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

Infants and Young Children (03 Years of Age)


Robert D. Baker, Frank R. Greer and The Committee on Nutrition
Pediatrics 2010;126;1040; originally published online October 5, 2010;
DOI: 10.1542/peds.2010-2576

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/126/5/1040.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly


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Guidance for the Clinician in
Rendering Pediatric Care

Clinical ReportDiagnosis and Prevention of Iron


Deciency and Iron-Deciency Anemia in Infants and
Young Children (0 3 Years of Age)
Robert D. Baker, MD, PhD, Frank R. Greer, MD, and THE
abstract COMMITTEE ON NUTRITION
This clinical report covers diagnosis and prevention of iron deciency KEY WORDS
iron deciency, iron-deciency anemia, iron intake, infants,
and iron-deciency anemia in infants (both breastfed and formula fed) toddlers, breastfeeding, formula
and toddlers from birth through 3 years of age. Results of recent basic ABBREVIATIONS
research support the concerns that iron-deciency anemia and iron IDiron deciency
deciency without anemia during infancy and childhood can have long- IDAiron-deciency anemia
Hbhemoglobin
lasting detrimental effects on neurodevelopment. Therefore, pediatri-
SFserum ferritin
cians and other health care providers should strive to eliminate iron IOMInstitute of Medicine
deciency and iron-deciency anemia. Appropriate iron intakes for WICSpecial Supplemental Program for Women, Infants, and
infants and toddlers as well as methods for screening for iron de- Children
CHrreticulocyte hemoglobin
ciency and iron-deciency anemia are presented. Pediatrics 2010;126: TfR1transferrin receptor 1
10401050 CRPC-reactive protein
AAPAmerican Academy of Pediatrics
INTRODUCTION This document is copyrighted and is property of the American
Iron deciency (ID) and iron-deciency anemia (IDA) continue to be of Academy of Pediatrics and its Board of Directors. All authors
have led conict of interest statements with the American
worldwide concern. Among children in the developing world, iron is the Academy of Pediatrics. Any conicts have been resolved through
most common single-nutrient deciency.1 In industrialized nations, de- a process approved by the Board of Directors. The American
spite a demonstrable decline in prevalence,2 IDA remains a common Academy of Pediatrics has neither solicited nor accepted any
commercial involvement in the development of the content of
cause of anemia in young children. However, even more important than this publication.
anemia itself is the indication that the more common ID without anemia The guidance in this report does not indicate an exclusive
may also adversely affect long-term neurodevelopment and behavior course of treatment or serve as a standard of medical care.
and that some of these effects may be irreversible.3,4 Because of the Variations, taking into account individual circumstances, may be
appropriate.
implications for pediatric health care providers and their patients, this
report reviews and summarizes this information.
This clinical report is a revision and extension of a previous policy
statement published in 1999,5 which addressed iron fortication of
formulas. This report covers diagnosis and prevention of ID and IDA in
infants (both breastfed and formula fed) and toddlers aged 1 through
3 years.

DEFINITIONS
Anemia: A hemoglobin (Hb) concentration 2 SDs below the mean Hb www.pediatrics.org/cgi/doi/10.1542/peds.2010-2576
concentration for a normal population of the same gender and age doi:10.1542/peds.2010-2576
range, as dened by the World Health Organization, the United Nations
All clinical reports from the American Academy of Pediatrics
Childrens Fund, and United Nations University.6 On the basis of the automatically expire 5 years after publication unless
1999 2002 US National Health and Nutrition Examination Survey, ane- reafrmed,revised, or retired at or before that time.
mia is dened as a Hb concentration of less than 11.0 g/dL for both PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
male and female children aged 12 through 35 months.7,8 For certain Copyright 2010 by the American Academy of Pediatrics
populations (ie, people living at high altitudes), adjustment of these
values may be necessary.

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Iron sufciency: A state in which there ing the third trimester of pregnancy. human milk ingestion; therefore, no
is sufcient iron to maintain normal Infants born prematurely miss this correction need be made for infant
physiologic functions. rapid accretion and are decient in to- weight. It should be pointed out, how-
Iron deciency: A state in which there tal body iron. A number of maternal ever, that although bigger infants may
is insufcient iron to maintain normal conditions, such as anemia, maternal ingest more milk, there is a large vari-
physiologic functions. ID results from hypertension with intrauterine growth ation in iron concentration of human
inadequate iron absorption to accom- restriction, or diabetes during preg- milk, and there is no guarantee that
modate an increase in requirements nancy, can also result in low fetal the iron content of the maternal milk
attributable to growth or resulting iron stores in both term and preterm matches the needs of the infant for
from a long-term negative iron bal- infants. iron.
ance. Either of these situations leads Preterm Infants For infants from 7 to 12 months com-
to a decrease in iron stores as mea- pleted age, the recommended dietary
sured by serum ferritin (SF) concen- The decit of total body iron in preterm allowance for iron, according to the
trations or bone marrow iron content. infants increases with decreasing ges- IOM, is 11 mg/day, which was deter-
tational age. It is worsened by the mined by using a factorial approach.
ID may or may not be accompanied by
rapid postnatal growth that many in- The amount of iron lost, primarily from
IDA.
fants experience and by frequent phle- sloughed epithelial cells from skin and
Iron-deciency anemia: An anemia (as botomies without adequate blood re-
dened above) that results from ID. the intestinal and urinary tracts, was
placement. On the other hand, sick added to the amounts of iron required
Iron overload: The accumulation of ex- preterm infants who receive multiple
for increased blood volume, increased
cess iron in body tissues. Iron overload transfusions are at risk of iron over-
tissue mass, and storage iron during
usually occurs as a result of a genetic load. The use of recombinant human
this period of life. It was noted that the
predisposition to absorb and store erythropoietin to prevent transfusion
iron needs of infants do not suddenly
iron in excess amounts, the most com- therapy in preterm infants will further
jump from 0.27 to 11 mg/day at 6
mon form of which is hereditary hemo- deplete iron stores if additional sup-
months of age; this disjuncture is the
chromatosis. Iron overload can also plemental iron is not provided. The
result of the use of very different meth-
occur as a complication of other hema- highly variable iron status of preterm
ods of determining these values. How-
tologic disorders that result in chronic infants, along with their risks for ID as
ever, it is clear that healthy, term new-
transfusion therapy, repeated injec- well as toxicity, precludes determining
born infants require very little iron
tions of parenteral iron, or excessive the exact requirement, but it can be
early in life compared with the signi-
iron ingestion. estimated to be between 2 and 4 mg/kg
cant amounts of iron required after 6
Recommended dietary allowance for per day when given orally.9
months of age.
iron: The average daily dietary intake Term Infants (Birth Through 12
that is sufcient to meet the nutrient Completed Months of Age) IRON REQUIREMENTS FOR
requirements of nearly all individuals TODDLERS (13 YEARS OF AGE)
(97%98%) of a given age and gender. The Institute of Medicine (IOM)10 used
the average iron content of human Using a similar factorial approach as
Adequate intake for iron: This term is milk to determine the adequate intake described for infants 7 to 12 months
used when there is not enough informa- of 0.27 mg/day for term infants from completed age, the IOM determined
tion to establish a recommended dietary birth through 6 months completed that the recommended dietary allow-
allowance for a population (eg, term in- age. The average iron content of hu- ance for iron for children from 1
fants, 0 6 months of age). The adequate man milk was determined to be 0.35 through 3 years of age is 7 mg/day.9
intake is based on the estimated average mg/L, and the average milk intake of an
nutrient intake by a group (or groups) of exclusively breastfed infant was deter- PREVALENCE OF ID AND IDA
healthy individuals. mined to be 0.78 L/day. Multiplying There are currently no national statis-
these 2 numbers determined the ade- tics for the prevalence of ID and IDA in
IRON REQUIREMENTS FOR INFANTS quate intake of 0.27 mg/day for term infants before 12 months completed
(UP TO 12 COMPLETED MONTHS infants from birth through 6 months of age. Hay et al11 reported on a cohort of
OF AGE) age in the IOM report. The IOM further 284 term Norwegian infants. Using the
Eighty percent of the iron present in a reasoned that there should be a direct denitions provided by Dallman12 in an
newborn term infant is accreted dur- correlation between infant size and IOM report, the prevalence of ID at 6

