Twin Pregnancy - Prenatal Issues PDF

9/5/2016
Twinpregnancy:Prenatalissues
OfficialreprintfromUpToDate
www.uptodate.com2016UpToDate
Authors
StephenTChasen,MD
FrankAChervenak,MD
SectionEditors
CharlesJLockwood,MD,MHCM
DeborahLevine,MD
DeputyEditor
VanessaABarss,MD,FACOG
Contributordisclosures
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Apr2016.|Thistopiclastupdated:Mar30,2016.
INTRODUCTIONTwinpregnancyisassociatedwithhigherratesofalmosteverypotentialcomplicationof
pregnancy,withtheexceptionsofposttermpregnancyandmacrosomia.Themostseriousriskisspontaneous
pretermdelivery,whichplaysamajorroleintheincreasedperinatalmortalityandshorttermandlongterm
morbidityobservedintheseinfants.Higherratesoffetalgrowthrestrictionandcongenitalanomaliesalso
contributetoadverseoutcomeintwinbirths.Inaddition,monochorionictwinsareatriskforcomplications
uniquetothesepregnancies,suchastwintwintransfusionsyndrome(TTTS),whichcanbelethalor
associatedwithseriousmorbidity.
Thistopicwillprovideanoverviewoftheantepartumcareofwomenwithtwinpregnancy.Intrapartum
managementisreviewedseparately.(See"Twinpregnancy:Laboranddelivery".)
ROLEOFEARLYULTRASOUNDEXAMINATIONUltrasoundexaminationistheonlysafeandreliable
methodfordefinitivediagnosisoftwingestation.Earlyultrasoundassessmentalsoprovidesaccurate
estimationofgestationalage,whichisimportantinallpregnancies,butparticularlyimportantinmanagementof
twinpregnanciesbecauseofthehigherrisksforpretermdeliveryandgrowthrestriction.Inaddition,chorionicity
andamnionicitycanbedeterminedbyultrasoundexamination(see'Assessmentofchorionicity'below).Thisis
criticalbecausemonochorionictwinshaveasharedfetoplacentalcirculation,whichputsthematriskfor
specificseriouspregnancycomplications,suchastwintwintransfusionsyndromeandtwinanemia
polycythemiasequence[15].Thesecomplicationsincreasetheriskforneurologicmorbidityandperinatal
mortalityinmonochorionictwinscomparedwithdichorionictwins[2,3,69].Inadditiontothecomplications
associatedwithmonochorionictwinning,monoamniotictwinsalsoareatriskforcordentanglementand
conjoinedtwins.
Mostpregnantwomeninresourcerichcountriesundergoroutinescreeningultrasoundexamination.
Randomizedtrialscomparingroutineultrasoundexaminationwithultrasoundperformedonlyforclinical
indicationshaveproventhatasignificantnumberoftwinpregnanciesarenotrecognizeduntilthethirdtrimester
ordeliveryinwomenwhodonotundergoroutineultrasoundexamination[10,11].Asanexample,theRADIUS
(RoutineAntenatalDiagnosticImagingwithUltrasoundStudy)studyofover15,000pregnantwomenreported
that38percentoftwinpregnanciesremainedunrecognizeduntilafter26weeksofgestationinwomenwhodid
nothavearoutinesecondtrimesterultrasoundexamination,and13percentoftwinswerenotdiagnoseduntil
delivery[10].TheHelsinkiUltrasoundTrialreportedsimilarfindings:Approximately25percentoftwin
pregnancieswerenotidentifieduntilafter21weeksofgestation[11].Inbothtrials,notwinpregnancieswere
missedonultrasoundexamination.
Apolicyofroutinefirstorsecondtrimesterultrasoundexaminationwoulddiagnosetwingestationsatatime
whenamnionicityandchorionicityareeasilydetermined[12].Prenatalultrasoundscreeningguidelinesvary
worldwide.IntheUnitedStates,theAmericanCollegeofObstetriciansandGynecologists(ACOG)doesnot
endorseroutineultrasoundexaminationbecause,inapopulationofwomenwithlowriskpregnancy,routine
diagnosticsonographyhasnotresultedinareductioninperinatalmorbidityandmortalityoralowerrateof
unnecessaryinterventionsinrandomizedtrials[10,11,13].Thismayberelatedtothesmallnumbersoftwinsin
thesetrialsandalackofastandardizedprotocolformanagementofmultiplegestations[14].ACOGendorses
ultrasoundexaminationwhentherearespecificindicationsforimaging,suchaswhentwinsaresuspected
becauseuterinesizeisgreaterthanexpectedformenstrualdates.(See"Routineprenatalultrasonographyasa
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screeningtool".)
AssessmentofchorionicityUltrasonographyisaneffectiveprenataltoolfordeterminingamnionicityand
chorionicity.Theoptimaltimeforperformingtheultrasoundexaminationisinthefirsttrimesterafter7weeks
(sensitivity98percent[15]),withlowerbutacceptableaccuracyintheearlysecondtrimester(sensitivity90
percent[15])[1622].Sonographicassessmentofthefetalmembranesismoredifficultandlessaccurateinthe
thirdtrimester,especiallyinthesettingofoligohydramnios.
