Collin, SM, Granell, R., Westgarth, C., Murray, J., Paul, ES, Sterne, JAC, & Henderson, AJ

15 Pages·2017·0.2 MB·English

Collin, S. M., Granell, R., Westgarth, C., Murray, J., Paul, E. S.,

Sterne, J. A. C., & Henderson, A. J. (2015). Associations of pet
ownership with wheezing and lung function in childhood: Findings
from a UK birth cohort. PLoS ONE, 10(6), [e0127756].
https://doi.org/10.1371/journal.pone.0127756
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RESEARCHARTICLE
Associations of Pet Ownership with Wheezing
and Lung Function in Childhood: Findings
from a UK Birth Cohort
SimonM.Collin1,2,RaquelGranell2,CarriWestgarth3,4,JaneMurray5,ElizabethS.Paul5,
JonathanA.C.Sterne2,A.JohnHenderson2*
1 CentreforChild&AdolescentHealth,UniversityofBristol,Bristol,UnitedKingdom,2 SchoolofSocial&
CommunityMedicine,UniversityofBristol,Bristol,UnitedKingdom,3 DepartmentofEpidemiology&
PopulationHealth,UniversityofLiverpool,Liverpool,UnitedKingdom,4 SchoolofVeterinaryScience,
a11111
UniversityofLiverpool,Liverpool,UnitedKingdom,5 SchoolofVeterinarySciences,UniversityofBristol,
Bristol,UnitedKingdom
* [email protected]
Abstract
OPENACCESS
Citation:CollinSM,GranellR,WestgarthC,Murray
J,PaulES,SterneJAC,etal.(2015)Associationsof
Background
PetOwnershipwithWheezingandLungFunctionin
Childhood:FindingsfromaUKBirthCohort.PLoS Asthmaisaheterogeneousconditionanddifferentialeffectsofpetownershiponnon-atopic
ONE10(6):e0127756.doi:10.1371/journal. versusatopicasthmahavebeenreported.Theaimofthisstudywastoinvestigatewhether
pone.0127756
petownershipduringpregnancyandearlychildhoodwasassociatedwithwheezingfrom
AcademicEditor:YunglingLeoLee,National
birthtoage7yearsandwithlungfunctionatage8yearsinaUKpopulation-based
TaiwanUniversity,TAIWAN
birthcohort.
Received:January15,2015
Accepted:April19,2015
Methods
Published:June10,2015
DatafromtheAvonLongitudinalStudyofParentsandChildren(ALSPAC)wereusedtoin-
Copyright:©2015Collinetal.Thisisanopen
vestigateassociationsofpetownershipatsixtime-pointsfrompregnancytoage7years
accessarticledistributedunderthetermsofthe
CreativeCommonsAttributionLicense,whichpermits withconcurrentepisodesofwheezing,wheezingtrajectories(phenotypes)andlungfunc-
unrestricteduse,distribution,andreproductioninany tionatage8yearsusinglogisticregressionmodelsadjustedforchild’ssex,maternalhistory
medium,providedtheoriginalauthorandsourceare
ofasthma/atopy,maternalsmokingduringpregnancy,andfamilyadversity.
credited.
DataAvailabilityStatement:Duetoethical
restrictionsregardingparticipantconfidentiality,data Results
usedforthissubmissionwillbemadeavailableon
4,706childrenhadcompletedataonpetownershipandwheezing.Frombirthtoage7
requesttotheALSPACexecutivecommittee(alspac-
[email protected]).TheALSPACdatamanagement years,catownershipwasassociatedwithanoverall6%loweroddsofwheezing(OR=0.94
plandescribesindetailthepolicyregardingdata (0.89-0.99)).Rabbitandrodentownershipwasassociatedwith21%(OR=1.21(1.12-1.31))
sharing,whichisthroughasystemofmanagedopen and11%(OR=1.11(1.02–1.21))higheroddsofwheezing,respectively,withstrongestef-
access(http://www.bristol.ac.uk/alspac/researchers/
fectsevidentduringinfancy.Rabbitandrodentownershipwaspositivelyassociatedwitha
data-access/documents/alspac-data-management-
plan.pdf). ‘persistentwheeze’phenotype.Petownershipwasnotassociatedwithlungfunctionatage
8years,withtheexceptionofpositiveassociationsofrodentandbirdownershipwithbetter
Funding:TheUKMedicalResearchCouncil,the
WellcomeTrustandtheUniversityofBristolprovide lungfunction.
PLOSONE|DOI:10.1371/journal.pone.0127756 June10,2015 1/14
HouseholdPets,WheezingandLungFunctioninChildhood
coresupportforALSPAC.Theprojectdescribedwas Conclusions
supportedbyGrantNumber1R03HD070663-01from
Catownershipwasassociatedwithreducedrisk,andrabbitandrodentownershipwithin-
theEuniceKennedyShriverNationalInstituteofChild
Health&HumanDevelopmentandMars-WALTHAM. creasedrisk,ofwheezingduringchildhood.Themechanismsbehindthesedifferentialef-
ThispublicationistheworkoftheauthorsandAJH fectswarrantfurtherinvestigation.
willserveasguarantorforthecontentofthispaper.
