Pediatrics and Neonatology (2014) 55, 466e469

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ORIGINAL ARTICLE

Iron Deficiency Anemia in PredominantlyBreastfed Young Children

Shu-Fan Tsai a, Shu-Jen Chen a,b,*, Hsiu-Ju Yen a,Giun-Yi Hung a, Pei-Chen Tsao a,c, Mei-Jy Jeng a,c,Yu-Sheng Lee a,c, Wen-Jue Soong a,c, Ren-Bin Tang a

a Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROCb Department of Pediatrics, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROCc Institute of Emergency and Critical Care Medicine, National Yang-Ming University School of Medicine,Taipei, Taiwan, ROC

Received Mar 13, 2013; received in revised form Jan 23, 2014; accepted Feb 11, 2014Available online 19 June 2014

Key Wordsbreastfeeding;iron deficiencyanemia;

young children

* Corresponding author. DepartmentTaiwan, ROC.

E-mail address: chensj@vghtpe.go

http://dx.doi.org/10.1016/j.pedneo.21875-9572/Copyright ª 2014, Taiwan

Background: Due to the increase of breastfeeding in infants, iron deficiency anemia (IDA)related to prolonged, predominant breastfeeding should be of concern. Mostly, the manifesta-tion of IDA is indistinguishable and the enthusiastic advocacy of breastfeeding without concom-itant education of complementary food may lead to ignorance of breast milk-related IDA,which may result in impaired psychomotor development of the baby. This retrospective studywas conducted to re-emphasize this easily ignored but still prevalent illness.Methods: This retrospective study involved 15 breastfeeding babies who were diagnosed withIDA between January 2007 and December 2010 at age 6e18 months. The clinical presentation,age at diagnosis, initial hemoglobin level and mean corpuscular volume, growth percentile,and duration of treatment were recorded and analyzed.Results: None of the babies was suspected to have anemia by caregivers. Pallor was noticed byphysicians in nine patients; one patient had seizure, one patient had pica, and, for the remain-ing four patients, IDA was diagnosed incidentally due to other medical events. Oral iron sup-plementation for an average of 3.6 months improved both hemoglobin level (from 8.0 g/dLto 11.5 g/dL) and mean corpuscular volume (from 57.5 fL to 73.9 fL). Most babies had appro-priate growth and normal neurological development; two babies had both IDA and thalassemia.Conclusion: Although the association of IDA with prolonged, predominant breastfeeding is wellknown, its presentation is so subtle that its detection relies mainly on alert medical personnel.Copyright ª 2014, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rightsreserved.

of Pediatrics, Taipei Veterans G

v.tw (S.-J. Chen).

014.02.005Pediatric Association. Published b

eneral Hospital, Number 201, Section 2, Shih-Pai Road, Taipei 112,

y Elsevier Taiwan LLC. All rights reserved.

Iron deficiency anemia in young children 467

1. Introduction

Iron deficiency is the most common micronutrient defi-ciency and the most common cause of anemia in child-hood.1 Iron is important for both growth and developmentof the infants. Ferropenic anemia caused by severe irondeficiency in infancy is associated with impaired healthand serious neurological impairment, such as mental,motor, social, emotional, neurophysiological, and neuro-cognitive dysfunction.2 In general, infants born at termwith adequate birth weight have sufficient iron stores forthe first 4e6 months of life, the recommended period ofexclusive breastfeeding by the World Health Organization(WHO).3 Breast feeding in this period reduces infantmortality that is caused by common childhood illnessessuch as diarrhea and pneumonia,4 and it also hastenschildren’s recovery from illness. After age 6 months, asthe children grow with concomitant expansion of bloodvolume, the body iron stores are depleted while body irondemand is increased; thus breast milk becomes insuffi-cient for iron supply. Therefore, infants who are pre-dominantly breastfed beyond age 6 months are potentiallyprone to have iron deficiency anemia (IDA)5; the additionof sufficient complementary foods is essential for infantgrowth at this time.

Due to the enthusiastic advocacy of breastfeeding in oursociety, the population of breastfed infants is increasing.Therefore, IDA related to prolonged predominant breast-feeding should be of concern in infant care. The manifes-tation of IDA is always indistinguishable; therefore, itsdetection relies mostly on the alertness of physicians. Inthis retrospective study, 15 cases of IDA are collected; themanifestations, diagnostic process, and treatment re-sponses are presented.

2. Methods

This is a retrospective chart review study. From January2007 to December 2010, fifteen babies were analyzed atthe age of 6e18 months; 10 were male and five female. Theenrollment criteria was as follows: predominant breast-feeding beyond 6 months of age; presence of microcyticanemia [hemoglobin (Hb) <11 g/dL and mean corpuscularvolume (MCV) <70 fL]; and confirmation of IDA throughlaboratory test or presence of adequate response to irontherapy. The laboratory criteria are ferritin <15 ng/mL,and adequate response to iron therapy is defined as in-crease in Hb level by 1 g/dL after 1 month of appropriateiron-replacement therapy.6 Three were full-term babies,whose mean birth body weight was 3126 � 692 g; and 12were preterm babies (gestational age <37 weeks) includingone pair of twins and a single twin, whose mean birth bodyweight was 1858 � 417 g. Predominant breastfeeding wasdefined as scanty addition of complimentary food. None ofthe babies had gross bloody stools, hematuria, or otherbleeding events.

