Iron Deficiency in Children: Detection and Prevention

Despite a plethora of papers, reports and consensus statements during the last 25 years concerning the high prevalence and complications of iron deficiency (ID), the problem is still with us. A recent national study in Britain showed that 12% of 2-year-olds were anaemic, rising to 29% in Asian immigrant groups (Lawson et al, 1998). What can be done about it? This paper reviews detection and prevention of iron deficiency anaemia (IDA) referring mainly to studies published in the last 5 years. Earlier substantial reviews of iron nutrition are available (Brock et al, 1994; British Nutrition Foundation, 1995; Hallberg & Asp, 1996). Reviews specifically related to children include those by Oski (1993) and Wharton (1999a). Detection is divided into indications for investigation, which investigations to apply, and their interpretation. There are obvious indications for determining iron status in some clinical presentations. An example is suspected malabsorption. One study found that an oral iron absorption test was more sensitive as a screening test for upper intestinal absorption than the commonly used D-xylose method (Stahlberg et al, 1991; De Vizia et al, 1992). Other deficiencies often coexist with ID partly because a poor diet may have many deficiencies but also because of micronutrient interaction, e.g. ID with deficiencies of vitamin A or D (Gujral & Gopaldesas, 1995; Underwood & Arthur, 1996; Wharton, 1999b). ID may play a role in or complicate such diverse disorders as ischaemic stroke, apparent asthma, cyanotic heart disease and gastric trichobezoar (Hartfield et al, 1997; Hetzel & Losek, 1998; Olcay et al, 1996; Phillips et al, 1998). In my view any child reaching hospital as an outpatient or inpatient should have their haemoglobin level and RBC indices determined. Some specialities argue this is unnecessary since the haemoglobin distribution in their patients is no different to that in the general population (e.g. in otolaryngology; Heaton et al, 1991). This seems a lost occasion for opportunistic screening for a common disorder. Clinical signs are helpful only in severe anaemia, but surveys show that pale conjunctivae (sensitivity 74%) and nail beds (specificity 96%) are useful signs (Thaver & Baig, 1994). Blue sclerae might be an extra sign (Beghetti et al, 1993). The highest prevalence of iron deficiency anaemia (IDA) occurs in toddlers and adolescents because the increment in haemoglobin iron per unit body weight is greatest at these ages (see Fig 1). . Changes in body iron during development: (a) total body iron and haemoglobin iron (mg) in males except where shown; (b) daily increment in body iron (mg/d): —-, male; - - - -, female; ...., female plus menstrual loss; (c) proportional daily increment in body iron (μg/kg/d); symbols as for (b). Two points should be noted. There is little increase in total body iron in the first 4 months or so of life. As the haemoglobin falls from around 18 g/dl at birth to 14 g/dl during the first 2 weeks of life the liberated iron is stored and then gradually reused as the total mass of circulating haemoglobin begins to increase with growth. Between 4 and 12 months total body iron increases by about 130 mg, and an external source of iron is necessary. If not met, ID occurs and frank anaemia develops usually after the first birthday. Note also that boys need more iron at adolescence because of the increase of muscle and myoglobin. Subsequently these increased requirements due to changes in body composition subside, but increased requirements continue in girls following menarche. Infants who continue to receive only breast milk after the first 6 months of life are at increased risk. Breast feeding may continue after 6 months without difficulty so long as other foods providing available iron are introduced. Also at risk are infants who, despite current policy, are changed from an infant formula to whole cows' milk before the age of 1 year. It is not clear whether the higher prevalence of IDA in these infants is mainly the effect of an inadequate intake of dietary iron or due in addition to increased intestinal iron loss (Ziegler et al, 1990; Fuchs et al, 1993a, b). In toddlers attending well child facilities in Cleveland, U.S.A., a simple dietary history predicted microcytic anaemia (sensitivity 71%, specificity 79%), but a quarter of the anaemic children were not identified (Boultry & Needlman, 1996). A community study in Sydney found a low consumption of meat (i.e. haem iron) and introduction of whole cows' milk before the first birthday were significant indicators of ID (Mira et al, 1996). Many adolescent girls try to control their weight and inadvertently limit iron intake. This was particularly marked 10 years ago in British girls who bought snacks from local shops rather than eating school lunch or food from home, but there has been evidence of improvement since then (Department of Health, 1989; Moynihan et al, 1994; Southon et al, 1994; Doyle et al, 1994). Many adolescents pass through a temporary period of vegetarianism because of concerns with animal welfare. Although adequate iron nutrition is achievable on a vegetarian diet it must provide iron sources (such as pulses) and enhancers of absorption (e.g. vitamin C and fish or poultry if acceptable), and the temporary amateur vegetarianism may not ensure sufficient absorbed iron. Preterm babies are born with a lower concentration of haemoglobin, so