Identificationoftwoseparateplacentasisahighlyreliableindicatorofdichorionictwins.Thisindicatoris
generallyonlyusefulinearlypregnancysinceseparateplacentasoftenappearfusedlateringestation.
Rarely,amonochorionicplacentathatisbilobedorhasasuccenturiatelobegivestheappearanceoftwo
separateplacentas[23].
Thepresence/absenceoftheintertwinmembraneshouldbedeterminedanditscharacteristicsassessed
earlyinpregnancy.
Theintertwinmembraneisabsentinamonochorionic/monoamniotictwinpregnancy.Visualizingthe
intertwinmembranebecomesmoredifficultwithadvancinggestationalagebecauseoffetal
crowding,progressivethinningofthemembrane,and,insomecases,developmentof
oligohydramniosinoneorbothsacs.Thesefactorsmayleadtoafalsediagnosisof
monochorionic/monoamniotictwins.Ontheotherhand,monochorionic/monoamniotictwinsmaybe
misdiagnosedasmonochorionic/diamniotictwinswhenseparationoftheamnionandchorionis
mistakenforanintertwinmembrane.
Anintertwinmembranewiththe"twinpeak"or"lambda"signindicatesdichorionictwins.Thetwin
peakorlambdasignreferstoatriangularprojectionoftissuethatextendsbetweenlayersofthe
intertwinmembranefromafuseddichorionicplacenta(image1)[24].Itisbestseenat10to14
weeks,becomeslessprominentafter20weeksofgestation,andmaydisappear.
Anadditionalcluethattwinsaredichorionicisthattheintertwinmembraneisthickerwith
dichorionicthanmonochorionictwinssincethedichorionic/diamnioticmembraneconsistsoffour
layers(ie,twolayersofbothamnionandchorion)(image2),whereastheintertwinmembraneina
monochorionic/diamnioticpregnancyonlyconsistsoftwolayersofamnion(image3).Thereisno
consensusaboutthecutoffbetweenthinandthickmembranesthresholdsof1.5to2mminthe
firsttrimesterhavebeensuggested[20,25].Thedifferenceinmembranethicknessislessobvious
laterinpregnancy[26,27].
Anintertwinmembranewiththe"T"signindicatesamonochorionicplacenta.Thissignreferstothe
appearanceofthethinintertwinmembranecomposedoftwoamnionsasittakesofffromthe
placentaata90degreeangle.
Thenumberofchorionandamnionmembranelayersintheintertwinmembranecanbecounted,but
itistechnicallydifficulttherefore,thismethodisnotcommonlyemployed.Itisbestaccomplished
between16and24weeksofgestationusinghighresolution,magnifiedimageswiththemembrane
perpendiculartotheultrasoundbeam.
Afterthefirsttrimester,identificationoffetusesofdifferentsexisahighlyreliablemeansofconfirminga
dichorionicpregnancy.
Inastudyincludingover600twinpregnanciesat11to14weeksofgestationatatertiaryreferralcenter,useof
theTsign,lambdasign,andnumberofplacentasfordeterminingmonochorionicityhadsensitivityof100
percentandspecificityof99.8percent,withonlyonedichorionicpregnancyincorrectlyassignedas
monochorionic[28].AplacentalhematomaprecludeddiagnosisoftheTorlambdasignintheincorrectly
assignedpregnancy.Othersmallerstudieshavereportedsensitivityof90to100percentandspecificityof97.4
to99.5percentusingthesemarkersandfetalsex.Thelowersensitivitiesinsomestudiesmayberelatedto
assessmentveryearly(<7weeks)inthefirsttrimester.
OthersignificantfindingsInadditiontoassessmentofgestationalage,numberoffetuses,and
amnionicity/chorionicity,firsttrimesterultrasoundexaminationmaydetectabnormalitiesassociatedwith
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adverseoutcome.Theseincludecongenitalanomalies,crownrumplengthdiscordance(associatedwith
aneuploidy,twintwintransfusionsyndrome[TTTS]),enlargednuchaltranslucency(associatedwithaneuploidy,
congenitalanomalies,TTTS).(See"Diagnosisandoutcomeoffirsttrimestergrowthdelay",sectionon
'Discordanttwins'and"Firsttrimestercystichygromaandincreasednuchaltranslucency".)
ZYGOSITYANDCHORIONICITYDizygoticorfraternaltwinsoccurfromovulationandfertilizationoftwo
oocytes,whichresultsindichorionic/diamnioticplacentationandtwoseparateplacentas.Rarecasesof
dizygotictwinswithmonochorionicplacentationafterassistedreproductivetechnology(ART)havebeen
reported,withunexplainedetiology[2932].
Monozygoticoridenticaltwinsresultfromovulationandfertilizationofasingleoocyte,withsubsequent
divisionofthezygote.Timingofeggdivisiongenerallydeterminesplacentation(figure1).Monozygotictwins
mayhavetwoseparateplacentasoroneplacentathatismonochorionic/monoamnioticor
monochorionic/diamniotic.However,casereportsofatypicaltwinning(eg,chimerictwins,mirrorimagetwins,
discordantmonozygotictwins,polarbodytwins)havepromptedhypothesesforothermechanismsof
monozygotictwinning[33].
