This summary is adapted from ‘Iron Requirements of Infants and Toddlers’ by Magnus et al. 2014
Iron deficiency is the most common micronutrient deficiency, with young children at a particularly high risk due to the increased iron requirements while rapidly growing. It is estimated that approximately 25% of preschool children have iron deficiency anaemia1. Prevalence is <2% before 6 months, and 2-3% at 6-9 months2. There are three stages to the development of iron deficiency anaemia. Firstly, there is iron depletion, where the body’s iron stores are reduced, followed by iron-deficient erythropoiesis where there is decreased iron levels included in developing red blood cells. Finally iron deficiency anaemia develops when there is decreased iron levels in the blood and red blood cells become misshapen. There are a wide range of markers used to detect this process, but many are not as sensitive when used in young children, thus extra care must be exercised to use the correct cut off points. Risk factors for iron deficiency anaemia include low birth weight, high cow’s milk intake and low intake of iron-rich foods. This paper aimed to review iron requirements in infants and toddlers and make corresponding recommendations.
Full-term, normal birth-weight infants have some iron stores, approximately 25% of their total body iron. Infants have a low requirement for iron until around 6 months of age, as iron is transferred from stores to the blood and back again at a rate that can be maintained. This is how infants can meet iron requirements while exclusively breast-feeding despite the low concentrations of iron in breast milk. Between 6 and 24 months of age the infant depends on additional iron from dietary sources. During this time the iron requirements per kilogram body weight are higher than in any other period of life, due to the rapid growth.
There are multiple potential health risks to iron deficiency in childhood and infancy. Neurodevelopment is the primary concern, as iron is crucial for the rapid growth of the central nervous system in the first years of life. Several studies have shown an association between iron deficiency anaemia in infancy and long-lasting poor cognitive and behavioural performance. Following this, iron supplementation has been shown to have a modest positive effect on mental development, and this is more pronounced in children who were initially anaemic. This was also more effective in children over 7 years of age, and there is no effect of iron supplementation on neurodevelopmental outcome in children under 2 years of age. However, there are possible negative effects of iron supplementation. Infants and children are at higher risk of iron overload, and this has been seen to increase risk of infections and impaired growth in infants.
The timing of umbilical cord clamping has large implications for iron deficiency. A significant amount of blood moves into the infant through the umbilical cord in the first few minutes after birth. Delayed cord clamping has been shown to significantly reduce the proportion of iron-deficient infants at 4 months of age, without any increased risk of adverse events3. Compared with dietary intervention, delayed cord clamping is a more effective and safe alternative and is therefore recommended for all newborns. Low birth weight infants are at increased risk of iron deficiency anaemia, as they have lower total body iron at birth and a more rapid relative growth rate leads to a greater dietary iron requirement. There are a few studies showing that iron supplementation reduces iron deficiency in this cohort, without adverse effects.
There is no convincing evidence that iron supplements should be provided to normal weight, breast fed infants during the first six months of life and is therefore not recommended. However, iron fortification of infant formula appears to be necessary. Absorption of iron from breast milk is thought to be around 50%, however absorption from infant formula and iron-fortified complementary foods is usually approximately 10%4. The bioavailability of iron in infant formula is thus much lower compared with breast milk, therefore infant formulas should have an increased concentration of iron. Yet, there has long been controversy over the exact concentration which should be used. The American guidelines suggest 10 to 12 mg/L of iron, whereas the ESPGHAN-coordinated global standards suggest 2 to 8.5 mg/L. The higher levels are based on the theoretical iron requirements from 0 to 12 months, however the iron requirements during the first 6 months are extremely low. Further studies are needed to determine the optimal levels for infant health.
As there is a large increase in iron requirements after 6 months of age, it is thought that the iron concentration in follow-on formulas should consequently be increased. There is some evidence that iron-fortified follow-on formulas reduce the risk of anaemia, however there has been one study showing that there was a negative effect on neurodevelopment which raises concern. These studies are difficult to conduct as the infants will be consuming different complementary foods which will affect their iron stores often more than the follow-on formula. Despite this, iron fortification of follow-on formulas to 10-14 mg/L iron is still recommended. In addition, iron-rich complementary foods are recommended for all infants after 6 months of age.
Exclusive breastfeeding after 6 months has been associated with an increased risk of iron deficiency anaemia, and accordingly there are some recommendations that these infants should receive iron supplementation. However, some have questioned this as there is little experimental evidence to prove it is effective in improving infant health. The evidence is only strong in populations with a high prevalence of iron deficiency anaemia. The same can be said for toddlers.
Further studies remain necessary to answer some important questions regarding iron supplementation in infants. Studies should focus on elucidating the optimum level of iron fortification in infant formulas and follow-on formulas. More long-term studies are also needed to investigate long term health effects, such as those on neurodevelopment.
- McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr. 2009 Apr;12(4):444-54. doi: 10.1017/S1368980008002401. Epub 2008 May 23. PMID: 18498676.
- Bramhagen AC, Axelsson I. Iron status of children in southern Sweden: effects of cow’s milk and follow-on formula. Acta Paediatr. 1999 Dec;88(12):1333-7. doi: 10.1111/j.1651-2227.1999.tb01046.x. PMID: 10626517.
- Andersson O, Hellström-Westas L, Andersson D, Clausen J, Domellöf M. Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: a randomized trial. Acta Obstet Gynecol Scand. 2013 May;92(5):567-74. doi: 10.1111/j.1600-0412.2012.01530.x. Epub 2012 Oct 17. PMID: 22913332.
- Domellöf M. Iron requirements, absorption and metabolism in infancy and childhood. Current Opinion in Clinical Nutrition & Metabolic Care. 2007 May 1;10(3):329-35.