Anaemia and Iron Deficiency Disease

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Anaemia and iron deficiency disease inchildren

Manuel Olivares, Tomds Walter, Eva Hertrampf andFernando PizarroInstitute of Nutrition and Food Technology (INTA),University of Chile, Santiago, Chile

Iron deficiency is the single most common n utrition al disorder world-wide and

the main cause of anaemia in infancy, childhood and pregnancy. It is prevalentin most of the developing world and it is probably the only nutritionaldeficiency of consideration in industrialised countries. In the developing worldthe prevalence of iron deficiency is high, and is due mainly to a low intake ofbioavailable iron. However, in this setting, iron deficiency often co-exists withother conditions such as, ma lnutrition , vitamin A deficiency, folate deficiency,and in fection . In tropical regions, parasitic infestation and haemoglobinopathiesare also a common cause of anaemia. In the developed world iron deficiency ismainly a single n utritional problem. The conditions previously mentioned migh tcontribute to the development of iron deficiency or they present difficulties inthe laboratory diagnosis of iron deficiency.

Correspondence to:Manuel Olivares,

Institute of Nutrition andFood Technology (INTA),

University of Chile, Macul5540, Casilla 138,

Santiago 11 , Chile

Iron deficiency is the single most common nutritional disorder world-wideand the main cause of anaemia in infancy, childhood and pregnancy. It isprevalent in most of the developing world and it is probably the onlynutritional deficiency of consideration in industrialised countries. Becauseof their high iron requirements, the most commonly affected groups areinfants, children, adolescents, and women of childbearing age andpregnancy1. In the developing countries, the prevalence is usually greatest

in infants and to a lesser extent in women; in contrast, in industrialisedcountries, it is present mainly in women due to the additional ironrequirements imposed by menstruation and pregnancy.

In the developing w orld , the prevalence of iron deficiency is high, an d isdue mainly to a low intake in bioavailable iron. However, in this setting,iron deficiency co-exists with other conditions such as, protein/energymalnutrition, vitamin A deficiency, folate deficiency, and infection2"5. Intropical regions, parasitic infestation and haemoglobinopathies are also

The prevalence of these pathologies is higher in lessc o m m o n3 -5

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Iron deficiency in children

developed countries than in areas with intermediate development. In thedeveloped world iron deficiency is mainly a single nutritional problem.The conditions previously mentioned might contribute to the develop-ment of iron deficiency or they present difficulties in the laboratory

diagnosis of iron deficiency.

Aetiology and pathogenesis of iron deficiency

Nutritional factors are the most frequent causes of iron deficiency ininfancy and childhood. The main aetiologies of iron deficiency at thisperiod of the life cycle are: (i) decreased iron stores at birth (preterminfants, twins, perinatal bleeding, early clamping of umbilical cord) (ii)inadequate iron supply (reduced dietary iron and/or low bioavailability ofdietary iron); (iii) increased iron requirements imposed by growth; and (iv)increased iron losses (gastrointestinal blood loss, diarrhoea). Ironrequirements of infants are not covered by their usual diet, which ismainly based on milk. This problem is more severe in children fed cows'milk, where the iron present is poorly absorbed6. Infants who are fedcows' milk starting in early infancy and those who are fed milk that is notiron fortified are at highest risk for the development of iron deficiency.The situation becomes critical when iron stores at birth are reduced. Inolder children, because of their slower growth rate and their more varieddiet, nutritional iron deficiency anaemia is less prevalent (when present it

is usually carry-over from earlier infancy) while other aetiologies becomemore prevalent, gastrointestinal blood loss among them.

When dietary iron cannot fulfil the requirements, a fall in body storesoccurs (iron depletion), which is characterised by a drop in serumferritin (SF) below 12 ng/1. If this negative ba lance persists, iron tissueavailability is compromised (iron deficient erythropoiesis). At this stage,an early progressive rise in the concentration of serum transferrinreceptor (TfR) values occurs, followed by an increase in free erythrocyteprotoporp hyrin (FEP), a decrease in transferrin saturation (Sat), and theslow fall in haemoglobin (Hb) begins7. If the iron deficit continues, the

last stage becomes evident when Hb falls below -2 standard deviationsfor that given population,i.e. iron deficiency anaemia.

Dietary iron absorption

The amount of iron absorbed from the diet is dependent on threefactors: (i) the quantity of iron; (ii) the composition of the diet; and (iii)the behaviour of the mucosa of the upper small bowel where two major

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Micronutrients in he alth and disease

factors that affect iron absorption occur: the body iron stores and therate of erythropoiesis8.

