Zinc and other micronutrients supplementation through the use of sprinkles: impact on the occurrence of diarrhea and respiratory infections in institutionalized children

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www.jped.com.br

ORIGINAL

ARTICLE

Zinc

and

other

micronutrients

supplementation

through

the

use

of

sprinkles:

impact

on

the

occurrence

of

diarrhea

and

respiratory

infections

in

institutionalized

children

夽

Danile

L.B.

Sampaio

a_,∗

_,

_Ângela

_P.

_de

_Mattos

b

_,

_Tereza

_Cristina

_M.

_Ribeiro

a

_,

Maria

Eﬁgênia

de

Q. Leite

a

_,

_Conrad

_R.

_Cole

c

_,

_Hugo

_{Costa-Ribeiro}

_Jr.

b

a_MD._Hospital_{Universitário}_Professor_Edgard_Santos,_Universidade_Federal_da_Bahia_(UFBA),_Salvador,_BA,_Brazil b_PhD._Hospital_{Universitário}_Professor_Edgard_Santos,_UFBA,_Salvador,_BA,_Brazil

c_MSc._Emory_University,_Atlanta,_GA,_USA

Received5June2012;accepted9November2012 Availableonline26April2013

KEYWORDS Zinc supplementation; Diarrhea; Respiratoryinfection; Zincdeﬁciency Abstract

Objective: Toevaluatetheincidenceofdiarrhealdisease(DD)andacuterespiratoryinfection (ARI)inchildrenundergoingsupplementationofzincandothermicronutrientsthroughtheuse ofsprinkles,aswellastheiracceptancebythesepatients.

Method: Thiswas arandomizeddouble-blindedclinicaltrialof143healthyinstitutionalized children,aged6to48months.Theywererandomizedintotwogroupsandreceiveddailyzinc andmicronutrients---testgroup (sprinkles),ormicronutrientswithoutzinc-controlgroup. Childrenweresupplementedfor90daysandfollowedregardingtheoutcomesofDDandARI. Results: Oftherandomizedchildren,52.45%belongedtothetestand47.55%tothecontrol group.TheincidenceofDDinthetestgroupwas14.7%andwas19.1%inthecontrolgroup.The testgroupshowedalowerriskofdevelopingDDwhencomparedtocontrols,butthisfinding wasnotstatisticallysignificant(RR=0.77[0.37to1.6],p=0.5088).ARIhadhighincidencein bothgroups,60%inthetestgroupand48.5%inthecontrolgroup,withanincreasedriskof developingthediseaseinthetestgroup,butwithnostatisticalsignificance(RR=1.24[0.91to 1.68],p=0.1825).Regardingacceptance,themeanpercentageofconsumption,indays,ofthe entirecontentofthesachetscontainingsprinkleswas95.72%(SD=4.9)and96.4%(SD=6.2)for thetestandcontrolgroups,respectively.

Conclusions: Zincsupplementationthroughtheuseofsprinklesdidnotreducetheincidence ofDDor ARI among theevaluated children.The sprinkles were wellaccepted by all study participants.

夽 _Please_cite_this_article_as:_Sampaio_DL,_de_Mattos_AP,_Ribeiro_TC,_Leite_ME,_Cole_CR,_{Costa-Ribeiro}_Jr_H._Zinc_and_other_{micronutrients}

supplementationthroughtheuseofsprinkles:impactontheoccurrenceofdiarrheaandrespiratoryinfectionsininstitutionalizedchildren.

JPediatr(RioJ).2013;89:286---93.

∗_{Corresponding}_author.

E-mail:danileleal@yahoo.com.br(D.L.B.Sampaio).

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PALAVRAS-CHAVE

Suplementac¸ãode zinco;

Diarreia;

Infecc¸ãorespiratória; Deﬁciênciadezinco

Suplementaçãodezincoeoutrosmicronutrientesatravésdousodesprinkles: impactonaocorrênciadedoençadiarreicaeinfecçõesrespiratóriasemcrianças institucionalizadas

Resumo

Objetivo: Avaliaraincidênciadedoençasdiarreicas(DA)einfecçãorespiratóriaaguda(IRA)em criançassubmetidasàsuplementaçãodezincoeoutrosmicronutrientesatravésdossprinkles, bemcomoaaceitaçãodestespelospacientes.