Thecontentissolelytheresponsibilityoftheauthors
anddoesnotnecessarilyrepresenttheofficialviews
oftheEuniceKennedyShriverNationalInstituteof
ChildHealth&HumanDevelopment,theNational
InstitutesofHealth,orMars-WALTHAM.Carri Introduction
WestgarthissupportedbyaUKMedicalResearch
CouncilPopulationHealthScientistFellowship.Jane Asthmaduringchildhoodhasaconsiderableimpactonquality-of-lifeandhealthcarecosts
MurrayisfundedbyCatsProtection.Thefundershad [1,2].Achild’ssusceptibilitytoasthmaislikelytobedeterminedbyinteractinggeneticanden-
noroleinstudydesign,datacollectionandanalysis, vironmentalfactors[3,4].Ownershipofhouseholdpetshasattractedattentionasanearly-life
decisiontopublish,orpreparationofthemanuscript.
environmentalexposurewhichmightplayaroleinthedevelopmentofasthmaandallergy.Pet
CompetingInterests:Theauthorsherebyconfirm ownershipiscommonamonghouseholdsincountrieswheretheincidenceandprevalenceof
thattheNIH/Mars-WALTHAMfundingdoesnotalter childhoodasthmaandallergieshavechangedsubstantiallyoverthepastfewdecades[5,6].
theauthors’adherencetoPLOSONEpolicieson
Wereportedpreviouslythatfamilyownershipofdomesticpetsduringearlylife,including
sharingdataandmaterials,andthatthefunders
duringthepre-natalperiod,wasassociatedwithloweroddsofatopicasthmabymid-childhood
playednoroleintheconductofthestudyorin
reportingitsfindings. comparedwithnopetownership[7],confirmingfindingsfrompreviousstudies[8–10].Con-
versely,wealsofoundthatpetownership,particularlyofrabbitsandrodents,tendedtobeas-
sociatedwithhigheroddsofnon-atopicasthma.Thesedifferentialeffectsofpetownership
probablyreflectheterogeneitywithinchildhoodasthma,whichisrecognizedtobeacomplex
conditioncharacterisedbydistinctphenotypes[11],assuggestedbyanalysisoftrajectoriesof
wheezingthroughchildhood[12,13].Differentialassociationsofearly-lifeenvironmentalex-
posureswithwheezingphenotypes,andwithphenotypictraitssuchaslungfunction,maypro-
videcluesastodistinctenvironmentalandpathophysiologicalprocessesinasthmacausation
andexacerbation[14].
HereweuseddatafromtheAvonLongitudinalStudyofParentsandChildren(ALSPAC),a
well-characterisedUK-basedbirthcohort,toinvestigateassociationsofpetownership(anypet
andspecificpettypes)atsixtime-points(frompregnancytoage7years)withepisodesof
wheezingreportedatannualintervalsfrom6monthsto7yearsofage,withlongitudinal
wheezingphenotypes[12],andwithlungfunction(ForcedExpiratoryVolumein1second
(FEV )andForcedVitalCapacity(FVC))measuredatage8years.
1
Methods
Studypopulation
TheAvonLongitudinalStudyofParentsandChildren(ALSPAC)isaUKpopulation-based
studywhichaimstoinvestigateenvironmentalandgeneticinfluencesonthehealthanddevel-
opmentofchildren[15].PregnantwomenresidingintheformerAvonHealthAuthorityin
south-westEnglandwhohadanestimateddateofdeliverybetween1April1991and31De-
cember1992wereinvitedtotakepart,resultinginacohortof14,541pregnanciesand13,978
childrenaliveat12monthsofage(excludingtripletsandquads).Theprimarysourceofdata
collectionwasviaself-completionquestionnairessenttomothersatfourtime-pointsduring
pregnancythenatapproximatelyannualintervalsfollowingbirth.Therepresentativenatureof
theALSPACsamplehasbeeninvestigatedbycomparisonwiththe1991NationalCensusdata
ofmotherswithinfantsunder1yearofagewhowereresidentsinthecountyofAvon.The
ALSPACsamplehadaslightlygreaterproportionofmotherswhoweremarriedorcohabiting,
whowereowner-occupiersandwhohadacarinthehousehold.Thestudyhadasmaller
PLOSONE|DOI:10.1371/journal.pone.0127756 June10,2015 2/14
HouseholdPets,WheezingandLungFunctioninChildhood
proportionofethnicminoritymothers.Datausedforthissubmissionwillbemadeavailable
onrequesttotheALSPACexecutivecommittee([email protected]).TheALSPACdata
managementplandescribesindetailthepolicyregardingdatasharing,whichisthroughasys-
temofmanagedopenaccess(http://www.bristol.ac.uk/alspac/researchers/data-access/
documents/alspac-data-management-plan.pdf).