The effect of the composition of the diet is based on: the type of iron(haem or non-haem); amount of haem iron, specially as meat, the content

of calcium in the meal, food preparation (time, temperature), iron statusof the individual, amount of potentially available non-haem iron(adjustment for fortification iron and con tamination iron) and the balancebetween enhancing (ascorbic acid, meat/poultry/fish, fermented foods)and inhibiting factors (phytate, polyphenols, calcium, soy protein).

There are two kinds of iron in the diet with respect to the mechanismof absorption haem iron and non-haem iron utilising two differentreceptors on the mucosal cells. After the uptake of haem iron into themucosal cells, the porphyrin ring is split by the haem-oxygenase withinthe cells and its iron is released. Non-haem and haem iron then have a

common pathway and leave the mucosal cells in the same chemicalform, utilising the same transfer system to the serosal side of the mucosalcells. Receptors on the luminal side probably compete for non-haemiron with complexing luminal ligands for the iron ions11.

Haem iron in meat and meat products constitute abou t 5-1 0% of thedaily iron intake in most industrialised countries. In developing coun-tries, the haem iron content of diets is usually negligible. Its absorptionis less influenced by body iron stores than non-haem iron12. The averageabsorption of haem iron in meat containing meals is about 25%,calcium being the only dietary factor that negatively influences theabsorption of haem-iron13.

Non-haem iron is the main form of dietary iron. The main sources arecereals, vegetables, pulses, beans, fruits, etc. The absorption of iron fromiron fortificants and contamination iron is influenced by the same hostand dietary factors as the native iron.

Studies of iron absorption from various representative meals havebeen done primarily in adults, but the results are also pertinent to themixed diet in late infancy. Absorption of non-haem iron from a mixedmeal is about 4 times greater when the major protein source is meat, fishor chicken in comparison to the dairy products, milk, cheese or eggs.

Term infants are protected from iron deficiency by their endowment at

birth and the iron supply from breast milk during the first 6 months oflife. The basis for the excellent absorption of iron from human milk isnot known. From this age on, iron status is mainly dependent on ironsources in the diet14. The increasing use of iron fortified formulae andiron rich weaning foods have determined a decrease of iron deficiencyanaemia among infants in highly developed countries15. The appropriatelevel of iron to fortify formulae is still under discussion. Recent evidenceshows a high iron bioavailability in these products, which is acompelling argument for lowering the level of iron fortification in North

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260 D ie t A D ie t B

V i t . A V i t . C F o l a t e Iro n Z i n c

Fig. 1 White rice based diets: percentage of recommended nutrient density per 1000kcal. Diet A composition: wh ite rice 598 g and vegetable o il 25 g. DietB composition:wh ite rice 428 g, vegetable oil 25 g, carrots 21 g, orange 60 g, beef 35 g, spinach raw 50

g, and lentils 45 g . Recommended nutrien t density of micronutrients was based on th erecommendations of the FAO/WHO".

D ie t A D ie t B

Vi t . A V i t . C F o l a te I r o n Z i n c

Fig. 2 Corn -tortilla based diets: percentage of recommended nutrien t density per 1000kcal. Diet A composition: corn -tortilla 368 g and vegetable oil 25 g. DietB composition:corn-tortilla 266 g, vegetable oil 20 g, carrots21 g, orange 60 g, beef 55 g, spinach raw 50g, and black beans 45 g. Recommended nutrient density of micronutrients was based onthe recommendations of the FAO/WHO".

American formulae1617. Home prepared complementary foods, based on

cereals and legumes fed to weanlings in the less developed world wheremost of the children younger than 2 years reside, contain relatively highlevels of phytic acid and negligible amounts of ascorbic acid or meat.

School-age children and adolescents at a global level are affected byseveral micronutrient deficiencies, because at presently staple foods suchas wheat, rice, corn or potatoes make up the largest proportion of thefood supply. Uauy and Oyarzun explored the adequacy of food patternsbased predominantly in rice and corn18. Theoretical d iets were developedand complemented with low cost micronutrient rich foods. The foodportion size considered in this exercise represent the usual amount eaten

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Micronutrien ts in hea lth and disease

in a meal or provided by a 1000 kcal food tray. Vitamin A, vitamin C,folate, iron and zinc were selected. The nutrient density of plain rice andcorn plus a regular portion of vegetable oil as a fat source was analysed.The content of selected micronutrients was computed per 1000 kcal. As

shown in Figures 1 and 2 in terms of percentage recommended nutrientdensity, both diets provide no vitamins A or C, and very low levels offolates, iron and zinc. Following a food based approach to improve themicronutrient content of the diets, small portions of carrots, orange,beef,spinach, and lentils or black beans were added. In both cases, allmicronutrient needs were covered (Figs 1 & 2).

