IRON METABOLISM A Review with Special Consideration of Iron Requirements During Normal Infancy

The infant has no route or organ for the physiologic excretion of iron. Clinically insignificant quantities are lost through the skin and gastrointestinal tract. Assimilation of iron by the adult does not exceed 10 per cent of that ingested in the food; natural foods have a relatively low content of iron. There is evidence from balance studies that at least some infants may have a greater capacity to absorb iron than adults; confirmatory studies using isotopic labeled iron in naturally occurring food, especially milk, would be most helpful in considering and re-evaluating this phase of iron nutrition in the infant. The intestinal mucosa tends to act as a barrier to the rapid entrance of iron into the circulation (mucosal block). Iron in serum is transported bound to a serum globulin (siderophilin); the latter is present in a two- to threefold excess of the concentration of iron in the serum (this represents the serum iron-binding capacity). Relative to adults, many normal infants have a reduced concentration of serum iron and increased iron-binding capacity. Similar changes are seen in iron deficiency states. Storage iron is found primarily in the liver and spleen in 2 chemical forms. One, ferritin, is detectable only by chemical means, and the other, hemosiderin, is visible microscopically and takes iron stains. The content of the latter in bone marrow is reduced in iron deficiency states. Also, hemosiderin is not found in the bone marrow of normal infants. The time required for the assimilation of iron, including metabolic transport across the intestinal mucosa, through the serum iron pool, into the bone marrow and out into the circulating erythrocytes, is very short; as little as 4 hours. The vast majority of iron metabolized internally comes from the daily breakdown of hemoglobin and, to a lesser extent, from other iron compounds such as myoglobin, cytochrome and ferritin. The dietary iron assimilated constitutes only a small percentage of the daily total iron turnover. Studies of iron turnover rates (ferro-kinetics) have not been performed in infants; the magnitude and significance of the additional factor created by rapid growth in such considerations is not known at present. The phyisologic anemia of late infancy is associated with evidence of depletion of iron in the various iron compartments: hemoglobin, serum iron, iron-binding capacity and iron stores. In view of recent data on the blood volume and concentration of hemoglobin of the newborn infant, considerable reduction in estimates of the total amount of iron present at birth are in order: A mean value of 200 mg. for a 3-kg. infant is consistent with these data, and is also consistent with studies of total iron content of stillborn fetuses over 3 kg. A relatively wide range in values, 120 to 320 mg. for total body iron are well within the limit9s of normal. Calculations are presented to show that those infants endowed with the smaller quantities of iron at birth and a relatively rapid growth factor will have to assimilate iron at 3 times the rate of other normal infants. In the normal infant with reduced iron content at birth, the drain of iron from hemoglobin by growth of muscle and myoglobin mass may constitute a significant factor contributing to a profound degree of anemia. Preliminary studies on the prophylactic use of intramuscular iron indicate that many of the manifestations of iron deficiency in normal infancy can be altered. A statistically significant higher mean concentration of hemoglobin (0.7 gm./100 ml.) was achieved. Infants, so treated, with values for hemoglobin less than 11.0 gm./ 100 ml. were not observed, whereas 20 per cent of normal infants at 1 year of age had values for hemoglobin ranging from 9.4 to 11 gm./100 ml. Highly significant reductions in the total iron-binding capacity, serum copper and free erythrocyte protoporphyrin were achieved. Increases in the concentration of serum iron and mean erythrocyte hemoglobin concentration were also significant. The average mean corpuscular volume in the treated group was 78.9 µm.; this was not significantly different from the value of 77.2 in the control group. In previous studies using oral iron in large doses, the only one of the above manifestations of iron deficiency which was altered significantly was the concentration of hemoglobin. Except for staining of the skin, the intramuscular iron preparation employed gave no reactions. The iron requirement for the first year of life was given in 3 injections of 1 to 2 ml. without difficulty.