do postnatal iron deficiency or maternal risk factors affect...

Dopostnatalirondeficiencyormaternalriskfactorsaffectcogni6vedevelopmentininfantsbornmoderate‐to‐latepreterm?

Infantsbornmoderate‐to‐latepreterm(32‐36weeksgesta6on)arenotcloselyfolloweda/erhospitaldischargeandhaveagreaterriskfordevelopingirondeficiencyandneurodevelopmentaldelays.Individualdifferencesinprenatalriskandneonatalriskfactorsmayimpactlong‐termcogni=veoutcomesinthesechildren.

Oneindividualdifferencethatlikelyimpactscogni=vedevelopmentininfantsbornmoderate‐to‐latepretermispostnatalironlevels.Irondeficiencyisacommonmicronutrientdeficiencythatcancausealteredcogni6vedevelopmentinchildrenifnottreated(ThorisdoBr,GunnarsdoBr,Palsson,Gretarsson,ThorsdoB,2013).Ironisessen=alforneurodevelopmentalprocessessuchasmyelina=on,neurotransmiKerproduc=on,anddevelopmentofthehippocampus;thusinfantscouldsufferfrommemoryproblemsasaresultoflowironlevels(Georgieff,2011).Maternalriskfactorsduringpregnancy,suchaspre‐eclampsiaandHELLPsyndrome,bothcharacterizedbyhypertension,havealsobeenassociatedwithlowerperformancebyinfantsinvariouscogni6vetasks(Kronenberg,Raz,andSander,2006).

Fewstudieshavebeendonespecificallywithmoderate‐to‐latepreterminfantsandriskfactorsthatcouldaffecttheircogni=vedevelopment.Basedonpreviousstudies,wehypothesizedthatinfantsbornmoderate‐to‐latepretermwouldperformmorepoorlyonmeasuresofinfantmemoryandgeneralcogni=vedevelopment,andthatindividualdifferencesinmaternalriskfactorhistory(presenceofhypertension)andpostnatalironlevels(hemoglobin)wouldalsopredictinfant’sperformance.

ThisresearchwassupportedbyaUniversityofMinnesotaGraduateSchoolFellowship(Hodel),DoctoralDisserta6onFellowship(Hodel),andUndergraduateResearchOpportuni6esProgramGrant(Sasson)andbytheNIHunderaRuthL.KircshteinNa6onalResearchServiceAward(T32HD007151)fromtheNICHD.Addi6onalsupportwasprovidedbytheUniversityofMinnesota’sIns6tuteofChildDevelopment,CenterforNeurobehavioralDevelopment,andGraduateStudentsoftheCollegeofEduca6onandHumanDevelopment.Theauthorsthankthefamiliesofthepar6cipantsandmembersofKathleenM.Thomas’Cogni6veDevelopment&NeuroimagingLab.

Ba]eryofprefrontal‐dependenttasksfor9‐montholdinfants

IronLevels:PTandFTinfantsdidnotdifferinHgBlevelsbetween9‐12monthsofage.

Bayley:PTandFTinfantsdidnotdifferonanyoftheBayleysubscales.

Habitua6onTask:Ofthosewhosuccessfullyhabituated,bothPTandFTgroupsshowedanoveltypreferenceattest(p<.01),althoughthiseffectwasreducedinPTchildren(p<.04)andwasrelatedtogesta=onalageatbirthacrosstheen=resample.

Full‐TermChildren(n=74) PretermChildren(n=70)

AgeatTestΜ=9.10months Μ=10.21months

(9.00monthsadjustedage)

Sex 36female,38male 33female,37male

Gesta,onalAge

Μ=39.84weeksrange=37.43–42.71weeks

Μ=35.34weeksrange=32.00–36.86weeks

NICU/SCNstay?

9.5%ofsample(<24hours) 68.6%ofsample

9‐12MonthHemoglobin

M=11.77mg/dLrange=10.1‐13.9mg/dL

M=11.78mg/dLrange=8.7‐13.5mg/dL

MaternalHypertension

0% 11.4%

Infantsbornmoderate‐to‐latepretermshowsubtlealtera6onsinworkingmemoryat9‐monthscorrectedage.Bothprenatal(maternalhypertension)andpostnatal(lowiron)riskfactorsalsoinfluenceinfants’earlycogni6vedevelopment.