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months of age was 4% and increased TABLE 1 ID, IDA, and Anemia in the 1999 2002 National Health and Nutrition Examination Survey,7
Children 12 to 35 Months of Age
to 12% at 12 months of age.
Population Sampled (No.) Proportion of US Toddler ID, % (SE) IDA, % (SE) All Anemia,
The prevalence of ID and IDA among Population, % (SE)a % (SE)
toddlers (13 years of age) in the General US population (672) 9.2 (1.3) 2.1 (0.6) 5.1 (0.8)
United States is listed in Table 1 and Above poverty line (355)b 66.4 (2.9) 8.9 (1.7) 2.2 (0.8)c 4.6 (1.1)
was derived from National Health and 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)
Nutrition Examination Survey data col- Non-Hispanic white (196) 58.0 (3.8) 7.3 (1.9) 2.0 (0.8)c 4.6 (1.2)
lected between 1999 and 2002.7,8 The Non-Hispanic black (173) 14.1 (2.1) 6.6 (1.8) 1.6 (0.9)c 8.3 (1.9)
overall prevalence of anemia and pos- 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
sibly ID and IDA in infants and toddlers
Shown are the unweighted number and weighted percentage and SEs for all children with complete data for Hb, SF,
has declined since the 1970s.2 Al- transferrin saturation, and zinc protoporphyrin. Anemia was dened as a Hb concentration of 11.0 g/dL; ID7 was dened
though there is no direct proof, this as an abnormal value for at least 2 of 3 indicators: SF (abnormal cutoff: 10 g/dL), zinc protoporphyrin (1.42 mol/L red
blood cells), and transferrin saturation (10%); and IDA was dened as anemia plus ID.
decline has been attributed to use a Proportion of row descriptor of all children in analytic sample (N 672).

b Children with income data (N 623).


of iron-fortied formulas and iron- c Estimate is statistically unreliable. Relative SE (SE of estimate/estimate 100) 30%.
fortied infant foods provided by the d Any member of household who received benets from WIC in the previous 12 months: children with food-security data (N

Special Supplemental Program for 668).

Women, Infants, and Children (WIC) in


the early 1970s and the decrease in
use of whole cow milk for infants.8 Still, out chelation therapy seems to in- ment of IDA improved psychomotor de-
ID remains relatively common and oc- crease blood lead concentrations and velopment was examined, stated that
curs in 6.6% to 15.2% of toddlers, de- decrease basal lead excretion.21,22 The there was inconclusive but plausible
pending on ethnicity and socioeco- effect of iron supplementation on evidence (only 2 randomized con-
blood lead concentrations in iron- trolled trials) demonstrating improve-
nomic status. The prevalence of IDA is
replete children with or without lead ment if the treatment extended for
0.9% to 4.4%, again depending on race/
poisoning is not known. Thus, in the- more than 30 days.27 McCann and
ethnicity and socioeconomic status,7,8
ory, selective rather than universal Ames28 recently reviewed the evidence
but only accounts for approximately
iron supplementation would be more of a causal relationship between ID/IDA
40% of the anemia in toddlers (Table
likely to reduce lead poisoning and and decits in cognitive and behav-
1). These numbers are comparable to
its potential harmful effects on these ioral function. They concluded that for
data collected in other industrialized
children. IDA, there is at least some support
countries.13,14
ID AND NEURODEVELOPMENT for causality, but because specicity
Related to the problem of ID/IDA is the
for both cause and effect have not
interaction of iron and lead. Results of The possible relationship between ID/ been established unequivocally, it is
both animal and human studies have IDA and later neurobehavioral develop-
premature to conclude the existence
conrmed that IDA increases intestinal ment in children is the subject of many
lead absorption.1517 A reasonably well- of a causal relationship between IDA
reports.3,2331 Results of a preponder-
established epidemiologic association and cognitive and behavioral perfor-
ance of studies have demonstrated an
has been made between IDA and in- mance. For ID, some evidence of cau-
association between IDA in infancy and
creased lead concentrations.18 Thus, sality exists, but it is less than that for
later cognitive decits. Lozoff et al3,25
primary prevention of IDA could also IDA.28
have reported detecting cognitive def-
serve as primary prevention of lead icits 1 to 2 decades after the iron- It is known that iron is essential
poisoning. This possibility is all the decient insult during infancy. How- for normal neurodevelopment in a
more attractive, because lead has ever, it has been difcult to establish a number of animal models. ID affects
been reported to induce neurotoxicity causal relationship because of the neuronal energy metabolism, the me-
at even very low blood concentra- many confounding variables and the tabolism of neurotransmitters, myeli-
tions.19,20 In addition, preexisting IDA difculty in designing and executing nation, and memory function. These
decreases the efciency of lead chela- the large, randomized controlled trials observations would explain the behav-
tion therapy, and iron supplementa- necessary to distinguish small poten- ioral ndings in human infants that
tion corrects this effect. In contrast, tial differences. The authors of a Co- have been associated with ID.2931
iron supplementation in a child with chrane Database systematic review, in Therefore, taking into account that
IDA who also has lead poisoning with- which the question of whether treat- iron is the worlds most common

