Am J Clin Nutr 2005 Schneider 1269 75

8/18/2019 Am J Clin Nutr 2005 Schneider 1269 75

1/7


2/7

Children (WIC) clinics. The information gathered was intendedto produce estimates of iron deficiency and iron deficiency ane-mia and determine the predictive value of hemoglobin in iden-tifying iron deficiency.

SUBJECTS AND METHODS

Study population

The, 12–36-mo-old participants were recruited from Califor-nia WIC waiting rooms between August 2000 and June 2002.TheWIC clinics arelocatedin ContraCostaCounty (Richmond)and Tulare County (Earlimart and Dinuba). Richmond is an ur-ban community with a population of 99 216, whereas Ear-limart and Dinuba have populations of 5881 and 16 849, respec-tively (16). Hispanics and Latinos constitute 27%, 75%, and88% of the populations in Richmond, Dinuba, and Earlimart,respectively (17). The median household incomes in Richmond,Dinuba, and Earlimart are $44 000, $33 000, and $21 000,respectively, and 13%, 21%, and 38% of the families in these 3counties fall below the poverty level (17). The Richmond clinic

has6800 WIC participants, Earlimart has1600 WIC partic-ipants, and Dinuba has3800 WIC participants.

Trained bilingual (English and Spanish), bicultural interview-ers (1 per county) approached all women in the WIC waitingrooms to recruit subjects for the study, 3–4 d/wk. The interview-ers were instructed to introduce themselves, briefly describe thestudy, and ask the women whether they had a child between 12and 36 mo of age. Men were excluded because the interviewincluded questions pertaining to pregnancy (data not shown).Subsequently,the interviewersasked whether the mothers wouldlike to participate in the study. Approximately 673 women withchildren aged 12–36 mo were approached, and 498 gave consentto participate in thestudy(74%of those whowere eligible). To

be eligible for the study, a mother could not have received infor-mation about iron deficiency anemia from a doctor or nurse,because this may have influenced feeding behaviors (only onemother with a child in the target age range was excluded for thisreason). Written informed consent was obtained from the moth-ers before participation in the study, and the University of Cal-ifornia, Davis, Institutional Review Board approved the studyprotocol.

Laboratory analysis

Venous blood samples were collected from the toddlers byphlebotomists in laboratories adjoining the respective WIC sitesfrom 0900 to 1900. The subjects were not required to fast. Forserum collection, blood (3 mL) was collected into trace min-eral–free tubes (Vacutainer; Becton Dickinson, Plymouth,United Kingdom) and allowed to coagulate (45 min) at roomtemperature. The coagulated blood was centrifugedat 1315g for8 min at 25 °C. Serum was divided into aliquots for the measure-ment of ferritin, transferrin receptors, transferrin saturation, andC-reactive protein (CRP). Whole blood (3 mL) was collected intoEDTA-containing tubes(Vacutainer)for automated bloodanalysis.Capillary samples were obtained on the same day as were the ve-nous samples from a subgroup of children and were analyzed witha Hemocue B-Hemoglobin system (Ängelholm, Sweden).

Serumsampleswere transportedon dryice to theUniversityof California, Davis, and stored at 80 °C. Batches of 50–100

samples were analyzed forserum ferritin with an immunoradiomet-ric assay (Coat-A-Count Ferritin; Diagnostic Products, Inc, LosAngeles, CA), serum transferrin receptor with a human transferrinreceptor immunoassay kit (Ramco, Houston, TX), serum trans-ferrin with a nephelometric assay (Beckman Coulter, Brea, CA),serum iron (18) with atomic absorption spectrophotometry (model300; Perkin-Elmer, Boston, MA), and serum CRP by radial immu-nodiffusion (Nanorid; The Binding Site, Birmingham, United

Kingdom). Transferrin saturation was determined on the basis of serum transferrin and serum iron concentrations. Total iron bindingcapacity (TIBC) was calculated as serum transferrin/0.68 (19). Thepercentage of transferrin saturation was subsequently calculated as(serum iron/TIBC) 100 (20).

