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Zikavirusinfection:Evaluationofpregnantwomenandinfants

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Zikavirusinfection:Evaluationofpregnantwomenandinfants
Author
EdwardRBMcCabe,MD,PhD

SectionEditors
MartinSHirsch,MD
CharlesJLockwood,MD,MHCM
DeborahLevine,MD

DeputyEditors
VanessaABarss,MD,FACOG
ElinorLBaron,MD,DTMH

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Apr2016.|Thistopiclastupdated:Apr21,2016.
INTRODUCTIONZikavirusisanarthropodborneflavivirustransmittedbymosquitoes.Thistopicwilldiscuss
issuesrelatedtoZikavirusinfectioninpregnantwomenandcongenitallyinfectednewborns.Otherissuesrelated
toZikavirusinfectionarereviewedseparately.(See"Zikavirusinfection:Anoverview".)
ACQUISITIONOFINFECTIONZikavirusmaybetransmittedtohumansviathefollowing(see"Zikavirus
infection:Anoverview",sectionon'Transmission'):
Biteofaninfectedmosquito
Maternalfetaltransmission(see'Congenitalinfection'below)
Sex(includingvaginal,anal,andoralsex)
Bloodtransfusion
Organortissuetransplantation
Laboratoryexposure
Preventivemeasuresarediscussedbelow.(See'Prevention'below.)
ThereisnoevidencetosuggestthatpregnantwomenaremoresusceptibletoZikavirusinfectionthanmenor
nonpregnantwomen[1,2].TransmissionofZikavirusinfectionthroughbreastfeedinghasnotbeendescribed[3,4].
However,transmissionofsomeotherflavivirusesviabreastmilkcanoccur[5,6].
CLINICALMANIFESTATIONS
MaternalinfectionClinicalmanifestationsofZikavirusinfectioninpregnantwomenarethesameasthosein
nonpregnantadults.(See"Zikavirusinfection:Anoverview",sectionon'Clinicalmanifestations'.)
Thereisnoevidencetosuggestthatpregnantwomenexperiencemoreseverediseasethannonpregnantwomen
[1,2].However,viremiamaypersistlongerinpregnantwomenthannonpregnantindividuals[7].
CongenitalinfectionZikavirusinfectioninalltrimestershasbeenassociatedwithfetalabnormalities,soit
shouldbepresumedthattheriskforcongenitalinfectionexiststhroughoutpregnancy[8,9].
Furtherstudyisneededtodeterminetherateofverticaltransmissionandtherateatwhichinfectedfetuses
manifestcomplications[10].Inacohortincluding88pregnantwomenwhopresentedtoaBrazilianclinicwitha
rashat5to38weeksofgestation,72women(82percent)hadapositivetestforZikavirusinfection[8].Among
42ofthesewomenwhounderwentultrasonography,fetalabnormalitiesweredetectedin12(29percent).Viremia
longerthantypicallyobservedmayindicatefetalinfection[7].
VerticaltransmissionofZikavirusfrommothertofetus[1,4,11,12]hasbeenassociatedwithseveralsequelae
(table1)[7,8,1320].Serioussequelaeinclude:
MicrocephalyZikavirusinfectionshavebeenconfirmedinthecerebrospinalfluid(CSF)andserumof
newbornswithmicrocephaly[13,15,16,21],althoughitisnotknownhowmanyofthemicrocephalycasesare
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causedbyZikavirusinfection[22,23].(See'DefinitionofZikavirusrelatedmicrocephaly'below.)
BetweenMarch2015andApril2016,morethan5000casesofmicrocephalywerereportedamongnewborns
borntoBrazilianmotherswithZikavirusinfectionthisrepresentsa>20foldincreaseinmicrocephaly
comparedwithpreviousyears[14,2430].Inonereportincluding574casesofmicrocephalyinBrazil
betweenJanuary2015andJanuary2016,theprevalenceofmicrocephalywassignificantlyhigherin15
stateswithactiveZikatransmissionthanin4stateswithouttransmission(2.8versus0.6casesper10,000
livebirths)[31].
BirthdefectswerenotrecognizedasacomplicationofZikavirusinfectionatthetimeoftheoutbreakinthe
YapIslandsofMicronesiain2007,perhapsbecauseoftherelativelysmallsizeofthepopulation.Similarly,
nofetalabnormalitieswereidentifiedinitiallyduringtheFrenchPolynesiaoutbreakin2013to2014however,
subsequentretrospectiveevaluationsidentified19casesoffetalorneonatalcentralnervoussystem
malformationsorbrainstemdysfunction[32,33],andretrospectivepolymerasechainreactiontestingof
storedamnioticfluidwaspositiveforZikavirusinsomeofthesecases[34].Furtherretrospectiveanalysis
ofthedatafromFrenchPolynesiaestimatedabaselinemicrocephalyprevalenceof2casesper10,000
neonatesandariskofmicrocephalyassociatedwithZikavirusinfectionrateof95casesper10,000women
infectedinthefirsttrimester[35]basedontheseestimates,theriskofmicrocephalyassociatedwithZika
virusinfectioninthefirsttrimesterduringthatoutbreakwasapproximately1percent.
DuringthecurrentZikaoutbreak,therehavebeenanumberofyetunsubstantiatedtheoriesaboutthe
pathogenesisofmicrocephaly[36].However,theWorldHealthOrganization(WHO)andtheUnitedStates
CentersforDiseaseControlandPrevention(CDC)concludedthattheZikaviruscausesmicrocephaly
[22,23].
FetallossandstillbirthZikavirusRNAhasbeendetectedinthepathologicspecimensofearlyandlate
fetallosses[8,13,15].
OcularabnormalitiesOcularabnormalitiesarecommonandincludefocalpigmentmottling,chorioretinal
atrophy,andopticnerveabnormalities(hypoplasiaandseverecuppingoftheopticdisk)[3739].
Othercentralnervoussystemabnormalities(eg,ventriculomegaly,globalhypogyria,hydranencephaly
[completeorpartialdestructionofcerebralhemisphereswithcerebrospinalfluidintheremainingcranial
cavity])[18,19,33]
Hydropsfetalis[18]
Fetalgrowthrestriction[8]
DIAGNOSISCasedefinitionsforZikavirusinfectionhavebeendevelopedbytheWorldHealthOrganization
thesearethesameinpregnantandnonpregnantindividualsandaresummarizedseparately.(See"Zikavirus
infection:Anoverview",sectionon'Diagnosis'and"Zikavirusinfection:Anoverview",sectionon'Case
definitions'.)
ANTEPARTUMMATERNALEVALUATIONApproachestoZikavirusdiagnosismayvarydependingon
availableresourcestheapproachoutlinedforpregnantwomeninthefollowingsectionsmayneedtobetailoredto
localcircumstances.
Inthefirstthreemonthsof2016,over3300pregnantwomenintheUnitedStateswhotraveledtoormovedfrom