Fromanimagingperspective,approximately80percentofdichorionicplacentasareassociatedwithdizygotic
twinsand20percentareassociatedwithmonozygotictwins.Allmonochorionicplacentasareassociatedwith
monozygotictwins,withtherareexceptionsdescribedaboveinpregnanciesconceivedbyART.
PREVALENCEANDEPIDEMIOLOGYTwinbirthsaccountforapproximately3percentoflivebirthsand
97percentofmultiplebirthsintheUnitedStates[34].Dizygotictwinsaremorecommonthanmonozygotic
twins,approximately70and30percentoftwins,respectively(intheabsenceofuseofassistedreproductive
technology[ART])[35].Theprevalenceofdizygotictwinsvariesamongpopulationswhereastheprevalenceof
monozygotictwinsisrelativelystableworldwideat3to5per1000births.
Themajorfactorsinfluencingtheprevalenceofdizygotictwinsare:
UseoffertilitystimulatingdrugsUseoffertilityenhancingtreatments(ARTandnonART)
substantiallyincreasestheprevalenceoftwinpregnancycomparedwithnaturalconception.These
therapiesaccountformostoftheincreaseintwinbirthsinrecentyears:IntheUnitedStatestwinbirths
increasedfrom1/53infantsin1980to1/29infantsin2014[34].Overonethirdofalltwininfantsbornin
theUnitedStatescanbeattributedtoiatrogenicinterventions(IVF,ovulationinduction,superovulation
plusintrauterineinsemination)[36].
Dizygotictwinsaremorecommoninpregnanciesconceivedwithinvitrofertilization(IVF)thanin
naturallyconceivedpregnancies(95percentversus70percent)sincedoubleembryotransferis
commonlyperformedaspartofIVF[35,37].Interestingly,IVFalsoappearstoincreasetheriskofembryo
cleavageresultinginmonozygotictwins.(See"Pregnancyoutcomeafterassistedreproductive
technology",sectionon'Monozygoticmultiples'.)
Dizygotictwinsarealsomorecommoninpregnanciesconceivedwithovulationinducingagentsalone
(withoutIVF)thaninnaturallyconceivedpregnanciessincethesedrugsincreasethelikelihoodof
ovulationandfertilizationofmultipleoocytes.
MaternalageAdvancingmaternalageisassociatedwithanincreasedprevalenceoftwinbirths.
Naturallyconceiveddizygotictwinningincreasesfourfoldbetweenage15andage35thismayberelated
torisingfolliclestimulatinghormoneconcentrationwithage[38].Olderwomenarealsomorelikelytouse
fertilitytreatments.Onethirdoftheincreaseinmultiplebirthsinrecentdecadeshasbeenattributedto
increasingageatchildbirth.
Althoughmaternalageaffectstheprevalenceoftwins,itdoesnotappeartoaffectpregnancyoutcome
significantly.Whenmatchedforchorionicity,women35yearsappeartohavethesameoralowerriskof
adverseperinataloutcomeasyoungerwomenwithtwinpregnanciesinobservationalstudies[3944].
Race/geographicareaSignificantethnic/racialvariationsintheprevalenceofnaturallyconceived
dizygotictwinsoccurworldwide.Inonereport:1.3/1000birthsinJapan,8/1000birthsinUnitedStates
andEurope,50/1000birthsinNigeria[45].
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ParityIncreasingparitycorrelateswithanincreasedlikelihoodoftwinbirth,evenafteradjustmentfor
maternalage[38].
FamilyhistoryTwinningappearstohaveageneticcomponentthatisexpressedinwomenbutcanbe
inheritedfromeitherparent[46].Thus,awomanisatincreasedriskofhavingtwinsifshehasafamily
historyoftwinbirths.Thefamilyhistoryofthebiologicfatherappearstohavelittleornoeffectonhis
partner'sriskofhavingtwinshowever,hecouldpassthefamilialtraittohisdaughter.Thistheoryis
supportedbygenemappingstudiesinanimalsandhumansthatfoundspecificgeneticmutations
expressedbyoocytesorovariancellswereatleastpartlyresponsiblefortwinning[46,47].
MaternalweightandheightObese(bodymassindex[BMI]30kg/m2)andtallwomen(65inches
[164cm])areatgreaterriskfortwinbirththanunderweight(BMI<20kg/m2)andshortwomen(<61
inches[155cm])[4850].
DietDietmaybeanimportantfactoraffectingthetwinningrateinsomegeographicareas,among
certainraces,andinwomenofparticularbodyhabitus[38,51,52].Asanexample,somestudieshave
reportedthatfolicacidsupplementationincreasedtherateoftwinning[53].However,therewereseveral
limitationstothesestudies,whichcouldhavebiasedtheresults.