Hemoglobin was determined with the use of automated ana-lyzers at theTom PowersRichmondHealth CenterClinicalLab-oratory for the Richmond clinic (Coulter Max M; Coulter, Ful-lerton, CA)and wastransported to Unilab forthe Earlimartclinic(Abbott Cell-Dyn 4000; Abbott Park, IL) or to the HillmanHealth Center Clinical Laboratory in Tulare, CA, for the Dinubaclinic (Abbott Cell-Dyn 3200).

Statistical analysis

General statistical analyses

Frequencies were run for prevalence data. Chi-square or Fish-er’s exact test was used to compare proportions, and t tests wereused tocomparemeans. Odds ratiosand 95%CIs were calculatedby using logistic regression analysis for anemia, low iron stores,and iron deficiency anemia. Receiver operator characteristic(ROC)curves,areaunder the curve (AUC), sensitivity,and spec-ificity were used to determine the performance of hemoglobinconcentration in the diagnosis of iron deficiency. All analysesusing iron-status variables other than hemoglobin excluded chil-dren whose serum showed evidence of hemolysis or who had an

elevated CRP concentration (10 mg/L) (21). The sample sizecalculation was based on an estimateof the prevalence of anemia,assuming an approximate prevalence of 15% and an error of 3.5% (probability 0.15, 0.05). This calculation indicateda need to recruit 400 children; however, 500 children were re-cruited to allow for unsuccessful blood draws, hemolyzed sam-ples, and elevated CRP concentrations. Both ferritin and trans-ferrin receptors had skewed distributions; therefore, these valueswerelog transformedfor allstatisticalcalculations and convertedback to the original units as geometric means and SDs. Statisti-cally significant results were those with values of P 0.05. Allstatistical analyseswere performed by using SPSSsoftware(ver-sion 10.0; SPSS, Inc, Chicago).

Determination of abnormal values for low iron stores, iron

deficiency, and iron deficiency anemia

A multiple-indicator model was used to define iron deficiencyon the basis of 2 of 3 abnormal values for ferritin, transferrinreceptors, or transferrin saturation. Iron deficiency anemia wasdefined as having iron deficiency and low hemoglobin. Lowhemoglobin was defined as hemoglobin 110 g/L for 12–24-mo-olds or 111 g/L for 24 –36-mo-olds (22).

To determine abnormal values for ferritin, transferrin recep-tors, and transferrin saturation, hemoglobin (dependent variable)was regressed on each iron-status variable (independent vari-able) by using a 2-phase segmented linear regression model (SAS

1270 SCHNEIDER ET AL

a t UNI VER SI TY OFI N

D ONE SI A onF e br u ar y 2 5 ,2 01 6

a j c n.n u t r i t i on. or g

D ownl o a d e df r om

http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/http://ajcn.nutrition.org/


3/7

for WINDOWS release 8; SAS Institute Inc, Cary, NC). Seg-mented regression analysis determined that the breakpoints wereas follows: low ferritin, 8.7 g/L (95% CI: 6.8, 11.1 g/L);hightransferrinreceptor, 8.4g/mL(95%CI:7.2,9.7g/mL);and low transferrin saturation,13.2% (95% CI: 8.9%, 17.6%).Segmented linear regression allows for data to be described by2 regression equations for the independent variable, precedingand following 1 flex point. The join model, a continuous y

value for each regression, was used to determine the abnormalvalues. Cases below the lowest detectible limit for ferritin (5.0g/L) were excluded from thedeterminationof the flex point forlow ferritin values. The flex points were determined in childrenwhose serum showed no evidence of hemolysis and did not havean elevated CRP concentration (10 mg/L) (21). The preva-lences of lowironstores(low serum ferritin), irondeficiency,andiron deficiency anemia were compared with those from previousstudies by using both the study-determined and literature-determined cutoffs. For the literature-determined cutoffs, lowironstores weredefined as serum ferritin10g/L(12,23).Irondeficiency based on literature-determined cutoffs was defined as2 of 3 abnormal values for ferritin, transferrin receptors (10

g/mL), and transferrin saturation (10%) (12, 24, 25).Regression against hemoglobin is informative in identifying

cutoff values (flex point) for the iron measures, because hemo-globin declines when abnormal values are reached. Hemoglobinis a late indicator of iron deficiency, and it can be argued that acutoff below this biological threshold would be more useful.Results of the analyses showed that the study-determined cutoffswere less restrictive for transferrin receptors and transferrin sat-uration than were the cutoffs used by Olivares et al (24) andLooker et al (23).