areaswithactiveZikavirustransmissionweretestedforZikavirus:0.8percenthadconfirmedZikavirusinfection
and64percentofthesewomenhadatleastoneZikavirusassociatedsymptom[40].Infectionwasconfirmedin
2.9percentofsymptomaticwomenand0.3percentofasymptomaticwomen.
HistoryInareaswithnoknownmosquitoborneZikavirustransmission(ie,noongoingriskofexposure),
healthcareprovidersshoulddeterminewhetherthepregnantwomanisatriskbecauseofhertravelorsexual
historybyaskingabout:
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PreviousresidenceinortraveltoanareawheremosquitobornetransmissionofZikavirusinfectionhasbeen
reported
Unprotectedsexualcontactwithapersonwhoresidesinorhastraveledtoanareawheremosquitoborne
transmissionofZikavirusinfectionhasbeenreported
WomenwhomeetoneorbothofthesecriteriaorwholiveinanareawithknownZikavirustransmissionshouldbe
askedaboutsymptomsconsistentwithZikavirusinfection.
WomenwithnoexposuretoZikavirusForpregnantwomenwithnorelevantepidemiologicexposure,
laboratorytestingorfetalscreeningforZikavirusinfectionisnotindicated[12].
WomenwithsymptomsconsistentwithpossibleZikavirusinfectionPregnantwomenwithclinicalillness
consistentwithZikavirusinfection(twoormoresymptomsconsistentwithZikavirusinfection[maculopapular
pruriticrash,arthralgia,conjunctivitis,orlowgradefever])withintwoweeksofepidemiologicexposureshould
havebothlaboratorytestingandultrasoundexamination[12,41,42]:
Forpatientspresenting<7daysafteronsetofsymptomsCheckserumZikavirusRNAbyreverse
transcriptionpolymerasechainreaction(RTPCR).Apositivetestisdiagnosticofinfection.
IftheRTPCRisnegativeandthepatientis4daysaftertheonsetofsymptoms,checkZikavirus
immunoglobulin(Ig)Mandneutralizingantibodytiters.Apositivetestispresumptiveofinfection.(See"Zika
virusinfection:Anoverview",sectionon'Diagnosis'.)
Screenforfetalinfection.(See'Screeningforfetalinfection'below.)
AsymptomaticwomenwithpossiblebutnotongoingexposuretoZikavirusAsymptomaticwomenwith
possibleexposuretoZikavirusshouldhavebothlaboratorytestingandultrasoundexamination:
AsymptomaticpregnantwomenshouldhaveZikavirusIgMandneutralizingantibodytiterschecked2to12
weeksfollowingexposure.
InterpretationofserologictestresultsforasymptomaticpregnantwomenwithZikavirusexposureis
complex,givencrossreactivityamongrelatedflaviviruses.However,anegativeIgMresult2to12weeks
followingexposuresuggestsabsenceofarecentinfection[41].(See"Zikavirusinfection:Anoverview",
sectionon'Diagnosis'.)
Screenforfetalinfection.(See'Screeningforfetalinfection'below.)
TheUnitedStatesCentersforDiseaseControlandPrevention(CDC)maintainsaclinicalconsultationservice
(available24hoursperday,7daysperweek)forhealthcareprovidersevaluatingandcaringforpregnantwomen
andinfantswithpossibleZikavirusinfection(telephone1800CDCINFOoremailatzikamch@cdc.gov)[43].
AsymptomaticwomenwithongoingriskforZikavirusinfectionAsymptomaticwomenwithongoingrisk
forZikavirusinfectionshouldhavebothlaboratorytestingandultrasoundexamination:
Forasymptomaticpregnantwomen,ZikavirusIgMandneutralizingantibodytitersarewarrantedatthe
initiationofprenatalcare[41,44].Apositivetestisdiagnosticofinfection.
Iftheinitialtestisnegativeandperformedinthefirstorearlysecondtrimester,repeattestingat18to20
weeks.
InterpretationofserologictestresultsforasymptomaticpregnantwomenwithZikavirusexposureis
complex,givencrossreactivityamongrelatedflaviviruses.However,anegativeIgMresult2to12weeks
followingexposuresuggestsabsenceofarecentinfection[41].(See"Zikavirusinfection:Anoverview",
sectionon'Diagnosis'.)
Screenforfetalinfection.(See'Screeningforfetalinfection'below.)
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EVALUATIONOFFETALLOSSANDSTILLBIRTHFetaltissuetestingiswarrantedforfetallossesin
womenwithhistoryofZikaexposure,togetherwitheithersymptomsconsistentwithZikavirusinfectionduringor
withintwoweeksofexposureorfindingsoffetalmicrocephaly.Insuchcases,Zikavirusreversetranscription
polymerasechainreactionandhistopathologicexaminationwithimmunohistochemicalstainingshouldbe
performedonfetaltissues,includingtheumbilicalcordandplacenta[12,45].
SCREENINGFORFETALINFECTIONUltrasoundisthemajormodalityusedtoscreenforfetalZikavirus
infection,butmagneticresonanceimaging(MRI)ismoresensitive[7].
UltrasonographyUltrasoundfindingsassociatedwithfetalZikavirusinfectionmaybedetectedasearlyas18
to20weeksgestationinsomecases[2,42,46,47].Thetwomajorultrasoundfindingssuggestiveofcongenital
Zikavirusinfectionarethefollowing[2]:
Microcephaly(headcircumferencemorethantwostandarddeviationsbelowthemean)Microcephalyasan
isolatedfindingisnotusuallyseenonultrasoundbeforethethirdtrimester.(See'DefinitionofZikavirus
relatedmicrocephaly'below.)
IntracranialcalcificationsIntracranialcalcificationsaresometimesevidentinthesecondtrimesterbutmore
ofteninthethirdtrimester.
Accurateassessmentofgestationalageearlyinpregnancyisimportantforestablishingadiagnosisof
microcephalylateinpregnancy.(See"Prenatalassessmentofgestationalageandestimateddateofdelivery".)
TheInternationalSocietyofUltrasoundinObstetricsandGynecology(ISUOG)interimguidanceonultrasoundfor
ZikavirusinfectioninpregnancyrecommendsabaselineultrasoundexaminationforwomenwithZikavirus
exposureandsymptoms,positiveserologyorprovenZikavirusinfection,orexposureand/orsymptomswithout
positiveserologyresults[48].
Thebaselineexaminationshouldincluderoutinebiometrytodetectmicrocephalyandassessmentforintracranial
calcifications.TheanatomicsurveyshouldalsolookforfindingsthatmaybeassociatedwithZikavirusinfection
andwhichmayoccurintheabsenceofmicrocephalyandintracranialcalcifications,including:

Irregularlyshapedventricularmargins
Increasedperiventricularechogenicity
Cysticlesions
Intraventricularadhesions
Callosalorvermiandysgenesis
Smalltranscerebellardiameter
Enlargedcisternamagna
Increasedamountofcerebrospinalfluidaroundthebrain

Ifthebaselineexaminationisnormalinthesewomen,theISUOGrecommendsserialultrasoundexaminations
everyfourtosixweeks,ifpossible.
Ifthebaselineexaminationisabnormal,referraltoaspecialistforneurosonographyofthefetalbrainis
recommended.Intheabsenceofmicrocephaly,iftheheadcircumferenceissmallornotenlargingappropriately,
MRImaydetectabnormalitiesnotvisibleonultrasoundandmaybeuseful[7].
AmniocentesisZikavirusreversetranscriptionpolymerasechainreaction(RTPCR)positivityinamnioticfluid
isdiagnosticoffetalviralexposurebutnotpredictiveofoutcome.Theindicationsfordiagnosticamniocentesis,
theappropriategestationalagefortesting,andtheinterpretationofthetestareuncertain.Decisionsregarding
amniocentesisshouldbetailoredtoindividualclinicalcircumstances[49].
Wesuggestofferingamniocentesistowomenwitheitherofthefollowing:

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Fetalmicrocephaly(threestandarddeviationsbelowthemeanforgestationalage),intracranialcalcifications,
and/orventriculomegaly,regardlessofmaternallaboratorytestresultsforZikavirusinfection
PositiveorinconclusivematernallaboratorytestresultsforZikavirusinfection
TimingForwomenwithcharacteristicsonographicfindingsoffetalZikavirusinfection,amniocentesisupon
diagnosisandasearlyas15to16weeksisreasonable.Ingeneral,amniocentesisisnotperformedbefore15
weeksbecauseofanincreasedriskofpregnancyloss.
ForwomenwithpositiveorinconclusiveZikavirustestresultsandanormalappearingfetus,theoptimaltimingfor
performanceofamniocentesisisuncertain.Wesuggestsixtoeightweeksaftermaternalinfection.Thesensitivity
ofamniocentesisfordiagnosisofcongenitalZikavirusinfectionmaybehigherat21weeksthanearlierin
pregnancybecause,byanalogywithothercausesofcongenitalinfection(suchcytomegalovirusandToxoplasma),
itislikelythatZikavirusisnotshedintoamnioticfluiduntilsufficienttimehaselapsedfollowingmaternalviremia
forthevirustobreachtheplacentalbarrierthisissixtoeightweeksaftermaternalinfection[5052].Inaddition,
fetalkidneydevelopmentmustbesufficientlyadvancedtoexcretethevirusintotheamnioticfluid(fetalurine
productionaccountsformostoftheamnioticfluidvolumeafter18to21weeksofgestation).However,
amniocentesisthislateingestationmaynotallowadequatetimetoarrangeterminationofpregnancyifdesired
becauseofpositiveresults.Therefore,ifamniocentesisisperformedsixtoeightweeksaftermaternalinfection
andfalsenegativeresultsaresuspected,arepeatamniocentesislateringestationmaybeconsidered.
InterpretationThesensitivityandspecificityofZikavirusRTPCRtestingofamnioticfluidfordiagnosisof
congenitalinfectionarenotknownandlikelydependontimingofamniocentesisafteronsetofmaternalinfection
[1].ApositiveRTPCRresultonamnioticfluidshouldbeconsideredsuggestiveofintrauterineinfection[12].Ifthe
testwasperformedbecauseofmaternallaboratoryfindingsorviralexposureandthefetusappearsnormal,itis
unknownwhetherapositiveamnioticfluidRTPCRresultispredictiveofasubsequentfetalabnormalityand,ifso,
whatproportionofinfantswillhaveabnormalities.
IftheRTPCRisnegativeandthefetusisabnormal,evaluationforothercausesofthefetalabnormalitiesshould
beconsidered[46].However,thedurationofamnioticfluidPCRpositivityisunknown[10].
PRENATALCARE
MaternaltreatmentThereisnospecifictreatmentforZikavirusinfection.Managementconsistsofrestand
symptomatictreatmentincludingdrinkingfluidstopreventdehydrationandadministrationofacetaminophento
relievefeverandpain[53].
Aspirinandothernonsteroidalantiinflammatorydrugs(NSAIDs)shouldbeavoideduntildengueinfectionhasbeen
ruledouttoreducetheriskofhemorrhage.NSAIDsshouldalsobeavoidedinpregnantwomenat32weeksof
gestationtominimizeriskforprematureclosureofductusarteriosus.(See"Inhibitionofacutepretermlabor",
sectionon'Fetalsideeffects'.)
TheWorldHealthOrganizationhasissuedinitialguidanceonpsychosocialsupportforpatientsandfamilies
affectedbyZikavirusinfectionandassociatedcomplications[54].
AntepartumfetalmonitoringInfectedfetusesareatriskforstillbirth.Ifantenataltestingisperformed(eg,
nonstresstest,biophysicalprofile)andresultsareabnormal,earlydeliverymaybeappropriate,dependingonthe
clinicalscenario.
NosocomialtransmissionTransmissionofZikavirusviaoccupationalexposureinahealthcaresettinghas
notbeendescribed.Standardprecautionsareappropriateforprotectionofhealthcarepersonnelandpatientsfrom
Zikavirusinfectioninthesesettings[55].(See"Generalprinciplesofinfectioncontrol",sectionon'Standard
precautions'.)
NEWBORNEVALUATIONTheapproachtopostnataldiagnosticevaluationforcongenitalZikavirusinfection
mayvarydependingonavailableresourceswherenecessary,theapproachoutlinedinthefollowingsectionsmay
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needtobetailoredtolocalcircumstances.
DefinitionofZikavirusrelatedmicrocephalyThereisnostandarddefinitionfordiagnosisofmicrocephaly.
(See"Microcephalyininfantsandchildren:Etiologyandevaluation".)
TheWorldHealthOrganizationhasdefinedmicrocephalyasthefollowing[5659]:
Occipitofrontalcircumference(headcircumference)greaterthantwostandarddeviationsbelowthemeanor
lessthanthethirdpercentilebasedonstandardgrowthchartsforsex,age,andgestationalageatbirth.
Theoccipitofrontalcircumferenceshouldbedisproportionatelysmallincomparisonwiththelengthofthe
infantandnotexplainedbyotheretiologiesorcongenitaldisorders.Ifaninfant'soccipitofrontalcircumference
is3rdpercentilebutisnotablydisproportionatetothelengthoftheinfantoriftheinfanthasdeficitsrelated
tothecentralnervoussystem,additionalevaluationforZikavirusinfectionmayalsobeappropriate.
Brazilianguidelinesfordiagnosisofmicrocephalyininfantsbornat37weeksofgestationhavebeen
modifiedovertimeinassociationwiththeZikavirusoutbreak,from33cmto31.9cmformalesand31.5
cmforfemales[60].Forprematureinfants,thediagnosisofmicrocephalyisbasedontablesestablishedby
theInterGrowthproject(table2)[61].
TheWorldHealthOrganizationhasfurtherdefined"Zikavirusrelatedmicrocephaly"asmicrocephalywitha
molecularorepidemiologiclinktoZikavirusintheabsenceofotherconditionsknowntocausemicrocephaly[42].
AmolecularorepidemiologiclinktoZikavirusisdefinedasoneofthefollowing:
MotherhadconfirmedcaseofZikavirusinfectionduringpregnancy.
MotherhadsexualcontactduringpregnancywithapersonwithconfirmedZikavirusinfection.
MotherhadtypicalclinicalmanifestationsofZikavirusinfection(twoormoreofthefollowing:maculopapular
pruriticrash,arthralgia,conjunctivitis,orfever)andrelevantepidemiologicexposureduringpregnancy
(residenceinortraveltoanareawheremosquitobornetransmissionofZikavirusinfectionhasbeen
reported).
AmniocentesiswithdetectionofZikavirusinamnioticfluidviapolymerasechainreaction(PCR).
PostmortemdetectionofZikavirusinfetalbraintissueviaPCR.
LaboratoryevaluationAllnewbornsshouldundergothoroughevaluationwithin24hoursofbirth.Infantswho
warrantZikaviruslaboratorytestinginclude[62]:
NewbornswithmicrocephalyorintracranialcalcificationsborntowomenwithZikavirusexposure
NewbornsofmotherswithpositiveorinconclusivelaboratorytestresultsforZikavirusinfection
Theapproachtolaboratorytestingofinfants(ineitheroftheabovecategories)forZikavirusinfectionincludesthe
following[62]:
TestinfantserumforZikavirusRNA(viareversetranscriptionPCR[RTPCR])aswellasZikavirus
immunoglobulin(Ig)Mandneutralizingantibodies.Inaddition,testfordenguevirusIgMandneutralizing
antibodiestodiscriminatebetweencrossreactingantibodies.Theinitialsampleshouldbecollectedfromthe
umbilicalcordordirectlyfromtheinfantwithintwodaysofbirth,ifpossible.
Ifinfantcerebrospinalfluid(CSF)isavailable,testCSFforZikavirusRNA(viaRTPCR)aswellasZika
virusIgMandneutralizingantibodies.Inaddition,testfordenguevirusIgMandneutralizingantibodiesto
discriminatebetweencrossreactingantibodies.CSFspecimensneednotbecollectedforthesolepurpose
ofZikavirustesting[63]butmaybereasonableforevaluationofinfantswithmicrocephalyorintracranial
calcifications.