RISKSANDOUTCOMES
Riskofearly,late,andpostnatallossEarlyspontaneousreductionfromtwintosingletonpregnancyis
common,andmaybeassociatedwithanincreasedriskoflatepregnancycomplications[54].Inonestudyof
549twinpregnancies,aninitialultrasoundexaminationwasperformed3.5to4.5weeksafterovulationand
repeatedeverytwoweeksuntil12weeksofgestation[55].Spontaneousreductionofonesac(vanishing
twin)occurredin27percentofpregnanciesdiagnosedastwinspriorto7weeksofgestationbothsacswere
lostin9percent.Interestingly,studieshaveconsistentlyshownthat,inpregnanciesconceivedusingassisted
reproductivetechnology(ART),therateofearlylossoftheentirepregnancyissignificantlylowerfortwinthan
singletongestations[56].
Ratesoflatefetalandinfantdeathareshowninthetable(table1).Infantmortalityintwinsissignificantly
higherthanthatofsingletons(table2)[57].
Chorionicityandamnionicityalsoplayarole.Whenbothfetusesarealiveat12weeksofgestation,onestudy
reportedthechanceofdeliveringatleastonelivebornneonatewas98.2percentfordichorionictwins,92.3
percentformonochorionicdiamniotictwins,and66.7percentformonochorionicmonoamniotictwins[58].The
chanceofdeliveringtwolivebornneonateswas96.0,86.2,and66.7percent,respectively.Thecohortincluded
3053dichorionictwins,544monochorionicdiamniotictwins,and24monochorionicmonoamniotictwinsfroma
Danishregistry.
Fetalcomplications
AlltwinsAlltwinpregnancieshavehigherratesofthefollowingfetalcomplicationsthansingleton
pregnancies,butlowerratesofposttermpregnancyandmacrosomia[59]:
Growthrestriction
Congenitalanomalies
Pretermdelivery
MonochorionictwinsThefollowingfetalcomplicationsareofparticularconcerninmonochorionictwin
pregnancies[15]:
Twintwintransfusionsyndrome(TTTS)Imbalancesinfetoplacentalbloodflowinthesharedplacental
circulationresultinTTTS,whichischaracterizedbyoligohydramniosinoneamnioticsacand
polyhydramniosintheothersac.Itisapotentiallylethaldisorderthatdevelopsin10to15percentof
monochorionictwins.(See"Twintwintransfusionsyndrome:Pathogenesisanddiagnosis"and"Twintwin
transfusionsyndrome:Management".)
Twinanemiapolycythemiasequence(TAPS)TAPSisavariantofTTTSinwhichonetwinisanemic
andtheothertwinispolycythemicbutwithoutamnioticfluidvolumediscordance.(See"Twintwin
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transfusionsyndrome:Pathogenesisanddiagnosis",sectionon'TAPS'.)
Twinreversedarterialperfusionsequence(TRAP)TRAPisararecomplicationofmonochorionictwins
inwhichalivingtwinperfusesanonliving(acardiac)twinthroughpatentvascularchannels.(See
"Diagnosisandmanagementoftwinreversedarterialperfusion(TRAP)sequence".)
SelectivefetalgrowthrestrictiondueunequalplacentalsharingSelectivegrowthrestrictionisvariously
definedasestimatedweightofonetwinbelowthe10thpercentileordiscordanceinestimatedtwin
weightsgreaterthan25percent.
Singlefetaldemiseofonetwinofamonochorionicpaircancausemorbidityormortalityinthecotwin
duetotheirsharedplacentalcirculation.(See'Deathofonetwin'below.)
Monochorionictwinshaveahigherrateofcongenitalanomaliesthandichorionictwinsandsingletons.
Theanomalieshaveahighrateofconcordance,butcanbediscordant.(See'Screeningforcongenital
anomalies'below.)
MonoamniotictwinsThefollowingfetalcomplicationsareofparticularconcerninmonoamniotictwin
pregnancies:
Intertwincordentanglement(see"Monoamniotictwinpregnancy",sectionon'Cordentanglement')
ConjoinedtwinsConjoinedtwinsareclassifiedaccordingtotheanatomicalsiteofunion(eg,chest,
head)withthesuffix"pagus"(meaningfixed,eg,thoracopagus).Findingsonultrasoundinclude
monoamnionicity,contiguousskin,sharedorgans,twinsthatstayinthesameorientationtooneanother,
fetalscoliosis,unusuallimbpositioning,andmorethanthreevesselsinthecord[60].Associated
congenitaldefectsunrelatedtotheareaoffusionarecommon,asisstillbirth.Detailedultrasonography
andechocardiography,possiblywithadditionalmagneticresonanceimaging,areessentialtodetermine
theextentofdeformity,tocounseltheparentsaboutprognosis,andtoprepareforpossiblepostnatal
surgicalmanagement[6063].Deliveryofpotentiallyviableinfantsisalwaysbycesarean.(See
"Monoamniotictwinpregnancy",sectionon'Conjoinedtwins'.)
MaternalrisksandcomplicationsAlthoughwomencarryingtwinsareathigherriskforsomeadverse
outcomesthanwomencarryingsingletons[64],chorionicitydoesnotappeartoimpactthisriskinmoststudies
[65].
