Clinical Report—Diagnosis and Prevention of IronDeficiency and Iron-Deficiency Anemia in Infants andYoung Children (0–3 Years of Age)

abstractThis clinical report covers diagnosis and prevention of iron deficiencyand iron-deficiency anemia in infants (both breastfed and formula fed)and toddlers from birth through 3 years of age. Results of recent basicresearch support the concerns that iron-deficiency anemia and irondeficiency without anemia during infancy and childhood can have long-lasting detrimental effects on neurodevelopment. Therefore, pediatri-cians and other health care providers should strive to eliminate irondeficiency and iron-deficiency anemia. Appropriate iron intakes forinfants and toddlers as well as methods for screening for iron defi-ciency and iron-deficiency anemia are presented. Pediatrics 2010;126:1040–1050

INTRODUCTIONIron deficiency (ID) and iron-deficiency anemia (IDA) continue to be ofworldwide concern. Among children in the developingworld, iron is themost common single-nutrient deficiency.1 In industrialized nations, de-spite a demonstrable decline in prevalence,2 IDA remains a commoncause of anemia in young children. However, evenmore important thananemia itself is the indication that themore common IDwithout anemiamay also adversely affect long-term neurodevelopment and behaviorand that some of these effects may be irreversible.3,4 Because of theimplications for pediatric health care providers and their patients, thisreport reviews and summarizes this information.

This clinical report is a revision and extension of a previous policystatement published in 1999,5 which addressed iron fortification offormulas. This report covers diagnosis and prevention of ID and IDA ininfants (both breastfed and formula fed) and toddlers aged 1 through3 years.

DEFINITIONS

Anemia: A hemoglobin (Hb) concentration 2 SDs below the mean Hbconcentration for a normal population of the same gender and agerange, as defined by the World Health Organization, the United NationsChildren’s Fund, and United Nations University.6 On the basis of the1999–2002 US National Health and Nutrition Examination Survey, ane-mia is defined as a Hb concentration of less than 11.0 g/dL for bothmale and female children aged 12 through 35 months.7,8 For certainpopulations (ie, people living at high altitudes), adjustment of thesevalues may be necessary.

Robert D. Baker, MD, PhD, Frank R. Greer, MD, and THECOMMITTEE ON NUTRITION

KEY WORDSiron deficiency, iron-deficiency anemia, iron intake, infants,toddlers, breastfeeding, formula

ABBREVIATIONSID—iron deficiencyIDA—iron-deficiency anemiaHb—hemoglobinSF—serum ferritinIOM—Institute of MedicineWIC—Special Supplemental Program for Women, Infants, andChildrenCHr—reticulocyte hemoglobinTfR1—transferrin receptor 1CRP—C-reactive proteinAAP—American Academy of Pediatrics

This document is copyrighted and is property of the AmericanAcademy of Pediatrics and its Board of Directors. All authorshave filed conflict of interest statements with the AmericanAcademy of Pediatrics. Any conflicts have been resolved througha process approved by the Board of Directors. The AmericanAcademy of Pediatrics has neither solicited nor accepted anycommercial involvement in the development of the content ofthis publication.

The guidance in this report does not indicate an exclusivecourse of treatment or serve as a standard of medical care.Variations, taking into account individual circumstances, may beappropriate.

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Iron sufficiency: A state in which thereis sufficient iron to maintain normalphysiologic functions.

Iron deficiency: A state in which thereis insufficient iron to maintain normalphysiologic functions. ID results frominadequate iron absorption to accom-modate an increase in requirementsattributable to growth or resultingfrom a long-term negative iron bal-ance. Either of these situations leadsto a decrease in iron stores as mea-sured by serum ferritin (SF) concen-trations or bone marrow iron content.ID may or may not be accompanied byIDA.

Iron-deficiency anemia: An anemia (asdefined above) that results from ID.

Iron overload: The accumulation of ex-cess iron in body tissues. Iron overloadusually occurs as a result of a geneticpredisposition to absorb and storeiron in excess amounts, the most com-mon form of which is hereditary hemo-chromatosis. Iron overload can alsooccur as a complication of other hema-tologic disorders that result in chronictransfusion therapy, repeated injec-tions of parenteral iron, or excessiveiron ingestion.

Recommended dietary allowance foriron: The average daily dietary intakethat is sufficient to meet the nutrientrequirements of nearly all individuals(97%–98%) of a given age and gender.

Adequate intake for iron: This term isused when there is not enough informa-tion to establish a recommended dietaryallowance for a population (eg, term in-fants, 0–6months of age). The adequateintake isbasedon theestimatedaveragenutrient intake by a group (or groups) ofhealthy individuals.

IRON REQUIREMENTS FOR INFANTS(UP TO 12 COMPLETED MONTHSOF AGE)

Eighty percent of the iron present in anewborn term infant is accreted dur-

ing the third trimester of pregnancy.Infants born prematurely miss thisrapid accretion and are deficient in to-tal body iron. A number of maternalconditions, such as anemia, maternalhypertension with intrauterine growthrestriction, or diabetes during preg-nancy, can also result in low fetaliron stores in both term and preterminfants.

