We are in the midst of a revolution in thinking about iron supplementation in infancy. While all of us understand the necessity for sufficient iron in fetal and neonatal development and the importance of this metal in biologic function, we are now beginning to see some problems associated with the over-abundant use of this mineral.
As you all know, iron is mandatory for the creation of hemoglobin. Hemoglobin is the iron-containing oxygen-transport metalloprotein found in the red blood cell. Hemoglobin transports oxygen from the lungs of mammals to other tissues, where it subsequently releases oxygen to the tissues. In the last trimester of pregnancy, the liver is packed full of additional iron. But this is only enough to last the full-term infant for about six months postpartum. The biologic relevance of this is obvious. It is to supply the infant with sufficient iron while the infant is fed with human milk, a food source that is relatively deficient in iron. Nature intended the GI tract to be deficient in iron to prevent the overgrowth of hazardous bacteria and to maintain Bifidus species of bacteria, which, interestingly, don’t require iron to grow. Thus, the infant has plenty of iron to create hemoglobin and grow for the first six months of life while its’ GI tract is relatively deficient in iron. Why? We are only now becoming aware that high levels of exogenous iron has some problems.
Interestingly, the point that is now becoming apparent is that too much iron may not be beneficial to the infant’s development. Hemoglobin concentrations change as we age from quite high in the fetus and at birth, to much lower levels over the next two months. We know with certainty that during gestation, iron-deficiency anemia may lead to developmental delays in one to two-year-old children that subsequently may not respond to prolonged iron therapy.
But the intriguing question now posed is, does the supplementation of infants with high oral doses of iron cause problems?
Iron is an essential growth stimulant for microbes and malignant cells. Human milk has lactoferrin that effectively chelates iron in an attempt to keep it away from microbes. Biologic fluids contain several other proteins that chelate iron and keep it in a form that is unavailable to microbial or neoplastic cells. Some evidence suggests that high iron loads may actually be a risk factor for certain malignancies because iron is a rate-limiting factor in neoplastic cellular growth.1
Studies in my laboratories have shown that iron dramatically stimulates bacterial and candida growth. In some of my studies, candida growth increased by as much as 35-fold with the addition of iron. The iron content could also account for the widely different bacterial content of the gut in formula-fed infants as compared to human milk-fed infants. When used routinely, iron has been found to increase the prevalence of severe sepsis by approximately 20-fold,2 and even the risk of malaria.3
New evidence just presented found that in a large cohort of infants fed iron-fortified formulas, these infants scored an average of 11 points lower on IQ tests at ten years of age compared to similar children fed low-iron formulas.4
Other such evidence in animal models suggests high oral iron loads may actually lead to reduced capillarization of various tissues, including the myocardium, leading to reduced function later in life. This work suggests that super iron-rich blood may lead the infant to produce fewer capillaries per cubic centimeter of tissue - because the blood is so rich, you don’t need as many capillaries.
All this data suggests, as we all know, that human milk continues to be the most perfect nutrition for a human infant. Everything we may have formerly deemed ‘deficient’ (such as iron) now seems to be just perfect. So do we need to supplement breastfed infants with oral iron? The answer is probably yes, but only premature infants who may not have the hepatic stores of iron. Do we need to supplement term infants? Probably not, unless they have documented iron deficiency anemia.
Do infants fed formula need supplementation? Maybe, but they need only minimal supplementation because the iron in formula may not be biologically well absorbed. Do they need high doses of exogenous iron? Probably not if we want them to be smart.

References:
1. Herrinton LJ, Friedman GD, Baer D, Selby JV. Transferrin saturation and risk of cancer. Am J Epidemiol. 1995 Oct 1;142(7):692-8.
2. Barry DM, Reeve AW. Increased incidence of gram-negative neonatal sepsis with intramuscula iron administration. Pediatrics. 1977 Dec;60(6):908-12.
3. Oppenheimer SJ, Gibson FD, Macfarlane SB, et al. Iron supplementation increases prevalence and effects of malaria: report on clinical studies in Papua New Guinea. Trans R Soc Trop Med Hyg. 1986;80(4):603-12.
4. Kerr ML, D. Neurodevelopmental delays associated with iron-fortified formulas for health infantsMedscape medical news 2008 [cited 2008; Available from: www.medscape.com/viewarticle/574363