UNIVERSITYOFGRANADA

SCHOOLOFMEDICINE.DEPARTMENTOFPAEDIATRICS

EURISTIKOSExcellenceCentreforPaediatricResearch

DoctoralThesis

Stunting,OverweightandChildDevelopmentImpairment

gohandinhandaskeyproblemsofearlyinfancy:

Uruguayancase

Malnutricin,SobrepesoyRezagoenelDesarrolloInfantilvan

delamanocomolosproblemasclavesdelaprimerainfancia:

elcasodeUruguay

DoctoralCandidate

MaraIsabelBove

Granada,December,2012

Editor: Editorial de la Universidad de GranadaAutor: Mara Isabel BoveD.L.: GR 1718-2013ISBN: 978-84-9028-557-2

Insanity:doingthesamething

overandoveragainand

expectingdifferentresults.

AlbertEinstein,1910

Thesispresentedby

MaraIsabelBove

ToachievethePhDdegreeinNutrition

MaraIsabelBove

ThisThesishasbeendirectedby

Prof.Dra.Da.CristinaCampoyDepartmentofPediatricsUniversityofGranadaSpain

Prof.Dra.Da.MTeresaMirandaDepartmentofBiostatisticsUniversityofGranadaSpain

Prof.Dr.D.RicardoUauyDepartmentofNutritionandPublicHealthLondonSchoolofHygieneandTropicalMedicineUniversityofLondonUnitedKingdom

3

Summary

Acknowledgements.................................................................................................................................4

Abstract....................................................................................................................................................5

Resumenenespaol................................................................................................................................6

Introduction.............................................................................................................................................7

Thesiscontext..........................................................................................................................................8

Objectives,methodologyandcontributiontoknowledge....................................................................21

Resultsandconclusion...........................................................................................................................24

Discussion..............................................................................................................................................27

Bibliography...........................................................................................................................................35

Annex1:................................................................................................................................................62

Stunting,OverweightandChildDevelopmentImpairmentgohandinhandaskeyproblemsofearlyinfancy:Uruguayancase........................................................................................................................62

Annex2:................................................................................................................................................68

Trendsinearlygrowthindices(stuntingandoverweight)inthefirst24monthsoflifeinUruguayoverthepastdecade.....................................................................................................................................69

Annex3:................................................................................................................................................89

Smokingduringpregnancy:ariskfactorforstunting,anaemiaandoverweightininfancy?...............90

4

Acknowledgements

ImgoingtosaythankyouinSpanish:

ACristinayRicardoporconfiarenm.

AMaraTeresaporsucalidezyporhabercompartidosuamorporlaestadstica

ParaNaniyNacho,misadoradoshijos,porensearmecadadaasermejorpersona.

ATiti,Gracie,Sylviymamiporestarcadadaamilado

AFloryMartaporelcarioyeldisfrutedeltrabajoconjunto

ASada,JessiyVeroporsermisamigasdeGranada

Amisadoradas/osprimas,amigas,madrina,ahijados,sobrinas,sobrinosytosporcompartirlavida

AGranada,quecuandosemepiantabaunlagrimnmedecaNo!Noversmibelleza

AmishermanosyenespecialapapyabuelitoporensearmequeNuncaestarde

5

Abstract

Background: Stunting, overweight and child development impairment are key problems affectingearly infancy and have short and longterm consequences on academic performance, socialcompetenceandadulthealth.

Objective: The aim of this Thesis is to identify linkages between stunting, overweight and childdevelopmentimpairmentaswellastoexaminetheirevolutioninthelasttenyearsinUruguay.

Studydesign:Weanalyseddatafrom5surveyscarriedoutinUruguay.Westudied2,069children

6

Resumenenespaol

Antecedentes:Elretrasode talla,elsobrepeso yelrezagoeneldesarrollo infantilsonproblemasclavesdelainfanciatempranaquetienenreconocidasconsecuenciasacortoyalargoplazosobreelrendimientoescolar,lascompetenciassocialesylasaludenlavidaadulta.

Objetivo:Elpropsitodelapresentetesisesidentificarlasinterrelacionesentreelretrasodetalla,elsobrepeso yel rezagoeneldesarrollo infantilas como tambinanalizar suevolucindurante laltimadcadaenelUruguay.

Diseo del estudio: El documento reorganiza los tres trabajos de investigacin enviados por ladoctorandoarevistascientficas.Laprincipal limitacindel trabajoeshaberanalizado informacindecortetransversalconslounamedidapornio,por loquesedescribe laasociacinperonosepuede establecer la relacin causal. La fortaleza del estudio es el gran tamao de lasmuestrasanalizadasascomo tambinquese incluyeronniosde familiasuruguayasdediferentecondicinsocial. Se analiz la informacinde5encuestas llevadas a caboenUruguay. Seestudiaron2.069niosmenoresde5aosdelreadeCanelonesycuatrograndesmuestrasrepresentativasdelnivelnacional y regional de nios desde el nacimiento hasta los 23meses de edad atendidos por elSistema Nacional de Salud los aos 1999 (N=2.571), 2003 (N=2.783), 2007 (N=3.003) y 2011(N=2.994).

Resultados: Se observ en nios

7

Introduction

Over the last2decades, Ithasbeenanaccumulationofevidencesuggesting that the rootsof the

inequalitiesare inearly infancy.Conceptionalperiodandthefirstyearsof lifearedeterminantsfor

thehealthandwellbeingover the lifecycle (Victoraetal.,2008;Uauyetal.,2011). Inaprevious

documentwerecognizedthisperiodasThirtythreemonthsdefiningthelifematch(UNICEF,2008).

ThemostunequalregionoftheworldisLatinAmerica.Itcouldbetheresultofitshistoricalprocess

goingbackatleasttothecolonialperiodinequalityoflandholdings,accesstoeducationandpolitical

power but the fact is that, for this continent equalization of opportunities, should be themost

significantchallenge (WorldBank,2008).Loweducationalmobilityconstitutesthemainchannelof

reproductionofhighincomeinequality(Lopez&Perry,2008).Thedifferencesineducationbetween

thepoorandtherichleadtomuchdifferentialinhealth,nutritionandopportunities,andthetrueis

that,incomeinequalityappearstobethemajordeterminantofcrimeandviolencelevels.

In Latin America young children are exposed to multiple developmental risk factors including

poverty,malnutrition,poorstimulationathome,andlackofcarethatadverselyaffecttheabilityto

reach their developmental potential (Engle et al., 2011;Walker et al., 2011). For their optimal

growth, and for greater longterm human capital development, children profit not only from

improvednutritionbutalsofromimprovedlearningopportunitiesintheearliestyearsoflife.Linking

thesetwocomponentswillresultinsynergiesofprogramactivities,andwillimpactonreducedcost

thaneitheractivityconductedseparately(GranthamMcGregoretal.,2007a).

Theaimof thisThesis is to identify linkagesbetween stunting,overweightandchilddevelopment

impairmentinearlyinfancyandanalysetheirevolutioninthelasttenyearsinUruguay.Thiscountry

despiteofbeingoneof themostequitable incomedistributions inLatinAmerica, inequalitiesand

povertycontinueaffectingespeciallyyoungpeople.

