Iron deficiency and impaired child development

Iron deficiency affects 20% to 50% of the world's population, making it the most common nutritional deficiency.¹ In developing countries about half of all cases of anaemia in women and children result from iron deficiency, but other important and often coexisting contributors include malaria, hookworm infestation, HIV, and deficiencies in other nutrients such as vitamin A and folates.²,³ Conversely, anaemia is just one manifestation of iron deficiency, and there are forms of mild to moderate iron deficiency in which anaemia is absent but tissue function is impaired.

In children iron deficiency develops slowly and produces few acute symptoms. As the deficiency worsens children become pale and weak, eat less, and tire easily. They gain weight poorly, have frequent respiratory and intestinal infections, and may develop pica. The most worrying association is that between iron deficiency and impaired development in behaviour, cognition, and psychomotor skills. Over the past three decades many studies have confirmed this relation, but whether iron deficiency is the sole cause of these deficits remains unclear. Last year a panel of experts concluded that a “significant body of causal evidence exists linking iron deficiency anaemia and child development.”⁴ A definitive link was excluded, because anaemia is associated with many other disadvantages such as poverty, low birth weight, malnutrition, poor education among mothers, and lack of stimulation in the home—all of which also affect child development.

A consistent finding in different countries is that severe, chronic iron deficiency in infancy identifies children with poorer cognitive function and lower scores in school achievement tests, suggesting that irreversible abnormalities result from a deficiency at a critical period of growth and differentiation of the brain.⁵ Poorer function, however, may also result from psychosocial and economic disadvantage.

How reversible, then, are these effects? A Cochrane review concluded that cognitive or psychomotor skills in anaemic children aged less than 3 years failed to improve within 5-11 days of giving iron. Trials with longer periods of supplementation have mostly lacked randomised placebo groups and failed to show benefits, but one of two small randomised studies found a clear benefit.⁶ In anaemic children 3 years or older the advantages of iron supplementation are more convincing: six of eight double blind trials showed benefits in measures such as achievement at school, concentration, efficiency, discriminant learning, short term memory, and IQ.⁷

The paper by Stoltzfus et al in this week's issue (p 1389) is an important contribution.³ Their finding of significant improvements in motor and language development after 12 months of supplemental iron is strong evidence that replenishing iron can positively influence development even in children with severe anaemia and iron deficiency. The study's large sample size and double blind design allow stronger causal inference. The paper also helps to clarify the contribution of anaemia and iron deficiency to developmental delay, indicating that although iron's effect on motor development is mediated through improved haemoglobin concentrations and oxygenation, development of language is promoted through other independent mechanisms.

What is the appropriate public health response to the high burden of anaemia and iron deficiency in preschool children in poor countries? Preventing iron deficiency is the obvious response. Promoting exclusive breast feeding for the first six months of life and providing appropriately fortified weaning diets is the best way forward; but, at best, 10% of mothers breast feed exclusively for six months in many poor countries, and diets can improve only if poverty is reduced.⁸ Fortification of food has been successful in developed countries but less so in the developing world—most poor families cannot afford infant foods fortified with iron. Currently, targeting pregnant women and young children for iron supplementation is the preferred strategy. Supplementation, however, is costly, distribution mechanisms are often ineffective, and compliance is low. Furthermore, the World Health Organization has said that, for maximum effectiveness in controlling anaemia, “integration should be sought with malaria prophylaxis, hookworm control, immunisation and environmental health programmes as well as programmes for prevention of micronutrient malnutrition and community based primary health care.”⁹ Unfortunately, implementation strategies have not kept pace with better scientific understanding of the disorder, and the gap between the necessary and the practical remains unbridged. There is no real prospect of a new generation of smarter and stronger children, replete with iron.

Is preventing iron deficiency in children a priority in areas with few resources? It has recently been proposed, somewhat idealistically, that as a minimum goal no child under two years should be allowed to become anaemic.¹⁰ Fortification of staple foods (cereals, flour, sugar, salt) to deliver micronutrients to children on a large scale is probably the most sustainable and affordable option, even though commitment from governments and the food industry is needed. Supplementation is a much less attractive alternative, and scarce resources may be better spent on increasing coverage of vaccination against measles and hepatitis B, supplying bed nets impregnated with insecticide in malarious areas, or improving access to nevirapine to prevent mother to child transmission of HIV. These are tough but unavoidable choices.

Papers p 1389