The clinical presentation, age at diagnosis, initial Hblevels and MCV, growth percentile, and duration of treat-ment were recorded and analyzed.

3. Results

Table 1 shows the baseline characteristics and laboratorydata of all patients. In nine cases, anemia was suspected bypediatricians owing to pallor; in four patients, anemia wasdetected on routine blood tests for other diseases such asfever, urinary tract infection, and respiratory tract infec-tion. One patient had seizure, and pallor was noticed by thephysician; another had pica, which was manifested aseating paper.

Confirmation of IDA through complete laboratory checkssuch as ferritin/iron levels and total iron-binding capacity(TIBC) were available in eight cases only. The mean valuesin these patients were as follows: ferritin 9.2 ng/mL (range,0.4e53.0 ng/mL; normal, <15 ng/mL); iron 15.6 mg/dL(range, 7e27 mg/dL; normal, 40e100 mg/dL); and TIBC462 mg/dL (range, 378e606 mg/dL; normal, 100e400 mg/dL). The only patient with normal ferritin level (53.0 ng/mL) at diagnosis was a case of pneumonia. Her initial ironlevel was low (14 mg/dL) and TIBC was borderline (378 mg/dL). She had normalization of both hemoglobin and MCVafter iron therapy for 2 months; therefore, this case wasenrolled. Excluding these extreme data, which might be aresponse to infection, the mean value of ferritin in thisgroup was 2.97 ng/mL (range 0.4e6.34 ng/mL). In theremaining seven patients, IDA was confirmed throughtherapeutic response. After iron therapy for an averageduration of 4 months (range, 2e6 months), their Hbincreased from 8.15 g/dL to 11.6 g/dL; and their MCVincreased from 58 fL to 75 fL. The therapeutic iron trialremains the most cost-effective strategy for the diagnosisof IDA in patients with mild microcytic anemia.7

Hb electrophoresis and staining for Hb H inclusion bodieswere performed to exclude thalassemia in eight patientswho had positive family history; one patient had a-thalas-semia, and another had b-thalassemia. For the case with a-thalassemia, the initial laboratory data were Hb 9.7 g/dL,MCV 69 fL, and Hb H stain positive; after 2 months of irontherapy, the Hb level was 12.1 g/dL, and MCV was 80 fL.Possibly, the baby had a-thalassemia trait, which is causedby the deletion of two a genes; MCV reduction in such casesmay be borderline. The initial laboratory data in the pa-tient with b-thalassemia were as follows: ferritin, 0.77 ng/mL; iron, 27 mg/dL; TIBC, 399 mg/dL; Hb A, 87.4%; Hb A2,6%; and Hb F, 6.6%. After 2 months of iron therapy with poorcompliance, no definite response was elicited, and thepatient was lost to follow-up.

The mean postnatal age at IDA diagnosis was 10.5months: 9.0 months in the full-term babies, and 10.8months in the preterm babies. The average initial Hb levelwas 8.0 g/dL (full-term group, 8.6 g/dL; preterm group,7.9 g/dL), and the average initial MCV was 57.5 fL (full-term group, 62.0 fL; preterm group, 56.4 fL). All babiesreceived oral iron supplements (Ferrum Hausmann drops50 mg/mL) at a dose of 4e6 mg/kg/day. The averageduration of treatment was 3.6 months (range 2e6 months).After treatment, the average Hb level was 11.5 g/dL, andthe average MCV was 73.9 fL (Table 1). All the babies,except for the case with b-thalassemia who was lost tofollow-up, were free from neurological sequelae. Most of

Table 1 Young children with iron deficiency anemia.

Case no. Sex GA (wk) Age atDx (mo)

Presentation Hb atDx (g/dL)

Hb afterTx (g/dL)

MCV atDx (fL)

MCV afterTx (fL)

IronTx (mo)

Comments

Full-term1 M 37 þ 6 7 Pallor 8.4 11.2 68 76 4.52 M 37 þ 6 8 Pallor 7.9 9.9 57 64 23 M 38 12 Pallor 9.6 10.9 61 68 2.5Mean � SD(range)

9.0 � 2.2(7e12)

8.6 � 0.7(7.9e9.6)

10.6 � 0.6(9.9e11.2)

62.0 � 4.5(57e68)

69.3 � 5.0(64e76)

3.0 � 1.1(2e4.5)