Preterm Infants

The deficit of total body iron in preterminfants increases with decreasing ges-tational age. It is worsened by therapid postnatal growth that many in-fants experience and by frequent phle-botomies without adequate blood re-placement. On the other hand, sickpreterm infants who receive multipletransfusions are at risk of iron over-load. The use of recombinant humanerythropoietin to prevent transfusiontherapy in preterm infants will furtherdeplete iron stores if additional sup-plemental iron is not provided. Thehighly variable iron status of preterminfants, along with their risks for ID aswell as toxicity, precludes determiningthe exact requirement, but it can beestimated to be between 2 and 4mg/kgper day when given orally.9

Term Infants (Birth Through 12Completed Months of Age)

The Institute of Medicine (IOM)10 usedthe average iron content of humanmilk to determine the adequate intakeof 0.27 mg/day for term infants frombirth through 6 months’ completedage. The average iron content of hu-man milk was determined to be 0.35mg/L, and the averagemilk intake of anexclusively breastfed infant was deter-mined to be 0.78 L/day. Multiplyingthese 2 numbers determined the ade-quate intake of 0.27 mg/day for terminfants from birth through 6 months ofage in the IOM report. The IOM furtherreasoned that there should be a directcorrelation between infant size and

human milk ingestion; therefore, nocorrection need be made for infantweight. It should be pointed out, how-ever, that although bigger infants mayingest more milk, there is a large vari-ation in iron concentration of humanmilk, and there is no guarantee thatthe iron content of the maternal milkmatches the needs of the infant foriron.

For infants from 7 to 12 months’ com-pleted age, the recommended dietaryallowance for iron, according to theIOM, is 11 mg/day, which was deter-mined by using a factorial approach.The amount of iron lost, primarily fromsloughed epithelial cells from skin andthe intestinal and urinary tracts, wasadded to the amounts of iron requiredfor increased blood volume, increasedtissue mass, and storage iron duringthis period of life. It was noted that theiron needs of infants do not suddenlyjump from 0.27 to 11 mg/day at 6months of age; this disjuncture is theresult of the use of very different meth-ods of determining these values. How-ever, it is clear that healthy, term new-born infants require very little ironearly in life compared with the signifi-cant amounts of iron required after 6months of age.

IRON REQUIREMENTS FORTODDLERS (1–3 YEARS OF AGE)

Using a similar factorial approach asdescribed for infants 7 to 12 months’completed age, the IOM determinedthat the recommended dietary allow-ance for iron for children from 1through 3 years of age is 7 mg/day.9

PREVALENCE OF ID AND IDA

There are currently no national statis-tics for the prevalence of ID and IDA ininfants before 12 months’ completedage. Hay et al11 reported on a cohort of284 term Norwegian infants. Using thedefinitions provided by Dallman12 in anIOM report, the prevalence of ID at 6

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months of age was 4% and increasedto 12% at 12 months of age.

The prevalence of ID and IDA amongtoddlers (1–3 years of age) in theUnited States is listed in Table 1 andwas derived from National Health andNutrition Examination Survey data col-lected between 1999 and 2002.7,8 Theoverall prevalence of anemia and pos-sibly ID and IDA in infants and toddlershas declined since the 1970s.2 Al-though there is no direct proof, thisdecline has been attributed to useof iron-fortified formulas and iron-fortified infant foods provided by theSpecial Supplemental Program forWomen, Infants, and Children (WIC) inthe early 1970s and the decrease inuse of whole cowmilk for infants.8 Still,ID remains relatively common and oc-curs in 6.6% to 15.2% of toddlers, de-pending on ethnicity and socioeco-nomic status. The prevalence of IDA is0.9% to 4.4%, again depending on race/ethnicity and socioeconomic status,7,8

but only accounts for approximately40% of the anemia in toddlers (Table1). These numbers are comparable todata collected in other industrializedcountries.13,14

Related to the problem of ID/IDA is theinteraction of iron and lead. Results ofboth animal and human studies haveconfirmed that IDA increases intestinallead absorption.15–17 A reasonably well-established epidemiologic associationhas been made between IDA and in-creased lead concentrations.18 Thus,primary prevention of IDA could alsoserve as primary prevention of leadpoisoning. This possibility is all themore attractive, because lead hasbeen reported to induce neurotoxicityat even very low blood concentra-tions.19,20 In addition, preexisting IDAdecreases the efficiency of lead chela-tion therapy, and iron supplementa-tion corrects this effect. In contrast,iron supplementation in a child withIDA who also has lead poisoning with-

out chelation therapy seems to in-crease blood lead concentrations anddecrease basal lead excretion.21,22 Theeffect of iron supplementation onblood lead concentrations in iron-replete children with or without leadpoisoning is not known. Thus, in the-ory, selective rather than universaliron supplementation would be morelikely to reduce lead poisoning andits potential harmful effects on thesechildren.

ID AND NEURODEVELOPMENT

The possible relationship between ID/IDA and later neurobehavioral develop-ment in children is the subject of manyreports.3,23–31 Results of a preponder-ance of studies have demonstrated anassociation between IDA in infancy andlater cognitive deficits. Lozoff et al3,25

have reported detecting cognitive def-icits 1 to 2 decades after the iron-deficient insult during infancy. How-ever, it has been difficult to establish acausal relationship because of themany confounding variables and thedifficulty in designing and executingthe large, randomized controlled trialsnecessary to distinguish small poten-tial differences. The authors of a Co-chrane Database systematic review, inwhich the question of whether treat-

ment of IDA improved psychomotor de-velopment was examined, stated thatthere was inconclusive but plausibleevidence (only 2 randomized con-trolled trials) demonstrating improve-ment if the treatment extended formore than 30 days.27 McCann andAmes28 recently reviewed the evidenceof a causal relationship between ID/IDAand deficits in cognitive and behav-ioral function. They concluded that forIDA, there is at least some supportfor causality, but because specificityfor both cause and effect have notbeen established unequivocally, it ispremature to conclude the existenceof a causal relationship between IDAand cognitive and behavioral perfor-mance. For ID, some evidence of cau-sality exists, but it is less than that forIDA.28