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single-nutrient deciency, it is impor- counted for most cases of anemia in mation about iron status are SF, CHr,
tant to minimize IDA and ID among in- children, anemia and IDA were and TfR1 concentrations.
fants and toddlers, even if an unequiv- roughly synonymous, and a simple SF is a sensitive parameter for the as-
ocal relationship between IDA and ID measurement of Hb concentration was sessment of iron stores in healthy sub-
and neurodevelopmental outcomes sufcient to make a presumptive diag- jects3436; 1 g/L of SF corresponds to 8
has yet to be established. nosis of anemia attributable to ID. Par- to 10 mg of available storage iron.34,37,38
ticularly in industrialized nations, the Measurement of SF concentration is
DIAGNOSIS
prevalence of ID and IDA has de- widely used in clinical practice and
Iron status is a continuum. At one creased, and other causes of anemia, readily available. Cook et al36 selected
end of the spectrum is IDA, and at such as hemolytic anemias, anemia of an SF concentration below 12 g/L as
the other end is iron overload. ID and chronic disease, and anemia attribut- diagnostic for ID after a comprehen-
IDA are attributable to an imbalance able to other nutrient deciencies, sive population survey in the United
between iron needs and available iron have become proportionately more States. Thus, a cutoff value of 12 g/L
that results in a deciency of mobiliz- common.32 has been widely used for adults and
able iron stores and is accompanied
No single measurement is currently denotes depletion of iron stores. In
by changes in laboratory measure-
available that will characterize the children, a cutoff value of 10 g/L has
ments that include Hb concentration,
iron status of a child. The limitations of been suggested.39 Because SF is an
mean corpuscular Hb concentration,
using Hb concentration as a measure acute-phase reactant, concentrations
mean corpuscular volume, reticulo-
of iron status are its lack of specicity of SF may be elevated in the presence
cyte Hb concentration (abbreviated
and sensitivity. Factors that limit eryth- of chronic inammation, infection, ma-
in the literature as CHr) content, to-
ropoiesis or result in chronic hemoly- lignancy, or liver disease, and a simul-
tal iron-binding capacity, transferrin
sis, such as genetic disorders and taneous measurement of C-reactive
saturation, zinc protoporphyrin, SF
chronic infections, may result in low protein (CRP) is required to rule out
concentration, and serum transferrin
Hb concentrations. Vitamin B12 or fo- inammation. Although Brugnara et
receptor 1 (TfR1) concentration. Mea-
late deciency, although uncommon in al40 found SF concentration to be less
surements that are used to describe
the pediatric population, also can re- accurate than either the CHr or TfR1
iron status are listed in Table 2.
sult in a low Hb concentration. The lack concentration in establishing iron sta-
In a child with ID, as the Hb concentra- of sensitivity is largely attributable to tus of children, combining SF concen-
tion falls 2 SDs below the mean for age the marked overlap in Hb concentra- tration with a determination of CRP is
and gender, IDA is present, by deni-
tions between populations with iron currently more readily available to as-
tion; for infants at 12 months of age,
sufciency and those with ID.33 Thus, to sess iron stores and is a reliable
this is 11.0 mg/dL.7,8 When IDA ac-
identify ID or IDA, Hb concentration screening test as long as the CRP level
must be combined with other mea- is not elevated41 (Table 2).
TABLE 2 Spectrum of Iron Status surements of iron status. Once the di- CHr and TfR1 concentrations are not
Parameter ID IDA Iron
agnosis of IDA has been established, affected by inammation (infection),
Without Overload however, following Hb concentration malignancy, or anemia of chronic dis-
Anemia is a good measure of response to ease and, thus, would be preferable as
SFa 2 22 1 treatment.
Transferrin 2 2 11
biomarkers for iron status. Only the
saturation In establishing the denitive iron sta- CHr assay is currently available for use
TfR1 11 111 2 tus of an individual, it is desirable to in children. The CHr content assay has
CHr 2 2 Normal
Hb Normal 2 Normal
use the fewest tests that will accu- been validated in children, and stan-
Mean corpuscular Normal 2 Normal rately reect iron status. Any battery of dard values have been determined.40,42
volume tests must include Hb concentration, The CHr assay provides a measure of
a Confounded by the presence of inammation. If SF is because it determines the adequacy iron available to cells recently re-
normal or increased and the CRP level is normal, then
there is no ID. If SF is decreased, then ID is present regard- of the circulating red cell mass and leased from the bone marrow. CHr
less of the measure of CRP. If SF is normal or increased whether anemia is present. One or content can be measured by ow cy-
and the CRP level is increased, then the presence of ID
cannot be determined. more tests must be added to the deter- tometry, and 2 of the 4 automated he-
Modied from American Academy of Pediatrics, Commit- mination of Hb concentration if ID or matology analyzers commonly used in
tee on Nutrition. Iron deciency. In: Kleinman RE, ed. Pedi-
atric Nutrition Handbook. 5th ed. Elk Grove Village, IL:
IDA is to be diagnosed. The 3 parame- the United States have the capability to
American Academy of Pediatrics; 2004:304. ters that provide discriminatory infor- measure CHr.43 A low CHr concentra-

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tion has been shown to be the stron- be given to establishing a diagnosis of breastfeeding for 6 months, and the
gest predictor of ID in children40,42,43 IDA by using the screening tests de- American Academy of Pediatrics (AAP)
and shows much promise for the diag- scribed previously. has recommended exclusive breast-
nosis of ID when the assay becomes feeding for a minimum of 4 months but
more widely available. PREVENTION OF ID AND IDA preferably for 6 months. Exclusive
TfR1 is a measure of iron status, de- Preterm Infants breastfeeding for more than 6 months
tecting ID at the cellular level. TfR1 is has been associated with increased
The preterm infant (37 weeks gesta- risk of IDA at 9 months of age.49,50 Rec-
found on cell membranes and facili-
tion) who is fed human milk should re- ommendations for exclusive breast-
tates transfer of iron into the cell.
ceive a supplement of elemental iron feeding for 6 months do not take into
When the iron supply is inadequate,
at 2 mg/kg per day starting by 1 month account infants who are born with
there is an upregulation of TfR1 to en-
of age and extending through 12 lower-than-usual iron stores (low
able the cell to compete more effec-
months of age.47 This can be provided birth weight infants, infants of diabetic
tively for iron, and subsequently, more as medicinal iron or in iron-fortied
circulating TfR1 is found in serum. An mothers), a condition that also has
complementary foods. Preterm infants been linked to lower SF concentrations
increase in serum TfR1 concentrations fed a standard preterm infant formula
is seen in patients with ID or IDA, al- at 9 months of age.51 In a double-blind
(14.6 mg of iron per L) or a standard study, Friel et al52 demonstrated that
though it does not increase in serum term infant formula (12.0 mg of iron
until iron stores are completely ex- exclusively breastfed infants supple-
per L) will receive approximately 1.8 to mented with iron between 1 and 6
hausted in adults.44 46 However, the 2.2 mg/kg per day of iron, assuming a
TfR1 assay is not widely available, and months of age had higher Hb concen-
formula intake of 150 mL/kg per day. tration and higher mean corpuscular
standard values for infants and chil- Despite the use of iron-containing for-
dren have yet to be established. volume at 6 months of age than did
mulas, 14% of preterm infants develop their unsupplemented peers. Supple-
Thus, to establish a diagnosis of IDA, ID between 4 and 8 months of age.48 mentation also resulted in better vi-
the following sets of tests can be used Thus, some formula-fed preterm in- sual acuity and higher Bayley Psy-
at the present time (when coupled fants may need an additional iron chomotor Developmental Indices at 13
with determination of a Hb concentra- supplement,47 although there is not months. Thus, it is recommended that
tion of 11 g/dL): (1) SF and CRP mea- enough evidence to make this a general exclusively breastfed term infants
surements or (2) CHr measurement. recommendation at this time. Exceptions receive an iron supplementation of 1
For diagnosing ID without anemia, to this iron-supplementation practice in mg/kg per day, starting at 4 months of
measure either (1) SF and CRP or (2) preterm infants would be infants who re- age and continued until appropriate
CHr. ceived multiple transfusions during hos- iron-containing complementary foods
Another approach to making the diag- pitalization, who might not need any iron have been introduced (Tables 3 and 4).
nosis of IDA in a clinically stable child supplementation. For partially breastfed infants, the pro-
with mild anemia (Hb concentration portion of human milk versus formula
between 10 and 11 g/dL) is to monitor Term, Breastfed Infants is uncertain; therefore, beginning at 4
the response to iron supplementation, Infants who are born at term usually months of age, infants who receive
especially if a dietary history indicates have sufcient iron stores until 4 to 6 more than one-half of their daily feed-
that the diet is likely to be iron de- months of age.49 Infants born at term ings as human milk and who are not
cient. An increase in Hb concentration have high Hb concentration and high receiving iron-containing complemen-
of 1 g/dL after 1 month of therapeutic blood volume in proportion to body tary foods should also receive 1 mg/kg
supplementation has been used to sig- weight. They experience a physiologic per day of supplemental iron.
nify the presence of IDA. This approach decline in both blood volume and Hb
requires that iron supplementation concentration during the rst several Term, Formula-Fed Infants
be adequate, iron be adequately ab- months of life. These facts have led to For the term, formula-fed infant, the
sorbed, and patient compliance with the supposition that breastfed infants level of iron fortication of formula to
adequate follow-up can be ensured. need very little iron. It is assumed that prevent ID remains controversial.53,54
However, because only 40% of the the small amount of iron in human For more than 25 years, 12 mg of iron
cases of anemia identied at 12 milk is sufcient for the exclusively per L has been the level of fortication
months of age will be secondary to IDA breastfed infant. The World Health in standard term infant formulas in
(Table 1), strong consideration should Organization recommends exclusive the United States, consistent with