8

Thesiscontext

Uruguay isamedium income countrywithonly3,369,000 inhabitants, lowbirth rate (2.1

childrenperwoman;only46,707births, in2011),with lowpercentagechildrenbelow the

ageof15(22.5%,2011)andahighpercentageofpeopleover65(14.1%in2011;INE,2012).

Uruguay has been described as South America's "first welfare state" as a result of its

pioneeringefforts inthe fieldsofeducation,healthcare,andsocialsecurity.However,the

stagnationoftheeconomystartinginthe1950sputincreasingstrainsonthissystemandby

the1970sUruguay'swelfarestatehaddeclinedsharply.(WorldBankInstitute,2010)

The severe economic crisis that affected the region from 1999 to 2002 had considerable

repercussionsandpovertyandinequalityrosemarkedly.Thenumbersofpeoplelivingbelow

thepovertylinerosefrom17.8%to32.1%affectingespeciallyyoungpeople(54%ofchildren

65yearslivinginpoorfamilies).Uruguay'seconomyresumed

mildgrowthin2003witha0.8%riseinGDPandhasgrownrobustlysincethen,withannual

averageratesof6.5%in20042008.Theglobalfinancialcrisisslowedgrowth,butapositive

growth rate of 2.9% in 2009 and robust growth of 8.5% and 5.9% for 2010 and 2011

respectively. This improvement has contributed to an important decrease in poverty

incidence from 30% to 17% between 2006 and 2011 (Alves, Amarante, Salas& Vigorito,

2012).

9

Today,Uruguayisfacedwithnewchallenges.Uruguayseducationneedstoprogressinits

secondaryschoolingandto improveeducationquality.Ahighnumberofstudentsdropped

out in the transition fromprimary to secondary school andUruguayhad in thePISA test

(Program for International Student Assessment), one of the greatest standard deviation

amongschools,suggestingsignificantvariabilitybysocioeconomiclevel.(NCES,2005)

Uruguay throughout the twentiethcenturywas losing its leadershipposition in thehealth

status. In the1930s ithad lostwith respect themostof theEuropeanCountries.Bymid

century Uruguay still held a special place in the Latin American context. But thereafter

UruguaywasrelegatedbyothercountriessuchasCostaRica,CubaandChile.(ECLAC,2011)

The pattern of disease reflects the mature demographic profile and Uruguay can be

consideredtobeintheposttransitionphase(RicardoUauy,Albala,&Kain,2001).Themain

causesofdeatharediseasesof thecirculatory system (30%),malignantneoplasms (24%),

andaccidents (5.2%). (Curto,Prats& Zelarayan,2011) Infantmortalityrate(8.9per1,000

birthsin2011)hasbeendecreasing.(MSP,2012)

Uruguay, like the rest of the world, is affected by the pandemic of obesity and

simultaneously stunting and anaemia persist (Bove & Cerruti, 2007, 2011; Illa, Moll,

Satriano,Ferreira, Estefanell&Sayagus).Adulthoodobesityrateshavebeenusuallyhigh.

Inthe1960sanationalsurveyreported46.1%ofwomenand30%ofmenobese(Committee

onNutritionUSA,1962).In2006and2009twodifferentnationalsurveysshowed20%(from

17.1%to22.9%)ofobesity inadults (BMI>30)withoutstatisticaldifferencesbysex (MSP,

2006;ENSO,2009).Theprevalenceofobesityinchildhoodhasbeenalsohigh:7.9%(6.1to9.6)at

6yearsold (ANEP,2002,2004)and9.0% (7.1% to10.9%)at9 to12yearsold (Pisabarro&

10

Kaufmann,2004).Percentageofobesity inpreschoolCAIFchildrenseems tobe increasing

from5.9%in1997to13.3%in2008.(INDA/CAIF,1997,2008)

Ontheotherhandfrom3.9to5.3%ofchildrenatthebeginningofprimaryschoolhavebeen

stuntedwithoutchange inthe lasttwodecades:4.0%,4.1%,4.6%, in1989,2002and2004

respectively(INDA,1989;ANEP2002and2004).Anaemiapersistsasapublichealthproblem

affectingespecially infantsfrom6to23months31%(27.7to34.3%;UNICEF,MSP,MIDES,

RUANDI,2011).7%(6.6to7.4%)ofwomenfrom15to45yearsshowedanaemiaandafter

20 weeks of gestation the anaemia upper to 20% (19.4 to 20.6%) (Moratorio X. MSP,

SIP/NUT2012).

Nationalstatisticsonchildrenscognitiveorsocialemotionaldevelopmentarenotavailable,

andthisgapcontributestothe invisibilityoftheproblem(SallyGranthamMcGregoretal.,

2007a).A survey in the1980s showedpoordevelopmentespecially inpreschool children

livinginpovertycondition.(Terra,JuanPablo1986)

Despiteprevalentearlyproblems,policymakersaswellashealthandsocialworkersareunawareof

their consequences, so they arent viewed as a public issue. The agenda does not include early

infancy problems, but it is warned about poor education, drugs, delinquency, inequalities and

poverty.

11

Childdevelopment,stuntingandoverweightinearlyinfancy

Earlystunting(Walkeretal., 2011;Mendez&Adair,1999), irondeficiency(GranthamMcGregor&

Ani,2001; Lozoff etal.,2006 ;Osendarpetal.,2010),environmental toxins (Oppenheimer,2001;

Osendarpetal.,2010),stress (Engleetal.,2011)aswellaspoorstimulationandsocial interaction

(GranthamMcGregoretal.,2007a;Webbetal.,2001;Engleetal.,2011)canaffectbrainstructure

and function, andhave lastingeffects.Childrensdevelopment consistsof several interdependent

domains, including sensorymotor, cognitive,and socialemotional.Thediscrepancybetween their

currentdevelopmental levelsandwhattheywouldhaveachieved inamorenurturingenvironment

with adequate stimulation and nutrition indicates the degree of loss of potential (Grantham

McGregor et al., 2007b).Deficits in development increasewith age and in later childhood these

childrenwillsubsequentlyhavepoor levelsofcognitionandeducation,bothofwhichare linkedto

laterearnings (Walkeretal.,2005;2011).Thus the failureofchildren to fulfil theirdevelopmental

potentialandachievesatisfactoryeducationallevelsplaysanimportantpartintheintergenerational

transmissionofpoverty(GranthamMcGregoretal.,2001;2007b).

Poverty isassociatedwithpoormaternaleducation, increasedmaternal stressanddepression,as

wellasinadequatestimulationathome(Engleetal.,2011).Variationsinthequalityofmaternalcare

can produce lasting changes in stress reactivity, anxiety, and memory function in the offspring

(GranthamMcGregoretal.,2001,2007b).Povertyisalsoassociatedwithinadequatefood,andpoor

sanitationandhygiene that increase infectionsand stunting in children.Poorphysicalgrowthand

developmentleadstopoorschoolachievement,whichisfurtherexacerbatedbyinadequateschools

and poor family support due to little appreciation of the benefits of education.All these factors

detrimentallyaffectchilddevelopment(Engleetal.,2011).