RESULTS

A summary of thesubjectsincludedin theanalysis is shown inFigure 1. Thirty-three children had elevated serum CRP, 32children had evidence of hemolysis, and 3 had both. In total, 425subjects provided data on anemia and 355 provided data on ironstatus. Subjects with normal serum CRP and no evidence of hemolysis who had only 2 of the 3 iron measures were retainedforanalysis if they could be clearly delineated as iron deficientoriron sufficient on the basis of both study- and literature-determined iron deficiency cutoffs; only 3 such subjects couldnot be classified and were excluded from the analysis.

The ethnic breakdown of the sample was as follows: 403(93.3%) Latinos, Hispanics, or Mexican Americans; 15 (3.5%)African Americans; 5 (1.2%) non-Hispanic whites; 3 (0.7%)

multiethnic, 2 (0.5%) Asians or Pacific Islanders, 2 (0.5%) Na-tive Americans, and 2 (0.5%) unknown. The average age was23.2 6.7 mo (range: 12.0–35.8 mo). The sample was com-posed of 52.3% boys and 47.7% girls.

The prevalence of anemia was 11.1% (47 of the 425 childrenwith hemoglobin values). The prevalences of anemia, low ironstores, irondeficiency,and irondeficiency anemia on the basis of study-determined and literature-determined cutoffs are pre-sented in Table 1 forboys and girls. The boys had a significantlygreater prevalence of both study- and literature-determined lowiron stores and iron deficiency than did the girls. Prevalenceestimates did not differ significantly between 12–24-mo-oldsand 24–36-mo-olds for anemia, low iron stores, iron deficiency,

or iron deficiency anemia. The exclusion of children with ele-

vated serum CRP concentrations may havebiased the prevalence

estimates for iron deficiency. Although mean transferrin satura-

tion was significantly lower in children with elevated CRP con-centrations than in those with normal CRP concentrations, there

was no significant difference in mean transferrin receptor con-centrations (data not shown). The inclusion of children with

elevated CRP concentrations did not change the prevalence es-

timates for iron deficiency (data not shown).The mean (SD) hemoglobin concentration for the 34 sub-

jects with both capillary and venous samples was 122.3 10.6

and 119.0 8.2 g/L, respectively (P 0.026, paired t test). The

odds ratios for anemia, low iron stores, and iron deficiency werenot significantly greaterfor low-birth-weight(2500g) children

than for normal-birth-weight children (2500 g) (Table 2), but

there were only 27 children with birth weights 2500 g. There

was no significant difference in sex or age between low-birth-weight children and normal-birth-weight children.

The oddsratios for anemia in iron-deficient childrenrelative toiron-sufficient children are shown in Table 3 by study-

determined and literature-determined values, respectively. The

odds of anemia was greater in children who had iron deficiency,low ferritin, high transferrin receptors, and low transferrin satu-

ration than in children who were iron sufficient or had adequate

values for ferritin, transferrin receptors, and transferrin satura-tion. Hemoglobin concentration was used to predict iron defi-

ciency on the basis of ROC curves (Table 4). The sensitivity at

the anemia cutoff was 23% for study-determined iron defi-ciency and 40% for literature-determined iron deficiency.

FIGURE 1. Flow diagram of subjects included in the cross-sectionalanalysis of anemia, low iron stores, and iron deficiency. Hb, hemoglobin;CRP, C-reactive protein. “Iron measures” includes serum ferritin, serumtransferrin receptors, and serum transferrin saturation.