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Considerhistopathologicexaminationoftheplacentaandumbilicalcord,withZikavirus
immunohistochemicalstainingonfixedtissueandZikavirusRNA(viaRTPCR)onfixedandfrozentissue.
Ifnotalreadyperformedduringpregnancy,testmaternalserumforZikavirusIgMandneutralizingantibodies
anddenguevirusIgMandneutralizingantibodies.
DiagnosticcriteriaforcongenitalinfectionCongenitalinfectionisdefinedasthepresenceofZikavirusRNA
inanyofthesamplescollected,includingamnioticfluid,placenta,umbilicalcord,newbornserum,ornewbornCSF
[62].Inaddition,congenitalinfectionmaybeestablishedbythepresenceofZikavirusIgMantibodiesinnewborn
serumorCSF,withconfirmatoryneutralizingantibodytitersthatare4foldhigherthandenguevirusneutralizing
antibodytiters.TestresultsareinconclusiveifZikavirusneutralizingantibodytitersare<4foldhigherthandengue
virusneutralizingantibodytiters.
ClinicalevaluationandfollowupofnewbornsInadditiontothelaboratoryevaluationdescribedabove,the
newbornshouldundergoclinicalevaluation.Theextentofevaluationdependsonwhethertheinfanthashadno
exposuretoZikavirus,possibleexposuretoZikavirus,orfindingssuggestiveofinfection.
Newbornswithoutmicrocephalyorintracranialcalcificationsonprenatalultrasoundorlaboratory
abnormalitieswhosemotherhadpositiveorinconclusivelaboratorytestresultsforZikavirus
infectionshouldreceiveroutinecare.Developmentalmonitoringmaybeindicatedifresourcesareavailable,
sincelongtermoutcomesareunknown.
Newbornswithoutmicrocephalyorintracranialcalcificationsonprenatalultrasoundwhosemother
hadnegativelaboratorytestresultsforZikavirusinfectionorwhosemotherwasnottestedforZika
virusinfectionshouldreceiveroutinecare[64].
NewbornswithpositiveorinconclusivetestresultsforZikavirusinfectionwithorwithout
microcephalyshouldundergotheassessmentdescribedintheTable(table3)andalsoanassessmentfor
possiblelongtermsequelae[56],withappropriatereferralifabnormalitiesaredetected.Thisincludes:
Repeathearingscreenatagesixmonths(evenifbaselinehearingscreenwasnormalbecauseof
potentialfordelayedhearingloss)(see"Screeningthenewbornforhearingloss"and"Hearing
impairmentinchildren:Evaluation")
Appropriatefollowupofhearingabnormalitiesdetectedthoughnewbornhearingscreening
Evaluationofoccipitofrontalcircumferenceanddevelopmentalmilestonesthroughoutthefirstyearof
life(see"Developmentalandbehavioralscreeningtestsinprimarycare")
NewbornswithnegativeresultsonalllaboratoryZikavirustestsbutmicrocephalyorintracranial
calcificationsshouldundergotheassessmentdescribedintheTable(table3),whichincludesevaluationfor
alternativeetiologiesofthesefindings.(See"Microcephalyininfantsandchildren:Etiologyandevaluation"
and"OverviewofTORCHinfections".)
EVALUATIONOFWOMENANDNEWBORNSWITHPERIPARTUMZIKAVIRUSEXPOSUREMaternal
fetaltransmissionofZikaviruscanoccurduringlaboranddelivery.TwocasesofintrapartumZikavirus
transmissiontoinfantsfrommothersinfectedwithinafewweeksofdeliveryhavebeenreportedoneofthese
infantshadnoclinicalmanifestations,andtheotherhadthrombocytopeniaandadiffuserash[1,64].Thereareno
reportsofZikavirusinfectionacquiredbyaninfantatthetimeofdeliveryleadingtomicrocephaly[65].
Maternalandnewbornlaboratorytestingisindicatedduringthefirsttwoweeksoflifeifthemotherhadrelevant
epidemiologicexposurewithintwoweeksofdeliveryandhad2ofthefollowingmanifestationsofZikavirus
infection:rash,conjunctivitis,arthralgia,orfever[64].
Ifthemotherandnewbornpresent<7daysafteronsetofmaternalsymptomsCheckserumZikavirus
RNAbyreversetranscriptionpolymerasechainreaction(RTPCR)inbothpatients.Apositivetestis
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diagnosticofinfection.
IftheRTPCRisnegativeandthemotheris4daysaftertheonsetofsymptoms,checkZikavirus
immunoglobulin(Ig)Mandneutralizingantibodytiters.Apositivetestispresumptiveofinfection.
Ifthenewbornissymptomaticandthemotherisasymptomatic,checkmaternalZikavirusIgMand
neutralizingantibodytiters.
Ifnewborncerebrospinalfluid(CSF)isobtainedforanyreason,CSFtestingforZikavirusRNA(viaRTPCR)is
appropriate[64].
PREVENTIONThereisnovaccineforpreventionofZikavirusinfection.
PregnantwomenToprotectagainstZikavirusinfection,pregnantwomenshould:
AvoidtraveltoareaswithmosquitotransmissionofZikavirusGivenanassociationbetweenZika
virusexposureduringpregnancyandcongenitalmicrocephaly,pregnantwomenshouldavoidorconsider
postponingtraveltoareasbelow6500feet(2000meters)wheremosquitotransmissionofZikavirusis
ongoing,unlesstheneedfortravelisessential[11,6670].
ThegeographicdistributionofZikavirusinfectionisdiscussedfurtherelsewhere.(See"Zikavirusinfection:
Anoverview",sectionon'Geographicdistribution'.)
UpdatesregardingthegeographicdistributionofZikavirusmaybeviewedattheUnitedStatesCentersfor
DiseaseControlandPreventionwebsiteandthePanAmericanHealthOrganization/WorldHealth
Organizationwebsite.
Adheretomosquitoprotectivemeasures(see"Zikavirusinfection:Anoverview",sectionon'Mosquito
protection').UseofEPAapprovedinsectrepellantsinpregnancyhasnoknownharmfuleffectsifused
accordingtodirections.(See"Preventionofarthropodandinsectbites:Repellentsandothermeasures",
sectionon'DEET'.)
Adheretomeasures(abstinenceorcondoms)toprotectfromsexualtransmissionRiskofsexual
transmission(vaginal,oral,anal),includingthedurationofrisk,isreviewedseparately.(See"Zikavirus
infection:Anoverview",sectionon'Sexualtransmission'.).
Adheretostandardinfectionprecautions.(See'Nosocomialtransmission'above.)
Inaddition,pregnantwomenandcliniciansshouldbeawarethatZikavirusistransmissibleviabloodproductsand
organortissuetransplantation[71,72].Issuesrelatedtodonorscreeningarediscussedseparately.(See"Blood
donorscreening:Medicalhistory",sectionon'Zikavirus'and"Blooddonorscreening:Laboratorytesting".)
BreastfeedingwomenBreastfeedingwomenshouldtaketheprecautionsdescribedabove.Transmissionof
Zikavirusthroughbreastfeedinghasnotbeendescribed,althoughthevirushasbeendetectedinbreastmilk.
Somehaverecommendedthatwomencontinuetobreastfeed[10,73,74].Thusfar,nodevelopmental
complicationshavebeenobservedinotherwisehealthychildrenwithpostnatalZikavirusinfectionorexposure
[75,76].
WomenplanningpregnancyThereisnoevidencethatwomenwhohavehadapriorZikavirusinfectionareat
riskofbirthdefectsinfuturepregnancies.TheUnitedStatesCentersforDiseaseControlandPrevention(CDC)
recommendsthatwomenwhohavehadaZikavirusinfectionshouldwaitatleasteightweeksaftersymptom
onsetbeforeattemptingconception[77].
OutsideareasofZikavirusmosquitotransmission,theCDChassuggestedthatmenwithsymptomaticZikavirus
infection(confirmedorsuspected)waitatleastsixmonthsbeforehavingunprotectedsexandthatasymptomatic
menwithZikavirusexposure(viatraveltomosquitotransmissionareasorsexualcontact)waitatleasteight
weeksbeforeunprotectedsex[78,79].(See"Zikavirusinfection:Anoverview",sectionon'Sexualtransmission'.)
http://www.uptodate.com.aure.unab.edu.co/contents/zikavirusinfectionevaluationofpregnantwomenandinfants?topicKey=ID%2F107211&elapsedTimeMs