MaternalhemodynamicchangesTwinpregnancyresultsingreatermaternalhemodynamicchanges
thansingletonpregnancy[6669].Womencarryingtwinshavea20percenthighercardiacoutputand10
to20percentgreaterincreaseinplasmavolumethanwomenwithsingletonpregnancy,whichincreases
theirriskofpulmonaryedemawhenotherriskfactorsarealsopresent[66,67].Physiologicalanemiais
common,eventhoughredcellmassincreasesmoreintwinpregnancythaninsingletonpregnancy.
GestationalhypertensionandpreeclampsiaGestationalhypertensionandpreeclampsiaaremore
commoninwomencarryingtwins.Inasecondaryanalysisofprospectivedatafromwomenwithtwin(n
=684)andsingleton(n=2946)gestationsenrolledinmulticentertrialsoflowdoseaspirinforprevention
ofpreeclampsia,ratesofgestationalhypertensionandpreeclampsiaweretwiceashighintwincompared
withsingletonpregnancies(13percentintwinsversus5to6percentinsingletonsforbothdisorders)
[70].EarlyseverepreeclampsiaandHELLPsyndrome(Hemolysis,ElevatedLiverenzymes,Low
Platelets)tendedtooccurmorefrequentlyinmultiplegestations.
Thediagnosis,management,andcourseofpreeclampsia/gestationalhypertensionarenotusually
affectedbythemultiplegestation[71],withsomeexceptions.Anumberofstudieshavereportedthat
maternaluricacidconcentrationincreaseswiththenumberoffetusesinbothnormotensiveand
preeclampticpregnancies,withtypicalvaluesof5.2and6.4mg/dL,respectively,intwinpregnancies[72
75].Inaddition,casereportshavedescribedresolutionofearlyseverepreeclampsiaupondeathofone
twin[7678].(See"Preeclampsia:Clinicalfeaturesanddiagnosis"and"Preeclampsia:Managementand
prognosis"and"Gestationalhypertension"and"Managementofhypertensioninpregnantandpostpartum
women".)
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GestationaldiabetesWhethergestationaldiabetesismorecommonintwinpregnanciesisunclear[79
83].Diagnosisandmanagementaresimilartothatinsingletonpregnancy.(See"Diabetesmellitusin
pregnancy:Screeninganddiagnosis"and"Gestationaldiabetesmellitus:Glycemiccontrolandmaternal
prognosis".)
AcutefattyliverAcutefattyliverisrarebutoccursmorefrequentlyinmultiplethansingleton
gestations.(See"Acutefattyliverofpregnancy".)
OtherOthermaternaldisordersobservedmoreofteninwomenwithmultiplegestationsincludepruritic
urticarialpapulesandplaquesofpregnancy(PUPPP),intrahepaticcholestasisofpregnancy,iron
deficiencyanemia,hyperemesisgravidarum,andthromboembolism[84,85].Theincreasedriskof
thrombosisrelates,atleastinpart,totheincreasedprevalenceofcesareandeliveryandbedrestinthese
pregnancies.(See"Dermatosesofpregnancy"and"Deepveinthrombosisinpregnancy:Epidemiology,
pathogenesis,anddiagnosis"and"Intrahepaticcholestasisofpregnancy"and"Treatmentandoutcomeof
nauseaandvomitingofpregnancy".)
Comparativeoutcomesofsingleton,twin,andtripletpregnancyComparativeoutcomes(otherthan
death)oftwinversussingletonandtripletpregnanciesareshowninthetable(table3).
PREGNANCYCOUNSELINGANDMANAGEMENTOurapproachtocounselingandmanagementof
womenwithtwinpregnanciesisdescribedbelow,andisgenerallyconsistentwithrecommendationsofmajor
organizationsworldwide(see'Guidelinesfromnationalorganizations'below).Clinicianswhoprovidecarefor
thesewomenshouldbeknowledgeableabouttheissuesinvolved.However,specializedantenatalclinicsfor
womenwithmultiplegestationshavenotbeenproventoimprovebirthoutcomescomparedwithstandardcare,
althoughdatafromrandomizedtrialsaresparse[86].
GestationalweightgainTheInstituteofMedicinerecommendsthefollowingcumulativeweightgainby
termforwomencarryingtwins[87]:
Bodymassindex(BMI)<18.5kg/m2(underweight)norecommendationduetoinsufficientdata
BMI18.5to24.9kg/m2(normalweight)weightgain37to54lbs(16.8to24.5kg)
BMI25.0to29.9kg/m2(overweight)weightgain31to50lbs(14.1to22.7kg)
BMI30.0kg/m2(obese)weightgain25to42lbs(11.4to19.1kg)
Thesethresholdsrepresentthe25ththrough75thpercentileweightgainsinwomenwhogavebirthtotwins
weighingatleast2500g[87].Incohortstudies,womenwithnormalprepregnancyBMIswhometorexceeded
theseguidelineshadfewerpretermbirthsandhigherbirthweightscomparedwithwomenwhodidnotmeetthe
minimumweightgainsuggestedbytheguidelines[88,89].Poorgestationalweightgainafter20weeksappears
tohaveagreaterimpactthanpoorfirsttrimesterweightgain[90].Otherguidelineshavealsobeendeveloped
[91].