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guidelines of WIC for iron-fortied for- TABLE 3 Foods to Increase Iron Intake and Iron Absorption
mula (at least 10 mg/L), thus creating Elemental Iron, mg
a natural experiment. The level of 12 a
Commercial baby food, heme iron
mg/L was determined by calculating Meat
Baby food, lamb, junior, 1 jar (2.5 oz) 1.2
the total iron needs of the child from 0 Baby food, chicken, strained, 1 jar (2.5 oz) 1.0
to 12 months of age, assuming average Baby food, lamb, strained, 1 jar (2.5 oz) 0.8
birth weight and average weight gain Baby food, beef, junior, 1 jar (2.5 oz) 0.7
Baby food, beef, strained, 1 jar (2.5 oz) 0.7
during the rst year. The calculation Baby food, chicken, junior, 1 jar (2.5 oz) 0.7
also assumed that formula was the Baby food, pork, strained, 1 jar (2.5 oz) 0.7
only source of iron during this period. Baby food, ham, strained, 1 jar (2.5 oz) 0.7
Baby food, ham, junior, 1 jar (2.5 oz) 0.7
Others have recommended lower
Baby food, turkey, strained, 1 jar (2.5 oz) 0.5
amounts of iron in infant formula,55 Baby food, veal, strained, 1 jar (2.5 oz) 0.5
and there have been studies to exam- Commercial baby food,a nonheme iron
ine iron-fortication levels of less than Vegetables
Baby food, green beans, junior, 1 jar (6 oz) 1.8
12 mg/L.56 61 However, it is the conclu- Baby food, peas, strained, 1 jar (3.4 oz) 0.9
sion of the AAP that infant formula that Baby food, green beans, strained, 1 jar (4 oz) 0.8
contains 12 mg of elemental iron per L Baby food, spinach, creamed, strained, 1 jar (4 oz) 0.7
Baby food, sweet potatoes, junior (6 oz) 0.7
is safe for its intended use. Although Cereals
there has been some concern about Baby food, brown rice cereal, dry, instant, 1 tbsp 1.8
linear growth in iron-replete infants Baby food, oatmeal cereal, dry, 1 tbsp 1.6
Baby food, rice cereal, dry, 1 tbsp 1.2
given medicinal iron,62 no published
Baby food, barley cereal, dry, 1 tbsp 1.1
studies have convincingly documented Table food, heme iron
decreased linear growth in iron-replete Clams, canned, drained solids, 3 oz 23.8
infants receiving formulas containing Chicken liver, cooked, simmered, 3 oz 9.9
Oysters, Eastern canned, 3 oz 5.7
high amounts of iron. Evidence is also Beef liver, cooked, braised, 3 oz 5.6
insufcient to associate formulas that Shrimp, cooked moist heat, 3 oz 2.6
contain 12 mg of iron per L with gas- Beef, composite of trimmed cuts, lean only, all grades, cooked, 3 oz 2.5
Sardines, Atlantic, canned in oil, drained solids with bone, 3 oz 2.5
trointestinal symptoms. At least 4 Turkey, all classes, dark meat, roasted, 3 oz 2.0
studies have shown no adverse ef- Lamb, domestic, composite of trimmed retail cuts, separable lean only, 1.7
fects.63 66 Reports have conicted on choice, cooked, 3 oz
Fish, tuna, light, canned in water, drained solids, 3 oz 1.3
whether iron fortication is associ-
Chicken, broiler or fryer, dark meat, roasted, 3 oz 1.1
ated with increased risk of infection. Turkey, all classes, light meat, roasted, 3 oz 1.1
Decreased incidence, increased inci- Veal, composite of trimmed cuts, lean only, cooked, 3 oz 1.0
dence, and no change in number of in- Chicken, broiler or fryer, breast, roasted, 3 oz 0.9
Pork, composite of trimmed cuts (leg, loin, shoulder), lean only, cooked, 3 oz 0.9
fections have all been reported.67,68 The Fish, salmon, pink, cooked, 3 oz 0.8
authors of a recent systematic review Table food, nonheme iron
concluded that iron supplementation Oatmeal, instant, fortied, cooked, 1 cup 14.0
Blackstrap molasses,b 2 tbsp 7.4
has no apparent harmful effect on Tofu, raw, regular, 12 cup 6.7
the overall incidence of infectious ill- Wheat germ, toasted, 12 cup 5.1
nesses in children, though it slightly Ready-to-eat cereal, fortied at different levels, 1 cup 4.5 to 18
Soybeans, mature seeds, cooked, boiled, 12 cup 4.4
increases the risk of developing diar-
Apricots, dehydrated (low-moisture), uncooked, 12 cup 3.8
rhoea.69 Finally, when examining spe- Sunower seeds, dried, 12 cup 3.7
cically infants given formula with 12 Lentils, mature seeds, cooked, 12 cup 3.3
mg of iron per L, Singhal et al70 were Spinach, cooked, boiled, drained, 12 cup 3.2
Chickpeas, mature seeds, cooked, 12 cup 2.4
unable to identify adverse health effects Prunes, dehydrated (low-moisture), uncooked, 12 cup 2.3
in older infants and toddlers consuming Lima beans, large, mature seeds, cooked, 12 cup 2.2
a high iron-containing formula. They Navy beans, mature seeds, cooked, 12 cup 2.2
Kidney beans, all types, mature seeds, cooked, 12 cup 2.0
found no difference between controls Molasses, 2 tbsp 1.9
and the treatment group in incidence of Pinto beans, mature seeds, cooked, 12 cup 1.8
infection, gastrointestinal problems, or Raisins, seedless, packed, 12 cup 1.6
general morbidity.