Stuntingandpovertyrepresentmultiplebiologicalandpsychosocialrisks.Stuntinginearlychildhood

iscausedbypoornutritionand infection rather thanbygeneticdifferences (Bhandarietal.,2002;

12

Dewey&Begum,2011).Earlychildhoodgrowthretardationandpovertyaregoodpredictorsofpoor

school achievement and cognition (Walker et al., 2005). Stunting at 24months was related to

cognitionat9years inPeruandat8 to11years in thePhilippines (Bhandarietal.,2002;Blacket

al.,2008).InJamaica,stuntingbefore24monthswasrelatedtocognitionandschoolachievementat

1718years(Shrimpton etal.,2001). InGuatemala,heightat36monthswasrelatedtocognition,

literacy, numeracy, and general knowledge in late adolescence, and stunting at 72months was

relatedtocognitionbetween2542years(Steinetal.,2008;Hoddinottetal.,2008).Glewweetal.in

the Philippine found that better nourished children perform significantly better in school, partly

becausetheyenterschoolearlierandthushavemoretimeto learnbutmostlybecauseofgreater

learningproductivityperyearofschooling (Glewweetal.2001;Olney,2007).Theirview isthat, in

addition to having direct health benefits, early childhood nutrition programs could also be an

instrument of education policy, emphasising the need to increase efforts to prevent childhood

growth retardation (Dewey&Begum,2011).Stuntingand lackofstimulationshouldbeaddressed

together for maximum effect, such as combining nutrition, responsive child feeding, and child

stimulationinterventions(Walkeretal.,2005;Mendez&Adair,1999;Johnstonetal.,1987).

Intelligence has been described as the best predictor of school achievement and significantly

explainedbymaternal intellectualquotient,bybrainvolumeandnutritionalstatusduring the first

year of life (Ivanovic et al., 2004a; 2004b). Studies have demonstrated a positive and significant

correlationbetweenheadcircumference,brainsizeand intelligence(Ivanovicetal.,2004a;2004b).

Thefirst2yearsoflifearetheperiodofmaximumbraingrowth,and70%ofadultbrainweighthas

been reached by the end of the first year.Head size at age 1 year has been considered a good

predictoroflaterintelligence(Ivanovicetal.,1989).

Irondeficiency, themostprevalentnutritionalproblem in theworld,also impactsonphysicaland

psychosocialdevelopment(Lozoff,2006a;2006b;2006c;Hovdenak&Haram,2012).Irondeficiency

affects neurotransmitters and other processes, such as myelination, dendritogenesis,

neurometabolism, and gene and protein profiles (Lozoff, 2011). Infantswith irondeficiency have

13

showed poorer functioning in the cognitive, affective, and motor domains (Engle et al., 2011).

Affectedinfantsaremorewary,hesitant,andeasilyfatiguedthanareinfantswithbetterironstatus

(Lukowski et al., 2010; Lozoff et al., 2006a). They alsodemonstrate affectivedifferences, such as

wariness, fearfulness,andunhappinessanddespite closer contactwith theirmothers,display less

positiveaffect,andarelessplayfulandattentive(Lukowskietal.,2010;Kazal,2002).Therelationship

betweenironanddevelopmentmaybedirect,throughaneffectonbrainfunctionandstructure,or

indirect,throughchangesinexploratorybehaviouroftheanaemicchild,whichsubsequentlyaffects

caregiverbehaviourand thequalityofparentchild interactions (Lozoffetal.,2006).Childrenwho

experiencebothanearlybiologicinsultandmoredisadvantagedbackgroundhavedoublejeopardy

ordoublehazard(Lozoff,2006b).

The negative effect of Iron deficiency on child development tends to be long lasting and these

effects seem irreversible (GranthamMcGregor&Ani,2001). Ina followup study fromCostaRica,

childrenwhohadbeen irondeficientas infantsscoredpersistentlypooreroncognitive testsup to

the age of 19 years, and these effects were greater in children from highrisk environments,

suggestingan interactionbetweenenvironmentorsocialstimulationand Irondeficiency(Lozoff,et

al.,2006c).InChile,neurophysiologicdifferenceshavebeenobservedthroughthepreschoolperiod,

andthe10yearfollowupsuggestingthatdifferencesstillpersist(Walteretal.,1989).Ontheother

hand,inThailandthepoorperformanceinThailanguageandmathematicstestsofchildrenwithlow

haemoglobin levelswas not reversed by iron supplementation (Sachdev et al., 2005). Even Iron

deficiencywithoutanaemiaaffects cognitionandmotordevelopment in childrenand adolescents

(Osendarpetal.,2010).Thesechildrenweremorelikelytohaverepeatedagrade,tohavereduced

arithmeticachievementandwrittenexpression,and toshowdifferences inmotor function,spatial

memory and selective recall. In addition, their behaviourwasmore likely to be characterized as

problematicbyparentsandteachers(Kazal,2002;Lukowskietal.,2010).Thepersistenceofnegative

outcomeshighlights theneed toprevent irondeficiency inearly infancyand to find interventions

that minimize the longterm effects of this widespread nutrient disorder (Lozoff, 2011). Iron

14

interventions alonewill not alleviate all disparities, nevertheless,micronutrient interventions for

children, including ironfortification,wereconsideredthemostcosteffectivesolution (Osendarpet

al.,2010).

Another importantconsequenceof irondeficiency isan increased riskofheavymetalpoisoning in

children. Irondeficient individualshavean increasedabsorptioncapacitythat isnotspecificto iron

(Osendarpetal.,2010).Absorptionofotherdivalentheavymetals, including toxicmetals suchas

lead and cadmium, is also increased. Prevention of iron deficiency, consequently, reduces the

numberofchildrensusceptibletoleadpoisoning.Suchpreventionmayalsohelptoreducetheirlead

burdenafterexposure tohigh levelsof lead frompaints,automobilepollutionorotherexcessive

exposuretoleadintheenvironment(Oppenheimer,2001;Osendarpetal.,2010).

With the increasing worldwide obesity prevalence, it has been evidenced that increased body

adiposetissue,particularlyvisceralfat,isassociatedwithincreasedriskofirondeficiency(Franchini

et al., 2010; CepedaLopez et al., 2011; Zimmermann et al., 2008). Cytokines increase hepcidin

synthesisresulting in increasedmacrophagesequestrationanddecreased intestinal ironabsorption

(Zafon et al., 2010; Coad& Conlon, 2011; Bekri, 2006).Hepcidin has been recognized as amain

hormonebehindanaemiaofchronicdisease(Aeberlietal.,2009).Hepcidinisproducedbytheliver

inresponsetoinflammatorystimuliandironoverload.Then,inflammationmayperpetuatetheiron

deficiencyofobesitybyhepcidinmediatedinhibitionofdietaryironabsorption.Serumhepcidinhas

beenfoundtobeelevatedinobesewomendespiteirondepletion,suggestingthatitisrespondingto

inflammationratherthan ironstatus(Singhetal.,2011;Franchinietal.,2010).Thecombinationof

Irondeficiency and obesity in vulnerable populations could bemore detrimental to health than

eitheroftheseconditionsbythemselves (CepedaLopezetal.,2011).Ashasbeenmentioned Iron

deficiencyislinkedwithimpairedcognitivefunctionandobeseindividualshavealsobeenshownto

havea relative intellectualdisadvantagewhencompared tononobese (Farretal.,2008;Yuetal.,

2009;Lietal.,2007;1995).OntheotherhandbothobesityandIronDeficiencyareassociatedwith

decreasedexercisecapacitywhichincreasesevenmoretherisks(CepedaLopezetal.,2011).