Toachieveappropriategestationalweightgain,anormalweightwomanneedstoincreaseherdietaryintakeby
approximately300kcal/dayabovethatforasingletonpregnancyor600kcal/dayabovethatofanonpregnant
woman.After20weeksofgestation,weightgainshouldbeapproximately1.75pounds/weekforunderweight
womenandapproximately1.5pounds/weekfornormalweightwomen,withthesameorslightlylowerweekly
weightgaininoverweightandobesewomen.
VitaminsandmineralsDietaryorvitamin/mineralsupplementationshouldincludeadequateironandfolic
acid.Womenwithtwinsareatincreasedriskofdevelopinganemia.TheSocietyofMaternalFetalMedicine
recommendationsfordailytotalintakeofvitaminsandmineralsintwinpregnancyinclude[92]:
Folicacid1mgthroughoutpregnancy
Iron30mgthroughoutpregnancy
Wecheckhematocritinthefirsttrimesterandrepeattestingearlyinthethirdtrimester.Weincreaseironto60
mg/dayinanemicwomen.
ScreeningforDownsyndrome
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CombinedtestWesuggestofferingDownsyndromescreeningwiththefirsttrimestercombinedtest,
whichcanprovidefetusspecificriskassessment.Increasednuchaltranslucencyat>10and<14weeks
ofgestationisamarkerforDownsyndrome,otheraneuploidies,congenitalmalformations,and
developmentoftwintwintransfusionsyndrome(TTTS).(See"Firsttrimestercombinedtestand
integratedtestsforscreeningforDownsyndromeandtrisomy18",sectionon'Firsttrimestercombined
test'.)
Maternalserumanalyteinterpretationisproblematicintwinpregnanciessincebothtwinscontributetothe
analyteconcentrationandanalytelevelsmaybeaffectedbyearlylossofoneormoreembryosofa
multiplegestation[93,94].Measurementofnuchalthicknesscanimprovethedetectionrateandhelp
identifywhichfetusisaffected[95,96].Ina2014systematicreviewoffirsttrimestercombinedrisk
assessment(nuchaltranslucencyandmaternalserumanalytes)intwinpregnancies,testsensitivityin
dichorionictwinswas86percent(95%CI7394)andtestsensitivityinmonochorionictwinswas87
percent(95%CI5398)[97].Inourinstitution,firsttrimestercombinedriskassessmentidentifiedallsix
affectedpregnancies(fivediscordantandoneconcordantforDownsyndrome)atascreenpositiverateof
5percent,whilenuchaltranslucencyalonedetectedfiveofsixaffectedfetuses[96].Although
biochemicaltestingenhancedriskassessment,serumanalytelevelsinaffectedtwinpregnancieswere
closertothemedianlevelsthaninaffectedsingletonpregnancies.
Ofnote,thefalsepositiverateofnuchaltranslucencyscreeningishigherinmonochorionicthanin
dichorionictwinsbecauseincreasednuchaltranslucencycanbeanearlymanifestationofTTTSaswell
asamarkerofaneuploidy[98].Also,invitrofertilizationaffectsanalytevaluesusedinDownsyndrome
screeningandmaybeconsideredbysomelaboratorieswhencalculatingscreeningresultsintwins
conceivedbythismethod[99].(See"LaboratoryissuesrelatedtomaternalserumscreeningforDown
syndrome",sectionon'Invitrofertilization'.)
Anadditionalfactorcomplicatingprenataldiagnosisofmonozygotictwinsisthatrarelythesetwinshave
differentgenotypesduetofetalmosaicismorconfinedplacentalmosaicism[100105].Moreover,fetuses
withthesamegenotypemayhavedifferentphenotypesasanexample,onlyonefetusoftwinswith
Downsyndromemayhaveincreasednuchaltranslucency.Inaseriesofeightmonochorionictwinpairs
discordantfornuchaltranslucencywhowerekaryotyped,discordancewasamarkerforconcordant
chromosomeabnormalitiesinonetwinpairanddiscordantchromosomalabnormalitiesintwotwinpairs
[105].Forthesereasons,bothfetusesofamonozygoticpairshouldbekaryotypedwhenkaryotypingis
performed,althoughthismaynotbepossiblewithchorionicvillusbiopsy.Insomecases,amniocytes,as
wellasfetalblood,maybeneededtomakeanaccuratediagnosis.
NoninvasivescreeningusingcellfreeDNANoninvasiveprenatalscreeningforDownsyndrome
usingcellfreeDNAischallengingbecausethefetalcellfreeDNAinthematernalcirculationderivesfrom
eachfetus.Testingiscommerciallyavailablefortrisomies13,18,and21,althoughlessvalidationdata
areavailablefromtwingestationsthanfromsingletons[106109].Becauseitisimpossibletodetermine
whichtwinisabnormalbasedoncellfreeDNAanalysisalone,resultsarereportedfortheentire
pregnancy,andinvasivetestingisrequiredtodistinguishwhichtwin,ifeitherone,isaffected.
AnadditionalchallengeintwinpregnancyisthattheamountofcellfreeDNAcontributedbyeachtwinis
lowerthaninasingletonpregnancyandmaybequitedifferentforthetwofetuses[110].Oneapproach,
therefore,istobasetheassessmentofriskonthelowerfetalfractionofthetwins,ratherthanonthe
totalfetalfraction[111].