ANEMIA AND IRON STATUS OF 12–36-MO-OLD CHILDREN 1271







4/7

DISCUSSION

Theresultsof this study areconsistent with theconceptthatthesole useof hemoglobin valuesto screenchildrenwill notidentifyall those who are iron deficient. A low hemoglobin value is aneffective indicator of irondeficiency when the prevalence of irondeficiency is high (21). However, iron deficiency in the UnitedStates has decreased, which has made anemia screening for irondeficiency less effective (12, 21, 26). We used ROC curves toevaluate the predictive value of hemoglobin for identifying irondeficiency. Although there was a significant relation betweenlow hemoglobin concentrations and irondeficiency,hemoglobinhad a low sensitivity for predicting iron deficiency (23% and40% for study- and literature-determined cutoffs, respectively).Thus,77% and60% of the iron-deficient children would not

have been identified on the basis of study- and literature-determined cutoffs. Furthermore, our values were determinedfromsamples obtainedthroughvenipunctureby using automatedanalyzers in clinicallaboratories. At the WICsites whereour datawere collected, hemoglobin is typically determined by finger-prick collection in nearby clinics.Had we usedcapillary samples,it is possible that more children would have been misdiagnosedas iron sufficient because hemoglobin values for capillary sam-

ples tend to be elevated (27). The difference in the mean hemo-globin values for children with both capillary and venous sam-ples was 3.2 g/L. Had all the venous hemoglobin valuesincreased by 3.2 g/L, the prevalence of anemia would have de-creased from 11.1% to 6.4%. This would have increased thenumber of childrenfalsely categorized as iron sufficient when,infact, they were actually iron deficientwith or without anemia(ie,reduced sensitivity).

The prevalence of anemia was 11% for this sample com-pared with the Pediatric Nutrition Surveillance System(PedNSS) report of 14 –15% in California for 12–35-mo-olds in2002 (28) and 13.1% nationally for children aged 5 y in 2001(29). PedNSS defines anemia as either low hemoglobin or low

hematocrit values. Our study and PedNSS used the same cutoffsfor hemoglobin (22); however, PedNSS reports anemia datafrom capillary, venipuncture, or both capillary and venipuncturesamples. These are critical considerations for comparisons of theprevalence of anemia across studies, because hemoglobin valuescan vary based on the method used. Thus, it is conceivable thatthe prevalence data obtained in our study differ from those re-ported in the PedNSS as a result of the multiple methods used toobtain bloodthroughout the state in clinicsthat report to PedNSS.Another possibility is that our prevalence estimate is biased bythe inability to collect samples from the children whose mothersdeclined to participate (26% of those who were eligible). If these children were at higher risk of anemia than those whose

mothers agreedto participate,the prevalence of 11%would be anunderestimate.

Confirmationof iron deficiency anemia shouldbe made on thebasis of iron measures in addition to hemoglobin. Values com-monly considered low forserumferritin are 10–12g/L (12, 20,30). We selected 10 g/L as a cutoff for serum ferritin to beconsistent with the most recent National Health and NutritionExamination Survey (NHANES) on the prevalence of iron defi-ciency in the United States (12). The cutoff for transferrin satu-rationwas also selected from theNHANES report(12). There areonly a relatively smallnumber of studies on transferrin receptorsin children aged 12–36 mo. However, a 2-site study in Hondurasand Sweden determined a cutoff of 11 g/mL for transferrin

TABLE 1

Prevalence of anemia, low iron stores, and iron deficiency in low-income

male and female children aged 12–36 mo1

Boys Girls

% (n)

Anemia2 9.9 (22 of 223) 12.4 (25 of 202)

Study-determined cutoffs

Low iron stores3 29.1 (55 of 189) 19.94 (33 of 166)

Iron deficiency5 19.8 (37 of 187) 12.1 (20 of 165)

Iron deficiency anemia6 3.2 (6 of 185) 3.7 (6 of 163)

Literature-determined cutoffs

Low iron stores7 34.9 (66 of 189) 22.38 (37 of 166)

Iron deficiency9 10.2 (19 of 187) 7.3 (12 of 165)

Iron deficiency anemia10 2.7 (5 of 185) 3.7 (6 of 163)

