hematocrit. Hemoglobin concentration and hematocrit (measurement of packed cell volume) are the tests most commonly used to screen for iron deficiency because they can be done quickly and easily using capillary blood. However, a low value on either test is a late sign of iron deficiency and results can be affected by infection, inflammation, and chronic disease. Thus, they are neither sensitive nor specific for diagnosing iron deficiency. Furthermore, because anemia has been defined as a hemoglobin or hematocrit value that is below the fifth percentile, even in a population without iron deficiency, roughly 5% will be anemic.

When iron status is compromised, the body will preferentially use the available iron for the synthesis of hemoglobin and synthesis of other iron-containing proteins in cells will be decreased. This decrease is responsible for the clinical signs of iron deficiency, including weakness, muscle fatigue, and decreased cognitive ability.3 These signs are not specific to iron deficiency. Consequently, many children with iron deficiency will not be diagnosed because they are not anemic. Iron deficiency that is severe enough to cause anemia has adverse consequences that include increased risk of lead poisoning,4 decreased resistance to infections,5 and alterations in behavioral, mental, and psychomotor development that may be permanent.6

Factors Influencing Iron Status
Infants and toddlers aged 6 to 24 months are particularly vulnerable to developing iron deficiency. They have a rapid rate of growth and blood volume expansion and the need for exogenous iron is high in proportion to body weight. After the age of 2, the rate of growth begins to slow and iron stores begin to build up, so the risk of iron deficiency is decreased. Full-term infants are born with an iron endowment that is adequate to prevent deficiency for roughly the first 4 to 6 months of life. How quickly and to what extent those iron stores are used up depend on the amount of iron stored before birth and the postnatal diet. The major factors that affect the absorption of dietary iron are iron stores and the synthesis of red blood cells. Dietary factors play a lesser but still important role in enhancing or inhibiting iron absorption.

Although the concentration of iron in human milk is low, absorption of that iron is high. The exact mechanism is not known but is believed to be a low molecular weight component in the whey portion of human milk.7 While unfortified infant formulas and whole cow’s milk have nearly the same iron content as human milk does, only approximately 10% of that iron is absorbed compared with approximately 50% of the iron in human milk. Iron-fortified infant formulas (1 milligram iron per 100 kilocalories) are good sources of iron for infants who are not breast-fed. They are readily available and are no more expensive than the low-iron version of the same formula. In a double-blind, placebo-controlled trial, the use of iron-fortified formula was not associated with symptoms of gastrointestinal distress.8

When weaning foods are introduced into an infant’s diet, include foods that provide good sources of readily available iron. The choice of weaning foods to ensure adequate iron status is particularly important for breast-fed infants. Although the iron in breastmilk is well-absorbed, that increased absorption does not entirely compensate for its lower iron content when compared with iron-fortified infant formula.9 Iron-fortified infant cereals are often the first nonmilk food to be introduced in an infant’s diet. These cereals are fortified with small particles of reduced iron that is fairly well-absorbed.

Iron in meat is in the form of heme iron, which is absorbed two to three times more efficiently than is nonheme iron from plant products. Typically, iron-fortified rice cereal is the first solid food that is introduced into an infant’s diet. Then, the usual practice has been to introduce fruits and vegetables into an infant’s diet before introducing meats. Recently, some have suggested that meats be the first foods introduced. As long as the introduction of solids is delayed until roughly 6 months of age, the order of introduction of weaning foods is not critical.9 It is important that infants be given plain meats as opposed to mixed dinners to meet iron needs. The amount of meat in mixed dinners is proprietary information but, per serving, they generally provide approximately 50% of the iron and protein provided by plain meats. The Feeding Infants and Toddlers Study (FITS), a large, nationwide study sponsored by the American Dietetic Association, showed that only 3% to 4% of infants aged 7 to 11 months consumed plain, strained meats, but 34% to 40% consumed mixed dinners.10 This practice could increase the risk for iron deficiency among these infants as they decrease their intake of milk-based sources of iron (human milk or iron-fortified formula).

Nonheme iron from vegetables and grains is not well-absorbed. Ascorbic acid and an unknown factor in meat will enhance the absorption of nonheme iron when consumed in the same meal.

Factors that have been shown in some studies to inhibit nonheme iron absorption include polyphenols in tea and some vegetables and phytates in cereals and legumes. Most of these studies were done with single foods, and the inhibitory effects in a mixed meal that also contains factors that enhance iron absorption may be much less important than once believed.

Calcium has been reported to inhibit heme and nonheme iron absorption in animal and human studies. Epidemiological studies have reported an inverse relationship between milk or calcium intake and serum ferritin. On the other hand, a study done in children aged 3 to 5 showed that a high calcium intake (1,100 milligrams) over time did not interfere with iron incorporation into red blood cells.11 Similar studies have not been done in younger children. In clinical practice, we often see toddlers who consume large volumes of milk to the exclusion of other foods. These toddlers are at risk for iron deficiency anemia.