DiagnostictestingDiagnostictestingforfetalaneuploidyisdiscussedseparately.(See"Diagnostic
amniocentesis",sectionon'Multiplegestation'and"Chorionicvillussampling",sectionon'Multiple
gestations'.)
ScreeningforcongenitalanomaliesWesuggestananatomicsurveyat18to22weeksofgestation[15].
Theincidenceofcongenitalanomaliesisthreetofivefoldhigherinmonozygotictwinsthaninsingletonsor
dizygotictwins,andhigherinmonochorionicmonozygotictwinsthanindichorionicmonozygotictwins[35,112
115].Theconcordancerateofmajorcongenitalmalformationsinmonozygotictwinsisapproximately20
percent[116].Dizygotictwinshaveasimilarcongenitalanomalyrateassingletonsandtheanomalieshavea
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lowconcordancerate.
Twinsarenotpredisposedtoanyspecifictypeofcongenitalanomaly,althoughcongenitalheartdiseaseis
moreprevalentinmonochorionictwins,particularlythosewithTTTS[113].Inadditiontoananatomicsurveyat
18to20weeksofgestation,fetalechocardiographyissuggestedat18to22weeksbecause5to7.5percent
ofmonochorionictwinsreferredforroutinefetalechocardiographyhavecongenitalheartdiseaseinatleastone
twin[117119].
Thereportedaccuracyofultrasoundfordetectionoffetalanomaliesintwinsvariesbecauseofdifferencesin
ascertainmentpostnatallyandatpregnancytermination,criteriafordefiningananomaly,andoperator
capability.Ultrasoundexaminationcandetectthemajorityofmajormalformationsintwins,butshouldbe
performedbysonographersexperiencedinbothanomalydetectionandassessmentofmultiplegestation.
Thediagnosisofacongenitalanomalyinonetwinisespeciallyproblematicsincedecisionsregarding
monitoring,therapy,anddeliveryaffectbothfetuses.Expectantmanagement,pregnancytermination,and
selectivefeticideshouldallbediscussed,ifappropriateforthetypeofabnormalityandgestationalage.
Womenwhochoosetocontinuethepregnancyshouldunderstandhowtheanomalousfetusmightaffectthe
cotwin'soutcome(eg,pretermbirth,organdamage),includingtheroleofchorionicity.
Selectiveterminationoftheanomalousfetuswithdichorionicplacentationisasafeandeffectiveoptionin
experthands,althoughthereisariskofmiscarriageorpretermdeliveryofthenormalcotwin.Becauseof
theserisks,expectantmanagementmaybeasaferoptionifthetwinwiththeanomalyisnotexpectedtohave
prolongedsurvivalorafavorableoutcome(eg,trisomy18)[120].Anencephalyisanexceptionsinceitis
associatedwithpolyhydramniosandpretermbirth.Ifpolyhydramniosdevelopsintheanencephalictwin'ssac,
selectivefeticideoramniodrainageappearstoresultinlongergestationandhigherbirthweightintheviabletwin
thanexpectantmanagement[121,122].Inourpractice,wesuggestselectiveterminationwheneverafetal
anomalyincompatiblewithsurvivalisidentifiedinonetwinifthisanomalyisassociatedwithpolyhydramnios.
Wedonotrecommendamnioreductionunlessmaternalrespiratorycompromiseispresent.
Inmonochorionictwins,selectivefeticideisperformedbyobstructingoneumbilicalcord(eg,radiofrequencyor
laserablation,bipolarcoagulation,ligation)ratherthanintravascularinjectionofpotassiumchlorideordigoxinto
reducerisktothecotwinassociatedwithsharedcirculations[123,124].(See"Multifetalpregnancyreduction
andselectivetermination",sectionon'Selectivetermination'.)
Monitoringinthesecond/thirdtrimestersBecausemonochorionictwinpregnanciesareassociatedwith
greateranddifferentrisksthandichorionictwinspregnancies,monitoringisbased,inpart,onchorionicity,and
protocolsformonochorionictwinshaveinvolvedmoreintensivesurveillancethanprotocolsfordichorionic
twins(see'Monochorionictwins'below).Inapopulationbasedstudyincludingover9000twins,stillbirthrates
weresignificantlyhigherinmonochorionicthandichorionictwins:44.4versus12.2per1000births(relativerisk
[RR]3.695%CI:2.65.1)neonataldeathratesalsoweresignificantlyhigher:32.4versus21.4per1000live
births(RR1.595%CI1.042.2)[8].Inotherseriesofmonochorionictwinpregnancies,fetalmortalityranged
from6to13percentmostdeathsoccurredbefore24weeks[2,6,7,125].Afterthisstage,asystematicreview
foundtheprospectiveriskoffetaldeathperpregnancywaslower(<2.5percent)butremainedatleastthreefold
higherinmonochorionicthandichorionicpregnancies[126].
Monochorionicmonoamniotictwinsareathighestriskofadverseoutcomemanagementofthesepregnancies
isreviewedseparately.(See"Monoamniotictwinpregnancy".)