1 There were no significant sex-by-age interactions and no significant

effect of age.2 Defined as hemoglobin 110 g/L (12–24 mo) or 111 g/L (24–36

mo) (20, 29).3 Defined as ferritin 8.7 g/L.4,8 Significantly different from boys (chi-square test): 4 P 0.050,

8 P 0.010.5 Defined as2 of 3 abnormalvalues forferritin8.7g/L, transferrin

receptors8.4 g/mL, or transferrin saturation 13.2%.6 Defined as2 of 3 abnormalvalues forferritin8.7g/L, transferrin

receptors8.4 g/mL,or transferrin saturation13.2% with lowhemoglo-

bin.7 Defined as ferritin 10.0 g/L (12, 21).9 Defined as2 of 3 abnormal values for ferritin10.0 g/L (12, 21),

transferrin receptors 10.0 g/mL (23), or transferrin saturation 10.0%

(12, 24).10 Defined as2 of 3 abnormal valuesfor ferritin10.0 g/L(12, 21),

transferrin receptors 10.0 g/mL (23), or transferrin saturation 10.0%

(12, 24) with low hemoglobin.

TABLE 2

Odds ratios (ORs) and 95% CIs for anemia, low iron stores, and iron deficiency for low-birth-weight (LBW; 2500 g) children and normal-birth-weight

(NBW; 2500 g) children

OR (95% CI)

LBW children with

abnormal values

NBW children with

abnormal values

n n

Anemia1 0.67 (0.15, 2.91) 2 of 26 44 of 395

Low iron stores2 1.56 (0.57, 4.29) 6 of 18 79 of 334

Iron deficiency3 2.81 (1.00, 7.83) 6 of 18 50 of 331

1 Defined as hemoglobin 110 g/L (12–24 mo) or hemoglobin 111 g/L (24–36 mo) (20, 29).2 Defined as ferritin 8.7 g/L.3 Defined as 2 of 3 abnormal values for ferritin 8.7 g/L, transferrin receptors8.4 g/mL, or transferrin saturation 13.2%.








5/7

receptors in 4- to 9-mo-old children (31). In a study in Chile,infants between 9 and 15 mo had a mean (SD) transferrinreceptor concentration of 12.0 4.6 g/mL when hemoglobin

was 100 –109 g/L and a mean transferrin receptor concentrationof 16.1 7.7 g/mL when hemoglobin was 100 g/L. Theinvestigators found that when transferrin receptors were 10g/mL, there was a sensitivity of 66% and a specificity of 71%for iron deficiency (24). Because the children in our study wereolder, a lower abnormal value for transferrin receptor concen-tration was expected (32–34), and the literature cutoff for trans-ferrin receptor concentration was selected at 10 g/mL.

Approximately 30 –35% of the boys and 20–22% of the girlshad low iron stores (low serum ferritin) on the basis of the study-and literature-determined cutoffs, respectively. The prevalenceof lowiron stores is substantially higherthan the18% prevalenceof lowiron status reported for1–3-y-old children attendingwell-

child visits at 4 pediatric offices in New York (35). This findingis notsurprising because thecurrentstudy recruited subjectsfromWIC,which preferentially enrolls childrenwho are at highrisk of iron deficiency. The New York study comprised children fromlower- and middle-socioeconomic groups and from a populationthat was only 40% Hispanic.

We didnot find an increasedrisk of anemia, lowiron stores, oriron deficiency in low-birth-weight children, although the oddsratio of 3 for iron deficiency is notable (Table 2). Comparedwith normal-weight infants, low-birth-weight infants havesmaller iron stores, which are taxed by subsequent catch-up

growth and red blood cell gains (25, 36). We expected that low-

birth-weight children would be more likely to be anemic, have

low iron stores, or be iron deficient. However, only 27 of the 432

subjects were low-birth-weight infants; thus, the power to detecta significantly increased risk was low.