Ethicalapproval
EthicalapprovalforthisstudywasobtainedfromtheALSPACEthicsandLawCommittee
(IRB00003312).Ethicalapprovalforthe‘Focus@8’researchclinicswasgrantedbyWeston
LocalResearchEthicsCommittee(NHSLRECref.E177,21stSeptember1999).Informedwrit-
tenconsentwasobtainedfromtheoriginalparticipantsandfromtheparent(s),nextofkin,
caretakers,orguardiansonbehalfoftheminors/childrenenrolledinALSPAC.
Outcomes
Episodesofwheezeandwheezingphenotypes. Parentalreportsofchildwheezingwere
obtainedfromquestionnairessenttothemothersatannualintervalsfrom6monthsto7years
ofage(atapproximateages6,18,32,42,54,69,and81months).Presenceofwheezewasbased
onapositiveresponsetothequestion“Inthepast12monthshas(yourchild)hadwheezing
withwhistlingonthechest?”orareportedoccurrenceofwheezewithinalistof15common
symptoms.Aspreviouslydescribed,thesedatawereusedinalongitudinallatentclassanalysis
todefinephenotypesofchildhoodwheezing,resultingin6wheezingphenotypesthatwerela-
belled‘never/infrequent’,‘transientearly’,‘prolongedearly’,‘intermediate-onset’,‘late-onset’
and‘persistentwheezing’[12].
Lungfunction. LungfunctionwasmeasuredbyspirometryaccordingtoAmericanTho-
racicSocietycriteria[16]in‘Focus@8’researchclinicstowhichallparticipantswereinvitedat
age8years(median103,range89to127months).Forcedexpiratoryvolumein1second
(FEV )andforcedvitalcapacity(FVC)wereconvertedtounitsofsex-,age-andheight-adjust-
1
edstandarddeviations(z-scores)[17].
Exposures
Petownership. Petownershipquestionswereasked(inquestionnairesaboutthemother
andherenvironment)duringpregnancy(upto28weeksgestation)andatchildagesof8
monthsand2,3,4,and7years.Thecarerofthechild(usuallythemother)wasasked‘doyou
haveanypets’and‘howmanyofthefollowingpetsdoyouhave’.Pettypesincludedcats,dogs,
rabbits,rodents(mice,hamster,gerbiletc.),andbirds.Forthepurposeofourstudy,wedefined
4-levelcategoricalvariablestoindicatewhetheracat,dog,rabbit,rodent,bird,oranypet,had
beenowned/acquiredasfollows:“Never”;“Atage3yearsorlater,notbefore”(ownedatage33
monthsoratanytimethereafter,butnotatage21monthsoratanytimebefore,includingdur-
ingpregnancy);“Beforeandafterage3years”(ownedatanytimebeforeage33months,includ-
ingduringpregnancy,andatanytimethereafter,referredtoas‘continuous’ownership);“Before
butnotafter3years”(ownedatanytimebefore,includingduringpregnancy,butnolonger
ownedatage33monthsoratanytimethereafter).Wechoseage3yearsasameaningfultime
pointfortheacquisitionofpetsbecausewewantedtoisolatepotentialreverse-causalityinasso-
ciationsofpetownershipwithasthmaandatopy,specifically,discontinuationofownershipdue
totheemergenceofasthmaoratopyduringinfancyorearlychildhood[18].Wealsodefineda
binaryexposureof“ever”or“never”havingownedanypetandspecificpettypes.Ownershipof
fish,turtlesandtortoiseswasrecordedfromage2yearsonwards,andwasnotcodedasa4-level
categoricalexposurevariableincludedinthe‘any’petownershipbinaryexposurevariable.
PLOSONE|DOI:10.1371/journal.pone.0127756 June10,2015 3/14
HouseholdPets,WheezingandLungFunctioninChildhood
Othervariables
Potentialconfounders. Acomposite‘familyadversity’indexandthreefactorspreviously
reportedtobeassociatedwithwheezingphenotypesinALSPAC(sexofchild,maternalhistory
ofasthmaorallergy,andmaternalsmokingduringpregnancy)[14]wereinvestigatedaspoten-
tialconfoundersoftheassociationbetweenexposuresandoutcomes.Maternalhistoryofasth-
maorallergywasabinaryvariablederivedfromresponsestoanantenatal(18–20weeks
gestation)questionnaireinwhichthemotherwasasked:a)“Haveyoueverhadanyofthefol-
lowingproblems?”withresponsesfor“Asthma”of“Yeshaditrecently”or“Yesinpast,not
now”codedas‘yes’;andb)“Wouldyousaythatyouwereallergictoanything?”,withaffirma-
tiveresponsestoanyof“cat”,“pollen”,“dust”,“insectstingsorbites”,or“somethingelse”
codedas‘yes’.Maternalsmokingduringpregnancywasabinaryvariablederivedfromre-
sponsestoquestionsputtothemotherinanantenatalandapostnatalquestionnaire,asking
whetherthemotherhadsmokedinthefirst3monthsofthepregnancy,atthemid-point
(18–20weeks),orinthelast2monthsofthepregnancy.