It is known that iron is essentialfor normal neurodevelopment in anumber of animal models. ID affectsneuronal energy metabolism, the me-tabolism of neurotransmitters, myeli-nation, and memory function. Theseobservations would explain the behav-ioral findings in human infants thathave been associated with ID.29–31

Therefore, taking into account thatiron is the world’s most common

TABLE 1 ID, IDA, and Anemia in the 1999–2002 National Health and Nutrition Examination Survey,7Children 12 to 35 Months of Age

Population Sampled (No.) Proportion of US ToddlerPopulation, % (SE)a

ID, % (SE) IDA, % (SE) All Anemia,% (SE)

General US population (672) 9.2 (1.3) 2.1 (0.6) 5.1 (0.8)Above poverty line (355)b 66.4 (2.9) 8.9 (1.7) 2.2 (0.8)c 4.6 (1.1)Below poverty line (268)b 33.6 (2.9) 8.6 (1.6) 2.3 (1.2)c 6.2 (1.3)Enrolled in WIC (360)d 44.4 (3.2) 10.7 (2.1) 3.1 (1.2)c 6.6 (1.4)Non-Hispanic white (196) 58.0 (3.8) 7.3 (1.9) 2.0 (0.8)c 4.6 (1.2)Non-Hispanic black (173) 14.1 (2.1) 6.6 (1.8) 1.6 (0.9)c 8.3 (1.9)Mexican American (231) 15.0 (2.2) 13.9 (3.1) 0.9 (0.7)c 3.2 (1.2)c

Other ethnicity (72) 13.0 (2.7) 15.2 (4.7)c 4.4 (2.7)c 5.5 (2.7)c

Shown are the unweighted number and weighted percentage and SEs for all children with complete data for Hb, SF,transferrin saturation, and zinc protoporphyrin. Anemia was defined as a Hb concentration of�11.0 g/dL; ID7 was definedas an abnormal value for at least 2 of 3 indicators: SF (abnormal cutoff:�10�g/dL), zinc protoporphyrin (�1.42�mol/L redblood cells), and transferrin saturation (�10%); and IDA was defined as anemia plus ID.a Proportion of row descriptor of all children in analytic sample (N� 672).b Children with income data (N� 623).c Estimate is statistically unreliable. Relative SE (SE of estimate/estimate� 100)� 30%.d Anymember of householdwho received benefits fromWIC in the previous 12months: childrenwith food-security data (N�668).

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single-nutrient deficiency, it is impor-tant to minimize IDA and ID among in-fants and toddlers, even if an unequiv-ocal relationship between IDA and IDand neurodevelopmental outcomeshas yet to be established.

DIAGNOSIS

Iron status is a continuum. At oneend of the spectrum is IDA, and atthe other end is iron overload. ID andIDA are attributable to an imbalancebetween iron needs and available ironthat results in a deficiency of mobiliz-able iron stores and is accompaniedby changes in laboratory measure-ments that include Hb concentration,mean corpuscular Hb concentration,mean corpuscular volume, reticulo-cyte Hb concentration (abbreviatedin the literature as CHr) content, to-tal iron-binding capacity, transferrinsaturation, zinc protoporphyrin, SFconcentration, and serum transferrinreceptor 1 (TfR1) concentration. Mea-surements that are used to describeiron status are listed in Table 2.

In a child with ID, as the Hb concentra-tion falls 2 SDs below the mean for ageand gender, IDA is present, by defini-tion; for infants at 12 months of age,this is 11.0 mg/dL.7,8 When IDA ac-

counted for most cases of anemia inchildren, “anemia” and “IDA” wereroughly synonymous, and a simplemeasurement of Hb concentrationwassufficient to make a presumptive diag-nosis of anemia attributable to ID. Par-ticularly in industrialized nations, theprevalence of ID and IDA has de-creased, and other causes of anemia,such as hemolytic anemias, anemia ofchronic disease, and anemia attribut-able to other nutrient deficiencies,have become proportionately morecommon.32

No single measurement is currentlyavailable that will characterize theiron status of a child. The limitations ofusing Hb concentration as a measureof iron status are its lack of specificityand sensitivity. Factors that limit eryth-ropoiesis or result in chronic hemoly-sis, such as genetic disorders andchronic infections, may result in lowHb concentrations. Vitamin B12 or fo-late deficiency, although uncommon inthe pediatric population, also can re-sult in a low Hb concentration. The lackof sensitivity is largely attributable tothe marked overlap in Hb concentra-tions between populations with ironsufficiency and those with ID.33 Thus, toidentify ID or IDA, Hb concentrationmust be combined with other mea-surements of iron status. Once the di-agnosis of IDA has been established,however, following Hb concentrationis a good measure of response totreatment.

In establishing the definitive iron sta-tus of an individual, it is desirable touse the fewest tests that will accu-rately reflect iron status. Any battery oftests must include Hb concentration,because it determines the adequacyof the circulating red cell mass andwhether anemia is present. One ormore tests must be added to the deter-mination of Hb concentration if ID orIDA is to be diagnosed. The 3 parame-ters that provide discriminatory infor-

mation about iron status are SF, CHr,and TfR1 concentrations.