As evident in Table 3, the children who had iron deficiency or

abnormal iron status values were more likely to be anemic, re-

gardless of whether study- or literature-determined cutoffs were

used. Iron-deficientchildrenhad a risk of anemiathatwas 3 times

and 7 times that of iron-sufficient children on the basis of the

study-determined and literature-determined cutoffs. These dif-

ferences in the risk of anemia between study- and literature-

determined iron deficiencies were largely due to the more strin-

gent cutoff of 10 g/mL, rather than 8.4 g/mL, for transferrin

receptors. Compared with children with adequate ferritin con-

centrations, children with low ferritin concentrations were alsomore likely to be anemic on the basis of both the study- and

literature-determined cutoffs. Children with transferrin receptor

concentrations10 g/mL had a risk of anemia 6 times that of

children with transferrin receptor concentrations 10 g/mL;

however, when the cutoff for transferrin receptor concentrations

was8.4 g/mL, children with elevated concentrations did not

have a greater risk of anemia. This indicates that transferrin

receptors may be a good biomarker for iron deficiency. A trans-

ferrin receptor concentration 10 g/mL indicates anemia;

however, at the study-determined cutoff of 8.4 g/mL, the

TABLE 3

Odds ratios (ORs) and 95% CIs for anemia in children with study-determined abnormal values for iron deficiency, low ferritin, high transferrin receptors,

and low transferrin saturation1

Cutoff

Ferritin2 Transferrin receptors3 Transferrin saturation4 Iron deficiency5,6

OR (95% CI) n OR (95% CI) n OR (95% CI) n OR (95% CI) n

Study-determined 3.407 (1.66, 6.96) 348 1.78 (0.83, 3.83) 348 1.84 (0.84, 4.05) 343 3.198 (1.48, 6.87) 348

Literature-determined 2.628 (1.29, 5.32) 348 6.197 (2.60, 14.74) 348 3.349 (1.38, 8.16) 343 7.097 (3.03, 16.61) 348

1 Anemia was defined as hemoglobin 110 g/L (12–24 mo) or hemoglobin 111 g/L (24 –36 mo) (20, 29).2 Study-determined and literature-determined low ferritin defined as 8.7 and 10 g/L (12, 21), respectively.3 Study-determined and literature-determined high transferrin receptor defined as 8.4 and 10 g/mL (23), respectively.4 Study-determined and literature-determined low transferrin saturation defined as 13.2% and 10% (12, 24), respectively.5 Study-determined cutoffs for irondeficiency:2 of3 abnormalvalues forferritin8.7g/L,transferrin receptors8.4g/mL,or transferrin saturation

13.2%.6 Literature-determined cutoffs for iron deficiency:2 of 3 abnormal values for ferritin 10.0 g/L (12, 21), transferrin receptors 10.0 g/mL (23),

or transferrin saturation 10.0% (12, 24).7–9 Significant in those with abnormal laboratory values (chi-square test): 7 P 0.001, 8 P 0.005, 9 P 0.05.

TABLE 4

Receiver operator characteristic curves of hemoglobin in predicting iron deficiency and corresponding sensitivity and specificity at anemic levels1

AUC P Sensitivity Specificity

Percentage

misclassification2

%

Hemoglobin

Study-determined iron deficiency3 0.692 0.001 0.232 0.904 20.4

Literature-determined iron deficiency4 0.767 0.001 0.400 0.909 13.5

1 n 348. Anemia was defined as hemoglobin 110 g/L (12–24 mo) or hemoglobin 111 g/L (24–36 mo) (20, 29). AUC, area under the curve.2 Percentage misclassification (1 sensitivity) (percentage iron-deficient subjects) (1 specificity) (percentage iron-sufficient subjects).3 Study-determined cutoff for iron deficiency:2 of 3 abnormal valuesfor ferritin8.7 g/L, transferrin receptors8.4 g/mL, or transferrin saturation

13.2%.4 Literature-determined cutoff for iron deficiency:2 of 3 abnormal values for ferritin10.0 g/L (12, 21), transferrin receptors10.0 g/mL (23), or

transferrin saturation 10.0% (12, 24).

ANEMIA AND IRON STATUS OF 12–36-MO-OLD CHILDREN 1273







6/7

transferrin receptor concentration may better reflect poor ironstatus before the onset of anemia.