FamilyAdversityIndex. ThestandardALSPACFamilyAdversityIndex(FAI)isderived
fromresponsestoquestionsaskedduringpregnancyaboutthefollowing10factors,compris-
ing18itemsintotal:1)ageofmotheratfirstpregnancy;2)housing,comprisinga)adequacy,
b)basicamenities,c)defects,damp,infestation;3)mother’sandfather’sloweducationalat-
tainment;4)financialdifficulties;5)relationshipwithpartner,comprisinga)status,b)lackof
affection,c)cruelty,d)lackofsupport;6)family,comprisinga)size,b)childincare,notwith
naturalmother,onat-riskregister;7)socialnetwork,comprisinga)lackofemotionalsupport,
b)lackofpracticalsupport;8)substanceabuse;9)crime,comprisinga)beingintroublewith
thepoliceandb)convictions;and10)psychopathologyofthemother(anxiety,depressionor
suicideattempts).Eachofthe18itemsisassignedavalueof1ifanadversityispresentand0if
itisnotpresenthence,theFAIhasatheoreticalrangeof0to18.FAIscoresarecalculated
wheremorethanhalfoftheitemsarevalid,andnon-adversityisassumedforanymissingdata
hence,FAIscoresareconservative.SeveralcomponentsoftheFAI(ageatfirstpregnancy,
overcrowding,familysize,rentedhousing,andmaternalanxiety)werepreviouslyshowntobe
associatedwithwheezingphenotypes[14].
Statisticalmethods
Associationsofpetownershipwithepisodesofwheezingatages6,18,32,42,and81months
andwithlungfunction(FEV andFVC)wereinvestigatedusinglogisticandlinearregression
1
models,respectively,adjustedforsexofchild,maternalhistoryofasthmaorallergy,maternal
smokingduringpregnancy,andfamilyadversityindex.FEV andFVCwerequantifiedas
1
unitsofstandarddeviations(z-scores).Therelationshipofpetownershipwithwheezeoverall
fivetime-pointswasinvestigatedusingrandomeffectslogitregressionmodels.Weanalysed
ownershipoffish,turtlesandtortoisesinrelationtowheezingepisodes(asanegativecontrol),
butwecouldnotcategorizeownershipasa4-levelcategoricalvariablebecausefish/turtle/tor-
toiseownershipwasrecordedonlyfromage2yearsonwards.Associationsofpetownership
withwheezingphenotypeswereestimatedusingmultinomiallogisticregressionmodels
weightedbytheprobabilityforeachindividualofbelongingtoeachphenotype.Theseproba-
bilitieswereestimatedpreviouslyandreferredtoastheposteriorprobabilities[12].According
tothismethod,eachchildcontributesalineofdatacorrespondingtoeachphenotypefor
whichthechildhasanon-zeroposteriorprobability.Forexample,achildmighthaveposterior
probability0.9ofpersistentwheeze,0.1oftransientearlywheezeandzeroforallotherpheno-
types.Intheregressionanalyses,thischildwouldcontributetwolinesofdata,thefirstforper-
sistentwheezewithweight0.9andthesecondfortransientearlywheezewithweight0.1.
PLOSONE|DOI:10.1371/journal.pone.0127756 June10,2015 4/14
HouseholdPets,WheezingandLungFunctioninChildhood
Adjustedrelativeriskratios(alsoknownasmultinomialoddsratios)werederivedinrelation
tothenever/infrequentwheezingphenotype(referencegroup).Heterogeneityp-valuescom-
paringestimatedeffectsacrosswheezingphenotypeswerecalculatedusingChi-squaredtests.
Modelswhichusedaspecificpettypeasexposurewerenotadjustedforthepresenceofother
pets.Petownershipstatusovertimewasmodelledbymeansofthe4-levelcategoricalpetown-
ershipvariable,whichwascodedtoindicatenon-ownership(i.e.neverowned,atanytime
point),‘continuous’ownership(ownedatanytimepointbeforeage33monthsandatanytime
pointthereafter),and‘discontinuous’ownership,comprising:pet‘acquired’afterage3years
(notpreviouslyowned),orpetowneduptoage3butnotafterwards.Estimatesforthetwo‘dis-
continuous’ownershiplevelsgivesomeindicationastowhether‘early’or‘late’ownershiphas
asimilareffectonoutcomescomparedwithnon-ownershipor‘continuous’ownership.All
analyseswereperformedusingStata(StataCorp,CollegeStation,TX,USA).
Results
Of13,978childreninALSPAC,4,706children(33.7%)hadcompletedataonwheezing,pet
ownershipandconfounders(maternalhistoryofallergy/asthma,maternalsmokingduring
pregnancyandfamilyadversityindex).Thedistributionsofexposuresandoutcomesinthe
completedatagrouparesummarizedinTable1.Ouranalysisoflungfunctionwasbasedon
4,177children(29.9%),andouranalysesofpetownershipduringpregnancyinrelationto
wheezeatage6months,wheezingphenotypesandlungfunctionwerebasedon8,661(62.0%),
5,735(41.0%)and5,278(37.8%)children,respectively.Childrenwithcompletedataweresimi-
lartochildrenwithmissingdata,exceptthatchildrenwithcompletedatawerelesslikelyto
havehadwheezeatage6months,hadmotherswhowerelesslikelytohavesmokedduring
pregnancy,andlivedinhouseholdswhichhadlowerlevelsofadversityandwhichwereless
likelytoownpets(S1Table).Asreportedpreviously,maternalsmokingduringpregnancyand
familyadversitywerestronglypositivelyassociatedwithpetownership,andpetownership
tendedtobelesscommonamongmotherswhoreportedahistoryofallergy[7].