any physiological haemolysis liberates less iron for stores; erythropoietin, if given, increases iron requirements, and so does catch up growth. Light for gestational age babies often have a raised haemoglobin at birth reflecting intrauterine hypoxia, and so initially, post haemolysis iron stores are higher but the rapid catch-up growth increases demands. In a normal term baby the total haemoglobin mass doubles during the first year of life (from 180 mg at birth to 340 mg at 1 year). In a preterm 1 kg baby the increase is 6-fold (50–300 mg). In a 2 kg baby born at term the increase is 3-fold (110–330 mg). Children of immigrants or refugees have a higher prevalence of iron deficiency, presumably due to such factors as socio-economic deprivation (living in inner city areas with overcrowding and limited parental income), language difficulties (health education is difficult), unfamiliarity with foods available in the new environment (often a tendency to rely on milk and puddings), food customs which are difficult to follow (e.g. halal meat for Muslims may not be easily available and so children are given a meat-free diet by a mother inexperienced in providing a balanced vegetarian diet). In a nationally representative survey of British 1.5–2.5-year-olds 12% had IDA but among children of immigrant families it was higher: India (20%), Pakistan (27%) and Bangladesh (29%) (Lawson et al, 1998). Other recent reports describe the problem in children from South-East Asia, Latin America and Eastern Europe living in U.S.A., Norway and Switzerland (Graham et al, 1997; Sargent et al, 1996). Athletic performance, particularly endurance sport, may lead to blood loss from the gut and urinary tract (Robertsson et al, 1987; Haymes & Lamanca, 1989). Therefore athletic girls who have passed menarche and are trying to slim may be at particular risk of iron deficiency. The staging of iron status by Oski et al (1983) is a useful concept and various measurements can be used to define the stages. Iron stores and erythropoiesis normal. Erythropoiesis normal but iron stores reduced (serum ferritin <12 μg/l) indicating a reduction of iron in the bone marrow, liver and other parts of the reticuloendothelial system (note that the exact cut-off point for normal/abnormal ferritin depends on the method used; a reference ferritin preparation to calibrate the assay is recommended). (i) Abnormal RBC biochemistry (free erythrocyte protoporphyrin (EPP) >99 mmol/mol haem; serum transferrin receptor raised, e.g. >8.5 mg/l but exact cut-off depends on age and the assay used); (ii) abnormal RBC morphology (microcytosis, MCV <80 fl, varying with age; anisocytosis, RDW > 15%); (iii) transport iron reduced (transferrin saturation <10%). The above plus haemoglobin <11 g/dl. There is no evidence that iron depletion or iron-deficient erythropoiesis alone have any adverse clinical effects, whereas iron deficiency anaemia is associated with alterations of immunological, gut and mental function. In the recent NHANES survey in the U.S.A. (Dallman et al, 1996) ID was defined as the presence of or more abnormal measurements as in Although can argue about the exact cut-off points used and the need for abnormal this of was to a of children and the haemoglobin (i.e. after children with more than abnormal are reference (see A recent survey in has a cut-off point for haemoglobin concentration in and as low as 10 but no was to iron-deficient children and the haemoglobin method used was the et al, It be to the whole of investigations in and for population and studies have been et al that haemoglobin alone be used in The of haemoglobin are in children and If the distribution is to the in children and of child age but not in then iron deficiency is If the distribution is to the in as then other factors are as e.g. or This has been used to dietary ID in iron from in and iron (from in et al, 1996). The has been in for children years of age in anaemia was associated with a low ferritin et al, 1996). on or are in common in The of iron deficiency may then be from the is of of blood rather than only of and in such as and distribution some are also available in which is haemoglobin concentration for & have the of blood and to high and for in g/dl about and about and in & (1993) have the of distribution and in in iron deficiency anaemia and MCV are RDW is increased (i.e. and haemoglobin distribution is increased (i.e. and the of the is and to the with a of in the microcytic a to iron are in the for and haemoglobin and the more in the The of these more to population screening has not been et al that a blood is a of community In their as well as had due to iron deficiency and et al that MCV and RDW be and this increases the for iron deficiency to & found RDW a useful of disease in the well baby alone has been used for screening and as an for a of iron in some et al, 1991; & 1994). In iron deficiency the iron in the protoporphyrin only of blood and is easily in a It also abnormal for a or if iron before the it is also abnormal in the of and in lead ferritin may also be on blood but of and of a reference ferritin preparation for are It is raised during disease and liver disease of the iron but iron deficiency is the only of a low transferrin receptor concentration has raised The concentration the of transferrin on and so in also the of bone Iron deficiency, also in an increase in the concentration et al, An increased concentration an and sensitive of iron deficiency, before the