Interactions b etween iron and vitamin A

Vitamin A is important not only for visual function but also for normaldifferentiation of various tissues. Early reports demonstrated anaemia andreduction in haemopoietic tissue in severe vitamin A deficiency.Thereafter, an array of epidemiological studies have shown that vitamin Adeficiency and anaemia often co-exist and that there is significant assoc-iation between retinol and biochemical indicators of iron deficiency20"21.

The re are several hypotheses to explain this interrelation: (i) that impro v-ing vitamin A status improves mobilisation of iron from the tissue stores;(ii) that vitamin A decreases infection and thus improves iron status; and(iii) that vitamin A improves iron absorption.

It is of interest to note that interactions are found only in vitamin Adeficient populations and no demonstration of these effects has beenshown in vitamin A sufficient subjects.

Animal experiments show that supplemental vitamin A enhances therecovery from iron deficiency in rats with chronic vitamin A deficiency.Vitamin A supplemen tation during the period of iron treatme nt produce da depletion of spleen and tibia iron concentration22. Other authors foundalso decreased liver iron in a similar experiment. Supplemental vitaminA also produced a reduction of Hb probably explained by a decrease inthe degree of haemoconcentration seen in vitamin A deficiency. Thesestudies in experimental animals suggest that supplemental vitamin Aduring iron repletion contributes to optimum erythropoeisis and ironmobilisation when baseline vitamin A status is impaired.

Several studies in anaemic children and pregnant women in endemicvitamin A deficient regions have shown a beneficial effect on iron statuswith vitamin A supplementation21-23"25.

Mejfa and Chew in Guatemala studied 99 children, 1-8 years of age,divided in 4 groups2 3. Each group was supplemented for 2 months with:(i) vitamin A; (ii) iron; (iii) vitamin A plus iron; or (iv) placebo. Vitamin

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A elevated retinol, Hb, serum iron (Fe) and Sat. Iron alone did not affectretinol but improved haematological and iron nutrition indicatorsincluding total iron binding capacity (TIBC) and SF. The conco mitantsupplementation of vitamin A and iron resulted in a better response of

Fe and Sat saturation than either alone. This study suggested thatvitamin A benefits haematological condition and iron metabolism.

Two studies showed the effect of a single oral massive dose of vitaminA on iron metabolism21-24. Kahn et al studied a group Pakistani children,of whom 16% had low serum vitamin A and 2% were deficient21: 42children were supplemented with a single oral vitamin A dose and 53children received p lacebo. After 6 weeks, there were significant differ-ences between the 2 groups for retinol, retinol binding protein andhaematocrit (Htc). However, no significant difference could be found forH b, red blood cell count, mean corpuscular volume, mean corpuscular

haemoglobin concentration, Fe, transferrin, andSF. In the ano ther study,a group of 134 school children, with signs of conjunctival xerosis, fromThailand were selected for a controlled study on the short-term effect ofa single, oral high dose of vitamin A on iron metabolism24. Childrenwithin villages were randomly assigned to receive the vitamin A or serveas control subjects. Two weeks after supplementation, significantincreases of retinol, retinol binding protein, Hb, Htc, Fe, and Sat werefound in the supplemented group. SF concentrations did not changesignificantly. These two studies provide further evidence of a causalassociation between vitamin A and iron metabolism.

The anti-infective properties of vitamin A are well know n, and there issome suggestion that the benefits of vitamin A on iron status may be doto reduced level of infection26.

Garci'a-Casal et al have shown the enhancer effect of vitamin A and P-carotene on non-haem iron absorption from Venezuelan cereal-baseddiets27. Vitamin A increased iron absorption up to 2-fold for rice, 0.8-fold for wheat and 1.4-fold for corn; |3-carotene increased absorptionmore than 3-fold for rice and1.8-fold for wheat and corn. The authorssuggested that both compounds prevented the inhibitory effect ofphytates and polyphenols on iron absorption, because both compoundsmay form a complex with iron , keeping it soluble in the intestinal lum en.