Petownershipandwheezing
Ownershipofanypetwasassociatedwith13%higheroddsofwheezingatage6–8months
(oddsratio(OR)=1.13;95%CI1.02–1.25)buttherewasnoassociationatanyofthelater
time-pointsandnooverallassociation.Catownershipwasassociatedwithloweroddsof
wheezingatages18and42monthswithanoverall6%loweroddsofwheezing(OR=0.94;
95%CI0.89–0.99)(Table2,S2Table).Conversely,owningarabbitorrodentincreasedthe
overalloddsofwheezingby21%(OR=1.21;95%CI1.12–1.31)and11%(OR=1.11;95%CI
1.02–1.21),respectively,withthestrongestassociationsevidentduringinfancy.Asexpected,
ownershipoffish,turtlesandtortoiseswasnotassociatedwithoccurrenceofwheezing.
Petownershipwasnotassociatedwithwheezingphenotypes,withtheexceptionofpositive
associationsofrabbitandrodentownershipwithpersistentwheeze(Table3,S3Table).There
wasnooverallheterogeneityinassociationsacrossthedifferentphenotypesforanypettype
(allP>0.2).Pointestimatessuggestedopposingeffectsofpetownershiponintermediateonset
(inverseassociation)versuspersistentwheeze(positiveassociation),andtherewasstatistical
evidenceofheterogeneitybetweenthesetwophenotypesforcontinuousownership(beforeand
afterage3years)ofanypettype:intermediateonsetOR=0.67(95%CI0.42–1.06);persistent
wheezeOR=1.26(95%CI0.88–1.80);heterogeneityP=0.03.
Dog,rabbitandbirdownershipduringpregnancywereassociatedwithhigheroddsof
wheezeatage6monthsbuttherewerenoassociationsofpetownershipduringpregnancy
withanyofthewheezingphenotypes(Table4,S2Table).Ofthe57.5%(2,708/4,706)of
PLOSONE|DOI:10.1371/journal.pone.0127756 June10,2015 5/14
HouseholdPets,WheezingandLungFunctioninChildhood
Table1. Outcomesandexposuresinchildrenwithcompletedata(N=4,706).
Wheezeatage 6months 23.2%
18months 25.5%
32months 21.1%
42months 16.7%
54months 17.6%
69months 14.6%
81months 13.2%
Wheezingphenotype* Never/infrequent 60.2%
Transientearly 16.1%
Prolongedearly 8.6%
Intermediateonset 2.7%
Lateonset 5.8%
Persistent 6.7%
Anypetowned/acquired** Never 15.6%
Age3yearsorlater,notbefore 19.4%
Beforeandafterage3years 61.3%
Beforebutnotafter3years 3.7%
Catowned/acquired** Never 57.6%
Age3yearsorlater,notbefore 7.7%
Beforeandafterage3years 29.6%
Beforebutnotafter3years 5.1%
Dogowned/acquired** Never 69.9%
Age3yearsorlater,notbefore 7.0%
Beforeandafterage3years 18.4%
Beforebutnotafter3years 4.8%
Rabbitowned/acquired** Never 72.1%
Age3yearsorlater,notbefore 14.9%
Beforeandafterage3years 8.7%
Beforebutnotafter3years 4.4%
Rodentowned/acquired** Never 65.0%
Age3yearsorlater,notbefore 25.5%
Beforeandafterage3years 6.8%
Beforebutnotafter3years 2.7%
Birdowned/acquired** Never 86.6%
Age3yearsorlater,notbefore 4.5%
Beforeandafterage3years 4.9%
Beforebutnotafter3years 4.0%
*Frequencydistributionweightedbyeachchild’sposteriorprobabilityofclassmembership.
**“Age3yearsorlater,notbefore”=ownedatorafterage33monthsbutnotatanytimebefore;“Before
andafterage3years”=ownedatanytimebeforeage33monthsandatanytimethereafter;“Beforebut
notafter3years”=ownedatanytimebefore,butnotownedatoratanytimeafter,age33months.