ferritin has et al, 1990; A is that it normal in many disorders if iron deficiency is not it is raised in the iron deficiency is not As in in infants and boys higher of the receptor were associated with a lower serum ferritin the normal physiological for ferritin et al, as an of iron deficiency in and adolescence has been et al, 1998; et al, 1998; et al, et al, 1996). It be to the test alone without other measurements of ID as of and various and lead may difficulties of interpretation. from the of are are associated with iron of but a of children have been with ID because of a in absorption The RBC in IDA and the have The of and the RDW is usually higher in particularly in to the of of indices have been to the the of is than the of microcytic in iron deficiency, whereas the is in et al, 1992). In there also may be an increase in there is any of a it is usually to to haemoglobin and but iron deficiency in with may the changes in and In a study a of with had a raised and so a quarter of those with haemoglobin or that may be abnormal in but the exact iron status of the was not defined (Graham et al, 1996). The of and are and but and in about a of after a many measurements in the as occurs in but ferritin and serum transferrin receptor normal (see reviews by and et al, the other such as not with the of and ferritin in the if ID of et al, In disease such as is Although measurements ID may be due to ID by bone may also serum transferrin receptor is raised in a of iron erythropoiesis which may to iron et al, 1996). The anaemia is and but ID is often as the RBC is raised, not because of iron to protoporphyrin to haem but because which the is by There is evidence iron deficiency with an increased risk of lead et al, 1995; et al, 1996). Some years ago anaemia with for but as lead has the is less If in the blood lead should be and the to iron noted. and reduction in blood lead following are less in iron-deficient children et al, 1996; et al, is a of and the before If at the age of 18 many children have been anaemic for some If e.g. months at the of a of children not anaemic then so some months In a quarter of children found to be anaemic at the age of 2 years had not been so at months et al, 1993). An age for screening is not children in particular groups might be if the prevalence of IDA is high in the e.g. in inner city children of immigrant or and toddlers in cows' milk was the before 12 months of have e.g. the for in of in such as the British and Nutrition many and & 1996). loss should be with which as the usually The of may In infants in the was not had had a higher at 2 months of age; this had no effect on serum ferritin at months of age in children et al, 1997; et al, of iron at birth is in haemoglobin, blood loss is a of anaemia in and the other stores in show little to the iron some studies in the and have Two have that iron status in is associated with a iron status in the infants at 1 year of age 1996; et al, This a effect of reduced iron stores or that mother and child have an iron-deficient babies there is little because total body iron does not increase during this If ID occurs then abnormal blood loss should be This may in the period or (e.g. from gastric in a of Breast feeding is or that a infant formula is the age 6 months a dietary source of iron is necessary. babies this is easily by of an infant formula which is iron or introduction of a of which are iron Breast milk alone not the extra iron but absorption of the of iron is This is less in babies formula or a and babies to receive foods from an age than et al, Although there is evidence that an introduction of foods with iron absorption from breast milk et al, should be from 6 months of because of haem is an providing as which may also a in breast A study showed that an intake of of meat a from the age of months to an intake of 10 to lower falls of haemoglobin in there were no on serum ferritin or transferrin receptor et al, 1998). many who continue to breast their infants vegetarian foods from which iron is less foods are available in the and some are with iron. of these foods a more diet less and than a diet alone & et al, in the of iron to children from about 4 months rather than the risk of which have low iron et al, 1998). In Britain of the total iron intake of children years is by as haem by such as and and This diet the for ages but not for toddlers age years intake was of is for girls of (Department of Health, 1989; et al, the total intake is only of the The absorption of iron is by the composition of the the of the and of haem iron increases anaemia is but is little by other of the of iron is by vitamin other in and such as and and animal is by and reviews specifically for and The of iron absorption is also by body the of and The receive from these factors to absorption are not In foods are less available at and and are higher et al, 1998). the other some foods are in iron to iron status than if are used & 1998). is used as a source of iron in et al, The role of cows' milk in intestinal blood loss has been to In many parts of the is the common of blood There are control at control of of of simple for and should be to children as with iron et al, 1998; et al, is less as a of anaemia, and have been as less of iron deficiency as a population problem et al, 1996). a clear should be a simple of is but of eating customs and is education have been e.g. in a in prevalence of microcytic anaemia at months from to during a but because it had to a 