Pathological blood loss

The digestive tract is the most frequent source of occult bleeding.Gastrointestinal blood loss may occur during the first months of lifewhen infants are fed fresh or pasteurised cows' milk, or during repeatedepisodes of acute diarrhoea, or less frequently, in cows' milk proteinallergy28-29. Alaskan natives have shown a high prevalence of iron

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deficiency anaemia despite an adequate iron intake. This population hasan increased frequency of elevated stool haem concentration30-31 . Thegastrointestinal blood loss has been attributed to an altered plateletfunction due probably a high intake of (n-3) fatty acid from marine

mammals and f ish30, or caused by chronic active gastritis associatedHelicobacter pylori infection31 .

In tropical areas, pathologic bleeding due to infestation with parasites isa contributing factor to nutritional iron deficiency3"5. Hookworms(Necator atnericanus and Ancylostoma duodenale) are the most prevalentparasites related to iron deficiency32. These haematophagous intestinalparasites produce intestinal blood loss that is proportional to the parasiticload. When faeces contain 1000 eggs/g, daily blood loss is 2 ml (1 mg ofiron) if the infection is du e toN. atnericanus, the corresponding figures forA. duodenale and Trichiuris trichiura infestations are 4 ml and 0.25 ml,

respectively33

. In areas endemic for u rinary schistosomiasis, blood loss dueto haematuria is a cofactor to the development of iron deficiency34.

Iron, inflammation and infection

Acute or chronic inflammatory diseases are a well-recognised cause ofmild to moderate anaemia35 . This reduction in haem oglob in level is due toseveral factors36 : (i) a block in iron release from the reticuloendothelialsystem and a reduction in iron intestinal absorption, with the consequent

reduction on iron available for erythropoiesis; (ii) inhibition oferythropoiesis; (iii) inappropriate erythropoietin production; and (iv)reduction of erythrocyte survival.

Immunoactivation releases cytokines that are mainly responsible for thechanges on iron metabolism, inhibition of eythropoiesis and lowererytropoietin production observed in inflammation or infection36.

Acute infections are very frequent in childhood, especially in subjects oflow socio-economic strata of developing countries. Even mild infectionsthat do not warrant medical consultation induce a significant decrease inH b , Fe, TIBC, and Sat, whereas, FEP and SF increase significantly37-38.

Most of the changes in iron laboratory indices persist for 2-3 weeks afterthe appearance of fever, and some measures may become abnormal evenduring the incubation period of the illness37-39. The modifications oflaboratory indicators of iron status are related to the severity of theinflammatory process40 . Changes in iron status parameters are moreprominent in subjects with increased C reactive protein, high band counts,or fever above 38C38-40.

Proper diagnosis of iron status is based primarily on multiple laboratorymeasures. However, in populations where infections are prevalent, classic

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Eum

Inflammation/infection (-)

IV(6-11 mo.) (12 mo.) (1 2- 69 mo.)

Studies

References

Fig. 3 Prevalence of anaemia in children with and with ou t inflamm ations/infections.Data of studies I, II, III, and IV were taken from Olivareset al 3 *, Jansonn et al*\ Reeves etat* 2 , and Freire e t a/*3, respectively.

iron measures might underestimate or overestimate the prevalence of irondeficiency depending on the measure used. Figure 3 shows the results ofseveral studies in which the prevalence of anaemia in subjects with andwithout inflammation/infection was studied. The prevalence of anaemiawas overestimated in subjects with clinical and/or laboratory evidence ofinflammatory or infectious processes38 '41"43. TfR assay has been shown tobe useful in evaluating iron status in these populations, since acute orchronic infection or inflammation does not affect it44-45. In the absence ofthis indicator, the interpretation of iron status measures should be madewith caution in populations or individuals during or shortly after aninflammatory process.