Método: Ensaioclínico,duplocego, randomizado,realizado com143crianc¸as institucional-izadas, saudáveis, de seis a 48 meses. As mesmas foram randomizadas em dois grupos e receberamdiariamentezinco+micronutrientes---grupoteste(sprinkles),ouapenas micronutri-entessemzinco--- grupocontrole.Ascrianc¸asforamsuplementadaspor90diaseacompanhadas quantoaosdesfechosdeDAeIRA.

Resultados: Dascriançasrandomizadas,52,45%pertenciamaogrupotestee47,55%aocontrole. AincidênciadeDAnotestefoide14,7%,enocontrole,19,1%.Ogrupotesteapresentoumenor riscodedesenvolverDAemrelaçãoaocontrole,porémesseachadonãofoiestatisticamente significante(RR=0,77[0,37-1,6];p=0,5088).AIRAapresentou incidênciaelevadaemambos osgrupos,sendo60%notestee48,5%nocontrole,comriscomaiordeapresentaradoença nogrupoteste,porémsemsignificânciaestatística(RR=1,24[0,91-1,68];p=0,1825).Quanto àaceitação,opercentualmédiodeconsumo,emdias,detodoconteúdodossachêscontendo sprinklesfoi95,72%(DP=4,9)e96,4%(DP=6,2),paraotesteecontrole,respectivamente. Conclusões: AsuplementaçãodezincoatravésdossprinklesnãoreduziuaincidênciadeDAou IRAentreascriançasavaliadas.Ossprinklesforambemaceitosportodososparticipantesdo estudo.

Introduction

Diarrheal diseases (DD) and acute respiratory infections (ARI)areaserioushealthproblemindevelopingcountries. Theyarethe leadingcausesof morbidityandmortalityin childrenyoungerthan5years.1,2_Estimates_published_by_the

WorldHealthOrganization(WHO)in2008showedthat respi-ratoryinfectionsaffected17%ofchildreninthisagegroup.3

Diarrheal diseases, in turn,are thecause of deathof 2.5 millionchildren/year.4

InBrazil,in2009,respiratoryinfectionskilled2,733 chil-dren youngerthan5years,whichcorrespondsto5.46%of deaths in this age group. The data also showed that ARI mortality (around 4.5% to 5.0%) was not much different in proportion amongthe regions of the country, although it was higher in the North (7.51%) and Midwest (6.47%) Regions.5

Between 1998and2008,33,363deathsrelatedto diar-rhea were recorded in the countryin individuals younger thanﬁveyears;ofthese,82%wereyoungerthanoneyear.6

Thesedatadifferaccordingtoregion.WhileintheSoutheast thenumberofepisodes/child/yearis1.04,intheNortheast, itincreasesto5.55.7,8

Ithasbeenobservedthatevenaftertheadventoforal rehydrationsolutionandvaccinationagainstrotavirus,both veryeffectivemethodstoﬁghtdiarrhealdiseases,their inci-dencestillremainshigh.6,9,10

WiththegoalofreducinginfantmortalitycausedbyDD, in 2001, the WHO analyzed 12 studies involving children aged1 months to5 yearswho had diarrheatoverify the effectofzinconthedisease.Theresultsshowedthatthis

mineralsupplementation wasassociated with areduction in the duration of episodes of DD by 25% and decreased progressiontopersistentdiarrhea.Thestudiesalsoshowed reducedincidenceofdiarrheabytwotothreemonthsafter supplementation.11

Based on these results, since 2006, the WHO and the United NationsChildren’s Fund (UNICEF) recommend zinc supplementation to treat and prevent future episodes of diarrhea,11,12 _considering _this _is _an _essential

micronutri-ent whose deﬁciency may increase the risk of infectious diseases.13

Zinchasalsobeen shown tobeeffectivein preventing infectiousdiseasesoftherespiratorytract.Ameta-analysis conductedbytheInternationalZincNutritionConsultative Group(IZiNCG)in 1999found a41% reductioninthe inci-denceofpneumoniaamongthesupplementedindividuals. Severalstudieshaveidentifiedthebenefitsofzincarenot limited to specific groups, and that intervention should include all children at risk, mainly those living in devel-opingcountrieswithhigh ratesofmorbidity andmortality from infectious diseases.14_In _Canada, _in _the _1990s, _with

the objective of preventing micronutrient deficiencies in children,sprinklesweredevelopedasastrategy forhome fortification of foods. The sprinkles are sachets contain-ingdried and predetermined micronutrientsencapsulated byathinlipidlayer,whichpreventsinteractionwithother nutrientsandconfersanalmostimperceptibleleveloffood modificationregardingcolor,flavor,andtexture,facilitating theiracceptancebychildren.15---17