2 years et al, 1993). have not been In a reaching about children in a of about of children in the and control groups were anaemic at 18 months of age et al, of foods may be if their to the is reduced of by from a or a The example is the and Infants and Children in the U.S.A. infant and are of to about a quarter of the was the prevalence of iron deficiency anaemia has and is less than in many other (e.g. in U.S.A. the prevalence of IDA among is Britain et al, 1997; et al, A recent showed that those the had less anaemia and a iron status than those who were not & The British to families on or the mother to an infant formula of which are in or whole cows' milk which little iron. are not are Many other have but many are on milk for and does little to iron The in iron of infant is in the U.S.A. about 12 mg/l and in Europe up to mg/l In without iron are by the current and in are around 4 mg There are to little or no iron to in the first months of life 1996). (a) body iron increases little during this breast milk only of and iron may have adverse on the & Wharton, 1991; et al, (b) higher the absorbed is only a little more iron in the gut (c) infants an infant formula with no or of iron in the first 4 months of life not ID et al, & 1996). infant used at this age iron. about 6 months of age more dietary iron and a of a intake The usually a formula but the level of is e.g. of a infant formula or an infant formula or introduction of a of these is to the introduction of cows' is that in in a level of lower than used can be in adequate absorption iron e.g. mg et al, mg et al, 2 mg et al, but the of were for months only and not follow infants into the year of life anaemia is iron infant in the of mg/l to provide 1 mg of absorbed iron et al, 1998). A is which of an infant formula iron Many studies have the effect of of cows' milk on iron status in infants months and in toddlers in the year of life. It is not to this the effect of a intake of or is due also to of an formula such as the absorption of iron because of the higher vitamin C less of absorption because of the lower of and study found that the addition of not iron et al, or less milk and iron the iron and the are British studies of the of or cows' milk from the age of 6 months that ID was in those an iron more common in those an formula and in those on milk et al, 1996; et al, 1997; & Iron is to a of particularly The are the and the with other of the iron. is well absorbed but it the of to and changes to is limited or rapid from to of and with was to school children and reduced the prevalence of iron deficiency from to et al, 1996). of if are well absorbed but have a if less the effect is less but so is the absorption An is to haem iron as the in effect blood to the food This in less ID and higher haemoglobin in in infants and school children et al, 1990; et al, 1993). A recent study in a of British showed iron from a meat and or a meat and was no higher if haem iron was than if were the to 6 et al, 1998). and with iron are commonly and are also with vitamin iron is not by does not and less than a and it is not as for general general reviews of iron and Other foods which have been with iron for consumption by children include in et al, milk also with vitamin C in et al, and in et al, 1992). is not for prevention because a is into the and is of oral iron have been is and in studies in are as as a daily because a daily the absorption of the for a and have this evidence to animal studies or particularly during but some in children are e.g. in et al, & et al, and et al, and also in in an improvement in growth as well as iron status was et al, 1997; et al, about this & found the absorption of iron by was whether daily or were given and the or need for to the daily can be found in the following the of the paper 1996; 1996). the of in serum in et al, have a A of British toddlers iron given at 2 months increases the risk of but oral iron was used in the prevalence of severe anaemia and not the of et al, The of micronutrient in is by and There is a of of different in A given in the absorption of but not are in e.g. a et al, 1991). The may be a for iron in a food or if given as a only those extra iron receive There is some raised measurements of iron heart and in but no can be and the of the raised measurements may rather than a high intake (see the reviews to British Nutrition Foundation, 1995; Hallberg & Asp, 1996). the of adverse of iron in children should be If an more dietary iron than need the control iron absorption there is increased erythropoiesis or (e.g. in or as is What is the effect of any unnecessary in breast milk is an in the in the evidence in is but if with iron the effect is Despite the of evidence in it is to iron in babies breast milk in the first 6 months of life. The addition of iron to an infant formula which of does not is not an in the of intestinal in in et al, Iron deficiency anaemia is common in particularly in toddlers living in inner city areas or children of also the problem but less Although the of microcytic anaemia and as well as iron deficiency, is usually not for prevention are as for any other deficiency, food and factors and of blood loss also need is the method of but extra of a to those who not need it is There seems little need to extra iron or during the first months of life. then dietary sources of available iron are many children not receive these sources in sufficient there is a for a of foods particularly can be by food by