1 DeM acyer E, Adiels-Tegman M. The prevalence of anaemia in the world.World Health Stat Q1985; 38: 302-16

2 Florentino RF, Guirriec RM . Prevalence of nu tritional anemia in infancy and childhoo d withemphasis on developing countries. In: Stekel A (Ed)Iron nutrition in infancy and childhood.Vevey/New York: Nestle/Raven Press, 1984: 61-74

3 Fleming AF. Iron deficiency in the tropics.Clin Haematol 1982; 2: 365-884 Masawe AEJ. Nutritional anaemias. Part 1. Tropical Africa.Clin Haematol1981; 3: 815-425 Baker SJ. Nutritional anaemias. Pan 2. Tropical Asia.Clin Haematol1981; 3: 843-716 Stekel A, Olivares M, Pizarro F, Chadud P, Lopez I, Amar M . Absorption of fortification iron

from milk formulas in infants.Am J Clin tiutr 1986; 43: 91 7-227 Skikne BS, Flowers CH, Cook JD . Serum transferrin receptor: a quantitative measure of tissue

iron deficiency. Blood 1990; 75: 1870-68 Charlton RW, Bothwell TH . Iron absorption.Annu Rev Med1983; 34: 55-6 8

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9 Rossander-H ulthen L, Hallberg L. Dietary factors influencing iron absorption - an overview.In: Hallberg L, Asp N-G (Eds)Iron Nutrition in Health and Disease. London: John Libbey,1996; 105-15

10 Hallberg L, Brunt M, Rossander L. Iron absorption in man: ascorbic acid and dose dependentinhibition by phytate.Am J Clin Nutr 1989; 49: 140-4

11 Wood JR, Han O. Recently identified molecular aspects of intestinal iron absorp tion. /Nutr1998; 128: 1841-4

12 Olivares M, Hertramp f E , Pizarro F. Effect of iron stores on heme iron absorptio n.Nutr Res1993; 13: 633-8

13 Hallberg L, Bjorn-Rasmussen E, Howard L. Dietary haem iron abso rption. A discussion ofpossible mechanisms for the absorption-promoting effect of meat and for the regulation of ironabsorption. Scand ] Gastroenterol 1979; 14: 769-7 9

14 Pizarro F, Yip R, Dallman PR, Olivares M, Hertramp f E, Walter T. Iron status with differentfeeding regimens: relevance to screening and prevention of iron deficiency. /Pediatr 1991; 118:687-92

15 Yip R, Walsh KM , Goldfarb MG , Binkin NJ. Declining prevalence of anemia in childhood in amiddle-class setting: a pediatnc success story?Pediatrics 1987; 80: 330-4

16 Her tramp f E, Olivares M, Pizarro F, Walter T. High absorption of fortification iron from

current infant formulas. /Pediatr Gastroenterol Nutr 1998; 27: 425-3017 Walter T, Pino P, Pizarro F, Lozoff B. Prevention of iron-deficiency anemia: comp arison of high-and low-iron formulas in term healthy infants after six months of life. /Pediatr 1998; 132:635^*0

18 Uauy R, Oyarziin M T. Food based approaches to meet vitamin and mineral needs: possibilitiesand limitations. Background paper to Joint FAO/WHO consultation on human vitamin andmineral requirements. Bangkok, Thailand, September 21-30, 1998

19 FAO/WHO. Preparation and use of food-based dietary guidelines.Report of a JointFAO/WHO consultation. Nicosia, Cyprus: WHO, 1996

20 Suharno D, West CE, Muh ilalB et al. Cross-sectional study on the iron and vitamin A statusof pregnan t wom en in West Java, Indonesia.Am ] Clin Nutr 1992; 56: 988 -93

21 Khan I, Baseer A. Hematologic effect of vitamin A supplem entation in anemic Pakistanichildren. / Pak Med Assoc1996; 46: 3 4-8

22 Rooden burg AJ, West CE, Hovenier R, Beynen AC. Supplemental vitamin A enhances therecovery from iron deficiency in rats with chronic vitamin A deficiency.Br J Nutr 1996; 75:623-36

23 Mejia LA, Chew F. Hematological effect of supplementing anemic children with vitamin Aalone and in combination with iron.Am J Cltn Nutr 1988; 48: 595-600

24 Bloem MW, Wedel M , van Agtmaal EJet al. Vitamin A intervention: short-term effects of asingle, oral, massive dose on iron metabolism.Am ] Clin Nutr 1990; 51 : 76-9

25 Suharno D , West CE, Mu hilal, Karyadi D, Hautvast JG. Supplementation with vitamin A andiron for nutritional anaemia in pregnant women in West Java, Indonesia.Lancet 1993; 342:1325-8

26 Northrop-Clewes CA, Paracha PI, McLoone UJ, Thurnham DI. Effect of improved vitamin Astatus on response to iron supplementation in Pakistani infants.Am J Clin Nutr 1996; 64 : 6949