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TABLE 3 Continued lets or as a component of either liquid
Elemental Iron, mg or chewable multivitamins. Iron sprin-
Prunes, dehydrated (low moisture), stewed, 12 cup 1.6 kles with or without additional zinc are
Prune juice, canned, 4 oz 1.5 available in Canada. Barriers to ade-
Green peas, cooked, boiled, drain, 12 cup 1.2
Enriched white rice, long-grain, regular, cooked, 12 cup 1.0 quate iron supplementation are (1)
Whole egg, cooked (fried or poached), 1 large egg 0.9 lack of education for care providers
Enriched spaghetti, cooked, 12 cup 0.9 and patients, (2) poor compliance
White bread, commercially prepared, 1 slice 0.9
Whole-wheat bread, commercially prepared, 1 slice 0.7 made worse by the perception of ad-
Spaghetti or macaroni, whole wheat, cooked, 12 cup 0.7 verse effects, including nausea, vomit-
Peanut butter, smooth style, 2 tbsp 0.6 ing, constipation, stomach upset, and
Brown rice, medium-grain, cooked, 12 cup 0.5
teeth staining, (3) cost, (4) current fed-
Note that all gures 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 baby eral supplemental nutrition programs
food 71 g (an infant would not be expected to eat 3 oz [approximately the size of a deck of cards] of pureed table meat at not providing iron supplements, and
a meal).
b Source of iron value was obtained from a manufacturer of this type of molasses. (5) risk of iron overload.
Source of iron values in foods: US Department of Agriculture, Agricultural Research Service. USDA National Nutrient
Database for Standard Reference, Release 20: Nutrient Data Laboratory home page. Available at: www.ars.usda.gov/ba/
bhnrc/ndl.
Screening for ID and IDA
The AAP has concluded that universal
screening for anemia should be per-
TABLE 4 Selected Good Vitamin C Sources to Increase Iron Absorption formed with determination of Hb con-
Fruits Vegetables centration at approximately 1 year of
Citrus fruits (eg, orange, tangerine, grapefruit) Green, red, and yellow peppers
Pineapples Broccoli age. Universal screening would also in-
Fruit juices enriched with vitamin C Tomatoes clude an assessment of risk factors as-
Strawberries Cabbages sociated with ID/IDA: history of prema-
Cantaloupe Potatoes
Kiwifruit Leafy green vegetables
turity or low birth weight; exposure to
Raspberries Cauliower lead; exclusive breastfeeding beyond 4
months of age without supplemental
iron; and weaning to whole milk or
Toddlers (13 Years of Age) various foods, including corn our,71 complementary foods that do not in-
The iron requirement for toddlers is 7 soy sauce,72 sh sauce,73 and rice.74 clude iron-fortied cereals or foods
mg/day. Ideally, the iron requirements However, there are many technical and naturally rich in iron (Table 3). Addi-
of toddlers would be met and ID/IDA practical barriers to a successful for- tional risk factors include the feeding
would be prevented with naturally tication program for toddlers. Not the problems, poor growth, and inade-
iron-rich foods rather than iron sup- least of these barriers is the determi- quate nutrition typically seen in infants
plementation. These foods include nation of which foods to fortify with with special health care needs as well
those with heme sources of iron (ie, iron. In the United States, fortication as low socioeconomic status, espe-
red meat) and nonheme sources of of infant formula and infant cereal has cially children of Mexican American
iron (ie, legumes, iron-fortied cere- been credited with the decline in IDA. descent, as identied in the recent
als) (Table 3). Foods that contain vita- However, toddlers in the United States National Health and Nutrition Examina-
min C (ascorbic acid), such as orange typically do not eat enough of any other tion Survey8,75 (Table 1). Selective
juice, aid in iron absorption and are food to serve as a vehicle for iron for- screening can be performed at any age
listed in Table 4. Foods that contain tication. Universal food fortication when these risk factors for ID and IDA
phytates (found in soy) reduce iron ab- for all ages is problematic, given the have been identied, including risk of
sorption. Through public education possible adverse effects of iron in cer- inadequate iron intake according to di-
and altering feeding practices, the tain subsets of older children and etary history.
amount of iron available to older in- adults. It has been acknowledged that screen-
fants and toddlers via a normal diet As an alternative for toddlers who do ing for anemia with a Hb determination
could be maximized (Table 3). not eat adequate amounts of iron- neither identies children with ID nor
In developing countries, iron require- containing food (Table 3), iron supple- specically identies those with IDA.76
ments of older infants and toddlers ments are available in the form of iron In the United States, 60% of anemia is
have been met by iron fortication of sulfate drops and chewable iron tab- not attributable to ID, and most tod-

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FROM THE AMERICAN ACADEMY OF PEDIATRICS

dlers with ID do not have anemia (Table remain regarding the timing and supplements are appropriate if
2). It is also known that there is poor methods used for screening for ID/IDA iron needs are not being met by the
follow-up testing and poor documenta- as well as regarding the use of iron intake of formula and complemen-
tion of improved Hb concentrations. In supplements to prevent ID/IDA. Al- tary foods.
1 study, 14% of the children had a pos- though further study is required to 4. Toddlers 1 through 3 years of age
itive screening result for anemia. How- generate higher levels of evidence to should have an iron intake of 7 mg/
ever, only 18.3% of these children settle these controversies, the cur- day. This would be best delivered by
with a positive screening result had rently available evidence supports the eating red meats, cereals fortied
follow-up testing performed, and of following recommendations. with iron, vegetables that contain
that group, only 11.6% had docu- 1. Term, healthy infants have suf- iron, and fruits with vitamin C,
mented correction of low Hb levels.77 cient iron for at least the rst 4 which augments the absorption of
Therefore, for infants identied with a months of life. Human milk contains iron (Tables 3 and 4). For toddlers
Hb concentration of less than 11.0 very little iron. Exclusively breast- not receiving this iron intake, liquid
mg/dL or identied with signicant fed infants are at increasing risk of supplements are suitable for chil-
risk of ID or IDA as described previ- ID after 4 completed months of age. dren 12 through 36 months of age,
ously, SF and CRP or CHr levels in addi- Therefore, at 4 months of age, and chewable multivitamins can be
tion to Hb concentration should be breastfed infants should be supple- used for children 3 years and older.
measured to increase the sensitivity mented with 1 mg/kg per day of oral 5. All preterm infants should have an
and specicity of the diagnosis. In addi- iron beginning at 4 months of age iron intake of at least 2 mg/kg per
tion, the AAP, the World Health Organiza- until appropriate iron-containing day through 12 months of age,
tion, and the European Society for Pedi- complementary foods (including which is the amount of iron sup-
atric Gastroenterology, Hepatology and iron-fortied cereals) are intro- plied by iron-fortied formulas. Pre-
Nutrition also support the use of the duced in the diet (see Table 3). For term infants fed human milk should
measurement of TfR1 as a screening test partially breastfed infants, the pro- receive an iron supplement of 2
once the method has been validated and portion of human milk versus for- mg/kg per day by 1 month of age,
normal values for infants and toddlers mula is uncertain; therefore, begin- and this should be continued until
have been established. ning at 4 months of age, partially the infant is weaned to iron-fortied
Another step to improve the current breastfed infants (more than half formula or begins eating complemen-
screening system is to use technology- of their daily feedings as human tary foods that supply the 2 mg/kg of
based reminders for screening and milk) who are not receiving iron- iron. An exception to this practice
follow-up of infants and toddlers with a containing complementary foods would include infants who have re-
diagnosis of ID/IDA. Reminders could should also receive 1 mg/kg per day ceived an iron load from multiple
be incorporated into electronic health of supplemental iron. transfusions of packed red blood
records, and there should be docu- 2. For formula-fed infants, the iron cells.
mentation that Hb concentrations have needs for the rst 12 months of life 6. Universal screening for anemia
returned to the normal range. The ef- can be met by a standard infant for- should be performed at approxi-
cacy of any program for minimizing ID mula (iron content: 10 12 mg/L) and mately 12 months of age with deter-
and IDA should be tracked scienti- the introduction of iron-containing mination of Hb concentration and
cally and evaluated through well- complementary foods after 4 to 6 an assessment of risk factors asso-
planned surveillance programs. months of age, including iron-fortied ciated with ID/IDA. These risk fac-
cereals (Table 3). Whole milk should tors would include low socioeco-
SUMMARY not be used before 12 completed nomic status (especially children of
Given that iron is the worlds most months of age. Mexican American descent [Table
common single-nutrient deciency 3. The iron intake between 6 and 12 1]), a history of prematurity or low
and there is some evidence of adverse months of age should be 11 mg/day. birth weight, exposure to lead, ex-
effects of both ID and IDA on cognitive When infants are given complemen- clusive breastfeeding beyond 4
and behavioral development, it is im- tary foods, red meat and vegetables months of age without supplemen-
portant to minimize ID and IDA in in- with higher iron content should be tal iron, and weaning to whole milk
fants and toddlers without waiting for introduced early (Table 3). To aug- or complementary foods that do not
unequivocal evidence. Controversies ment the iron supply, liquid iron include iron-fortied cereals or