SF is a sensitive parameter for the as-sessment of iron stores in healthy sub-jects34–36; 1�g/L of SF corresponds to 8to 10mg of available storage iron.34,37,38

Measurement of SF concentration iswidely used in clinical practice andreadily available. Cook et al36 selectedan SF concentration below 12 �g/L asdiagnostic for ID after a comprehen-sive population survey in the UnitedStates. Thus, a cutoff value of 12 �g/Lhas been widely used for adults anddenotes depletion of iron stores. Inchildren, a cutoff value of 10 �g/L hasbeen suggested.39 Because SF is anacute-phase reactant, concentrationsof SF may be elevated in the presenceof chronic inflammation, infection, ma-lignancy, or liver disease, and a simul-taneous measurement of C-reactiveprotein (CRP) is required to rule outinflammation. Although Brugnara etal40 found SF concentration to be lessaccurate than either the CHr or TfR1concentration in establishing iron sta-tus of children, combining SF concen-tration with a determination of CRP iscurrently more readily available to as-sess iron stores and is a reliablescreening test as long as the CRP levelis not elevated41 (Table 2).

CHr and TfR1 concentrations are notaffected by inflammation (infection),malignancy, or anemia of chronic dis-ease and, thus, would be preferable asbiomarkers for iron status. Only theCHr assay is currently available for usein children. The CHr content assay hasbeen validated in children, and stan-dard values have been determined.40,42

The CHr assay provides a measure ofiron available to cells recently re-leased from the bone marrow. CHrcontent can be measured by flow cy-tometry, and 2 of the 4 automated he-matology analyzers commonly used inthe United States have the capability tomeasure CHr.43 A low CHr concentra-

TABLE 2 Spectrum of Iron Status

Parameter IDWithoutAnemia

IDA IronOverload

SFa 2 22 1Transferrinsaturation

2 2 11

TfR1 11 111 2CHr 2 2 NormalHb Normal 2 NormalMean corpuscularvolume

Normal 2 Normal

a Confounded by the presence of inflammation. If SF isnormal or increased and the CRP level is normal, thenthere is no ID. If SF is decreased, then ID is present regard-less of the measure of CRP. If SF is normal or increasedand the CRP level is increased, then the presence of IDcannot be determined.Modified from American Academy of Pediatrics, Commit-tee on Nutrition. Iron deficiency. In: Kleinman RE, ed. Pedi-atric Nutrition Handbook. 5th ed. Elk Grove Village, IL:American Academy of Pediatrics; 2004:304.

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tion has been shown to be the stron-gest predictor of ID in children40,42,43

and shows much promise for the diag-nosis of ID when the assay becomesmore widely available.

TfR1 is a measure of iron status, de-tecting ID at the cellular level. TfR1 isfound on cell membranes and facili-tates transfer of iron into the cell.When the iron supply is inadequate,there is an upregulation of TfR1 to en-able the cell to compete more effec-tively for iron, and subsequently, morecirculating TfR1 is found in serum. Anincrease in serum TfR1 concentrationsis seen in patients with ID or IDA, al-though it does not increase in serumuntil iron stores are completely ex-hausted in adults.44–46 However, theTfR1 assay is not widely available, andstandard values for infants and chil-dren have yet to be established.

Thus, to establish a diagnosis of IDA,the following sets of tests can be usedat the present time (when coupledwith determination of a Hb concentra-tion of�11 g/dL): (1) SF and CRP mea-surements or (2) CHr measurement.For diagnosing ID without anemia,measure either (1) SF and CRP or (2)CHr.

Another approach to making the diag-nosis of IDA in a clinically stable childwith mild anemia (Hb concentrationbetween 10 and 11 g/dL) is to monitorthe response to iron supplementation,especially if a dietary history indicatesthat the diet is likely to be iron defi-cient. An increase in Hb concentrationof 1 g/dL after 1 month of therapeuticsupplementation has been used to sig-nify the presence of IDA. This approachrequires that iron supplementationbe adequate, iron be adequately ab-sorbed, and patient compliance withadequate follow-up can be ensured.However, because only 40% of thecases of anemia identified at 12months of age will be secondary to IDA(Table 1), strong consideration should

be given to establishing a diagnosis ofIDA by using the screening tests de-scribed previously.

PREVENTION OF ID AND IDA

Preterm Infants

The preterm infant (�37 weeks’ gesta-tion) who is fed human milk should re-ceive a supplement of elemental ironat 2 mg/kg per day starting by 1 monthof age and extending through 12months of age.47 This can be providedas medicinal iron or in iron-fortifiedcomplementary foods. Preterm infantsfed a standard preterm infant formula(14.6 mg of iron per L) or a standardterm infant formula (12.0 mg of ironper L) will receive approximately 1.8 to2.2 mg/kg per day of iron, assuming aformula intake of 150 mL/kg per day.Despite the use of iron-containing for-mulas, 14% of preterm infants developID between 4 and 8 months of age.48

Thus, some formula-fed preterm in-fants may need an additional ironsupplement,47 although there is notenough evidence to make this a generalrecommendationat this time. Exceptionsto this iron-supplementation practice inpreterm infantswouldbe infantswhore-ceivedmultiple transfusions during hos-pitalization, whomight not need any ironsupplementation.