doi:10.1371/journal.pone.0127756.t001
householdsrecordedasowninganypettypeduringpregnancy,themajority(87.9%(2,381/
2,708))alsoreportedowningapetwhenthechildwas6monthsold.However,therewassome
variationbypettype:ofhouseholdsrecordedduringpregnancyasowningacat(32.5%),dog
(21.4%),rabbit(7.7%),rodent(5.1%)orbird(6.5%),theproportionsowningthesetypesof
petswhenthechildwas6monthsoldwere87.8%(cats),86.1%(dogs),68.0%(rabbits),53.1%
PLOSONE|DOI:10.1371/journal.pone.0127756 June10,2015 6/14
HouseholdPets,WheezingandLungFunctioninChildhood
Table2. Associationsofpetownershipatdifferenttime-pointsduringchildhoodwithconcurrentwheezingepisodes. *
Age6months Age18months Age32months Age42months Age81months Overall
Anypet 1.13(1.02,1.25) 0.96(0.87,1.07) 1.02(0.91,1.14) 1.00(0.88,1.13) 0.94(0.78,1.13) 1.01(0.96,1.07)
Cat 0.97(0.87,1.09) 0.90(0.80,1.01) 1.03(0.91,1.16) 0.87(0.76,1.00) 0.91(0.78,1.07) 0.94(0.89,0.99)
Dog 1.11(0.99,1.26) 0.91(0.80,1.04) 1.01(0.88,1.17) 1.03(0.88,1.20) 0.90(0.75,1.08) 1.00(0.94,1.06)
Rabbit 1.38(1.17,1.64) 1.07(0.90,1.27) 1.22(1.03,1.44) 1.23(1.03,1.46) 1.14(0.93,1.38) 1.21(1.12,1.31)
Rodent 1.37(1.10,1.71) 1.02(0.83,1.27) 1.13(0.93,1.37) 1.09(0.90,1.32) 1.02(0.86,1.21) 1.11(1.02,1.21)
Bird 1.13(0.92,1.38) 0.92(0.74,1.14) 0.99(0.78,1.26) 1.15(0.89,1.48) 1.15(0.86,1.54) 1.04(0.94,1.17)
Fish/turtle/tortoise Nodata 0.95(0.82,1.11) 0.97(0.84,1.13) 0.93(0.79,1.09) 1.11(0.94,1.32) 0.99(0.91,1.07)
*Oddsratios(95%CI)fromlogisticregressionmodelsadjustedforsexofchild,maternalhistoryofasthmaorallergy,maternalsmokingduring
pregnancy,andfamilyadversityindex.Petownershipwasascertainedbyself-completedquestionnaireat8,21,33,47,and85months.Overallestimates
foreachpettypearefromrandomeffectslogitregressionmodelsacrossallfivetime-points.
doi:10.1371/journal.pone.0127756.t002
(rodents),and66.7%(birds).Acquisitionofapetinthe6monthsafterthebirthofthechildby
householdswhichhadpreviouslynotownedthatpettypewasuncommon:cats(1.5%(46/
3,178)),dogs(1.0%(38/3,701)),rabbits(2.7%(118/4,344)),rodents(2.0%(89/4,467)),and
birds(1.3%(56/4,400)).
Petownershipandlungfunction
Petownershipwasnotassociatedwithlungfunctionatage8years(Table5),withtheexcep-
tionofpositiveassociationsofrodentandbirdownershipwithbetterlungfunction.Forrodent
ownership(comparingeverownedversusneverowned),themeandifferenceinFEV z-score
1
was0.072(95%CI0.008to0.136,P=0.03),andthemeandifferenceinFVCz-scorewas0.065
(95%CI0.003to0.127,P=0.04);forbirdownership,themeandifferenceinFEV z-scorewas
1
0.105(95%CI0.014to0.195,P=0.02).Therewerenoconsistentpatternsinthesignofthe
pointestimate(greaterorlessthanzero)forthemeandifferencesinFEV andFVCacrosslev-
1
elsofpetownershiporbetweenpettypes.
Discussion
Rabbitandrodentownershipinthisbirthcohortwasassociatedwithanincreasedrisk,andcat
ownershipwithaslightlyreducedrisk,ofepisodesofwheezingduringearlychildhood.The
positiveassociationsofrabbitandrodentownershipweremostevidentduringinfancy,and
alsomanifestedasanincreasedriskofa‘persistentwheeze’phenotype.Catownershipwasnot
associatedwithanyofthesixwheezingphenotypes.Wefoundweakevidenceofapparently
paradoxicalpositiveassociationsofrodentandbirdownershipwithbetterlungfunction(FEV
1
andFVC)atage8years,butthesearemostplausiblyascribedtochance.Dog,rabbitandbird
ownershipduringpregnancywaspositivelyassociatedwithwheezingatage6months.These
associationsmaysimplyreflectthefactthatthemajorityofthesehouseholdsalsoownedthese
pettypesatage6months,ratherthanindicatingspecificinuteroeffects.