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foods naturally rich in iron (Table 10. If IDA (or any anemia) or ID has tutes of Health (NIH), and the Food and
3). Additional risk factors are the been conrmed by history and lab- Drug Administration (FDA), because
feeding problems, poor growth, and oratory evidence, a means of care- these governmental agencies were in-
inadequate nutrition typically seen fully tracking and following infants volved in the development of the state-
in infants with special health and toddlers with a diagnosis of ment and will necessarily deal with its
care needs. For infants and tod- ID/IDA should be implemented. impact. As it was developed it was ex-
dlers (13 years of age), additional Electronic health records could be tensively reviewed and revised by
screening can be performed at any used not only to generate re- members of the AAP Committee on Nu-
time if there is a risk of ID/IDA, in- minder messages to screen for trition, who unanimously approved
cluding inadequate dietary iron IDA and ID at 12 months of age but this clinical report. It is openly ac-
intake. also to document that IDA and ID knowledged that where the highest
7. If the Hb level is less than 11.0 have been adequately treated levels of evidence are absent, the opin-
mg/dL at 12 months of age, then fur- once diagnosed. ions and suggestions of members of
ther evaluation for IDA is required the Committee on Nutrition as well as
to establish it as a cause of anemia. ADDENDUM other groups consulted for this state-
If there is a high risk of dietary ID as Development of This Report ment were taken into consideration in
described in point 6 above, then fur- developing this clinical report.
This report was written by the primary
ther testing for ID should be per- authors after extensive review of the LEAD AUTHORS
formed, given the potential adverse literature using PubMed, previous AAP Robert D. Baker, MD, PhD, Former Committee
effects on neurodevelopmental out- reports, Cochrane reviews, and re- Member
comes. Additional screening tests Frank R. Greer, MD, Immediate Past
ports from other groups.1,6,7,48,77 Chairperson
for ID or IDA should include mea-
surement of: The report was also submitted to the COMMITTEE ON NUTRITION,
following sections and committees of 2009 2010
SF and CRP levels; or Jatinder J. S. Bhatia, MD, Chairperson
the AAP that were asked to comment
CHr concentration. on the manuscript: Committee on Fe- Steven A. Abrams, MD
Stephen R. Daniels, MD, PhD
8. If a child has mild anemia (Hb level tus and Newborn (COFN); Committee Marcie Beth Schneider, MD
of 10 11 mg/d) and can be closely on Psychosocial Aspects of Child and Janet Silverstein, MD
monitored, an alternative method Family Health (COPACFH); Section on Nicolas Stettler, MD, MSCE
Dan W. Thomas, MD
of diagnosis would be to document Administration and Practice Manage-
a 1 g/dL increase in plasma Hb con- ment (SOAPM); Section on Develop- LIAISONS
Laurence Grummer-Strawn, PhD Centers for
centration after 1 month of appro- mental and Behavioral Pediatrics Disease Control and Prevention
priate iron-replacement therapy, (SODBP); Section on Gastroenterology, Rear Admiral Van S. Hubbard, MD, PhD
especially if the history indicates Hepatology, and Nutrition (SOGHN); National Institutes of Health
Valrie Marchand, MD Canadian Paediatric
that the diet is likely to be iron Section on Hematology and Oncology Society
decient. (SOHO); and Section on Breast Feeding Benson M. Silverman, MD Food and Drug
(SOBr). Administration
9. Use of the TfR1 assay as screening
Valery Soto, MS, RD, LD US Department of
for ID is promising, and the AAP sup- Additional comments were sought Agriculture
ports the development of TfR1 stan- from the Centers for Disease Control STAFF
dards for use of this assay in in- and Prevention (CDC), the Department Debra L. Burrowes, MHA
fants and children. of Agriculture (WIC), the National Insti- dburrowes@aap.org

REFERENCES
1. United Nations Administrative Committee on income infants and children in ve states. fects of iron supplementation in non-
Coordination/Sub-Committee on Nutrition Pediatrics. 2001;107(4):677 682 anemic iron-decient adolescent girls.
and International Food Policy Research Insti- 3. Lozoff B, Jimenez E, Smith JB. Double burden Lancet. 1996;348(9033):992996
tute. Fourth Report of the World Nutrition Sit- of iron deciency in infancy and low socioeco- 5. American Academy of Pediatrics, Committee
uation. Geneva, Switzerland: United Nations nomic status: a longitudinal analysis of cogni- on Nutrition. Iron fortication of infant formu-
Administrative Committee on Coordination/ tive test scores to age 19 years. Arch Pediatr las. Pediatrics. 1999;104(1 pt 1):119 123
Sub-Committee on Nutrition; 2000 Adolesc Med. 2006;160(11):1108 1113 6. World Health Organization. Iron Deciency
2. Sherry B, Mei Z, Yip R. Continuation of the 4. Bruner AB, Joffe A, Duggan AK, Casella JF, Anemia: Assessment, Prevention, and Con-
decline in prevalence of anemia in low- Brandt J. Randomized study of cognitive ef- trolA Guide for Program Managers. Ge-

1048 FROM THE AMERICAN ACADEMY OF PEDIATRICS


Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on June 3, 2014
FROM THE AMERICAN ACADEMY OF PEDIATRICS

