Title: The diagnosis of iron deficiency in young children
Key words: iron, deficiency, micronutrient, children, cognitive function, psychomotor development, supplementation, fortification, haemoglobin, serum ferritin, iron status, transferring, zinc protoporphyrin, race, diet,
Date: Sept 2006
Category: Specific conditions
Author: Morgan, G
The diagnosis of iron deficiency in young children
Worldwide, iron deficiency continues to be the leading micronutrient deficiency (Hallberg 2000). Prevalence rates are highest in the developing countries but, even in developed countries with higher nutritional standards, iron deficiency remains a problem. Concern is greatest for the most vulnerable, of whom those under 2 years of age are at greatest risk, due to the depleted iron reserves and rapid rate of growth between 6-12 months of age. The rate of iron deficiency in this group in developed countries has been put at around 5% (Looker 1997).
The major concern associated with iron deficiency relates to its putative role in impairing normal brain development. Inadequate provision of iron during the first 18 months of life is thought to impair neurotransmitter function, cognitive function and psychomotor development (Roncagliolo 1998). Even with delayed supplementation residual long-term effects have been identified (Lozoff 2000). Analysis of the data is complicated by the presence of many confounding factors but, even allowing for these, iron deficiency appears to be a significant factor and one which is quantifiable, the impairment being related to increasing levels of deficiency (Hurtado 1999). Concern over the issue has helped to promote various public health measures such as the fortification of cereals and earlier weaning at 4-6 months.
Against this background, several criteria for the diagnosis of iron deficiency have been set. The WHO criterium for haemoglobin concentrations, for example, gives a threshold value of <110g/L for the diagnosis of iron deficiency in under 5 year olds (WHO 1998). Such figures, however, make no reference to the children under 2 years of age who are at greatest risk and take no account of cultural, geographic and other factors. As a percentile risk factor they may significantly overestimate the size of the problem: one UK survey (Emond 1996), for example, showed a 5th percentile cutoff level of only 97g/L for 8 month old infants. Serum ferritin levels are thought to be the most accurate measure of iron status, cutoff levels reaching their lowest at 9-12 months (Siimes 1974) but levels range from 12 microg/L at 8 months to 16 microg/L at 18 months in the UK (Emond 1996, Sherriff 1999) and are subject to diurnal variation and the effect of infection and inflammation (Hallberg 2000): after 6 months such factors render ferritin estimations unreliable, particularly in developing countries with high endemic infection rates (Aggett 2002). The same caveats also apply to serum transferrin levels (Aggett 2002). More recent tests such as zinc protoporphyrin (ZPP) and serum transferrin receptor levels do not have these drawbacks and are accurate indices of deficiency. Unfortunately they are not widely used and have not been calibrated across a wide spectrum of populations (Aggett 2000).
The lack of a precise definition of iron deficiency in very young children has led to the adoption of multiple criteria in the assessment of possible deficiency states (Expert Scientific Working Group 1985). Defining deficiency as the presence of at least 2 subnormal values for ferritin, MCV or ZPP, in one infant survey for example (Domellof 2001), reduced the incidence of iron deficiency (Hb<110g/L) in the population from 20% to 3%. The fact that an iron-supplemented group showed no reduction in the values of the chosen indices argues that the incidence of deficiency was indeed overestimated in this group.
In another Swedish study (Persson 1998), reducing the criteria of iron deficiency from the WHO serum ferritin level of 12 to 10 microg/L, reduced the incidence of deficiency from 25% to 16%. This dropped to just 7% if multiple criteria were employed diagnostically. There was no correlation between Hb and ferritin levels and, again, no variation of the selected parameters with iron supplementation. Such studies confirm that the levels of significant iron deficiency has been overestimated in developed countries. In developing countries, on the other hand, such protocols have confirmed the continuing presence of significant iron deficiency in the community. These facts argue for the adoption of more precise thresholds and the selection of multiple diagnostic criteria in order to define the extent of iron deficiency within a community (Aggett 2002). Such criteria can only, at best, serve as statistical guides as they do not truly reflect the functional and pathophysiology of the processes underlying iron deficiency. Other factors such as sex, race, diet, infection and vaccination need to be taken into consideration (Domellof 2002, Johnson-Spear 1994, Hallberg 1981, Walter 1997). Their role in iron deficiency and, indeed they are pathogenic or protective needs to be defined. Given the important role played by iron in brain maturation, it seems wise to continue with the present policy of supplementation but these and other factors need to be taken account of in future research.
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