Strengthsandlimitations
ALSPACisawell-characterizedbirthcohortwhichhasprovideddataforseveralstudiesintoin
uteroandearlychildhoodfactorsinrelationtochildhoodasthma,wheezingandatopy[7,14,19–
23].Akeystrengthofourstudywastheavailabilityofexposuremeasuresderivedfromidentical
questionnaireitemsforspecificpettypesatmultipletime-points,frompregnancythroughtoage
7years,plusdataforpotentialconfounders.Themainlimitationofourstudy,aswithanybirth
PLOSONE|DOI:10.1371/journal.pone.0127756 June10,2015 7/14
HouseholdPets,WheezingandLungFunctioninChildhood
Table3. Associationsofpetownershipduringchildhoodwithwheezingphenotypes. *
Transientearly Prolongedearly Intermediateonset Lateonset Persistent
Anypet Never 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref)
Age3yearsorlater, 1.11(0.85,1.46) 1.17(0.82,1.69) 0.76(0.43,1.34) 1.10(0.72,1.67) 1.21(0.79,1.85)
notbefore
Beforeandafterage3 1.10(0.87,1.38) 1.14(0.84,1.55) 0.67(0.42,1.06) 1.05(0.74,1.51) 1.26(0.88,1.80)
years
Beforebutnotafter3 1.13(0.72,1.80) 1.05(0.56,1.97) 1.38(0.61,3.14) 1.63(0.87,3.05) 1.24(0.62,2.47)
years
Cat Never 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref)
Age3yearsorlater, 1.13(0.84,1.52) 1.09(0.75,1.59) 1.27(0.68,2.35) 0.95(0.58,1.54) 1.09(0.70,1.68)
notbefore
Beforeandafterage3 0.98(0.82,1.16) 0.90(0.72,1.14) 0.76(0.50,1.15) 1.02(0.77,1.33) 1.03(0.80,1.34)
years
Beforebutnotafter3 0.88(0.60,1.28) 0.75(0.45,1.25) 1.54(0.79,2.99) 1.19(0.70,2.01) 1.04(0.62,1.74)
years
Dog Never 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref)
Age3yearsorlater, 1.16(0.86,1.56) 0.96(0.63,1.46) 0.71(0.33,1.56) 0.99(0.61,1.60) 1.46(0.98,2.16)
notbefore
Beforeandafterage3 0.99(0.81,1.21) 1.20(0.93,1.55) 0.59(0.34,1.00) 1.00(0.73,1.37) 1.00(0.74,1.34)
years
Beforebutnotafter3 1.05(0.72,1.52) 1.44(0.93,2.22) 1.20(0.56,2.55) 0.89(0.48,1.65) 0.83(0.46,1.49)
years
Rabbit Never 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref)
Age3yearsorlater, 1.13(0.91,1.40) 1.14(0.86,1.52) 0.96(0.58,1.59) 0.92(0.64,1.32) 1.36(1.00,1.86)
notbefore
Beforeandafterage3 1.07(0.82,1.41) 1.27(0.90,1.77) 0.69(0.33,1.42) 1.06(0.69,1.62) 1.28(0.87,1.89)
years
Beforebutnotafter3 1.12(0.75,1.65) 1.00(0.59,1.71) 0.94(0.37,2.37) 1.39(0.79,2.42) 1.74(1.07,2.85)
years
Rodent Never 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref)
Age3yearsorlater, 1.07(0.89,1.29) 1.17(0.92,1.49) 0.80(0.52,1.25) 1.04(0.78,1.39) 1.31(1.01,1.71)
notbefore
Beforeandafterage3 1.31(0.98,1.76) 1.14(0.76,1.70) 0.84(0.40,1.78) 1.18(0.74,1.87) 1.45(0.96,2.21)
years
Beforebutnotafter3 0.93(0.56,1.53) 1.04(0.57,1.92) 1.25(0.48,3.28) 0.71(0.30,1.69) 1.16(0.60,2.25)
years
Bird Never 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref)
Age3yearsorlater, 0.83(0.56,1.24) 1.00(0.62,1.63) 1.36(0.65,2.86) 1.23(0.72,2.09) 0.75(0.41,1.48)
notbefore
Beforeandafterage3 1.05(0.75,1.49) 1.11(0.72,1.71) 0.97(0.43,2.17) 0.83(0.46,1.48) 0.94(0.56,1.57)
years
Beforebutnotafter3 1.04(0.70,1.54) 0.94(0.55,1.59) 0.83(0.30,2.26) 0.69(0.34,1.43) 0.82(0.44,1.52)
years
*Relativeriskratios(95%CI)frommultinomiallogisticregressioncomparedwith‘never/infrequent’wheezingphenotype,adjustedforsexofchild,
maternalhistoryofasthmaorallergy,maternalsmokingduringpregnancy,andfamilyadversityindex.
**“Age3yearsorlater,notbefore”=ownedatorafterage33monthsbutnotatanytimebefore;“Beforeandafterage3years”=ownedatanytime
beforeage33monthsandatanytimethereafter;“Beforebutnotafter3years”=ownedatanytimebefore,butnotownedatoratanytimeafter,age
33months.
doi:10.1371/journal.pone.0127756.t003
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HouseholdPets,WheezingandLungFunctioninChildhood
Table4. Associationsofpetownershipduringpregnancywithwheezeat6–8monthsandwithwheezingphenotypes.