neva, Switzerland: World Health Organization; Food iron and lead absorption in humans. opment: fetal iron deciency and the devel-
2001. WHO/NHD/01.3 Am J Clin Nutr. 1986;44(2):248 256 oping hippocampus. Biochem Soc Trans.
7. Centers for Disease Control and Prevention, 18. Wright DO, Shannon MW, Wright RJ, Hu H. 2008;36(pt 6):12671271
National Center for Health Statistics. Na- Association between iron deciency and 30. Carlson ES, Tkac I, Magid R, et al. Iron is
tional Health and Nutrition Examination low-level lead poisoning in an urban pri- essential for neuron development and
Survey. Available at: www.cdc.gov/nchs/ mary care clinic. Am J Public Health. 1999; memory function in mouse hippocampus. J
nhanes.htm. Accessed September 29, 2008 89(7):1049 1053 Nutr. 2009;139(4):672 679
8. Cusick SE, Mei Z, Freedman DS, et al. Unex- 19. Caneld RL, Henderson CR Jr, Cory-Slechta 31. Tran PV, Fretham SJ, Carlson ES, Georgieff
plained decline in the prevalence of anemia DA, Cox C, Jusko TA, Lanphear PB. Intellec- MK. Long-term reduction of hippocampal
among US children and women between tual impairment in children with blood lead brain-derived neurotrophic factor activity
1988 1994 and 1999 2002. Am J Clin Nutr. concentration below 10 microg per decili- after fetal-neonatal iron deciency in adult
2008;88:16111617 ter. N Engl J Med. 2003;348(16):15171526 rats. Pediatr Res. 2009;65(5):493 498
9. Rao R, Georgieff MK. Microminerals. In: 20. Finkelstein Y, Markowitz ME, Rosen JF. Low- 32. Yip R, Binkin NJ, Fleshood L, Trowbridge FL.
Tsang RC, Uauy R, Koletzko R, Zlotikin SH, level lead-induced neurotoxicity in children: Declining prevalence of anemia among low-
eds. Nutrition of the Preterm Infant. Scien- an update on central nervous system ef- income children in the United States. JAMA.
tic Basis and Practical Guidelines. Cincin- fects. Brain Res Brain Res Rev. 1998;27(2): 1987;258(12):1619 1623
nati, OH: Digital Educational Publishing Inc; 168 176 33. Garby L, Irnell L, Werner I. Iron deciency in
2005:277310 21. Angle CR, Stelmak KL, McIntyre MS. Lead and women of fertile age in a Swedish
10. Institute of Medicine. Dietary Reference In- iron deciency. In: Hemphill DD, ed. Trace community: II. Efciency of several labora-
takes for Vitamin A, Vitamin K, Arsenic, Bo- Substances in Environmental Health. Vol IV. tory tests to predict the response to iron
Columbia, MO: University of Missouri; 1975: supplementation. Acta Med Scand. 1969;
ron, Chromium, Copper, Iodine, Iron, Man-
367386 185(12):107111
ganese, Molybdenum, Nickel, Silicon,
Vanadium, and Zinc. Washington, DC: Na- 22. Ruff RA, Markowitz ME, Bijur PE, Rosen JF. 34. Jacobs A, Miller F, Worwood M, Beamish MR,
tional Academies Press; 2003 Relationship among blood lead levels, iron Wardrop CA. Ferritin in the serum of normal
deciency and cognitive development in two subjects and patients with iron deciency
11. Hay G, Sandstad B, Whitelaw A, Borch-
year old children. Environ Health Perspect. and iron overload. Br Med J. 1972;4(5834):
Iohnsen B. Iron status in a group of Norwe-
1996;104(2):180 185 206 208
gian children aged 6 24 months. Acta Pae-
diatr. 2004;93(5):592598 23. Idjradinata P, Pollitt E. Reversal of develop- 35. Walters GO, Miller FM, Worwood M. Serum
mental delays in iron-decient anemic in- ferritin concentration and iron stores in
12. Dallman PR. Iron deciency anemia: a syn-
fants treated with iron. Lancet. 1993; normal subjects. J Clin Pathol. 1973;26(10):
thesis of current scientic knowledge and
341(8836):1 4 770 772
U.S. recommendations for prevention and
24. Lozoff B, Jimenez E, Wolf AW. Long-term de- 36. Cook JD, Lipschitz DA, Miles LE, Finch CA.
treatment. In: Earl R, Woteki CE, eds. Iron
velopmental outcome of infants with iron Serum ferritin as a measure of iron stores
Deciency Anemia: Recommended Guide-
deciency. N Engl J Med. 1991;325(10): in normal subjects. Am J Clin Nutr. 1974;
lines for Prevention, Detection and Manage-
687 694 27(7):681 687
ment Among U.S. Children and Women of
Childbearing Age. Washington, DC: National 25. Lozoff B, Jimenez E, Hagen J, Mollen E, 37. Birgegrd G, Hgman C, Killander A,
Academies Press; 1993:4197 Wolf AW. Poorer behavioral and develop- Levander H, Simonsson B, Wide L. Serum fer-
mental outcome more than 10 years after ritin and erythrocyte 2,3-DPG during quanti-
13. Gregory JR, Collins DL, Davies PSW, Hughes
treatment for iron deciency in infancy. tated phlebotomy and iron treatment.
JM, Clarke PC. National Diet and Nutrition
Pediatrics. 2000;105(4). Available at: www. Scand J Haematol. 1977;19(4):327
Survey: Children Aged 112 to 412 Years: Vol- pediatrics.org/cgi/content/full/105/4/e51 38. Jacob RA, Sandstead HH, Klevay LM, John-
ume 1Report of the Diet and Nutrition
26. Lozoff B, De Andraca I, Castillo M, Smith JB, son LK. Utility of serum ferritin as a mea-
Survey. London, England: Her Majestys Sta-
Walter T, Pino P. Behavioral and develop- sure of iron deciency in normal males un-
tionery Ofce; 1995
mental effects of preventing iron-deciency dergoing repetitive phlebotomy. Blood.
14. Male C, Persson LA, Freeman V, Guerra A, anemia in healthy full-term infants [pub- 1980;56(5):786 791
vant Hof MA, Haschke F; Euro-Growth Iron lished correction appears in Pediatrics. 39. Dallman PR, Siimes MA, Stekel A. Iron de-
Study Group. Prevalence of iron deciency 2004;113(6):1853]. Pediatrics. 2003;112(4): ciency in infancy and childhood. Am J Clin
in 12-mo-old infants from 11 European ar- 846 854 Nutr. 1980;33(1):86 118
eas and inuence of dietary factors on iron
27. Logan S, Martins S, Gilbert R. Iron therapy 40. Brugnara C, Zurakowski D, DiCanzio J, Boyd
status (Euro-Growth study). Acta Paediatr. for improving psychomotor development T, Platt O. Reticulocyte hemoglobin content
2001;90(5):492 498 and cognitive function in children under the to diagnose iron deciency in children.
15. Six KM, Goyer RA. The inuence of iron de- age of three with iron deciency anemia. JAMA. 1999;281(23):22252230
ciency on tissue content and toxicity of in- Cochrane Database Syst Rev. 2001;(2): 41. World Health Organization. Assessing the
gested lead in rats. J Lab Clin Med. 1972; CD001444 iron status of populations: report of a Joint
79(1):128 136 28. McCann JC, Ames BN. An overview of evi- World Health Organization/Centers for Dis-
16. Barton JC, Conrad ME, Nuby S, Harrison L. dence for a causal relation between iron ease Control and Prevention technical con-
Effects of iron in the absorption and reten- deciency during development and decits sultation on the assessment of iron status
tion of lead. J Lab Clin Med. 1978;92(4): in cognitive or behavioral function. Am J at the population level. Geneva, Switzerland;
536 547 Clin Nutr. 2007;85(4):931945 April 6 8, 2004. Available at: http://
17. Watson WS, Morrison J, Bethel MI, et al. 29. Georgieff MK. The role of iron in neurodevel- whqlibdoc.who.int/publications/2004/