Preterm4 M 31 þ 2 6 Pallor 7.5 11.9 59 71 35 M 31 þ 2 8 Pallor 7.0 12.4 55 70 36 M 32 8 Pallor 6.6 10.5 51 79 27 M 32 14 Pallor 6.2 11.6 49 74 5 Twin A8 F 30 16 Incidental Dx 9.7 12.1 69 80 2 Twin A,

a-thalassemia9 F 30 16 Incidental Dx 8.6 11.3 61.7 77 2 Twin B10 M 32 þ 3 6 Seizure 6.3 11.5 50 76 311 F 33 9 Incidental Dx 7.1 12.3 50.5 81 512 M 35 þ 6 9 Incidental Dx 7.7 12.4 52.3 80 613 M 36 12 Pallor 10.4 10.7 60 60 2 b-thalassemia14 F 36 þ 6 9 Pallor 7.8 12.1 56 74 615 F 36 þ 5 17 Pica 10.2 11.7 63 78 6Mean � SD(range)

10.8 � 3.8(6e17)

7.9 � 1.4(6.2e10.4)

11.7 � 0.6(10.5e12.4)

56.4 � 6.0(49e69)

75 � 5.7(70e81)

3.8 � 1.6(2e6)

Dx Z diagnosis; GA Z gestational age; Hb Z hemoglobin; MCV Z mean corpuscular volume; SD Z standard deviation; Tx Z treatment.

468 S.-F. Tsai et al

the patients had appropriate growth with parameterswithin the 3rde85th percentile in mode; three pretermcases had body height <3rd percentile and one also hadbody weight <3rd percentile. After iron therapy, there wasno remarkable change in their growth status, possibly dueto the short duration of observation.

4. Discussion

A variety of heterogeneous agents that possess antimicro-bial activity are found in human milk. As a result, infantswho are exclusively breastfed in the initial 4 months of lifehave fewer episodes of diarrhea, otitis media, pneumonia,bacteremia, and meningitis during the 1st year of life incomparison with infants who are formula-fed.8e10 In addi-tion, breastfeeding facilitates the maternaleinfant rela-tionship, and its psychological advantages are wellrecognized. Owing to its numerous beneficial effects oninfant health, exclusive breastfeeding is recommendedduring the initial 4e6 months of life by WHO.3 However, theiron content of human milk is low (0.2e0.4 mg/L); so irondepletion is a potential risk in infants who are predomi-nantly or exclusively breastfed beyond age 6 months.Before this age, the better absorption of breast milk ironand the iron stores in most full-term babies may preventiron deficiency.11,12 Calvo et al5 reported that, at age 6months, IDA was detected in 44.0% of the breastfed babies,but only in 14.3% of the formula-fed babies; at 9 months,the incidence was 27.8% and 7.1%, respectively. Preterminfants, who have smaller iron stores, more iatrogenicblood loss during the neonatal period, and faster growth

rates thereafter, are at higher risk of developing IDA.5 Inthis study, 80% of the cases were preterm babies, whoseinitial Hb levels and MCV were lower than the term babies(Hb, 7.9 g/dL vs. 8.6 g/dL; MCV, 56.4 fL vs. 62.0 fL). Otherrisk factors for IDA include maternal anemia, previous bloodloss, low birth weight, and being fed cow’s milk instead ofbreast or formula milk before the age of 1 year.13e15

A survey conducted in Taiwan showed that 45.6% of 6-month-old babies were exclusively breastfed in 2011.16

Physicians should be vigilant for the possibility of IDA inthese babies. To prevent IDA, breastfed infants shouldreceive iron supplementation in the form of complemen-tary infant foods such as iron-fortified cereals, red meat, oregg after age 6 months; and they should be offered iron-fortified infant formula after weaning breast milk. Boththe WHO3 and the Taiwan Pediatric Association17 emphasizethe addition of iron-fortified and zinc-fortified foods forbreastfed infants after age 4e6 months.

The treatment of IDA includes dietary changes as well asiron administration. Under good compliance to therapy, theincrease in Hb by 1 g/dL after 4 weeks of iron supplemen-tation can confirm the diagnosis of IDA.6 The potentialcauses of failure of response include incompliance withtherapy and coexistence of other diseases such as a- and b-thalassemia, which affect approximately 6e8% and 1e2% ofthe Taiwanese population, respectively.18 In this study, allbabies except for the one with b-thalassemia showed agood response to iron therapy; the initial presentation,including pallor, seizure, or pica, resolved with an increasein Hb and MCV. Oral iron supplementation is recommendedfor an additional 2 months after Hb levels return to thenormal range for the child’s age10; however, most patients

Iron deficiency anemia in young children 469

in this study did not complete the full course. The healthyappearance of these patients may make the caregivers feelcomplacent and lead to premature cessation of iron sup-plementation. Physicians should take greater responsibilityin advocating complete treatment.

Because this was a retrospective case-collection study,we could not determine the true prevalence of IDA in in-fants or compare breastfed and formula-fed babies.Because the manifestations of IDA are subtle, both thecaregivers and the pediatricians may miss the detection orbe loose in compliance with therapy. Our study is to re-emphasize the importance of this historic disease. Educa-tion of adding iron-fortified supplement food at 4e6 monthsold should be included in the advocacy of breastfeeding todecrease the occurrence of IDA in infants.

Conflicts of interest

All authors declare no conflicts of interest.

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