ThisstudyaimedtoevaluatetheincidenceofDDandARI inchildren receivingzinc supplementation combinedwith

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othermicronutrientsthroughtheuseofsprinkles,aswellas theiracceptance.

Methods

Studydesignandsetting

BetweenAugustandNovemberof2009,arandomized, con-trolled,double-blindedstudywasconductedinanon-proﬁt day care center located in a lower socioeconomic class neighborhood of Salvador, capital of the state of Bahia, Brazil.DatawerecollectedbythestaffofCentrodePesquisa FimaLiﬁshitz--- UniversidadeFederaldaBahia.Thesprinkles weredonatedbyEmoryUniversity,Atlanta,USA.

Samplesizecalculation

Asample wascalculatedtodetect a20% reductioninthe occurrenceofdiarrhealepisodesandrespiratoryinfections comparedtocommonlyobservedratesoveraperiodofthree monthsinthechildrenattendingthestudieddaycare cen-ter.Consideringabetaerrorof0.80andanalphaerrorof 0.05,it was necessary torecruit at least 60 subjects per group.

Eligibility

Theinclusion criteriawere:healthy childrenaged6to48 months,ofbothgenders,whoseparentsorlegalguardians consentedtoparticipationbysigninganinformedconsent, whoagreed not toofferany vitamin and/or mineral sup-plementduringthestudyperiod,exceptfor thesprinkles, whichweresenthomeonweekendsandholidays.

The exclusion criteria were: participants with severe malnutrition (z-score W/H<-3), severe anemia (Hb<9.0mg/dL);anyactivesevereillness requiring hospi-talization, including DD or ARI; and history of underlying diseasethatcouldeventuallyinterfereintheevaluation.

Randomization

Childrenenrolledinthe institutionconsidered eligiblefor thestudywererandomizedintotwogroups:groupA(test) and group B (control). Randomization was performed by rooms and nurseries, according to a computer-generated sequence. The study’s medical team was responsible for identifyingeligiblesubjects,collectingthemedicalhistory, andperformingthephysicalexamination.Finally,bloodwas collectedfor complete blood countanalysis, toeliminate subjectswithsevereanemiafromtheanalysis.

Nutritionalassessment

The nutritional assessment and diagnosis were made at baseline and at the end of the intervention. Weight was measured using a digital scale, appropriately calibrated andsuitablefor every age group.Lengthmeasurement in childrenyoungerthan2yearswasperformedusingan infan-tometer; a stadiometer was used for the older children. Thez-scoresoftheweight/height(W/H),height/age(H/A),

Table1 Sprinklecomposition.

Components Sachet(1g)

VitaminA(vitaminAacetate) 375mcg VitaminB1(thiaminemononitrate) 0.5mg VitaminB2(riboﬂavin) 0.5mg VitaminB6(pyridoxine) 0.5mg VitaminB12(cyanocobalamin) 0.9mcg VitaminC(ascorbicacid) 35mg VitaminD3(cholecalciferol) 5.0mcg VitaminE(vitaminEacetate) 6.0mg

Niacin(niacinamide) 6.0mg

Copper(coppersulfate) 0.6mg Iodine(potassiumiodide) 50mcg Iron(ferrousfumarate) 12.5mg Zinc(zincgluconate)a _5.0_mg

Maltodextrin(carrier) Q.S. Silicondioxide(carrier) Q.S.