15

Tobaccoisclearlythehumandevelopmenttoxicantandteratogenwiththegreatestadverseimpact

ondevelopment(Rogers,2009;Tremblayetal.,2005).Despitedecadesofresearch,press,counter

advertising, and litigation regarding its adverse effects, an increasingnumberof teenage girls are

initiatingsmoking,andsmokingratesaredeclining lessrapidlyamongwomenthanamongmen,so

cigarette smoking remains common among women who are of childbearing age, pregnant or

breastfeeding (Ino,2010). Smokingparticularly impactspregnancies in youngerand lesseducated

women.Whileapproximately13%ofwomenreportedsmokingduringpregnancy,prevalencewasin

excessof20% inwomenwith less than12yearsofeducation inUSA (Rogers,2009; Okenetal.,

2008).

Eachcigarettesmokingduringpregnancyreducesflowfromtheuterustotheplacentacompromising

thedeliveryofoxygenandnutrients to the foetus.Carbonmonoxide incigarette smoke is rapidly

absorbedandbindstohaemoglobin,formingcarboxyhemoglobininbothmaternalandfoetalblood.

Carbonmonoxideexposureduringpregnancyhasbeenrepeatedlyandconsistentlyassociatedwith

decreasedbirthweightandpretermbirth.Cadmiummaybealsoimportant(Rogers,2009).Maternal

smokingreducestheweightandheightofnewborns(Kawakitaetal.,2008).Ithasbeenestimateda

birthweightdecrementof150>300ginoffspringofsmokingmothers(Okenetal.,2008;Meyer&

Comstock, 1972). Maternal smoking during pregnancy is the most common avoidable cause of

pretermbirth,intrauterinegrowthretardation,andperinatalmortalityintheWesternworld(Braillon

etal.,2010;Bruinetal2010;Higgins,2002).

Prenatalexposuretomaternalsmokinghasbeenshowntoadverselyaffectchildrensperformance

on intelligence and achievement tests, as well as performance in school (DiFranza et al., 2004;

Rogers, 2009). Numerous epidemiology studies support a relationship between developmental

tobacco smoke exposure and neurobehavioral effects including attention deficit hyperactivity

disorder, hyperaggressive behaviour, oppositional behaviour, conduct disorder, depression,

antisocial behaviour, delinquency in adolescence and criminality in adults (Pauly& Slotkin, 2008;

Rogers,2009;DiFranzaetal.,2004).Althoughotheragentswithintobaccoundoubtedlycontributeto

16

alterationsinbraindevelopment,itisquiteclearthatnicotinedoesproducelongtermalterationsin

brainandbehaviour(Dwyeretal.,2008;Pauly&Slotkin,2008).

Longitudinal studies, in theUSAandUKhavealsodemonstrateda significantnegativeassociation

between thenumbersof cigarettes smokeddailyby themotherwith the reachedheightof their

children(Kyuetal.,2009;Ronaetal.,1985;Berkeyetal.,1984).Cigarettesmokingadverselyaffects

endochondralossificationduringthecourseofskeletalgrowth(Kawakitaetal.,2008).Nicotineisone

oftheprimarycandidatecompoundsresponsibleforthecauseofsmokinginduceddelayedskeletal

growth(Kawakitaetal.,2008).Nicotineactsdirectlyonhumangrowthplatechondrocytesthrougha

specific receptorofnicotine,causingdelayed skeletalgrowth (Kyuetal.,2009).Maternal smoking

impacts not only skeletal growth but also is associatedwith decreased bone density and lower

mineralcontent (Godfreyetal2001;Adair&Guilkey1997;Jonesetal2003;Kyu2009).Cadmium,

presentinhighconcentrationshasspecificeffectsonosteoblastfunctionandontrophoblastcalcium

transport(Godfreyetal2001a;Jonesetal.,1999;2011).

Ontheotherhand,maternalsmokingduringpregnancyalsoseemstoincreasetheriskofobesityin

theoffspring.Themechanismsunderlyingtheseassociationsmayincludedevelopmentaladaptations

(Durmuetal.,2011;Okenetal.,2008;Ino,2010;Dubois&Girard,2006;Toschkeetal.,2002;Von

Kries,etal.,2002).Differentpossiblemechanismsmaybeconsideredtoexplainthedevelopmentof

obesityinoffspringofmotherswhosmoked.Oneofthemislowbirthweight,followedtorapidcatch

upweightgain,ademonstratedriskfactorforoverweightandthemetabolicsyndrome later in life

(Beyerleinetal.,2011;Herrmannetal2008;Kyuetal2009;Ino,2010;Bruinetal.,2010).Butthere

areanothertwopossiblemechanismsconsideredtoexplainthedevelopmentofobesityinoffspring

ofmotherswhosmoked.Oneinvolveshypothalamicfunctionandthesecondinvolvesabnormalities

infatcells(Ino,2010).Ithasbeenpostulatedthatfoetalnicotineexposuremayresult inpersistent

deficits in impulse control and possible decreased control of food consumption. Higher food

efficiencyafter intrauterinenicotineexposuremightbeanotherpossiblemechanism (Beyerleinet

al.,2011).Foetalexposuretonicotinemayleadtopermanentchangesinhypothalamicregulationof

17

food intakeandenergyexpenditure (Ino,2010).Studiesofcontemporarypopulationsalsosuggest

thatsmokeexposure inuterohas lifelongadversehealthconsequences in termsof adultobesity,

diabetes,hypertension,ischaemicheartdisease,cerebrovascularaccidents,obstructivelungdisease,

osteoporosisandotherchronicdiseases(Harveyetal2007;Blakeetal2000;Montgomery&Ekbom

2002;Beyerleinetal2011,Higgins2002).Animalstudiesindicatethatadverseeffectsarenotlimited

to the first generation but have trans generational consequences (Bruin et al 2010). In countries

undergoing theepidemiologic transition, thecontinuing increase in smokingamongyoungwomen

could contribute to spiralling increases in rates of obesityrelated health outcomes in the 21st

century(Okenetal.,2008).

The rapid increase in the incidence of chronic noncommunicable diseases cannot be explained

exclusivelybygeneticandadult lifestyle factors. Epidemiologicevidencehasshown thatearlylife

conditions influence patterns of growth, body composition, and later risk of noncommunicable

chronicdiseases(Uauy,Kain,&Corvalan,2011;Victoraet.,2008;Lillycrop,2011;Barker,2008;Fisher

etal.,2006).

Theorganismsadapt to theirenvironmentduring their lifecourse.Suchprocessesallowgenotypic

variation to be preserved through transient environmental changes (Painter et al., 2005). Adult

phenotypedependsonenvironmentalsignalsoperatingduringintrauterinedevelopmentandduring

earlypostnatal life (Gluckmanetal.,2005).Epigeneticmechanismsallow thedeveloping foetus to

adapt to nutritional cues from themother and adjust its developmental trajectory to produce a

phenotypematchedtothepredictedpostnatalenvironment (Gluckmanetal.,2005).Thesealtered

epigeneticmarksarestablymaintainedthroughoutthe lifecourse (Lillycrop,2011).Changes inthe

intrauterineavailabilityofnutrients,oxygen,andhormonesprogramtissuedevelopmentandleadto

abnormalitiesinadultmetabolicfunction(Fowdenetal.,2006).Theprocessbywhichearlyinsultsat

criticalstagesofdevelopment leadtopermanentchanges intissuestructureandfunction isknown

as intrauterine programming (Gluckman et al., 2008;Wu& Chen, 2009; . Burdge et al., 2007).