Term, Breastfed Infants

Infants who are born at term usuallyhave sufficient iron stores until 4 to 6months of age.49 Infants born at termhave high Hb concentration and highblood volume in proportion to bodyweight. They experience a physiologicdecline in both blood volume and Hbconcentration during the first severalmonths of life. These facts have led tothe supposition that breastfed infantsneed very little iron. It is assumed thatthe small amount of iron in humanmilk is sufficient for the exclusivelybreastfed infant. The World HealthOrganization recommends exclusive

breastfeeding for 6 months, and theAmerican Academy of Pediatrics (AAP)has recommended exclusive breast-feeding for aminimum of 4months butpreferably for 6 months. Exclusivebreastfeeding for more than 6 monthshas been associated with increasedrisk of IDA at 9 months of age.49,50 Rec-ommendations for exclusive breast-feeding for 6 months do not take intoaccount infants who are born withlower-than-usual iron stores (lowbirth weight infants, infants of diabeticmothers), a condition that also hasbeen linked to lower SF concentrationsat 9 months of age.51 In a double-blindstudy, Friel et al52 demonstrated thatexclusively breastfed infants supple-mented with iron between 1 and 6months of age had higher Hb concen-tration and higher mean corpuscularvolume at 6 months of age than didtheir unsupplemented peers. Supple-mentation also resulted in better vi-sual acuity and higher Bayley Psy-chomotor Developmental Indices at 13months. Thus, it is recommended thatexclusively breastfed term infantsreceive an iron supplementation of 1mg/kg per day, starting at 4 months ofage and continued until appropriateiron-containing complementary foodshave been introduced (Tables 3 and 4).For partially breastfed infants, the pro-portion of human milk versus formulais uncertain; therefore, beginning at 4months of age, infants who receivemore than one-half of their daily feed-ings as human milk and who are notreceiving iron-containing complemen-tary foods should also receive 1 mg/kgper day of supplemental iron.

Term, Formula-Fed Infants

For the term, formula-fed infant, thelevel of iron fortification of formula toprevent ID remains controversial.53,54

For more than 25 years, 12 mg of ironper L has been the level of fortificationin standard term infant formulas inthe United States, consistent with

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guidelines of WIC for iron-fortified for-mula (at least 10 mg/L), thus creatinga natural experiment. The level of 12mg/L was determined by calculatingthe total iron needs of the child from 0to 12months of age, assuming averagebirth weight and average weight gainduring the first year. The calculationalso assumed that formula was theonly source of iron during this period.Others have recommended loweramounts of iron in infant formula,55

and there have been studies to exam-ine iron-fortification levels of less than12 mg/L.56–61 However, it is the conclu-sion of the AAP that infant formula thatcontains 12 mg of elemental iron per Lis safe for its intended use. Althoughthere has been some concern aboutlinear growth in iron-replete infantsgiven medicinal iron,62 no publishedstudies have convincingly documenteddecreased linear growth in iron-repleteinfants receiving formulas containinghigh amounts of iron. Evidence is alsoinsufficient to associate formulas thatcontain 12 mg of iron per L with gas-trointestinal symptoms. At least 4studies have shown no adverse ef-fects.63–66 Reports have conflicted onwhether iron fortification is associ-ated with increased risk of infection.Decreased incidence, increased inci-dence, and no change in number of in-fections have all been reported.67,68 Theauthors of a recent systematic reviewconcluded that “iron supplementationhas no apparent harmful effect onthe overall incidence of infectious ill-nesses in children, though it slightlyincreases the risk of developing diar-rhoea.”69 Finally, when examining spe-cifically infants given formula with 12mg of iron per L, Singhal et al70 were“unable to identify adversehealth effectsin older infants and toddlers consuminga high iron-containing formula.” Theyfound no difference between controlsand the treatment group in incidence ofinfection, gastrointestinal problems, orgeneral morbidity.

TABLE 3 Foods to Increase Iron Intake and Iron Absorption

Elemental Iron, mg

Commercial baby food,a heme ironMeatBaby food, lamb, junior, 1 jar (2.5 oz) 1.2Baby food, chicken, strained, 1 jar (2.5 oz) 1.0Baby food, lamb, strained, 1 jar (2.5 oz) 0.8Baby food, beef, junior, 1 jar (2.5 oz) 0.7Baby food, beef, strained, 1 jar (2.5 oz) 0.7Baby food, chicken, junior, 1 jar (2.5 oz) 0.7Baby food, pork, strained, 1 jar (2.5 oz) 0.7Baby food, ham, strained, 1 jar (2.5 oz) 0.7Baby food, ham, junior, 1 jar (2.5 oz) 0.7Baby food, turkey, strained, 1 jar (2.5 oz) 0.5Baby food, veal, strained, 1 jar (2.5 oz) 0.5

Commercial baby food,a nonheme ironVegetablesBaby food, green beans, junior, 1 jar (6 oz) 1.8Baby food, peas, strained, 1 jar (3.4 oz) 0.9Baby food, green beans, strained, 1 jar (4 oz) 0.8Baby food, spinach, creamed, strained, 1 jar (4 oz) 0.7Baby food, sweet potatoes, junior (6 oz) 0.7CerealsBaby food, brown rice cereal, dry, instant, 1 tbsp 1.8Baby food, oatmeal cereal, dry, 1 tbsp 1.6Baby food, rice cereal, dry, 1 tbsp 1.2Baby food, barley cereal, dry, 1 tbsp 1.1Table food, heme ironClams, canned, drained solids, 3 oz 23.8Chicken liver, cooked, simmered, 3 oz 9.9Oysters, Eastern canned, 3 oz 5.7Beef liver, cooked, braised, 3 oz 5.6Shrimp, cooked moist heat, 3 oz 2.6Beef, composite of trimmed cuts, lean only, all grades, cooked, 3 oz 2.5Sardines, Atlantic, canned in oil, drained solids with bone, 3 oz 2.5Turkey, all classes, dark meat, roasted, 3 oz 2.0Lamb, domestic, composite of trimmed retail cuts, separable lean only,choice, cooked, 3 oz