The sprinkleswereproduced byHexagonNutritionPvt Ltd

---India,underlicensebySGHI,Canada.

a _Present_only_in_the_sachets_given_to_test_group.

andweight/age(W/A)indicatorswerecalculatedusingthe Anthro program, available fromthe WHO. The nutritional diagnosiswasmadefollowingtheWHOcriteria.18

Before the intervention, all meals served to the chil-dren(fourperday)werecalculatedusingfoodcomposition tables19,20_and_product_labels,_in_order_to_quantify_the_macro

andmicronutrientspresent in aservingof100g,followed by estimates of daily consumption. To quantify the con-sumption,thepreparationswereweighedbeforeandafter ingestion of each meal using a scale accurate to 1g. All recordsofconsumption andanthropometryweremade by thestudydietitians.

Intervention

During 90 days, the subjects in group A received one sachetofsprinkleswithaddedzincandmicronutrientsdaily, whereasgroupBreceivedthesamemicronutrients,without zinc(Table1).

The supplementsweremixedin a smallportionof the meal, always at the same time. Due to the nutritional compositionandday-careroutine,themostadequatemeal for additionofsupplementsandtheonebestaccepted by thechildren wasthe afternoonsnack(silver banana).The supplementswereonlyopenedandaddedtofood immedi-atelybeforeserving,bydietitiansnotblindedtothestudy, asthesachetswereidentiﬁedforthepresenceofzinc.The snacks were monitored by the team members (physicians anddietitiansblindedtothestudy)topreventexchangeof platesor loss of thefood servingthat containedthe sup-plements, aswell asto identifythosewho didnot ingest it.

Basedontheassessmentofwhathadbeeneatenatthe afternoon snack, it was recorded in a form whether the childhadingestedallthesupplement(theentiresnack),at leasthalfofit(halfthesnack),ornoneofit.Basedonthis information,acceptanceofthesupplementwasassessed.

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Table2 CharacteristicsatadmissionofgroupsA(test)andB(control). Characteristics GroupA n(%) GroupB n(%) p-valuea n 75 68 Gender Male 48(64) 35(51.5) 0.1745 Female 27(36) 33(48.5) Age(months) 0.8675 6-24 38(50.7) 33(48.5) 24-48 37(49.3) 35(51.5)

Meanageb_(months) _25.2 _26.11

Nutritionalstatus(W/H) Malnourished 02(2.7) 01(1.5) 0.596 Normalweight 62(82.7) 55(80.9) Riskofoverweight 08(10.7) 11(16.2) Overweight 03(4.0) 01(1.5) Obesity 0(0) 0(0)

Nutritionalstatus(H/A)

Adequatestature 53(70.7) 55(80.9)

Lowstature 18(24.0) 8(11.8) 0.1604

Severelowstature 4(5.3) 5(7.4)

H/A,height/age;W/H,weight/height.

a _Fisher’s_exact_test.

b _Student’s_t-test.

Onweekends,holidays,andplannedabsences,toensure the continuity of the intervention process, parents or guardiansweregivenenoughsupplementsforconsumption duringtheperiod.Theywereinstructedtoofferthemonce perday,inamealsimilartothatservedatthedaycare.

DiagnosisofDDandARI

DDwasdeﬁnedasthepresenceofthreeor moreliquidor semi-liquidstoolsin24hours,lastinglessthan14days.The BrazilianMinistryofHealthcriteriawasusedforthe diagno-sisofARI.21_Daily,_prior_to_the_start_of_the_day_at_the_daycare,

theparents/guardianswerequestionedbythenursingstaff, whichwereproperlytrained,astothehealthstatusofthe children.Ifanychildwasidentiﬁedashavingoneofthe out-comes(DDand/orARI),heorshewasreferredforevaluation bythephysiciansofthisproject.Thechildrenwereassessed ontheﬁrstdayoftheirreturnaftertheweekends,holidays, andabsences,andparentsor tutorswereaskedabout the children’shealthstatus.Themedicalteamperformeddaily roundstoidentifyeventsofinterest.Allphysiciansinvolved wereblindedtothestudy.

Ethicscommittee

Theproject wasregisteredat theNationalCommissionon ResearchEthics(CONEP) on10/28/2008, andapprovedby theResearchEthicsCommitteeoftheHospitalUniversitário ProfessorEdgard Santos,underprotocolNo.042/2008, on November6,2008.

