Iron Deficiency, Part 1: Three Aspects of Iron Deficiency

Iron deficiency is an important topic but one that is very broad. This paper is limited to only three aspects of the problem: classification, definitions, and prevention.

1. Classification
   The staging of iron status by Oski et al (1983) is a useful concept.

   Iron sufficiency: iron stores and erythropoiesis are normal

   Iron depleted: erythropoiesis is normal but iron stores are reduced (serum ferritin is less than 12mcg/l but value is dependent on the exact method used) indicating a reduction of iron in the bone marrow, liver and other parts of the reticuloendothelial system. Infection may lead to a raised serum ferritin even in an iron deficient child.

   Iron deficient erythropoiesis:

   1. Abnormal red blood cell (RBC) biochemistry (free erythrocyte protoporphyrin greater than 99mmol/mol haem; serum transferrin receptor raised, for example, greater than 8.5mg/l but the exact cut off depends on age and the assay used.) 
   2. Abnormal RBC morphology - microcytosis, mean corpuscular volume (MCV) is below 80 fl,
      varying with age; anisocytosis, red blood cell distribution width (RDW) is greater than 15 percent.
   3. Transport iron is reduced (transferrin saturation is less than 10 percent.

   Iron deficiency anaemia: the above plus haemoglobin measures less than 110g/l.

   There is no evidence that iron depletion or iron deficient erythropoiesis alone has any adverse clinical effects. However, iron deficiency anaemia is associated with alterations of immunological, gut and mental function.
   

   

2. Definitions and reference values
   In the recent National Health and Examination Survey (NHANES) in the United States, iron deficiency (ID) was defined as the presence of two or more abnormal measurements shown in Table 1(below.) This battery of tests was applied to a large number of children and the haemoglobin ranges produced (after excluding children with more than 1 abnormal test) are suitable reference standards. (See Table 1 below, Dallman 1996.)

   Serum transferrin receptor concentration has attracted considerable interest, however, its use as an index of iron deficiency in infancy and adolescence has been questioned. It would be unwise to use the test alone without other measurements of ID as well.
   
   

3. Prevention
   At birth
   Since three quarters of the iron ‘stored’ at birth is in the form of haemoglobin, perinatal blood loss (from the cord, twin to twin, fetus to mother) is a major cause of anaemia in early and later infancy. In many studies, iron stores in newborns show little relationship to the mothers’ iron status; but some studies, particularly of severe deficiency in developing counties, have shown a direct relationship.

   Suckling period (0 - 4 months)
   For normal-sized babies there is little concern about ID at this stage, since total body iron does not decrease during this time. If ID occurs, then abnormal blood loss should be considered.

   

   Weaning (4-12 months) - breastfeeding babies
   Breast milk alone will not supply extra iron but the absorption rate of the small amount of iron present is high; and breastfeeding should continue if the mother wishes. It becomes essential at this stage to introduce iron-containing foods. Among family foods, meat is an excellent choice because of its large amount of haem iron. Meat also provides zinc, which may become a limited nutrient in prolonged breastfeeding. Many mothers also introduce convenience weaning foods (See below.)

   Bottle-feeding babies
   A fortified formula provides sufficient iron, for example, a European infant formula containing 1 mg per 100kcal, an American infant formula containing 1.8 mg per 100kcal, or a European-style “follow on formula” containing about 1.8 mg per 100kcal. Formulas containing less iron may also be effective. Any of these options is preferable to the early introduction of ordinary cow’s milk. In addition to iron content, other ingredients in a formula may contribute to improved iron status of the infant. High vitamin C content may cause increased absorption of iron. Lower concentrations of protein, calcium and phosphorus may decrease the inhibition of iron absorption, and cause less immunologically induced milk enteropathy and iron loss.

   

   Introduction of weaning (complementary) foods containing available iron
   This is less critical in bottle fed babies receiving iron fortified formula or a follow on milk. Convenience weaning foods are widely available in the ‘western’ world. Some studies have shown that these foods provided a more satisfactory diet (more iron, less protein, salt and sugar) than a homemade diet alone.

   Iron is added to a variety of manufactured weaning foods, particularly cereals. One problem with these foods is the availability of the iron used for fortification and its reactivity with other nutrients. For example, ferrous sulphate is relatively well absorbed but it catalyses the oxidation of unsaturated fats, which leads to rancidity, discoloration and flavour changes unless access to oxygen is limited through vacuum or nitrogen packing, and/or rapid turnover times from fortification to consumption. In developing countries, fortified foods are less available at affordable prices, and fibre and phytate intakes are higher. On the other hand, some foods in these countries are cooked in iron pots, which leads to higher iron intake than if aluminium pots are used

   Fiscal measures
   The consumption of suitable foods may be increased if their price to the consumer is reduced (even free of charge) through subsidies from a government or a charity. The well-known example is the Women, Infants and Children Programme in the USA (WIC) where iron-fortified infant formulas and weaning cereals are supplied free of charge to about a quarter of all infants.

   

   Avoidance of blood loss
   Pasteurised cow’s milk given before the age of 12 months may lead to intestinal blood loss. In many countries, hookworm infestation is the most common cause of blood loss in infants old enough to sit on the floor and then walk. Control programmes (intermittent antihelminthic medication - at least twice yearly, control of faecal contamination of soil, use of simple shoes) should be used in combination with iron supplementation. Bilharzia, Trichuris and Giardia are less important as causes of anaemia,

   Iron supplementation (giving iron as a medicine)
   Supplementation is generally not favoured for prevention because it puts a toxic medicine into the household and compliance is poor. Regimens of oral iron every 5 - 7 days have been promoted. Compliance is better with these regimens and, in field studies of adults in developing countries, they are as effective as a daily dose. This may occur because the daily dose saturates the enterocyte, blocking absorption of the next doses for a few days.

   Micronutrient Supplementation
   The use of micronutrient supplements in developing countries is being actively considered by UNICEF and USAID and field trials have been successful. There is a possibility of interaction between different minerals in multimicronutrient supplements. A zinc supplement given in water depresses the absorption of iron, but this does not occur when both minerals are present in food. The interaction may be a further reason for giving iron in a food vehicle (fortification), or as an individual supplement, if given as a medicine.

This material has been prepared by members of the IFM's Advisory Committe on Child Health and Nutrition.

See Also: Iron Deficiency, Part 2 and Iron Deficiency, Part 3

December 2002