27 Garria-Casal M N, Layrisse M , Solano L, etal. Vitamin A and [}-carotene can improve nonhemeiron absorption from rice, wheat and corn by humans. /Nutr 1998; 128: 646-50

28 Ziegler EE, Fomon SJ, Nelson SEet al. Cow milk feeding in infancy: further observations onblood loss from the gastrointestinal tract./Pediatr 1990; 116: 11-8

29 Walter T, Hertrampf E, Arredondo M. Gastrointestinal iron losses in infancy: effect of the diet.In: Hercberg S, Galan P, Dupin H (Eds)Recent Knowledge on Iron and Folate Deficiencies inthe World. Colloque INSERM Vol 197, Paris: INSERM, 1990; 283-90

30 Petersen KM , Parkinson AJ, Nobmann ED, Bulkow L, Tip R, Mokdad A. Iron deficiencyanemia among Alaska natives may be due to fecal loss rather than inadequate intake. /Nutr1996; 126: 2774-83

31 Yip R, Limburg PJ, Ahlquist DAet al. Pervasive occult gastrointestinal bleeding in an Alaskanative population with prevalent iron deficiency. Role ofHelicobacter pylori gastritis. JAMA1997; 277: 1135-9

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32 Stoltzfus RJ, Dreyfuss ML, Chwaya HM , Albonico M. Hook worm control as a strategy toprevent iron deficiency.Nutr Rev 1997; 55: 223-32

33 Roche M, Layrisse M. The nature and causes of 'hookw orm anem ia'.Am } Trop Med Hyg1966; 15: 1029-102

34 Prual A, Daouda A, Develoux M , Sellin B, Galan P, Hercberg S. Consequences ofScbistosoma

haematobium infection on the iron status of school children in Niger.Am J Trop Med Hyg1992; 47: 291 -7

35 Yip R, Dallman PR. The roles of inflammation and iron deficiency as causes of anem ia.Am JClin Nutr 1988; 48: 1295-1300

36 Means RT, Krantz SB. Progress in understanding the pathogenesis of the anemia of chronicdisease. Blood 1992; 80: 1639-47

37 Olivares M , WalterT, Osono M , ChadudP, Schlesinger L. Anemia ofa mild viral infection: themeasles vaccine as a model.Pediatrics 1989; 84: 851-5

38 Olivares M , Walter T, Llaguno Set al. Modificaciones del hemograma y de los parametrosindicadores del metabolismo de hierro en infecaones virales leves (Changes of blood eel] countsand laboratory indices related to iron metabolism in mild viral infections).Sangre 1993; 38:211-6

39 Hulthen L, Lindstedt G, Lundberg P-A, Hallberg L. Effect of a mild infection on serum ferritin

concentration clinical and epidemiological implications.Eur J Clin Nutr 1998; 52: 376940 Olivares M, Walter T, Oso rio M , Chadu d P, Schlesinger L. Effect of a mild viral infection on

laboratory measures of iron nutriture. The measles vaccine as a model. In: Hercberg S, GalanP, Dupin H (Eds) Recent Knowledge on Iron andFolate Deficiencies in the World. ColloqueINSERM Vol 197, Paris: INSERM, 1990; 209-15

41 Janso nn LT, Kling S, Dallman PR . Anemia in children with acu te infections seen in a prim arycare pediatric ou tpatient clinic.Pediatr Infect Dts 1986; 5: 424- 7

42 Reeves JD, Yip R, Kiley VA, Dallman PR. Iron deficiency in infants: the influence of m ildantecedent infection. / Pediatr 1984; 105: 874-9

43 Freire WB, Dirren H, Barclay D. The influence of infection and inflammation on the estimationof the prevalence of iron deficiency anemia. In: Hercberg S, Galan P, Dupin H (Eds)RecentKnowledge on Iron andFolate Deficiencies in the World. Colloque INSERM Vol 197, Paris:INSERM, 1990; 205-8

44 Ferguson BJ, Skikne BS, Simpson K M, Baynes RD , Cook JD . Serum transferrin receptordistinguishes the anemia of chronic disease from iron deficiency anemia.J Lab Clin M ed 1992;19: 385-90

45 Olivares M , Walter T, Cook JD , Llaguno S. Effect of acute infection on measurem ent of ironstatus: usefulness of the serum transferrin receptor.Int] Pediatr Hematol Oncol1995; 2:31-3

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Anaemia and Iron Deficiency Disease