18

Intrauterineprogrammingmayinvolvestructuralandfunctionalchangesingenes,cells,tissues,and

evenwholeorgans(Fowdenetal.,2006).

Thechanges inducedbymaternalunderorovernutritionmayreflectanadaptiveresponseofthe

foetustoenvironmentalcues.Itallowsanorganismtoadjustitsmetabolismandphysiologyinorder

tobebetteradapted to the futureenvironment (Gluckmanetal.,2007).However, if theoffspring

doesnotpredict correctly the environmentexperienced afterbirth, then it is at increased riskof

developing cardiovascular and metabolic disease (Burdge et al., 2007). Poor maternal nutrition

possiblywillsignaltothe foetusthatnutrientsarescarceandanuncertain lifecourse liesahead

(Lillycrop,2011).Thefoetusmaythenadaptitsmetabolismtoconserveenergydemands,increaseits

propensity to store fat, accelerate puberty and invest less in bone and musclemass. If in the

postnatalenvironmentnutritionisindeedpoor,thentheorganismsmetabolismwillbematchedto

theenvironmentand that individualwouldbeof lowdiseaserisk (Lillycrop,2011).However, ifthe

offspringdoesnotpredictcorrectlytheenvironmentexperiencedafterbirth,then it isat increased

riskofdevelopingmetabolicdisease (Gluckmanetal.,2007).Thismismatchpathwaymayexplain

whyanutritionalconstraint inearly lifefollowedbyanadequateornutritionallyrichpostnataldiet

willresult inan increasedriskofmetabolicdisease in later life.Thiswouldalsoexplainwhyhuman

populations undergoing socioeconomic change or migration from rural to urban areas show

increasedriskofchronicdisease(Gluckmanetal.,2007;Gluckman&Hanson,2005b;2005b).

Bothhigherbirthweightandfasterinfantgrowthareassociatedwithchildhoodobesitywithlifelong

adverse consequences (Baird et al., 2005b). Low birthweight, has been linked to hypertension,

ischemic heart disease, glucose intolerance, insulin resistance, type 2 diabetes, hyperlipidemia,

hypercortisolemia,obesity,obstructivepulmonarydisease,and reproductivedisorders in theadult

(Fowdenetal.,2006;Wu&Chen,2009).Thepredispositiontoadultdiseaseconferredbylowbirth

weight may therefore be related to excess fat deposition, in particular central fat, and the

developmentofinsulinresistance(Ong&Dunger,2004;Ong&Loos,2006).Longitudinalgrowthdata

insubjectsfromFinlandwhowentontodeveloptype2diabetesinadultlifeshowedthatbothlarger

19

andsmallerbirthweightpatternsareassociatedwithincreaseddiseaserisk(Erikssonetal.,2003).At

thehighestbirthweight,theriskofdiseaseagainincreased,resultinginaUorJshapedrelationship

between birthweight and later disease risk (Lillycrop, 2011; Pneau et al., 2011;Ong&Dunger,

2004).Thehighestbirthweight increases the riskofdiabetes (Erikssonetal.,2003),breastcancer

(Gluckmanetal.,2007)andobesity(Erikssonetal.,2003;RollandCachera&Pneau,2011;Stettler

&Iotova,2010;Bairdelal.,2005;Huietal.2008;Curhanetal.,1996).

Reduced birth weight is not a necessary a prerequisite for programming during foetal life. The

evidenceindicatesthatbirthweightpersehasalowsensitivitytoassesstheprenatalenvironment;

it serves to capture only rather extreme deprivations (Uauy etal., 2011;Gluckman et al., 2005;

Stettler&Iotova,2010).StudiesofthefaminethatoccurredintheNetherlandsduringthewinterof

1944have shown that individualswhosemotherswereexposedpreconceptional and in the first

trimesterofpregnancydidnothavereducedbirthweightscomparedtounexposed individuals,but

did as adults exhibit an increased risk of obesity and cardiovascular disease.On the other hand

individualswhosemotherswereexposed inthe laterstagesofgestationhadreducedbirthweights

and showed an increased incidence of insulin resistance and hypertension (Painter et al., 2005;

Ravelli,1976).Thesefindingsshowthatmaternaldietduringgestationcanhaveprofoundeffectson

health in later life,evenwhen thedietary insultwasof shortdurationandhadnoeffectonbirth

weight. The timing of the nutritional insult determineswhich organ system is affected (Lillycrop,

2011;Painteretal.,2005;Ravellietal.,1976).

Theriskoflaterdiseaseoccursnotonlyinthefoetalperiodbutalsoduringearlystagesofembryonic

lifeaswellasininfancyduringsuckling(Gluckmanetal.,2007;Harveyetal.,2007).Thefindingthat,

thecombinationoflowerbirthweightandsubsequentoverweightisrelatedtolaterdiseaserisk,has

shownthatpostnatalenvironmentalparticularlybeforeweaning,mayameliorateorexaggeratethe

morphologicaland functional changesprogrammed inutero (Fowdenetal.,2006;Ong&Dunger,

2004;Dungeretal.,2007).Thepossibilityofprogrammingduringinfancy,arelativelyshortperiod,

highlight the importanceofprotective factors such asbreastfeeding to reduce theeffectof risks.

20

Breastfeedingpresentsclearshorttermbenefitsforchildhealth,mainlyprotectionagainstmorbidity

andmortality from infectiousdiseases.On theotherhand, there issomecontroversyon the long

term consequences of breastfeeding. Whereas some studies reported that breastfed subjects

presentahigherlevelofschoolachievementandperformanceinintelligencetests,aswellaslower

bloodpressure, lowertotalcholesterolanda lowerprevalenceofoverweightandobesity(Hortaet

al.,2007),othershavefailedtodetectsuchassociations(Ochoaetal.,2007).Breastfeedingseemsto

haveasmallbutconsistentprotectiveeffectagainstobesityinchildren(Arenzetal.,2004;Lietal.,

2007)Earlybottlefeedingacceleratesthecatchupgrowthphaseoflowerbirthweightinfantsduring

the first years of life (Ino, 2010; Owen et al., 2005; Horta et al., 2007; Harder, Bergmann,

Kallischnigg,&Plagemann,2005).Althoughearlychildhoodobesity isonlymoderatelypredictiveof

laterobesity,the increase inexcessiveweightamongtoddlers is likelytoresult inworseningofthe

obesityepidemicoverthecomingdecades.(NStettler,2007).

21

Objectives,methodologyandcontributiontoknowledge

Theaimof thisThesis is to identify linkagesbetween stunting,overweightandchilddevelopment

impairmentaswellastoexaminetheirevolutioninthelasttenyearsinUruguay.

ThepresentThesisincludesthreeresearchpaperspublishedorsubmittedbythedoctoralcandidate

topeerreviewscientificjournals.

Annex1:Stunting,overweightandchilddevelopmentimpairmentgohandinhandaskeyproblems

ofearly infancy:UruguayancaseBove I,MirandaT,CampoyC,UauyR,NapolM..EarlyHumDev.

2012Sep;88(9):74751.Epub2012May5.PubMedPMID:22560815.