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RESOURCESOnlineupdatesregardingZikavirusinfectionmaybeviewedatthefollowingwebsites:
PanAmericanHealthOrganization/WorldHealthOrganizationwebsite
UnitedStatesCentersforDiseaseControlandPreventionwebsite
EuropeanCentreforDiseasePreventionandControlwebsite
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,"TheBasics"and
"BeyondtheBasics."TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortable
withsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
"patientinfo"andthekeyword(s)ofinterest.)
Basicstopic(see"Patientinformation:Zikavirusinfection(TheBasics)")
SUMMARY
Zikavirusistransmittedtohumansviathebiteofaninfectedmosquito,maternalfetaltransmission,sex,
bloodproducts,laboratoryexposure,andorganortissuetransplantation.Thereisnoevidencethatpregnant
womenaremoresusceptibletoZikavirusinfectionthanmenornonpregnantwomen.Transmissionthrough
breastfeedinghasnotbeendescribed,buttheZikavirusispresentinbreastmilk,soitmaybepossible.
(See'Acquisitionofinfection'above.)
ClinicalmanifestationsofZikavirusinfectioninpregnantwomenarethesameasthoseinnonpregnant
adults.Viremiamaypersistlongerinpregnantwomenthannonpregnantindividuals.(See'Maternalinfection'
above.)
VerticaltransmissionofZikavirusfrommothertofetusduringpregnancyhasbeenassociatedwithserious
sequelae(table1).(See'Congenitalinfection'above.)
CasedefinitionsforZikavirusinfectionhavebeendevelopedbytheWorldHealthOrganizationtheseare
thesameinpregnantandnonpregnantindividualsandaresummarizedseparately.(See"Zikavirusinfection:
Anoverview",sectionon'Diagnosis'and"Zikavirusinfection:Anoverview",sectionon'Casedefinitions'.)
InareaswithnomosquitoborneZikavirustransmission(ie,noongoingriskofexposure),healthcare
providersshouldaskpregnantwomenaboutrelevantpastepidemiologicexposureasaresultoftravelor
unprotectedsexualcontactwithapersonatriskofinfection.(See'History'above.)
Forpregnantwomenwithnorelevantepidemiologicexposure,maternallaboratorytestingorfetalscreening
forZikavirusinfectionisnotindicated.(See'WomenwithnoexposuretoZikavirus'above.)
Laboratoryevaluationofsymptomaticpregnantwomenpresenting<7daysafteronsetofsymptomsconsists
oftestingforserumZikavirusRNAbyreversetranscriptionpolymerasechainreaction(RTPCR).Apositive
testisdiagnosticofinfection.IftheRTPCRisnegativeandthepatientis4daysaftertheonsetof
symptoms,serumZikavirusimmunoglobulin(Ig)Mandneutralizingantibodytitertestingshouldbe
performed.Apositivetestispresumptiveofinfection.(See'Womenwithsymptomsconsistentwithpossible
Zikavirusinfection'above.)
Laboratoryevaluationofasymptomaticpregnantwomendependsonwhethertheyhadnonrecurrentrelevant
exposureorongoingexposuretoZikavirus.Interpretationofserologictestresultsforasymptomaticpregnant
womenwithZikavirusexposureiscomplex,givencrossreactivityamongrelatedflaviviruses.(See
http://www.uptodate.com.aure.unab.edu.co/contents/zikavirusinfectionevaluationofpregnantwomenandinfants?topicKey=ID%2F107211&elapsedTimeMs

