Albertine Donker

Chapter 2 70 adjusting towards the genetically predicted trajectory. 54 Preterm babies have overall greater nutritional needs and higher iron requirements than healthy full-term babies, since their iron stores are smaller at birth and extra iron is needed for catch-up growth. 148 To meet these substantial physiological needs, iron is mobilized from iron stores, recycled from hemoglobin breakdown and absorbed from dietary sources. Human infants are born with relatively high iron contents per kilogram; a full term infant of 3 kg is endowed with approximately 330 mg iron (110 mg/kg), which is per kg roughly 1.5 times more than the iron content of a male adult of 70 kg containing approximately 5000 mg (70 mg/kg) ( Figure 1, Table 2 ). 147 Moreover, the normal decline in Hb due to the breakdown of fetal Hb significantly increases iron stores in newborns. Therefore, healthy, term and breastfed infants are initially independent of additional external iron and can double their birth weight before iron stores are depleted. 8,9,149 During infancy, ID and IDA may negatively affect growth that might improve after correction of the iron deficit according to one observational study and one RCT, 150,151 although meta-analyses fail to demonstrate such a beneficial effect. 93,152 Moreover, iron supplementation in iron-replete infants may have detrimental effects on growth, 93 possibly by competition with the absorption of zinc and other micronutrients. 9 Other mechanisms include the induction of oxidative stress via NTBI 153 , or perturbation of the gut microbiota. 154 Iron and lactation For suckling infants, breast milk and/or infant formula are the only sources of dietary iron. Although relatively low in iron content, the bioavailibility of iron in breast milk is higher (~50%) than in formula milk and cowmilk (~3-4%), explaining the need for a higher iron content in infant formula. 155-158 This relatively high bioavailability of breast milk iron is explained by the unique properties of lactoferrin, a single polypeptide chain that is closely related to transferrin, the iron-carrier protein in plasma, also capable of binding 2 iron atoms. 159-162 In comparison to transferrin, lactoferrin has a 300 times greater affinity for iron and can retain iron down to more acidic environments (~pH 3), e.g. in the stomach or in infected tissues, as transferrin releases iron already at a pH below 5.5. 160,162-164 Lactoferrin is relatively resistant against proteolysis since it appears in the stools of breastfed infants in intact form. 165 Lactoferrin receptors have been identified in the small intestine