Annex2:Trends inearlygrowth indices (stuntingandoverweight) in the first24monthsof life in

Uruguayoverthepastdecade.SubmittedtoHealth,PopulationandNutritionJournal.September9,

2012.Inreview

Annex3:Smokingduringpregnancy:ariskfactorforstunting,anaemiaandoverweight in infancy?

SubmittedtoMaternalandChildNutritionJournal.August8,2012.Inreview

Table1summarizesthemainobjectives,methodologyandcontributiontoknowledgeofthisThesis.

22

Table1Objectives,methodologyandcontributiontoknowledgeofthisThesis.

Annex1:Stunting,overweightandchilddevelopmentimpairmentgohandinhandaskeyproblemsofearlyinfancy:Uruguayancase

Annex2:Trendsinearlygrowthindices(stuntingandoverweight)inthefirst24monthsoflifeinUruguayoverthepastdecade

Annex3:Smokingduringpregnancy:ariskfactorforstunting,anaemiaandoverweightininfancy?

Objectives Toidentifylinkagesandfactorsthatmaysimultaneouslycontributetostunting,overweightandchilddevelopmentimpairment.

Toexaminetrendsofoverweightandstuntingamonginfants0to23monthsoverthepastdecade(19992011)inUruguay.

Tostudyassociationofactivematernalsmokingduringpregnancyforstunting,anaemiaandoverweightininfantslessthan24months.

Subjects Thesamplesizewas2,069householdswherelivedpregnantwomenandchildren

23

belowagerange. surveywasapprovedbytheethicscommitteeofMSP.

Dataanalysis Descriptivestatistics,StudentsttestandChisquare.MultiplelogisticregressionforsimultaneousassesstherelationshipbetweenLBW,macrosomia,reducedheadcircumference,stunting,overweightandchilddevelopmentimpairment.Confounderfactors:age,gender,prematurity,SGA,feedingpractices,socioeconomicconditions,smoking,overweight,statureandbreedingpatternsassingsongs,playortellstories.ThedataanalyseswereperformedusingSPSS15.0.

Dependentvariables:overweightandstunting.Independentvariable:yearofthestudy.Birthweight,age,gender,breastfeedingduration,rapidweightgainandsocioeconomiclevelwereconsideredaspotentialconfounders.Descriptivestatistics,Studentsttest,Chisquare,linearandbinarylogisticregressionanalysis.Statisticalsignificancelevelwasdefinedby()

24

Resultsandconclusion

ThemainresultsofthepresentThesiscanbesummarizedinthefollowingconclusions:

1. Considering the demographic, social and economic characteristics of Uruguay child

developmentimpairment,stuntingaswellasoverweightratesremainexcessivelyhigh.

2. Stuntingandchilddevelopment impairmentare linkedto lowbirthweightandmacrosomia

tooverweight.Publicpolicyshouldbefocusedonthehealthandwellbeingofyoungwomen.

3. Highprevalenceandcloseassociationstuntingwithoverweightduringthefirsttwoyearsof

life show that is necessary rethink new measures to improve linear growth while preventing

excessiveweightgaininearlylife.

4. Smoking,deficientqualityofmaternalcare,povertyandpoornutritionareassociatedwith

stunting, psychosocial development impairment, anaemia aswell as being overweight. The close

linkages and the complexity of these problems require to be considered in the designing of

integratedandcoordinatedcommunitystrategies.

Table2summarizesthemainresultsandconclusionsofthisThesis.

25

Table2Mainresultsandconclusion

Conclusion Annex Mainresults

a)Consideringthedemographic,socialandeconomiccharacteristicsofUruguaychilddevelopmentimpairment,stuntingaswellasoverweightratesremainexcessivelyhigh.

Annex1,Table1

a) Prevalenceinchildren2SD)14.9%(13.7%16.9%);Boys16.3%andGirls13.4%,P=0.03

Childdevelopmentimpairment(nonacquisitionofmilestonesexpectedinthebelowagerange)10.3%(8.9%11.7%);Boys13.1%andGirls7.6%,P

26

growthwhilepreventingoverweightinearlylife.

d)Smoking,deficientqualityofmaternalcare,povertyandpoornutritionareassociatedwithstunting,psicosocialdevelopmentimpairment,anaemiaaswellasbeingoverweight.Thecloselinkagesandthecomplexityoftheseproblemsrequiretobeconsideredinthedesigningofintegratedandcoordinatedcommunitystrategies.

Annex1,Table2andFigure1

a) LawbirthweightwasariskofstuntingOR:3.2(1.85.6)andreducedheadcircumferencegrowthOR:3.9(1.98.0);InfantswithreducedheadcircumferencehadanincreasedchanceofdelayedpsychomotordevelopmentOR:2.4(1.25.1)andofbeingstuntedOR:3.2(1.76.3);StuntedinfantswereatincreasedriskofbeingoverweightOR:2.4(1.63.5)

b) HouseholdpovertyincreasedprobabilityofbeingstuntedOR:1.5(1.012.1)aswellaschilddevelopmentimpairmentOR:1.7(1.22.4)

c) MaternalsmokingwasariskfactorofchilddevelopmentimpairmentOR:1.5(1.12.1)aswellasofbeingoverweightOR:1.3(1.11.7)

d) WhenmotherdidnotusetosingsongsdoubledprobabilityofchilddevelopmentimpairmentOR:2.0(1.42.8)

27

Discussion

Inspiteofbeingastrongsenseofcivicresponsibilityandcommitmenttodemocracy,withthemost

equitabledistributionofincomeinLatinAmerica,theresultsofthisThesissuggestthatUruguayneeds

torethinknewstrategiestoimprovephysicalgrowthandpsicosocialdevelopmentinearlyinfancyfor

optimalhealthandwellbeingthroughthelifecourse.

Themain limitation of this Thesis is the fact that,we analyse cross sectional datawith only one

measureperchild,soweonlycoulddescribeassociationandnottoestablishcausalrelationship.The

strengthof this study is the robust samples sizes analysed aswell as that children included in the

analysiswerefromdifferentsocioeconomicUruguayanfamilies.

In the present Thesiswe confirm that underweight (lowweightforage)was not a problem 1.2%

(0.4%1.4%)butstunting(lowheightforage)8.0%(6.8%9.2%),suboptimalheadcircumference3.5%

(2.7% 4.3%), childdevelopment impairment10.3% (8.9% 11.7%)andoverweight14.9% (13.7%

16.9%)ratesamongpreschoolchildrenremainupperthanexpectedinacontextasUruguay.

Despite robust incomegrowthsand importantdecreases inpovertymentioned in the first chapter,

stunting prevalence fell only 2.7% in the last decade. Stunting prevalence (

28

reducedheadcircumferencewereespeciallyprevalentinUruguayansinfantslessthan12months,and

persisted only in children living in poor families.On the other hand, the discrepancy between the

currentdevelopmentallevelsandwhattheywouldhaveachievedincreasedwithage,especiallyinthe

poorestchildrenashasbeenreportedbymanystudies(GranthamMcGregoretal.,2007a;Mendez&

Adair,1999;Johnstonetal.1987).