1.7

Fish, tuna, light, canned in water, drained solids, 3 oz 1.3Chicken, broiler or fryer, dark meat, roasted, 3 oz 1.1Turkey, all classes, light meat, roasted, 3 oz 1.1Veal, composite of trimmed cuts, lean only, cooked, 3 oz 1.0Chicken, broiler or fryer, breast, roasted, 3 oz 0.9Pork, composite of trimmed cuts (leg, loin, shoulder), lean only, cooked, 3 oz 0.9Fish, salmon, pink, cooked, 3 oz 0.8

Table food, nonheme ironOatmeal, instant, fortified, cooked, 1 cup 14.0Blackstrap molasses,b 2 tbsp 7.4Tofu, raw, regular, 1⁄2 cup 6.7Wheat germ, toasted, 1⁄2 cup 5.1Ready-to-eat cereal, fortified at different levels, 1 cup �4.5 to 18Soybeans, mature seeds, cooked, boiled, 1⁄2 cup 4.4Apricots, dehydrated (low-moisture), uncooked, 1⁄2 cup 3.8Sunflower seeds, dried, 1⁄2 cup 3.7Lentils, mature seeds, cooked, 1⁄2 cup 3.3Spinach, cooked, boiled, drained, 1⁄2 cup 3.2Chickpeas, mature seeds, cooked, 1⁄2 cup 2.4Prunes, dehydrated (low-moisture), uncooked, 1⁄2 cup 2.3Lima beans, large, mature seeds, cooked, 1⁄2 cup 2.2Navy beans, mature seeds, cooked, 1⁄2 cup 2.2Kidney beans, all types, mature seeds, cooked, 1⁄2 cup 2.0Molasses, 2 tbsp 1.9Pinto beans, mature seeds, cooked, 1⁄2 cup 1.8Raisins, seedless, packed, 1⁄2 cup 1.6

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Toddlers (1–3 Years of Age)

The iron requirement for toddlers is 7mg/day. Ideally, the iron requirementsof toddlers would be met and ID/IDAwould be prevented with naturallyiron-rich foods rather than iron sup-plementation. These foods includethose with heme sources of iron (ie,red meat) and nonheme sources ofiron (ie, legumes, iron-fortified cere-als) (Table 3). Foods that contain vita-min C (ascorbic acid), such as orangejuice, aid in iron absorption and arelisted in Table 4. Foods that containphytates (found in soy) reduce iron ab-sorption. Through public educationand altering feeding practices, theamount of iron available to older in-fants and toddlers via a normal dietcould be maximized (Table 3).

In developing countries, iron require-ments of older infants and toddlershave been met by iron fortification of

various foods, including corn flour,71

soy sauce,72 fish sauce,73 and rice.74

However, there aremany technical andpractical barriers to a successful for-tification program for toddlers. Not theleast of these barriers is the determi-nation of which foods to fortify withiron. In the United States, fortificationof infant formula and infant cereal hasbeen credited with the decline in IDA.However, toddlers in the United Statestypically do not eat enough of any otherfood to serve as a vehicle for iron for-tification. Universal food fortificationfor all ages is problematic, given thepossible adverse effects of iron in cer-tain subsets of older children andadults.

As an alternative for toddlers who donot eat adequate amounts of iron-containing food (Table 3), iron supple-ments are available in the form of ironsulfate drops and chewable iron tab-

lets or as a component of either liquidor chewable multivitamins. Iron sprin-kles with or without additional zinc areavailable in Canada. Barriers to ade-quate iron supplementation are (1)lack of education for care providersand patients, (2) poor compliancemade worse by the perception of ad-verse effects, including nausea, vomit-ing, constipation, stomach upset, andteeth staining, (3) cost, (4) current fed-eral supplemental nutrition programsnot providing iron supplements, and(5) risk of iron overload.

Screening for ID and IDA

The AAP has concluded that universalscreening for anemia should be per-formed with determination of Hb con-centration at approximately 1 year ofage. Universal screening would also in-clude an assessment of risk factors as-sociated with ID/IDA: history of prema-turity or low birth weight; exposure tolead; exclusive breastfeeding beyond 4months of age without supplementaliron; and weaning to whole milk orcomplementary foods that do not in-clude iron-fortified cereals or foodsnaturally rich in iron (Table 3). Addi-tional risk factors include the feedingproblems, poor growth, and inade-quate nutrition typically seen in infantswith special health care needs as wellas low socioeconomic status, espe-cially children of Mexican Americandescent, as identified in the recentNational Health and Nutrition Examina-tion Survey8,75 (Table 1). Selectivescreening can be performed at any agewhen these risk factors for ID and IDAhave been identified, including risk ofinadequate iron intake according to di-etary history.