Dataanalysis

Theanalyseswereperformedconsideringonlythedata col-lectedatthedaycare.Toassessthemainvariables(presence ofDDandARI),measuresofoccurrence(incidence)andof association(relativerisk-RR)werecalculated,aswell as therelativerisk reduction(RRR)andtherespective conﬁ-denceintervals(CI).Fisher’sexacttestwasusedtocompare characteristicsbetweengroupsatbaseline.Theparametric Student’st-testwasusedtoanalyzethecontinuous varia-bles(anthropometricindicators)withnormaldistribution.A Poissonregressionmodelwasusedtoidentifyinteractions andconfoundingfactorsforDD andARI. TheKaplan-Meier testwasusedtoassessdurationofDD episodes.The over-allsigniﬁcancelevelwassetat5%.Thedatabasewasbuilt usingtheEpiDatasoftware,release3.3.1,andtheanalyses wereperformedusingR.

Results

Of the 150 children enrolled in the study, seven were excluded:threefor age less thansix monthsandfour for nolongerattendingthedaycare.Thus,143wererandomly assignedtothetwogroups.Ofthese,52.45%(n=75)were assignedto group A (test) and 47.55% (n=68) to group B (control).Allchildrencompletedthestudy.Thegroupswere similarregarding admissioncharacteristics --- gender, age, andnutritionalstatus(Table2).Severeanemiawasnot iden-tiﬁedinanyoftheparticipants.

TheanthropometricindicatorsW/H,W/AandH/Awere alsosimilarbetweengroupsatbaseline(Table3).However,

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Table3 Medians(Md)andinterquartileintervals(IqI)ofz-scoresofanthropometricindicatorsW/H,H/A,andW/Ainthetest (GroupA)andcontrol(GroupB)groupsbeforeandaftertheintervention.

Anthropometricindicators GroupA GroupB p-value*

Md IqI Md IqI Beforeintervention W/H 0.10 1.18 0.22 1.59 0.6334 H/A -0.52 1.09 -0.33 1.22 0.1577 W/A -0.15 1.24 0.06 1.71 0.4582 Afterintervention W/H 0.12 1.15 0.32 1.45 0.4177 H/A -0.57 1.10 -0.38 1.32 0.7726 W/A -0.1 1.14 0.08 1.39 0.3937

H/A,height/age;W/A,weight/age;W/H,weight/height.

* _Mann-Whitney_test.

aftertheintervention(p-valuesnotshowninTable),there was an increase in mean z-scores of W/H and W/A in both groups, whereas in controls this improvement was statistically signiﬁcant for both W/H (p=0.033) and W/A (p=0.005).ThesameresultwasnotobservedfortheH/A ratio: in the test group, it maintained the same mean (p=0.9634) and in controls, it showed a slight decrease (p=0.007).

The calculation of ingestion, including the addition of sprinkles,showednodifferencein themean consumption ofenergy(A:72.09kcal/kgvs.B:72.96kcal/kg;p=0,728), ﬁbers(A:6.7gvs.B:6.83g;p=0.564),proteins(A:2.08g/kg vs. B: 2.11g/kg; p=0.654), carbohydrates (A: 9.31g/kg

vs. B:9.48g/kg; p=0.602) and lipids (A: 2.95g/kg vs. B: 2.95g/kg; p=0.949)between thegroups. Only zinc levels weredifferentbetweenthegroups,duetothe supplemen-tationinthetestgroup(A:7.16mgvs.B:2.3mg;p<0.001). Itcanbeobserved thatcalorieconsumption accounted for over 80% of the recommended for the age range. Macronutrients were within the recommended levels by DRIs, except for proteins, which exceeded nearly50% of the recommendations. Fibers accounted for 1/3 of those proposedfortheagerange.

TheincidenceofDDinthetestgroupwas14.7%(n=11), whereasinthecontrolgroupitwas19.1%(n=13). Descrip-tively,thetestgroupshowedalowerriskofdevelopingDD whencomparedtocontrols,butthisﬁndingwasnot statisti-callysigniﬁcant(RR[95%CI]=0.77[0.37to1.6],p=0.5088). TheRRRwas23.3%.

Variableadjustment(gender, agerange,andtotal con-sumptionofsprinkles)wasmadeusingthePoissonregression model (Table 4); none of them acted as confounders for theassociation withthetest group. The incidenceof DD, aswell asthe agerange, wasnotan interactionvariable (p=0.4219).Therewas,however,alowerriskofdeveloping DDinthoseolderthan24months,regardlessofthegroup (RR[95%CI]=0.41[0.157to0.94],p=0.045).