One dietary practice known to impair iron status is the introduction of unmodified cow’s milk into an infant’s diet before the age of 12 months. This practice carries two risk factors: the low concentration of iron in cow’s milk and the risk of occult blood loss from the gastrointestinal tract. Blood loss decreases after roughly 8 months of age and disappears at around 12 months of age.12

Primary Prevention of Iron Deficiency in Infants and Toddlers
From conception to approximately 24 months of age, children grow and develop at a very rapid rate. This is a particularly critical time for brain growth, and iron deficiency anemia can have adverse effects on cognitive and motor development that may not be reversible even after the anemia is corrected. Prevention of iron deficiency is crucial. Both the Centers for Disease Control and Prevention and the American Academy of Pediatrics have published recommendations for the primary prevention of iron deficiency in infants and toddlers.13,14 Each organization developed its recommendations independently, but the recommendations are similar and are summarized here:

• All infants younger than 12 months of age should receive only breast milk or iron-fortified infant formula for any milk-based part of the diet. There is no common medical indication for the use of low-iron formula.

• Encourage exclusive breast-feeding for the first 4 to 6 months of life in infants who are breast-fed.

• After 4 to 6 months, when the infant is developmentally ready, encourage a supplemental source of iron, preferably from complementary foods. Iron-fortified infant cereals and/or meats are a good source of iron for initial introduction of an iron-containing food. Infants will need approximately 1 ounce (1/2 cup) of dry infant cereal per day to meet their iron requirements.

• A breast-fed infant who is not able to consume sufficient iron from dietary sources after 6 months of age should be given iron drops.

• By the age of 6 months, encourage one feeding per day of foods rich in vitamin C, preferably with meals, to improve iron absorption.

• Children aged 1 to 5 should consume no more than 24 ounces of cow’s milk, goat’s milk, or soymilk per day because of the concern that milk will replace iron-rich foods in the diet. Twenty-four ounces of milk per day will meet the dietary intake recommendation for calcium for children aged 1 to 8.

The transition from human milk or infant formula to table food and unmodified cow’s milk is a particularly vulnerable time for the development of iron deficiency. Parents need specific guidance on feeding their older infant and young toddler. Dietitians are well-qualified to provide that guidance.

— Cindy Fitch, PhD, RD, is an assistant professor of human nutrition and food at West Virginia University.

References
1. Health and Human Services. Healthy People 2010 (conference edition, in two volumes). Washington, D.C. January 2000;2:19-35.

2. Iron Deficiency - United States. 1999-2000. Centers for Disease Control and Prevention. Morb Mort Wkly Rep. 2002;51(40):897-899.

3. Committee on Nutrition, American Academy of Pediatrics. Iron fortification of infant formulas. Pediatrics. 1999;104(1):119-123.

4. Wright RO, Shannon MW, Wright RJ, Hu H. Association between iron deficiency and low-level lead poisoning in an urban primary care clinic. Am J Public Health. 1999;89(7):1049-1053.

5. Chandra RK, Saraya AK. Impaired immunocompetence associated with iron deficiency. J Pediatr. 1975;86(6):899-902.

6. Grantham-McGregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr. 2001;131(2)(suppl):649S-668S.

7. Etcheverry P, Miller DD, Glahn RP. A low-molecular-weight factor in human milk whey promotes iron uptake by Caco-2 cells. J Nutr. 2004;134(1):93-98.

8. Nelson SE, Ziegler EE, Copeland AM, et al. Lack of adverse reactions to iron-fortified formula. Pediatrics. 1988;81(3):360-364.

9. Committee on Nutrition, American Academy of Pediatrics. Pediatric Nutrition Handbook. 5th ed. RE Kleinman, editor. American Academy of Pediatrics, Elk Grove Village, Ill.; 2004:110.

10. Briefel RR, Reidy K, Vatsala K, Devaney B. Feeding Infants and toddlers study: Improvements needed in meeting infant feeding recommendations. J Am Diet Assoc. 2004;104(1)(suppl):S31-S37.

11. Ames SK, Gorham BM, Abrams SA. Effects of high compared with low calcium intake on calcium absorption and incorporation of iron by red blood cells in small children. Am J Clin Nutr. 1999;70(1):44-48.

12. Ziegler EE, Jiang T, Romero E, et al. Cow’s milk and intestinal blood loss in late infancy. J Pediatr. 1999;135(6):720-726.

13. Recommendations to prevent and control iron deficiency in the United States. Centers for Disease Control and Prevention. Morb Mortal Wkly Rep. 1998;47(RR-3):1-36.

14. Committee on Nutrition, American Academy of Pediatrics. Pediatric Nutrition Handbook. 5th ed. RE Kleinman, editor. American Academy of Pediatrics, Elk Grove Village, Ill.; 2004:307-308.

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