Stuntingwasclosedassociatedwithheadcircumferencebelow2SD(HCZ,OMS)andsimultaneously

reducedheadcircumferencewasthemainpredictorfactorofpoorchilddevelopment.Ivanovic,etal.

reported thatvariations inbrain sizeestimated indirectlybymeasuringhead circumference, is the

mostrelevantphysicalindexassociatedwithintellectualabilityinschoolagechildren(Ivanovicetal.,

2000;2004).Severalcommunicationshavedescribedthatheadcircumferenceinthefirstyearoflife

may predict later intelligence (Vernon et al., 2000; Martyn et al., 1996; Botting et al., 1998;

Thompson&Nelson,2001). InthepresentThesis8%of infants lessthan12monthsevidenced low

headcircumference.

Manystudieshavenotedcoexistingstuntingandpoorschoolprogress.Astudycarriedout inPublic

School System inUruguay showed that11.6% (8.714.2)of childrenwho repeated first gradewere

stunted;thisratefellto3.2%(2.63.9)onfirsttimeenrolledchildren(Amarante,Arim,Severi,Vigorito

& Aldabe, 2007). Stunted children, compared with nonstunted, were less likely to attain lower

achievementlevelsfortheirageandhavepoorercognitiveability(GranthamMcGregoretal.,2007a;

DeOnisetal.,2011;Victoraetal.,2008;Dewey&Begum,2011).

As has been reported by other authors, our results showed that boys weremore vulnerable to

postponedpsychosocialdevelopmentcomparedwithgirls (Lundgren&Tuvemo,2008;Linnetetal.,

2003; Johnstonetal.,1987;Bedregaletal.,2010). Male studentsofpovertyareas inUruguayare

thosewiththepooresteducationalperformanceandthegreatestbehaviouralproblems(Kaztman &

Filgueira,2006).Poorchildrenhavedecreasedattentionandmemory,poorlearningskillsespeciallyin

29

languageaswellastheyarelessabletotoleratestress(Farahetal.,2006;Lebeletal.,2012;Nobleet

al.,2005;Caseyetal.,2000;Johnstonetal.,1987).Simultaneouslymotherslivinginpovertycondition

have demonstratedmore likely to exhibit socio emotional andmental disturbances and children

receive lessstimulation(Hackman&Farah,2009).InthepresentThesischildrenofmotherswhonot

usuallysingsongstothemorwhosmokeddemonstratedpoorerdevelopment.Thesetwoapproaches

probablysynthesizedthequalityofcare intheenvironmentsurroundingthechild.Additionally ithas

been recognized that nicotine impacts in the brain at critical developmental stages and cause

cognitive,emotionalandbehaviouralproblems(Rogers,2009;Okenetal.,2008;DiFranzaetal.,2004;

Dwyeretal.,2008;Pauly&Slotkin,2008).

Our results also confirm the association between smoking exposure in utero with stunting and

anaemia in early infancy (Mishra& Retherford 2007;Godfrey 2001).Anaemia continues being the

mostcommonnutritionaldisorderinUruguayaffectingapproximately28%to34%ofinfantfrom6to

23months (Bove&Cerruti,2011).Anaemia isassociatedwithpoorerdevelopment, lowercognitive

function and educational achievement in children. The negative effect of anaemia on child

developmenttendstobe long lasting(Lozoffetal.,2006a;2006b;2011;GranthamMcGregor&Ani,

2001;Beard,2003;Lozoff&Georgieff,2006;Walter,DeAndraca,Chadud,&Perales,1989;Lukowski

etal.,2010;Lozoff,Beard,etal.,2006;Kazal,2002;Osendarpetal.,2010).

As has been evidenced in many epidemiologic studies we could also notice maternal smoking

associatedwithbeingoverweight inoffspring lessthan60months(Toschkeetal.,2002; DiFranzaet

al.,2004;Baxteretal.,2010;Morleyetal,1995;Okenetal.,2008;Durmuetal.,2011;Dubois&

Girard,2006).Wecouldntobservesmokingexposure inuteroassociatedwithoverweight in infants

from0 to23monthsprobablydue to theveryyoungage.Howeverweobserved thatdespitehave

beensmalleratbirth,tobaccoexposureinfantsat12monthsequalledprevalenceofoverweightthan

nonexposure. Foetal growth retardation and subsequent catchup growth may be the major

mechanismunderlyingtheassociationbetweenmaternalsmokingandoffspringsobesity(Okenetal.,

30

2008;Owenetal.,2005;Bairdetal.,2005a;Monasta,2010;Beyerleinetal.,2011).Howeverstudies

over the past years suggest that this is not the only causal pathway (Oken 2005; Higgins, 2002;

DiFranzaetal.,2004). Intrauterinetobaccoexposure infantssufferadaptations leadingtochanges in

bodycomposition,aswellasmodifytheirfoodintakebehaviour(Okenetal.,2008;Beyerlein2011;Ino

2010;Durmu2011;Roger,2009;Tremblayetal.,2005; Ino,2010).Consequentlyefforts toprevent

smokingshouldbeacornerstoneinpromotinghealthychildgrowthanddevelopment.

InthepresentThesis,theprobabilityofbeingoverweightinstuntedinfantsalmosttripled,indicating

therecognizebondbetweenpovertyandobesityaswellasthedoubleburdeninthesocial,economic,

andhealthcare systems (Popkin&GordonLarsen,2004;Caballero,2001;Sawaya&Roberts,2003;

Uauyetal.,2001;2008).Sawayahasrevealedthatstuntingcausesaseriesofchangessuchas lower

energy expenditure, higher susceptibility to the effects of highfat diets, lower fat oxidation, and

impairedregulationoffoodintakethatmightexplainthissusceptibility(Sawaya,2003).

Thisstudyalsoshowedsignificantassociationbetweenobesemothersandobesechildren(Ino,2010;

Monasta,2010;RollandCachera&Pneau,2011;Stettler&Iotova,2010;Bairdelal.,2005;Huietal.

2008;Erikssonetal.,2003;Ino,2010;Corvalnetal.,2009;Kainetal.,2009).Humanobesityiscaused

byacomplexinterplayofgenesandenvironmentanddefinitelyparentsprovideboth(Owenetal.,

2005). In the present Thesis maternal waist > 88cm almost doubled macrosomia likelihood and

evidencesuggeststhatovernutritioninfoetallifecandirectlycontributetoanintergenerationalcycle

ofobesity (McMillen et al.,2008;Monasta et al.,2010;Dubois&Girard,2006;Chen et al.,2012).

Behaviouralfactorsinteractingwithgeneticpredispositionscanproducepatternsoffoodpreferences,

foodconsumption,andphysicalactivitythatcanpromotechildhoodobesityinsusceptibleindividuals

(Owenetal.,2005;Elksetal.,2012;Parsonsetal.,1999).Bray said thata childsgeneticmakeup

loadsthegunwhiletheirenvironmentpullsthetrigger(BrayG.citedbyLobsteinetal.,2004).