Regardingthedurationofepisodes,itwasobservedthat mostparticipantshadonlyonedayofDDinbothgroups;in thetestgroup,sixdayswasthemaximumduration(n=1), andinthecontrolgroup,ﬁve(n=1).Therewasnosigniﬁcant differencebetweenthegroups(p=0.846).

ARI had high incidence in both groups, 60% (n=45) in the test and 48.5% (n=33) in the control group; the test

groupshowedagreaterriskofhavingthedisease,but with-outstatisticalsigniﬁcance(RR[95%CI]=1.24[0.91to1.68], p=0.1825).

ThePoissonregressionmodelwasusedtoadjustvariables forARI(Table4),whichdidnotidentifyanyconfoundersfor theassociationbetweenthetestgroupandtheincidenceof ARI.Theagerangewasnotshowntobeaninteraction vari-able(p=0.482).However,unlikewhatwasobservedforDD, therewasalowerriskofdevelopingARIinchildrenyounger than24months,regardlessofthegroup(RR[95%CI]=0.65 [0.48to0.89],p=0.007).

Sprinkleacceptancewasevaluatedthroughthe consump-tionatthedaycare.Themeanpercentageofdaysonwhich thetest andcontrol groupsconsumed theentire contents of the sachets was95.72% (SD=4.9) and 96.4% (SD=6.2), respectively.Partialacceptancewas2.5%(SD=3.4)forthe testand1.5%(SD=2.5)forthecontrolgroup.

Discussion

Over several years,researchershave been makingefforts aimedatreducingthehighrates ofmorbidityand mortal-ity caused by ARI and DD. In this scenario, some studies havebeen publishedshowingthepositiveresultsobtained with zinc supplementation in the treatment and preven-tionofthesediseases.11,14 _Despite_the_scientiﬁc_evidence,

thepresentstudyresultsshowednostatisticallysigniﬁcant differencesregardingsupplementation.

Concerning the nutritional status, improvement was observed in mean z-scores of weight indicators in both groups.However,duetothesigniﬁcantincreaseinthe con-trol group, the result cannot be solelyattributed to zinc supplementation ---other factors, suchasthe presence of othermicronutrients,mightbeactingtoimprovethese chil-dren’sweight.

As for height, no alteration was observed in the test group. In thecontrol group, the decreasein the mean z-score for H/A, although statistically signiﬁcant, was not relevant from a clinical viewpoint, considering that this decreasedidnotcausealterationsinthenutritionalstatus. Inthisrespect,thisstudydiffersfromanotherrecently published study,which showed that zinc supplementation effectivelycontributedtothegrowthofchildrenunderthe

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Table4 Relativerisks,95%conﬁdenceintervals,andp-valuesfortheassociationbetweentypeofsupplementation,agerange, gender,andtotalconsumptionofsprinklesadjustedbyPoissonregression.

Variables crudeRR adjustedRR 95%CI p-value

Diarrhea 0.77 - [0.37---1.6] 0.5088

Completemodel

Group

Control 1 -

-Test 0.78 [0.34-1.77] 0.555

Agerange(months)

[6-24] 1 -

-[25-48] 0.40 [0.15-0.96] 0.049

Gender

Male 1 -

-Female 1.37 [0.61-3.11] 0.440

Totalconsumptionofsprinkles 1.00 [0.94-1.10] 0.949

ARI 1.24 - [0.91---1.68] 0.1825

Completemodel

Group

Control 1 -

-Test 1.25 [0.80-1.99] 0.335

Agerange(months)

[6-24] 1 -

-[25-48] 0.67 [0.42-1.06] 0.093

Gender

Male 1 -

-Female 1.06 [0.67-1.67] 0.796

Totalconsumptionofsprinkles 1.01 [0.97-1.07] 0.551

Residualdeviance(ARI):89.807at138degreesoffreedom;AIC(Akaike’sInformationCriterion):255.8.

Residualdeviance(Diarrhea):80.158at138degreesoffreedom;AIC:138.2.