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'AsymptomaticwomenwithpossiblebutnotongoingexposuretoZikavirus'above.)
Followingnonrecurrentexposure,asymptomaticpregnantwomenshouldhaveZikavirusIgMand
neutralizingantibodytiterschecked2to12weeksaftertheexposure.
Forwomenwithongoingexposure,ZikavirusIgMandneutralizingantibodytitersarewarrantedatthe
initiationofprenatalcare.Apositivetestisdiagnosticofinfection.Iftheinitialtestisnegativeand
performedinthefirstorearlysecondtrimester,repeattestingat18to20weeks.
WeagreewiththeInternationalSocietyofUltrasoundinObstetricsandGynecology(ISUOG)interim
guidanceonultrasoundforZikavirusinfectioninpregnancy,whichrecommendsabaselineultrasound
examinationforwomenwithZikavirusexposureandsymptoms,positiveserologyorprovenZikavirus
infection,orexposureand/orsymptomswithoutpositiveserologyresults.
Thebaselineexaminationshouldincluderoutinebiometrytodetectmicrocephalyandassessmentfor
intracranialcalcificationsandotherabnormalities,whichmaybepresentwithoutmicrocephaly.
Ifthebaselineexaminationisnormal,serialultrasoundexaminationsarerepeatedeveryfourtosixweeks,if
possible.(See'Ultrasonography'above.)
Wesuggestofferingamniocentesistowomenwitheitherofthefollowing(see'Amniocentesis'above):
Fetalmicrocephaly(threestandarddeviationsbelowthemeanforgestationalage),intracranial
calcifications,and/orventriculomegaly,regardlessofmaternallaboratorytestresultsforZikavirus
infection
PositiveorinconclusivematernallaboratorytestresultsforZikavirusinfection
ZikavirusRTPCRinamnioticfluidisdiagnosticoffetalviralexposurebutnotpredictiveofoutcome.
AllnewbornswhowarrantZikaviruslaboratorytestingshouldbeevaluatedwithin24hoursofbirth.These
infantsinclude(see'Laboratoryevaluation'above):
NewbornswithmicrocephalyorintracranialcalcificationsborntowomenwithZikavirusexposure
NewbornsofmotherswithpositiveorinconclusivelaboratorytestresultsforZikavirusinfection
TheextentofnewbornclinicalevaluationdependsonwhetherthenewbornhashadnoexposuretoZika
virus,possibleexposuretoZikavirus,orfindingssuggestiveofinfection(table3).(See'Clinicalevaluation
andfollowupofnewborns'above.)
Ifthemotherhadrelevantepidemiologicexposurewithintwoweeksofdeliveryandthemotherornewbornis
symptomatic,maternalandnewbornlaboratorytestingareindicated.(See'Evaluationofwomenand
newbornswithperipartumZikavirusexposure'above.)
ThereisnospecifictreatmentforZikavirusinfection,andthereisnovaccineforprevention.(See
'Prevention'above.)
ToprotectagainstZikavirusinfection,pregnantwomenshould(see'Pregnantwomen'above):

AvoidtraveltoareaswithknownmosquitotransmissionofZikavirus
Adheretomosquitoprotectivemeasures
AdheretomeasurestoprotectfromsexualtransmissionofZikavirus
Adheretorecommendationsregardingblooddonation
Adheretorecommendationsforstandardinfectionprecautions

WomenwithZikavirusexposuremaybreastfeed.TransmissionofZikavirusthroughbreastfeedinghasnot
beendescribed,althoughthevirushasbeendetectedinbreastmilk.(See'Breastfeedingwomen'above.)
http://www.uptodate.com.aure.unab.edu.co/contents/zikavirusinfectionevaluationofpregnantwomenandinfants?topicKey=ID%2F107211&elapsedTimeM

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UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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CaringforWomenofReproductiveAgewithPossibleZikaVirusExposureUnitedStates,2016.MMWR
MorbMortalWklyRep201665:315.
79.OsterAM,BrooksJT,StrykerJE,etal.InterimGuidelinesforPreventionofSexualTransmissionofZika
VirusUnitedStates,2016.MMWRMorbMortalWklyRep201665:120.