31

Foetalgrowthisanimportantdeterminantoffuturehealthanddevelopment(Guilloteauetal.,2009;

Ong&Dunger,2004;Gluckman&Hanson,2004;McMillenetal.,2008;Gluckman,etal.2007;Burdge,

Hansonetal.,2007;Ross&Desai,2005;Uauyetal.,2011;Fowdenetal.,2006;Gluckmanetal.,2005;

Monastaetal.,2010). In thepresentThesis lowbirthweight (LBW)hasbeenassociatedwithbeing

stunted,reducedheadcircumferenceandpoorpsychomotordevelopmentaswellasmacrosomiawith

beingoverweightinpreschoolchildren.Bothlargerandsmallerbirthweightcanincreaseconsiderable

risks along life span. Low birth weight has been linked to hypertension, ischemic heart disease,

glucose intolerance, insulin resistance, type2diabetes,hyperlipidaemia,hypercortisolemia,obesity,

obstructivepulmonarydisease,andreproductivedisorders in theadult (Fowdenetal.,2006; Wu&

Chen,2009;Ong&Dunger,2004a;Lillycrop,2011;Pneauetal.,2011;C.Li,Goranetal.,2007).On

theotherhand thehighestbirthweight increases the riskofdiabetes (Erikssonetal.,2003),breast

cancer (Gluckmanetal.,2007)andobesity (Erikssonetal.,2003;RollandCachera&Pneau,2011;

Stettler&Iotova,2010;Bairdelal.,2005;Huietal.2008;Curhanetal.,1996).

Nochanges inLBWprevalence8.3% (7.88.8%)ormacrosomia6.3% (5.96.7%)wereobservedover

the lastdecades inUruguay (MSP,2011).LBWhasremainedexcessivelyhighcomparedwithothers

countries as Chile, Costa Rica and Cuba (Kramer et al., 2005; Rosero, 1997; Prendes ,2001).

Interventions toprevent LBWandprematurityhavehadonlymodest success (Krameretal.,2005)

However,maybe some strategieswithdemonstratedeffectiveness couldbenecessary to rethink in

Uruguay. We identified small size at birth linked with maternal condition as smoking during

pregnancy,shortstature(

32

McMillenetal.,2008;Ahlssonetal.,2007) including intensivecounsellingand treatment to reduce

cigarette smokinghave tobegivenpriority (DiFranza,etal.,2004; Filionetal.,2011;Baxteretal.,

2010;McEwenetal.,2006). Betterqualityofprenatalhealthcareservices, (Smaill ,2002; Johnson,

2012;Wilkinson&McIntyre,2012;Panthongviriyakuletal.,2012;Krishnanet al.,2012),decreasing

anaemiarates(Hovdenak&Haram,2012;Coad&Conlon,2011;McLeanetal.,2009)andperhapsfish

oilsupplementationmaypossiblybealsorequired(Larqu,etal.,2012;Galvnetal.,2012;Glaseret

al.,2011).

Ontheotherhandthemostcommongrowthpatternrelatedtolaterdiseaseriskisthecombinationof

lowerbirthweightsandsubsequentlybecomingoverweightorobeseeitherduringchildhoodoradult

life (Hales&Barker,2001;Ong&Dunger,2004a;Gluckmanetal,2005;Lietal.,2007). Infantswho

havebeengrowthrestrainedinutero,tendtogainweightorcatchupmorerapidlyduringtheearly

post natal period, which leads to increased central fat deposition and greater insulin resistance

(Monastaet al2010;Dubois&Girard2006;Okenetal2005; Ino2010;RollandCachera&Pneau

2011;Rogers2009;FabriciusBjerreetal.,2011;Guilloteauetal.,2009;Wu&Chen,2009;Lillycrop,

2011a;Wu&Chen,2009;Burdge,Hansonetal.,2007;Monteiro&Victora,2005).

Thefindingthat,thecombinationoflowerbirthweightandsubsequentoverweightisrelated

to laterdiseaseriskhasrevealed thatpostnatalenvironmentmayameliorateorexaggerate

themorphologicalandfunctionalchangesprogrammedinutero(Fowdenetal.,2006;Ong&

Dunger, 2004b;Dunger&Ong, 2007;Gage et al., 2011). Early infancy constitutes a critical

period for theonsetofoverweight, consequentlypreventionofexcessweightgain, should

beginevenfrombirth(Bissetetal.,2012;Pneauetal.,2011;Ino,2010;Bairdetal.,2005b;

Huietal.,2008;Gageetal.,2011;Ong&Loos,2006).InthepresentThesisinfantsfrom6to

23months showed almost twofold increase in the chance of overweight than infants

33

under 6 months (Bove & Cerruti, 2007; 2011) and emphasizes the relevance of

complementary feedingpractices(RollandCachera&Pneau,2011;Stettler& Iotova,2010;

Toschkeetal.,2004;Ong&Dunger,2004a;Stettler,2007;Bairdetal.,2005b).Breastfeeding

seems to have a small but consistent protective effect against obesity (Arenz et al., 2004;

Hortaetal.,2007;C.Lietal.,2007;Harderetal.,2005;Koletzkoetal.,2009;Huietal.,2008;

Stettler & Iotova, 2010). In order to improve linear growth and at the same time to address

measurestoavoidexcessiveweightgain,seems likeUruguayshouldcontinueencouragingexclusive

breastfeedingparticularly in LBWand smokersoffspringaswellas improving complementary food

practices(Uauyetal.,2008).Governmentshouldalsoconsiderthebeststrategiestoassureadequate

intakesofironandzincininfantsfrom6to24months.

Overweightinchildren0to60months14.9%(13.7%16.9%)wasupperthanBuenosAires,Argentina

11.3 (9.713.2) (Durn et al. 2009),but similar toChile (Kain et al.,2009).Both countries showed

significantlyhigheroverweightrateinboysthangirls(Boys:16.3%and17.5%;Girls13.4%and12.5%

inChileandUruguayrespectively).Chiledeclinedstuntingfrom10%in1985to2%in1998butinthe

sameperiodnearlydoubledobesity inpreschool children (Stanojevicetal.,2007; Corvaln etal.,

2009) The prevalence of obesity in 6yearold Chilean children has almost tripled in the past two

decades,from7.0% in1987to19.4% in2006(Kainetal.,2009).The lastreported(2004)Uruguayan

obesity rate7.9% (6.1 to9.6%)was similar than1987Chilean rate.So,ashasbeen recognizedby

RicardoUauyitshouldsignaltheroadaheadforothercountries(Uauy,etal.,2001).

In conclusion, the present Thesis showed that risk factors in early infancy are likely to cooccur,

emphasising the importance of integrated interventions involving the simultaneous reduction of

multiplerisks.Stunting,beingoverweightandpoorchilddevelopmentcoexistinthesameinfantsand

predicteachother.Therelevanceoftheseproblemsindefiningshortandlongtermhealthaswellas

educationalperformanceandlabourproductivityhasbeenenoughdemonstrated(Walkeretal.,2011;

34

Victoraetal.,2008;Blacketal.,2008;Dewey&Begum,2011;Engleetal.,2011;Ongetal.,2000;Baird

etal.,2005;Stettler&Iotova,2010;Uauy&Kain,2002;Gluckman,etal.,2005;Okenetal.,2008).

Moreofthesameisnotenough:wemustchangetrendsandpresentconditions,ratherthansimply

perpetuate them (Victoraetal.,2003). It isnecessary to scaleup interventions in the timeof the

greatestpotential for lifelong effect: during periconceptionperiod and early yearsof life the the

windowopportunity(Victoraetal.,2010;Guilloteauetal.,2009;Uauy,etal.,2011;Dewey&Begum,

2011).Weconsider inUruguay it isnecessarymorepersuasivedata foradvocacy; healthandsocial

workerscommittedandpolicymakersconvincedthatearlyinterventionaremoreeffectivetoprevent

inequalitythanlater.

35

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