PEDIATRICS Volume 126, Number 5, November 2010 1049


Downloaded from pediatrics.aappublications.org at Indonesia:AAP Sponsored on June 3, 2014
9241593156_eng.pdf. Accessed September element absorption during infancy. Physiol milk-based formulas during infancy. Pediat-
29, 2008 Rev. 1997;77(3):643 669 rics. 1993;91(5):908 914
42. Ullrich C, Wu A, Armsby C, et al. Screening 54. Pizarro F, Yip R, Dallman PR, Oilvares M, Her- 66. Hyams JS, Treem WR, Etienne NL, et al. Effect
healthy infants for iron deciency using re- trampf E, Walter T. Iron status with different of infant formula on stool characteristics of
ticulocyte hemoglobin content. JAMA. 2005; infant feeding regimens: relevance to young infants. Pediatrics. 1995;95(1):50 54
294(8):924 930 screening and prevention of iron deciency. 67. Murray MJ, Murray AB, Murray MB, Murray
43. Brugnara C, Schiller B, Moran J. Reticulo- J Pediatr. 1991;118(5):687 692 CJ. The adverse effect of iron repletion on
cyte hemoglobin equivalent (Ret He) and as- 55. Agostoni C, Domellof M. Infant formulae: the course of certain infections. Br Med J.
sessment of iron-decient states. Clin Lab from ESPGAN recommendations towards 1978;2(6145):11131115
Haematol. 2006;28(5):303308 ESPGHAN-coordinated global standards. J 68. Baqui AH, Zaman K, Persson LA, et al. Simul-
44. Skikne BS, Flowers CH, Cook JD. Serum Pediatr Gastroenterol Nutr. 2005;41(5): taneous weekly supplementation of iron
transferrin receptor: a quantitative mea- 580 583 and zinc is associated with lower morbidity
sure of tissue iron deciency. Blood. 1990; 56. Walter T, Pino P, Pizarro F, Lozoff B. Preven- due to diarrhea and acute lower respira-
75(9):1870 1876 tion of iron-deciency anemia: comparison tory infection in Bangladeshi infants. J Nutr.
45. Ferguson BJ, Skikne BS, Simpson KM, of high- and low-iron formulas in term 2003;133(12):4150 4157
Baynes RD, Cook JD. Serum transferrin re- healthy infants after six months of life. J 69. Gera T, Sachdev HP. Effect of iron supple-
ceptor distinguishes the anemia of chronic Pediatr. 1998;132(4):635 640 mentation on incidence of infectious illness
disease from iron deciency anemia. J Lab 57. Haschke F, Vanura H, Male C, et al. Iron nu- in children: systematic review. BMJ. 2002;
Clin Med. 1992;119(4):385390 trition and growth of breast- and formula- 325(7373):1142
46. Worwood M. Serum transferrin receptor fed infants during the rst 9 months of life. 70. Singhal A, Morley R, Abbott R, Fairweather-
assays and their application. Ann Clin Bio- J Pediatr Gastroenterol Nutr. 1993;16(2): Tait S, Stephenson T, Lucas A. Clinical safety
chem. 2002;39(pt 3):221230 151156 of iron-fortied formulas. Pediatrics. 2000;
47. American Academy of Pediatrics, Commit- 58. Haschke F, Ziegler EE, Edwards BB, Fomon 105(3). Available at: www.pediatrics.org/
tee on Nutrition. Nutritional needs of the SJ. Effect of iron fortication of infant for- cgi/content/full/105/3/e38
premature infant. In: Kleinman RE, ed. Pedi- mula on trace mineral absorption. J Pediatr 71. Layrisse M, Garca-Casal MN, Mndez-
atric Nutrition Handbook. 6th ed. Elk Grove Gastroenterol Nutr. 1986;5(5):768 773 Castellano H, et al. Impact of fortication of
Village, IL: American Academy of Pediatrics; 59. Hernell O, Lnnerdal B. Iron requirements ours with iron to reduce the prevalence of
2008:79 112 and prevalence of iron deciency in term anemia and iron deciency among school-
48. Grifn IJ, Cooke RJ, Reid MM, McCormick KP, infants during the rst six months of life. In: children in Caracas, Venezuela: a follow-up.
Smith JS. Iron nutritional status in preterm Hallberg L, Asp NG, eds. Nutrition in Health Food Nutr Bull. 2002;23(4):384 389
infants fed formulas fortied with iron. and Disease. London, England: John Libbey 72. Chen J, Zhao X, Zhang X, et al. Studies on the
Arch Dis Child Fetal Neonatal Ed. 1999;81(1): & Co Ltd; 1996 effectiveness of NaFeEDTA-fortied soy
F45F49 60. Lnnerdal B, Hernell O. Iron, zinc, copper sauce in controlling iron deciency: a
49. Dallman PR. Nutritional anemias in child- and selenium status of breast-fed infants population-based intervention trial Food
hood: iron, folate and vitamin B12. In: Sus- and infants fed trace element fortied milk- Nutr Bull. 2005;26(2):177186; discussion
kind RM, Lewinter-Suskind L, eds. Textbook based infant formula. Acta Paediatr. 1994; 187189
of Pediatric Nutrition. 2nd ed. New York, NY: 83(4):367733 73. Ho M. NaFeEDTA-fortied sh sauce: the
Raven Press; 1993:91105 61. Dewey KG, Domellof M, Cohen RJ, Landa cure to iron deciency anemia in Vietnam?
50. Meinzen-Derr JK, Guerrero ML, Altaye M, Rivera R, Hornell O, Lnnerdal B. Iron sup- Nutr Noteworthy. 2005;7:11
Ortega-Gallegos H, Ruiz-Palacios GM, Mor- plementation effects growth and morbidity 74. Haas JD, Beard JL, Murray-Kolb LE, del
row AL. Risk of infant anemia is associated of breast-fed infants: results of a random- Mundo AM, Felix A, Gregorio GB. Iron-
with exclusive breast-feeding and maternal ized trial in Sweden and Honduras. J Nutr. biofortied rice improves the iron stores of
anemia in a Mexican cohort. J Nutr. 2006; 2002;132(11):3249 3255 nonanemic Filipino women. J Nutr. 2005;
136(2):452 458 62. Iannotti LL, Tielsch JM, Black MM, Black RE. 135(12):28232830
51. Georgieff MK, Wewerke SW, Nelson CA, de- Iron supplementation in early childhood: 75. Centers for Disease Control and Prevention.
Regnier RA. Iron status at 9 months of in- health benets and risks. Am J Clin Nutr. Iron deciency: United States, 1999 2000.
fants with low iron stores at birth. J Pediatr. 2006;84(6):12611276 MMWR Morb Mortal Wkly Rep. 2002;51(40):
2002;141(3):405 409 63. Oski FA. Iron-fortied formulas and gastro- 897 899
52. Friel JK, Aziz K, Andrews WL, Harding SV, intestinal symptoms in infants: a controlled 76. White KC. Anemia is a poor predictor of iron
Courage ML, Adams RJ. A double-masked, study. Pediatrics. 1980;66(2):168 170 deciency among toddlers in the United
randomized control trial of iron supplemen- 64. Nelson SE, Ziegler EE, Copeland AM, Ed- States: for heme the bell tolls. Pediatrics.
tation in early infancy in healthy term wards BB, Fomon SJ. Lack of adverse reac- 2005;115(2):315320
breast-fed infants. J Pediatr. 2003;143(5): tions to iron-fortied formula. Pediatrics. 77. Biondich PG, Downs SM, Carroll AE, et al.
582586 1988;81(3):360 364 Shortcomings in infant iron deciency
53. Lnnerdal B. Effects of milk and milk com- 65. Bradley CK, Hillman L, Sherman AR, Leedy D, screening methods. Pediatrics. 2006;
ponents on calcium, magnesium and trace Cordano A. Evaluation of two iron-fortied, 117(2):290 294

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Diagnosis and Prevention of Iron Deficiency and Iron-Deficiency Anemia in
Infants and Young Children (03 Years of Age)
Robert D. Baker, Frank R. Greer and The Committee on Nutrition
Pediatrics 2010;126;1040; originally published online October 5, 2010;
DOI: 10.1542/peds.2010-2576
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