Although there has been a steady decline in the prevalence of anemia in the United States (37), iron deficiency remains high inseveral subgroups. In a 5-state study, Sherry et al (38) reported adecline in the prevalence of anemia on the basis of hematocritonly. The decline was attributed to better iron nutrition, but theauthors acknowledged that the 5-state study did not measure

additional iron indexes. In contrast, using multiple indicators of iron deficiency, we observed a 16% prevalence of iron defi-ciency, which is a substantially higher value than is the HealthyPeople 2010 goal of 1–5% (13).

The challenges of reducing anemia and iron deficiency inhigh-risk populations, such as toddlers, have been addressedthrough programs such as WIC, the iron fortification of infantformulas and cereals, and surveillance monitoring by PedNSSand NHANES. WIC enrolls women and children who are at thehighest risk of anemia and iron deficiency and provides vouchersto purchase WIC-approved foods, including, but not limited to,iron-fortified cereals,iron-rich formulasand infant cereals,juice,and beans. The WIC program screens children for low hemoglo-

bin to educate and reduce the incidence of anemia in their pop-ulation. There is a need to identify children with depleted ironstores and iron deficiency before they develop iron deficiencyanemia. We question the validity of focusing efforts only onreducing anemia and ignoring the need to detect and treat irondeficiency. This is especially significant given recent findingsthat iron deficiency without anemia has been associated withdevelopmental delays (5).In addition, Konofal et al (39)reportedthat low ferritin concentrations were correlated with moresevereattention deficit hyperactivity disorder symptoms and suggestthat low iron stores contribute to attention deficit hyperactivitydisorders in children. Given the severity of the consequences of iron deficiency anemia, including delayed psychomotor devel-

opment and impaired cognitive performance (2, 30), impairedgrowth, and increased morbidity, it is evident that additionalefforts are needed to reduce iron deficiency in at-risk popula-tions. In addition to identifying children with iron deficiency, werecommend that health care providers educate all parents aboutiron-rich foods and food enhancers of iron absorption, such asheme and vitamin C (40).

We thank the following members of the University of California, Davis:

Jan Peerson (Program for International Nutrition) for statistical consulta-

tions, Shannon Kelleher (Department of Nutrition) for analyzing CRP and

transferrin receptor concentrations, Andrea Bersamin and Nadine Kirk-

patrick (Department of Nutrition) for data entry, and Marianna Castro and

Francisca Ramos [Cooperative Extension, Contra Costa County (Pleasant

Hill, CA) andTulareCounty (Tulare,CA)]for data collection. Wealso thank

the Clinical Nutrition Research Unit and the Department of Nutrition, Uni-versity of California, Davis, for the laboratory analysis of serum ferritin,

serum iron, and serum transferrin.

JMS was responsible for the studydesign,acquisition of data,analysisand

interpretation of data, and drafting of the manuscript. MLF and CLL con-

tributedto theconception of thestudy, acquisition ofdata,and revision of the

manuscript. KGDand BL contributed to thestudy design and therevision of

the manuscript. SZ-C contributed to the conception and design of the study,

interpretation of data, andwriting of themanuscript.None of theauthors had

a conflict of interest.

REFERENCES1. BeardJL, ConnorJR. Iron statusand neural functioning.AnnuRev Nutr

2003;23:41–58.

2. Grantham-McGregor S, Ani C. A review of studies on the effect of irondeficiency on cognitive development in children. J Nutr 2001;131:649S–66S; discussion 666S–8S.

3. Lozoff B. Perinataliron deficiencyand thedevelopingbrain.PediatrRes2000;48:137–9.

4. Oski FA, Honig AS, Helu B, Howanitz P. Effect of iron therapy onbehavior performance in nonanemic, iron-deficient infants. Pediatrics1983;71:877–80.

5. AkmanM, CebeciD, Okur V,AnginH, AbaliO, AkmanAC. Theeffectsof iron deficiency on infants’ developmental test performance. ActaPaediatr 2004;93:1391–6.

6. Algarin C, Peirano P, Garrido M, Pizarro F, Lozoff B. Iron deficiencyanemia in infancy: long-lasting effects on auditory and visual systemfunctioning. Pediatr Res 2003;53:217–23.