Oddsratio* Relativeriskratio(95%CI)comparedwith‘never/infrequent’wheezingphenotype*
Wheezeatage6months Transientearly Prolongedearly Intermediateonset Lateonset Persistent
Anypet 1.09(0.98,1.20) 0.99(0.85,1.16) 0.98(0.80,1.19) 0.86(0.61,1.21) 1.04(0.82,1.32) 1.01(0.81,1.27)
Cat 0.94(0.84,1.05) 0.94(0.80,1.10) 0.90(0.73,1.11) 0.89(0.61,1.29) 1.00(0.78,1.28) 0.98(0.78,1.24)
Dog 1.13(1.01,1.27) 1.00(0.83,1.20) 1.16(0.92,1.45) 0.76(0.48,1.20) 0.94(0.70,1.25) 0.94(0.72,1.23)
Rabbit 1.23(1.04,1.45) 1.04(0.78,1.37) 1.06(0.74,1.52) 0.64(0.29,1.40) 0.98(0.63,1.52) 1.30(0.89,1.89)
Rodent 1.04(0.84,1.27) 1.33(0.97,1.83) 1.09(0.60,2.58) 1.24(0.60,2.58) 1.25(0.77,2.04) 1.16(0.73,1.86)
Bird 1.22(1.02,1.46) 1.10(0.82,1.48) 1.18(0.82,1.70) 1.22(0.64,2.34) 0.72(0.42,1.22) 0.86(0.54,1.36)
*Adjustedforsexofchild,maternalhistoryofasthmaorallergy,maternalsmokingduringpregnancy,andfamilyadversityindex;petownership
questionnairecompletedfrom8thupto28thweekofpregnancy.
doi:10.1371/journal.pone.0127756.t004
cohort,relatestolossestofollow-up;specifically,thepossibleeffectsofhigherratesofattrition
amongchildrenfromlessaffluentfamilies[15].Giventhatsuchchildrenweremorelikelytobe
exposedtohouseholdpetsandtoexperiencewheezing,wewouldtendtounder-estimateassocia-
tionsbetweenpetownershipandwheezing.However,wefoundthatcrudeassociationswereaf-
fectedlittlebyadjustmentforfamilyadversityorpotentialconfoundingfactorssuchassmoking
duringpregnancy,andtheresultsofcomplete-dataanalysesweresimilartoresultsobtained
usingthemaximumamountofavailabledata.Thissuggeststhatourresultswouldnotbesub-
stantiallybiasedbyhigherlossestofollow-upinthelowersocialstrata.
Table5. Associationsofpetownershipwithlungfunctionatage8years(N=4,177).
MeandifferenceinFEV z-score* MeandifferenceinFVCz-score*
1
Anypet** Age3yearsorlater,notbefore 0.007(-0.096,0.110) -0.019(-0.120,0.081)
Beforeandafterage3years 0.013(-0.073,0.100) 0.006(-0.078,0.091)
Beforebutnotafter3years -0.063(-0.240,0.113) -0.043(-0.216,0.129)
Cat** Age3yearsorlater,notbefore 0.038(-0.081,0.157) 0.028(-0.089,0.144)
Beforeandafterage3years 0.005(-0.063,0.074) 0.010(-0.057,0.077)
Beforebutnotafter3years -0.018(-0.161,0.125) 0.033(-0.107,0.173)
Dog** Age3yearsorlater,notbefore 0.005(-0.117,0.127) -0.026(-0.146,0.093)
Beforeandafterage3years 0.035(-0.045,0.116) 0.029(-0.049,0.108)
Beforebutnotafter3years -0.065(-0.212,0.081) -0.054(-0.197,0.089)
Rabbit** Age3yearsorlater,notbefore 0.023(-0.064,0.110) 0.005(-0.080,0.090)
Beforeandafterage3years -0.029(-0.137,0.080) -0.048(-0.154,0.058)
Beforebutnotafter3years 0.036(-0.116,0.188) 0.093(-0.056,0.241)
Rodent** Age3yearsorlater,notbefore 0.078(0.007,0.148) 0.057(-0.012,0.126)
Beforeandafterage3years 0.082(-0.042,0.206) 0.134(0.013,0.256)
Beforebutnotafter3years -0.012(-0.203,0.178) -0.026(-0.212,0.160)
Bird** Age3yearsorlater,notbefore 0.127(-0.018,0.272) 0.102(-0.040,0.244)
Beforeandafterage3years 0.009(-0.137,0.156) -0.009(-0.152,0.134)
Beforebutnotafter3years 0.190(0.032,0.349) 0.043(-0.112,0.198)
*Comparedwithchildrenfromhouseholdswherepetwasneverowned,adjustedforsexofchild,maternalhistoryofasthmaorallergy,maternalsmoking
duringpregnancy,andfamilyadversityindex.
**“Age3yearsorlater,notbefore”=ownedatorafterage33monthsbutnotatanytimebefore;“Beforeandafterage3years”=ownedatanytime
beforeage33monthsandatanytimethereafter;“Beforebutnotafter3years”=ownedatanytimebefore,butnotownedatoratanytimeafter,age
33months.
doi:10.1371/journal.pone.0127756.t005
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