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Zikavirusinfection:Evaluationofpregnantwomenandinfants

Topic107211Version2.0

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Zikavirusinfection:Evaluationofpregnantwomenandinfants

GRAPHICS
ikavirusinfection:Reportsofclinicalfindingsofinfantsand
Z
fetuses

Citation
BrasilPetal,
2016 [1]

Cases
88pregnant
women

Imagingfindings
Fetalabnormalitiesseenin
29percentof42US

Clinicalfindings
and/orlaboratory
findings
Fetaldeaths(at36and38
weeksofgestation).

performed(USperformed
at20to40weeks).
Microcephaly,cerebral
calcifications,
ventriculomegaly,IUGR,
cerebellarand/orvermis
agenesis,megacisterna
magna,oligohydramnios,
abnormalmiddlecerebral
arteryDoppler.
SchulerFacciniL
etal,2016 [2]

35infantswith
microcephaly

CTandtransfontanellar
cranialUSperformed
findingsincluded:

(Furtherstudypending.)

Braincalcifications,
mainlyinthe
periventricular,
parenchymal,and
thalamicareasandin
thebasalganglia.
Ventricular
enlargement
secondaryto
cortical/subcortical
atrophy.
MartinesRBetal,
2016 [3]

MlakarJetal,
2016 [4]

Fourinfantstwo

(Noneperformed.)

with
microcephalywho
diedwithin20
hoursofbirth,
andtwofetal
losses
(miscarriagesat
11and13
weeks)
Onepregnancy
terminationat29
weeks

Placentaandinfantbrain
positiveforZikaviralRNA
andantigens.

USat29weeks
demonstratedmicrocephaly
andintracranial

Zikavirusdetectedinbrain
viareversetranscription
PCRtestingandEM.

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Zikavirusinfection:Evaluationofpregnantwomenandinfants

calcificationsanearlierUS
performedduringthe
secondtrimesterdidnot
detectanyabnormalities.
CalvetGetal,
2016 [5]

Twopregnant
womenwith
symptomsofZika
virusinfectionin
firsttrimester

USat22weeksshowed
microcephalyinbothcases.

Amnioticfluidobtainedat
28weeksdemonstrated
ZikavirusRNAZikavirus
RNAwasnotdetectablein
bloodorurineineither
case.

SarnoMetal,
2016 [6]

Onestillbirthat
32weeks

USinthesecondandthird
trimestersdemonstrated
severemicrocephaly,
hydranencephaly,
intracranialcalcifications,
destructivelesionsof

Hydropsfetalis,
microcephaly,and
hydranencephaly.*Zika
virusRNAwasdetectablein
centralnervoussystem
tissuesandamnioticfluid.

posteriorfossa,andhydrops
(hydrothorax,ascites,
subcutaneousedema).
DriggersRWetal,
2016 [7]

HazinANetal,
2016 [8]

Onematernal

Fetalheadcircumference

infectionat11
weeks
pregnancy
terminationat21
weeks

decreasedfromthe47 thto
24 thpercentilebetween16
and21weeksofgestation.
Ventriculomegaly,cortical
thinning,hypoplasticcorpus
callosum.

23infantswith
microcephaly

CTfindings:
Intracranial
calcifications(all

ZikavirusRNAwas
detectedinmaternalserum
at16and21weeks.Fetal
braindemonstrateddiffuse
cerebralcorticalthinning
andZikaviruswasdetected
byRNAandculture.
CSFwaspositiveforZika
virusIgMinsevenoutof
sevencases.

cases)mainlyin
frontalandparietal
lobesoftenatthe
corticomedullary
junction.
Ventriculomegaly(all
cases)severein
approximatelyhalf.
Globalhypogyrationof
thecerebralcortex
(allcases)severein
morethanthree
fourths.
Abnormalwhite
matterhypodensity
(inallcases).
deFatimaVasco
AragaoMetal,
[9]

23infantswith
microcephaly

CT/MRIfindings:
Intracranial

CSFwaspositiveforZika
virusIgMinsevencases,

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Zikavirusinfection:Evaluationofpregnantwomenandinfants

2016 [9]

calcifications(junction
betweencorticaland
subcorticalwhite
matterinallcases,
basalganglia,
periventricular,
brainstem,
cerebellum).

17caseshadnodata.

Simplifiedgyral
patternandother
cortical
malformations.
Ventriculomegaly.
Hypogeneticor
hypoplasticcorpus
callosum
abnormalities.
Cerebellumor
brainstemhypoplasia
andenlargedcisterna
magna.
Decreasedbrain
volume.
Delayedmyelination.
US:ultrasoundCT:computedtomographyPCR:polymerasechainreactionEM:electronmicroscopy
MRI:magneticresonanceimagingCSF:cerebrospinalfluidIgM:immunoglobulinMIUGR:intrauterine
growthrestriction.
*Hydranencephalyistheabsenceorpartialdestructionofcerebralhemisphereswithcerebrospinalfluid
intheremainingcranialcavity.
References:
1.BrasilP,PereiraJPJr,RajaGabagliaC,etal.ZikavirusinfectioninpregnantwomeninRiode
JaneiroPreliminaryreport.NEnglJMed2016.
2.SchulerFacciniL,RibeiroEM,FeitosaIM,etal.PossibleassociationbetweenZikavirusinfection
andmicrocephalyBrazil,2015.MMWRMorbMortalWklyRep201665:59.
3.MartinesRB,BhatnagarJ,KeatingMK,etal.Notesfromthefield:EvidenceofZikavirusinfection
inbrainandplacentaltissuesfromtwocongenitallyinfectednewbornsandtwofetallosses
Brazil,2015.MMWRMorbMortalWklyRep201665:159.
4.MlakarJ,KorvaM,TulN,etal.Zikavirusassociatedwithmicrocephaly.NEnglJMed2016
374:951.
5.CalvetG,AguiarRS,MeloAS,etal.DetectionandsequencingofZikavirusfromamnioticfluidof
fetuseswithmicrocephalyinBrazil:acasestudy.LancetInfectDis2016.
6.SarnoM,SacramentoGA,KhouriR,etal.Zikavirusinfectionandstillbirths:Acaseofhydrops
fetalis,hydranencephalyandfetaldemise.PLoSNeglTropDis201610:e0004517.
7.DriggersRW,HoCY,KorhonenEM,etal.Zikavirusinfectionwithprolongedmaternalviremiaand
fetalbrainabnormalities.NEnglJMed2016.
8.HazinAN,PorettiA,DiCavalcantiSouzaCruzD,etal.Computedtomographicfindingsin
microcephalyassociatedwithZikavirus.NEnglJMed2016.
9.deFatimaVascoAragaoM,vanderLindenV,BrainerLimaAM,etal.Clinicalfeaturesand
http://www.uptodate.com.aure.unab.edu.co/contents/zikavirusinfectionevaluationofpregnantwomenandinfants?topicKey=ID%2F107211&elapsedTimeM