7. Roncagliolo M, Garrido M, Walter T, Peirano P, Lozoff B. Evidence of altered central nervous system development in infants with iron defi-ciency anemia at 6 mo: delayed maturation of auditory brainstem re-sponses. Am J Clin Nutr 1998;68:683–90.

8. LozoffB, Klein NK,Nelson EC,McClish DK,Manuel M, ChaconME.Behavior of infants with iron-deficiency anemia. Child Dev 1998;69:24–36.

9. Beard JL. Iron biology in immune function, muscle metabolism andneuronal functioning. J Nutr 2001;131:568S–79S; discussion 580S.

10. Lozoff B, Jimenez E, Hagen J, Mollen E, Wolf AW. Poorer behavioraland developmental outcome more than 10 years after treatment for iron

deficiency in infancy. Pediatrics 2000;105:E51.11. Metallinos-Katsaras E, Valassi-Adam E, Dewey KG, Lonnerdal B,Stamoulakatou A, Pollitt E. Effect of iron supplementationon cognitionin Greek preschoolers. Eur J Clin Nutr 2004;58:1532–42.

12. Centers for Disease Control and Prevention. Iron deficiency–UnitedStates, 1999–2000. MMWR Morb Mortal Wkly Rep 2002;51:897–9.

13. US Department of Health and Human Services.Trackinghealthy people2010. Washington, DC: US Government Printing Office, 2000.

14. PilchSM, SentiFR,eds.Assessmentof theironnutrition statusof theUSpopulation based on data collected in the second National Health andNutrition Examination Survey, 1976-1980. Bethesda, MD: Federationof American Societies for Experimental Biology, 1984.

15. Cook JD, Finch CA, Smith NJ. Evaluation of the iron status of a popu-lation. Blood 1976;48:449 –55.

16. US Census Bureau. Table SUB-EST2002-07-06- California incorpo-rated place population estimates, sorted alphabetically: April 1, 2000 to

July 1, 2002. Washington, DC: US Census Bureau, 2003.17. USCensus Bureau.Americanfactfinder. 2000.Internet: http://factfinder.census.gov/home/saff/main.html?_langen (accessed 20 June 2005).

18. Clegg MS, Keen CL, Lonnerdal B, Hurley LS. Influence of ashingtechniques on the analysis of trace elements in animal tissue. I. Wetashing. Biol Trace Elem Res 1981;3:107–15.

19. TietzNW. Fundamentalsof clinical chemistry.3rd ed.Philadelphia,PA:Saunders, 1987.

20. Tietz NW, ed. Clinical guide to laboratory tests. 3rd ed. Philadelphia,PA: WB Saunders Co, 1995.

21. Luwel K, Beem AL,Onghena P, Verschaffel L. Using segmented linearregression models with unknown change points to analyze strategyshifts in cognitive tasks. Behav Res Methods Instrum Comput 2001;33:470–8.

22. Centers for Disease Control and Prevention. Recommendations to pre-vent andcontrolirondeficiencyin theUnited States. Centers forDisease

Control and Prevention. MMWR Morb Mortal Wkly RepRecomm Rep1998;47:1–29.

23. Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CL. Prev-alence of iron deficiency in the United States. JAMA 1997;277:973–6.

24. Olivares M, Walter T, Cook JD, Hertrampf E, Pizarro F. Usefulness of serum transferrin receptor and serum ferritin in diagnosis of iron defi-ciency in infancy. Am J Clin Nutr 2000;72:1191–5.

25. Dallman PR, Siimes MA, Stekel A. Iron deficiency in infancy andchildhood. Am J Clin Nutr 1980;33:86–118.

26. White KC.Anemia is a poor predictorof iron deficiency amongtoddlersin the United States: forheme the belltolls. Pediatrics 2005;115:315–20.

27. Hinchliffe RF, Anderson LM. Haemoglobin values in venous and skinpuncture blood. Arch Dis Child 1996;75:170–1.

28. Centers for Disease Control and Prevention. 2002 California PedNSSTable21C. Atlanta, GA: US Department of Health and Human Services,2002.








7/7

Documents

Am J Clin Nutr 2005 Schneider 1269 75