ARI,acuterespiratoryinfection;RR,relativerisk.

ageof5years,andthatthedoseof10mg/day,offered dur-ing24weeks,promotedbestresultsforheightincrease.22

Althoughitisnotpossibletoidentifythereasonsforthe abovementioned discrepancy, both the short intervention period,perhaps insufﬁcienttoidentifychanges in anthro-pometryespeciallywithregardtoheight,andthedoseof zincused,mayhavebeenlimitingfactorsinthisstudy.

Regarding DD,although theincidencewaslowerin the test group,the differencecomparedtothe control group wasnotsigniﬁcantand,additionally,therewasnodifference inthedurationofdiseaseepisodesbetweenthegroups.This resultissimilartothoseoftwootherstudieswithchildren supplementedwithzincfor 14days,whichshowedno sig-niﬁcanteffectsinreducingtheincidenceorprevalenceof DD.23,24

The different result obtained in a study conducted in Brazilisnoteworthy.Inthatstudy,zincsupplementationwas proventobeeffectiveinreducingthedurationandnumber ofstoolsinchildrenaged3to60monthswhohadDD.25

Contrary towhatwasdescribed forDD, the test group showedahigherrisk ofdevelopingARIwhencomparedto controlgroup;however,theseﬁndingswerenotstatistically signiﬁcant. A meta-analysis published by Aggarwal et al. evaluated the performance of zinc supplementation and concludedthatitreducedtheincidenceofARIinchildren by8%.26

A Brazilian study with children with low birth weight founda33%reductionintheprevalenceofcoughingamong the group supplemented with 5mg/day of zinc. No sig-niﬁcant difference, however, was observed when other characteristic symptoms of respiratory infection (fever, increasedrespiratoryrate,andfatigue)wereanalyzed.27

The fact that this study found no positive results regarding zinc supplementation on the occurrence of the assesseddiseasesmaybeduetothehealthystatusofthe study population. Most published studies used as a sam-plechildrenwhoalreadyhad DD or ARI,23,24 _{malnutrition,}

or impaired immune function, such as those with human immunodeﬁciencyvirus(HIV)infection.28

Itisworthmentioningthatseveralfactors,suchaslow immunity,malnutrition,andpoorhygiene10,29_are_involved_in

theetiologyofthediseasesbeingassessed.Theetiologyof ARI,forinstance,hasmultipleconditioningfactorsthatare difﬁculttocontrol,suchasweatherchangesandpollution.30

The zinc dose used in this study is another important variable to consider, as it may have been insufﬁcient to achieve the expected effect, as the recommended dose for treatment and prevention of DD and ARI is 10 to 20mg/day.12_Larger_amounts_of_zinc_were_not_offered_as_the

objectivewastoevaluatethesupplementationthroughthe useof sprinkles with5mg/zinc,whose recommendeduse isofonesachet/day.15_Therefore,_in_a_healthy_population,

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zincsupplementationwith5mg/daymaynotbeaseffective inthepreventionofinfectiousdiseases.

Regarding acceptance, sprinkles appear to be an effi-cient way of supplementing zinc intake,as well as other micronutrients.The data analyzedin thisstudy reflectan acceptance>90%.Itisnoteworthythefactthatthesprinkles wereaddedtothefoodthatwasbestacceptedbythe par-ticipantsand,astheyprovidealmostnochangeinflavoror colorofpreparations,theirconsumptionmaybeassociated withtheacceptanceofthefoodofferedtothechildren.

Other studies that assessed the acceptance of

sprinkles16,17 _also _showed _similar _results, _suggesting

theyareagoodoption toﬁghtmicronutrientdeﬁciencies, especially because they do not alter the organoleptic characteristicsoffood.

Basedonthepresentstudy,itcanbeconcludedthatzinc supplementationthroughtheuseofsprinkleshadnoimpact inreducingthe incidenceofDD andARI, norinﬂuence on thenutritionalstatusofthestudypopulation.However,the goodacceptanceofsprinklesoffersanewformtoadminister supplementalmicronutrients,representinganinnovationin themanagementofchildren’snutritionaldeﬁciencies.

Funding

The sprinkleswere donated by Emory University,Atlanta, GA,USA.

Conﬂicts

of

interest

Theauthorsdeclarenoconﬂictsofinterest.

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2.BlackRE,Morris SS, BryceJ. Where and whyare 10million childrendyingeveryyear?Lancet.2003;361:2226---34.

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