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Zikavirusinfection:Evaluationofpregnantwomenandinfants

neuroimaging(CTandMRI)findingsinpresumedZikavirusrelatedcongenitalinfectionand
microcephaly:retrospectivecaseseriesstudy.BMJ2016353:i1901.
Graphic107662Version2.0

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Zikavirusinfection:Evaluationofpregnantwomenandinfants

Internationalbirthheadcircumferencecentiles
Boys

Numberof
observations

Girls

Centilesforheadcircumference
(cm)
3 rd

10 th

50 th

90 th

97 th

Numberof
observations

Centilesforheadcircum
(cm)
3 rd

10 th

50 th

33
weeks

33

28.25

29.11

30.88

32.71

33.62

17

27.92

28.76

30.46

34
weeks

48

28.93

29.76

31.47

33.23

34.11

65

28.64

29.44

31.08

127

29.56

30.37

32.02

33.73

34.58

111

29.28

30.06

31.64

36
weeks

322

30.15

30.93

32.53

34.19

35.02

293

29.87

30.62

32.14

37
weeks

848

30.69

31.46

33.02

34.63

35.43

798

30.40

31.13

32.61

38
weeks

2032

31.21

31.95

33.47

35.04

35.83

1783

30.88

31.59

33.03

39
weeks

2985

31.69

32.42

33.90

35.44

36.20

2849

31.32

32.01

33.41

40
weeks

2532

32.15

32.86

34.31

35.81

36.56

2486

31.72

32.39

33.76

41
weeks

1147

32.58

33.28

34.70

36.17

36.91

1180

32.08

32.74

34.08

42
weeks

204

32.99

33.68

35.07

36.52

37.24

218

32.41

33.06

34.37

Total

10,278

9800

35
weeks

Internationalstandardsfornewbornheadcircumferencebygestationalageandsexfromthe
NewbornCrossSectionalStudyoftheINTERGROWTH21 stProject.Thetableshowssmoothed
centilesforbirthheadcircumferenceofboysandgirlsaccordingtogestationalage.
cm:centimeter.
Reproducedfrom:VillarJ,CheikhIsmailL,VictoraCG,etal.Internationalstandardsfornewbornweight,
length,andheadcircumferencebygestationalageandsex:theNewbornCrossSectionalStudyofthe
INTERGROWTH21stProject.Lancet2014384:857.TableusedwiththepermissionofElsevierInc.All
rightsreserved.
Graphic107271Version1.0

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Zikavirusinfection:Evaluationofpregnantwomenandinfants

Recommendedclinicalevaluationandlaboratorytestingforinfants
withpossiblecongenitalZikavirusinfection
ForallinfantswithpossiblecongenitalZikavirusinfection,performthe
following:
Comprehensivephysicalexamination,includingcarefulmeasurementoftheoccipitofrontal
circumference,length,weight,andassessmentofgestationalage.
Evaluationforneurologicabnormalities,dysmorphicfeatures,splenomegaly,hepatomegaly,
andrashorotherskinlesions.Fullbodyphotographsandanyrash,skinlesions,or
dysmorphicfeaturesshouldbedocumented.Ifanabnormalityisnoted,consultationwithan
appropriatespecialistisrecommended.
Cranialultrasound,unlessprenatalultrasoundresultsfromthirdtrimesterdemonstratedno
abnormalitiesofthebrain.
Evaluationofhearingbyevokedotoacousticemissionstestingorauditorybrainstem
responsetesting,eitherbeforedischargefromthehospitalorwithinonemonthafterbirth.
Infantswithabnormalinitialhearingscreensshouldbereferredtoanaudiologistforfurther
evaluation.
Ophthalmologicevaluation,includingexaminationoftheretina,eitherbeforedischargefrom
thehospitalorwithinonemonthafterbirth.Infantswithabnormalinitialeyeevaluation
shouldbereferredtoapediatricophthalmologistforfurtherevaluation.
Otherevaluationsspecifictotheinfant'sclinicalpresentation.

Forinfantswithmicrocephalyorintracranialcalcifications,additional
evaluationincludesthefollowing:
Consultationwithaclinicalgeneticistordysmorphologist.
Consultationwithapediatricneurologisttodetermineappropriatebrainimagingand
additionalevaluation(eg,ultrasound,computerizedtomographyscan,magneticresonance
imaging,andelectroencephalogram).
Testingforothercongenitalinfectionssuchassyphilis,toxoplasmosis,rubella,
cytomegalovirusinfection,lymphocyticchoriomeningitisvirusinfection,andherpessimplex
virusinfections.Considerconsultingapediatricinfectiousdiseasespecialist.
Completebloodcount,plateletcount,andliverfunctionandenzymetests,includingalanine
aminotransferase,aspartateaminotransferase,andbilirubin.
Considerationofgeneticandotherteratogeniccausesbasedonadditionalcongenital
anomaliesthatareidentifiedthroughclinicalexaminationandimagingstudies.
Reproducedfrom:StaplesJE,DziubanEJ,FischerM,etal.InterimGuidelinesfortheEvaluationand
TestingofInfantswithPossibleCongenitalZikaVirusInfectionUnitedStates,2016.MMWRMorb
MortalWklyRep201665:1.
Graphic106389Version1.0

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ContributorDisclosures
EdwardRBMcCabe,MD,PhDNothingtodisclose.MartinSHirsch,MDNothingtodisclose.CharlesJ
Lockwood,MD,MHCMConsultant/AdvisoryBoards:Celula[Aneuploidyscreening(Nocurrentproductsordrugs
intheUS)].DeborahLevine,MDNothingtodisclose.VanessaABarss,MD,FACOGNothingtodisclose.
ElinorLBaron,MD,DTMHNothingtodisclose.
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovided
tosupportthecontent.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDate
standardsofevidence.
Conflictofinterestpolicy

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