ADDITIONALMEASURESMEDICALRECORDABSTRACTION

BAYLEYSCALESOFINFANTDEVELOPMENT

(Bayley,2006)

WorkingMemoryHABITUATIONTASK

• Cogni-onisassessedbyexamininghowinfantsreactandlearnabouttheirsurroundings• Languageisassessedbymeasuringtherecogni=onofsoundsandobjectsandproduc=onofspeechsoundsandgestures• Motorskillsmeasuredincludebothfine(e.g.infant’sgrasp)andgrossskills(e.g.crawling)

• Parentsconsentedtoreleasetheirchild’sbirthhospitaliza=on,well‐babycheckrecords,andanyiron‐relatedlabs

• Allrecordswereabstractedforgesta-onalageandpregnancyandbirth‐relatedriskfactors;hemoglobinlabsatbirthandbetween9‐12monthsofagewerecollected

• Infantdriven,slidingwindowdesignusingNimS=mfacials=muli(basedonMarkantetal.,2014)

• Noveltydetec=onanddishabitua=onareprefrontaldependentinyounginfants(Nakanoetal.,2008)

AKen=ongeKers=mulus(variabledura=on)

Eyemovementstrackedandcodedonline

Testphase–sixtrialsofnovelandfamiliars=muluswithonefacepertrial

• Completeinfanttaskba=eryalsoincludeseye‐trackingmeasuresofreversallearning,processingspeed,andbehavioralmeasuresofinhibitorycontrol(AnotBtask)andproblemsolving

• Completeparentques-onnaireba=eryalsoincludesparent‐reportmeasuresofparentaldepressionandlifestress,paren=ngstyles,infanttemperament,andinfantsleepandfeedingpaKerns

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NoveltyPreferenceatTest

(Novel‐FamiliarLoo

kDura6

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Gesta6onalAgeatBirth(inweeks)

Gesta6onalAgeatBirthPredictsMagnitudeofNoveltyPreference

r=.21,p<.03

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NoveltyPreferenceatTest

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kDura6

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PretermInfantsDemonstratedaSmallerNoveltyPrefenceatTest

Faces=mulus(maximum15seconds)

Habitua-oncriterion–averagelookdura=onoverthreeconsecu=vetrials<50%ofprevioustrialset(maximum21trials)

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BayleyRecep

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guageScore

9‐12MonthHemoglobinLevel

HigherIronLevelsPredictBe]erRecep6veLanguageAbili6es

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Maternalhypertension Nomaternalhypertension

NoveltyPreferenceatTest

(Novel–Fam

iliarLoo

kDura6

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MaternalHypertensionPredictsPoorerInfantWorkingMemoryPerformance

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NoveltyPreferenceatTest

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9‐12MonthHemoglobinLevel

IronLevelsWereUnrelatedtoInfantWorkingMemory

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Cogni=ve R.Language E.Language F.Motor G.Motor

BayleySub

scaleScore

MaternalHypertensionDoesNotPredictInfantBayleyScores

Nohypertension Maternalhypertension

Moderate‐to‐latepreterminfantsexhibitedpoorerworkingmemorydevelopmentat9monthsofage.Addi=onally,therewasevidencethatirondeficiencyandmaternalriskfactorssuchashypertensionaffectinfant’smemoryandcogni6vedevelopment.

Limita6ons:Manyofthepreterminfantsinthisstudyweresupplementedwithironwhichlikelycontributedtotheirnormalironlevelsat9‐12monthsofage.Addi-onally,thelackofrela-onshipbetweenironlevelsandmemoryperformancemaybespecifictothetaskused.Thehabitua-ontaskmeasuresworkingmemory,whichreliesontheprefrontalcortex.Irondeficiencyhasbeenmoststronglyassociatedwithhippocampaldevelopment,soothermemorytaskscouldhaveyieldeddifferentresults.Last,infantsborntomotherswithhypertensioncouldhaveotherriskfactorsdrivingtheirpoorerperformance.

Futurestudiesshouldcon=nuetoinves=gatetheeffectsofirondeficiencyoncogni=veoutcomesininfants,includingthosebornmoderate‐to‐latepreterm.Moreover,thesestudiesshouldinves=gatewhichpregnancy‐relatedriskfactorspredictchildren’soutcomesinordertoensureappropriateinterven=onstakeplacetopreventcogni=vedevelopmentaldelays.

Bayley:InfantswithhigherHgBlevelshadhigherrecep6velanguagescores(r=.22,p<.03).

Habitua6onTask:Ironlevelswerenotrelatedtonoveltypreferencescores(r=‐.04,p<.71).

Bayley:InfantsdidnotdifferonanyoftheBayleyscales.Therewasatrend(p<.12)towardlowercogni=vescoresintheriskgroup.

Habitua6on:Theriskgroupfailedtoshowanoveltypreferenceattest(p<.62)andsignificantlydifferedfromthenon‐riskgroupinnoveltypreferencemagnitude(p<.03).