It has been acknowledged that screen-ing for anemiawith a Hb determinationneither identifies children with ID norspecifically identifies those with IDA.76

In the United States, 60% of anemia isnot attributable to ID, and most tod-

TABLE 3 Continued

Elemental Iron, mg

Prunes, dehydrated (low moisture), stewed, 1⁄2 cup 1.6Prune juice, canned, 4 fl oz 1.5Green peas, cooked, boiled, drain, 1⁄2 cup 1.2Enriched white rice, long-grain, regular, cooked, 1⁄2 cup 1.0Whole egg, cooked (fried or poached), 1 large egg 0.9Enriched spaghetti, cooked, 1⁄2 cup 0.9White bread, commercially prepared, 1 slice 0.9Whole-wheat bread, commercially prepared, 1 slice 0.7Spaghetti or macaroni, whole wheat, cooked, 1⁄2 cup 0.7Peanut butter, smooth style, 2 tbsp 0.6Brown rice, medium-grain, cooked, 1⁄2 cup 0.5

Note that all figures are rounded.a Baby food values are generally based on generic jar, not branded jar; 3 oz of table-food meat� 85 g; a 2.5-oz jar of babyfood� 71 g (an infant would not be expected to eat 3 oz [approximately the size of a deck of cards] of pureed table meat ata meal).b Source of iron value was obtained from a manufacturer of this type of molasses.Source of iron values in foods: US Department of Agriculture, Agricultural Research Service. USDA National NutrientDatabase for Standard Reference, Release 20: Nutrient Data Laboratory home page. Available at: www.ars.usda.gov/ba/bhnrc/ndl.

TABLE 4 Selected Good Vitamin C Sources to Increase Iron Absorption

Fruits VegetablesCitrus fruits (eg, orange, tangerine, grapefruit) Green, red, and yellow peppersPineapples BroccoliFruit juices enriched with vitamin C TomatoesStrawberries CabbagesCantaloupe PotatoesKiwifruit Leafy green vegetablesRaspberries Cauliflower

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dlerswith ID do not have anemia (Table2). It is also known that there is poorfollow-up testing and poor documenta-tion of improved Hb concentrations. In1 study, 14% of the children had a pos-itive screening result for anemia. How-ever, only 18.3% of these childrenwith a positive screening result hadfollow-up testing performed, and ofthat group, only 11.6% had docu-mented correction of low Hb levels.77

Therefore, for infants identified with aHb concentration of less than 11.0mg/dL or identified with significantrisk of ID or IDA as described previ-ously, SF and CRP or CHr levels in addi-tion to Hb concentration should bemeasured to increase the sensitivityand specificity of the diagnosis. In addi-tion, the AAP, the World Health Organiza-tion, and the European Society for Pedi-atric Gastroenterology, Hepatology andNutrition also support the use of themeasurement of TfR1asa screening testonce themethod has been validated andnormal values for infants and toddlershave been established.

Another step to improve the currentscreening system is to use technology-based reminders for screening andfollow-up of infants and toddlers with adiagnosis of ID/IDA. Reminders couldbe incorporated into electronic healthrecords, and there should be docu-mentation that Hb concentrations havereturned to the normal range. The effi-cacy of any program for minimizing IDand IDA should be tracked scientifi-cally and evaluated through well-planned surveillance programs.

SUMMARY

Given that iron is the world’s mostcommon single-nutrient deficiencyand there is some evidence of adverseeffects of both ID and IDA on cognitiveand behavioral development, it is im-portant to minimize ID and IDA in in-fants and toddlers without waiting forunequivocal evidence. Controversies

remain regarding the timing andmethods used for screening for ID/IDAas well as regarding the use of ironsupplements to prevent ID/IDA. Al-though further study is required togenerate higher levels of evidence tosettle these controversies, the cur-rently available evidence supports thefollowing recommendations.

1. Term, healthy infants have suffi-cient iron for at least the first 4months of life. Humanmilk containsvery little iron. Exclusively breast-fed infants are at increasing risk ofID after 4 completed months of age.Therefore, at 4 months of age,breastfed infants should be supple-mentedwith 1mg/kg per day of oraliron beginning at 4 months of ageuntil appropriate iron-containingcomplementary foods (includingiron-fortified cereals) are intro-duced in the diet (see Table 3). Forpartially breastfed infants, the pro-portion of human milk versus for-mula is uncertain; therefore, begin-ning at 4 months of age, partiallybreastfed infants (more than halfof their daily feedings as humanmilk) who are not receiving iron-containing complementary foodsshould also receive 1mg/kg per dayof supplemental iron.

2. For formula-fed infants, the ironneeds for the first 12 months of lifecan be met by a standard infant for-mula (iron content: 10–12 mg/L) andthe introduction of iron-containingcomplementary foods after 4 to 6months of age, including iron-fortifiedcereals (Table 3). Whole milk shouldnot be used before 12 completedmonths of age.

3. The iron intake between 6 and 12months of age should be 11mg/day.When infants are given complemen-tary foods, redmeat and vegetableswith higher iron content should beintroduced early (Table 3). To aug-ment the iron supply, liquid iron

supplements are appropriate ifiron needs are not being met by theintake of formula and complemen-tary foods.

4. Toddlers 1 through 3 years of ageshould have an iron intake of 7 mg/day. This would be best delivered byeating red meats, cereals fortifiedwith iron, vegetables that containiron, and fruits with vitamin C,which augments the absorption ofiron (Tables 3 and 4). For toddlersnot receiving this iron intake, liquidsupplements are suitable for chil-dren 12 through 36 months of age,and chewable multivitamins can beused for children 3 years and older.

5. All preterm infants should have aniron intake of at least 2 mg/kg perday through 12 months of age,which is the amount of iron sup-plied by iron-fortified formulas. Pre-term infants fed humanmilk shouldreceive an iron supplement of 2mg/kg per day by 1 month of age,and this should be continued untilthe infant is weaned to iron-fortifiedformulaorbeginseatingcomplemen-tary foods that supply the 2 mg/kg ofiron. An exception to this practicewould include infants who have re-ceived an iron load from multipletransfusions of packed red bloodcells.

6. Universal screening for anemiashould be performed at approxi-mately 12 months of age with deter-mination of Hb concentration andan assessment of risk factors asso-ciated with ID/IDA. These risk fac-tors would include low socioeco-nomic status (especially children ofMexican American descent [Table1]), a history of prematurity or lowbirth weight, exposure to lead, ex-clusive breastfeeding beyond 4months of age without supplemen-tal iron, and weaning to whole milkor complementary foods that do notinclude iron-fortified cereals or

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foods naturally rich in iron (Table3). Additional risk factors are thefeeding problems, poor growth, andinadequate nutrition typically seenin infants with special healthcare needs. For infants and tod-dlers (1–3 years of age), additionalscreening can be performed at anytime if there is a risk of ID/IDA, in-cluding inadequate dietary ironintake.

7. If the Hb level is less than 11.0mg/dL at 12months of age, then fur-ther evaluation for IDA is requiredto establish it as a cause of anemia.If there is a high risk of dietary ID asdescribed in point 6 above, then fur-ther testing for ID should be per-formed, given the potential adverseeffects on neurodevelopmental out-comes. Additional screening testsfor ID or IDA should include mea-surement of:

● SF and CRP levels; or

● CHr concentration.

8. If a child has mild anemia (Hb levelof 10–11 mg/d) and can be closelymonitored, an alternative methodof diagnosis would be to documenta 1 g/dL increase in plasma Hb con-centration after 1 month of appro-priate iron-replacement therapy,especially if the history indicatesthat the diet is likely to be irondeficient.

9. Use of the TfR1 assay as screeningfor ID is promising, and the AAP sup-ports the development of TfR1 stan-dards for use of this assay in in-fants and children.

10. If IDA (or any anemia) or ID hasbeen confirmed by history and lab-oratory evidence, a means of care-fully tracking and following infantsand toddlers with a diagnosis ofID/IDA should be implemented.Electronic health records could beused not only to generate re-minder messages to screen forIDA and ID at 12 months of age butalso to document that IDA and IDhave been adequately treatedonce diagnosed.

ADDENDUM

Development of This Report

This report was written by the primaryauthors after extensive review of theliterature using PubMed, previous AAPreports, Cochrane reviews, and re-ports from other groups.1,6,7,48,77

The report was also submitted to thefollowing sections and committees ofthe AAP that were asked to commenton the manuscript: Committee on Fe-tus and Newborn (COFN); Committeeon Psychosocial Aspects of Child andFamily Health (COPACFH); Section onAdministration and Practice Manage-ment (SOAPM); Section on Develop-mental and Behavioral Pediatrics(SODBP); Section on Gastroenterology,Hepatology, and Nutrition (SOGHN);Section on Hematology and Oncology(SOHO); and Section on Breast Feeding(SOBr).

Additional comments were soughtfrom the Centers for Disease Controland Prevention (CDC), the Departmentof Agriculture (WIC), the National Insti-

tutes of Health (NIH), and the Food andDrug Administration (FDA), becausethese governmental agencies were in-volved in the development of the state-ment and will necessarily deal with itsimpact. As it was developed it was ex-tensively reviewed and revised bymembers of the AAP Committee on Nu-trition, who unanimously approvedthis clinical report. It is openly ac-knowledged that where the highestlevels of evidence are absent, the opin-ions and suggestions of members ofthe Committee on Nutrition as well asother groups consulted for this state-ment were taken into consideration indeveloping this clinical report.

LEAD AUTHORSRobert D. Baker, MD, PhD, Former CommitteeMemberFrank R. Greer, MD, Immediate PastChairperson

COMMITTEE ON NUTRITION,2009–2010Jatinder J. S. Bhatia, MD, ChairpersonSteven A. Abrams, MDStephen R. Daniels, MD, PhDMarcie Beth Schneider, MDJanet Silverstein, MDNicolas Stettler, MD, MSCEDan W. Thomas, MD

LIAISONSLaurence Grummer-Strawn, PhD – Centers forDisease Control and PreventionRear Admiral Van S. Hubbard, MD, PhD –National Institutes of HealthValérie Marchand, MD – Canadian PaediatricSocietyBenson M. Silverman, MD – Food and DrugAdministrationValery Soto, MS, RD, LD – US Department ofAgriculture

STAFFDebra L. Burrowes, MHAdburrowes@aap.org

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DOI: 10.1542/peds.2010-2576; originally published online October 5, 2010; 2010;126;1040Pediatrics

Robert D. Baker, Frank R. Greer and The Committee on Nutrition3 Years of Age)−Infants and Young Children (0

Diagnosis and Prevention of Iron Deficiency and Iron-Deficiency Anemia in  

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rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.Grove Village, Illinois, 60007. Copyright © 2010 by the American Academy of Pediatrics. All and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elkpublication, it has been published continuously since 1948. PEDIATRICS is owned, published, PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

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DOI: 10.1542/peds.2010-2576; originally published online October 5, 2010; 2010;126;1040Pediatrics

Robert D. Baker, Frank R. Greer and The Committee on Nutrition3 Years of Age)−Infants and Young Children (0

Diagnosis and Prevention of Iron Deficiency and Iron-Deficiency Anemia in  

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of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2010 by the American Academy published, and trademarked by the American Academy of Pediatrics, 141 Northwest Pointpublication, it has been published continuously since 1948. PEDIATRICS is owned, PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

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