Itisimportanttoaccuratelyidentifyeachtwinconsistentlyoverserialexaminations.Thisisrelativelyeasyto
dowhenthetwinsareofdifferentsexes.Insamesextwins,eachtwinisidentifiedbasedonitsorientation
relativetotheothertwin:leftorrightlateralfortwinspositionednexttoeachotherandtop(fundal)orbottom
(cervical)fortwinspositionedvertically.Thepresentingtwininlaterallyorientedtwinsmayappeartochange
overtime,butthebottomtwinofverticallyorientedtwinsislikelytoremainthepresentingtwinthroughout
pregnancy[127].Documentationofthesitesofplacentalimplantation(anterior,posterior,lateral)andofthe
sitesandtypesofplacentalcordinsertion(eg,marginalversuscentralnormalversusvelamentous)isalso
useful.
EvaluationoffetalgrowthEvaluationoffetalgrowthisparticularlyimportantintwinpregnancybecause
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growthrestrictionandprematurityaremajorcausesofthehighermorbidity/mortalityratesintwinscompared
withsingletongestations[3,128135].Neurologicmorbidityisamajorconcern,andhasseveraletiologies(eg,
prematurity,hemodynamiceffectsfromdeathofonetwin,growthrestriction)[136].
Inthefirstandsecondtrimesters,thegrowthrateoftwinsisnotsignificantlydifferentfromthatofsingletons
[137].Inthethirdtrimester,particularlyafter30to32weeksofgestation,moststudieshavedescribedslower
fetalgrowthinuncomplicatedtwinpregnanciesthaninuncomplicatedsingletongestations[137,138].The
slowergrowthratehasbeenattributedtoplacentalcrowdingandanomalousumbilicalcordinsertion.
Growthcurveshavebeenderivedspecificallyfortwinsbutareoflimitedusefulnesssincetheywerederived
fromsmallpopulationsanddidnotconsiderchorionicityoroutcome.Weandothersfeelthatsingletongrowth
curvesarethebestpredictorofadverseoutcomeintwinpregnanciesandshouldbeusedforevaluatingtwins
forgrowthabnormalities[139].
Twingrowthshouldbemonitoredwithserialultrasoundexaminations.Discordanceincrownrumplengthmay
beobservedasearlyasthefirsttrimesterandpredictslaterweightdiscordance(see"Diagnosisandoutcome
offirsttrimestergrowthdelay",sectionon'Discordanttwins').Discordanceinbiometricmeasurements
associatedwithadverseobstetricandneonataloutcomemaybenotedasearlyasapproximately18weeksof
gestation[140,141].
Werecommendserialultrasoundexaminationsoftwinpregnanciesinthesecondandthirdtrimesterstoscreen
forfetalgrowthrestrictionandgrowthdiscordance,giventheriskofadverseoutcomeassociatedwiththese
conditions[142144](see'Chorionicitybasedfollowup'below).Althoughtheabilityofultrasoundtoaccurately
identifydiscordanttwins(sensitivity23to93percent,specificity60to98percent)andadverseperinatal
outcomeislimited[145149],fundalheightdeterminationisinsensitiveforidentifyingfetalgrowthabnormalities
intwins.Ifultrasoundexaminationidentifiesgrowthdiscordanceorgrowthrestrictionineithertwin,thenmore
intensivefetalmonitoringisinitiated,asinsingletons.(See"Twintwintransfusionsyndrome:Pathogenesis
anddiagnosis"and"Twintwintransfusionsyndrome:Management"and"Fetalgrowthrestriction:Evaluation
andmanagement",sectionon'Pregnancymanagement'.)
Growthabnormalitiesmanifestinthreeways:(1)onetwincanbesmallforgestationalage,(2)bothtwinscan
besmallforgestationalage,or(3)onetwincanbesignificantlysmallerthantheothertwin(ie,growth
discordance)althoughneitherissmallforgestationalage.Inalmosttwothirdsofdiscordanttwinpairs,the
smallertwinhasabirthweight<10thpercentile[130].Thereisnoconsensusregardingtheoptimumthreshold
fordefiningdiscordanceintwins.Discordanceinbirthweightrangingfrom15to40percenthasbeen
consideredpredictiveofadverseoutcome[129,131133,150152].Weuseanestimatedweightdifference20
percentasthethresholdfordefiningdiscordance,but25percentisalsocommonlyused.Approximately15
percentoftwinsare20percentdiscordantinweight[134].
Apopulationbasedserieswith128,168twinsetsreportedfetalgrowthlessthanthe10thpercentilewas
significantlymorecommonamonghighlydiscordanttwinsthannondiscordanttwins,60versus5percent
[132].Inaddition,theneonatalmortalityrateofthesmallertwinincreasedwithincreasingdiscordance:no
discordance(3.8/1000livebirths),15to19percentdiscordance(5.6/1000),20to24percentdiscordance
(8.5/1000),25to30percent(18.4/1000),and30percentormore(43.4/1000).Largetwinsofdiscordant
pairswerealsoatincreasedriskofneonatalmortality.
Anotherpopulationbasedserieswith269,287twinbirthsfoundasignificantlyincreasedriskofneonatal
deathwithbirthweightdiscordancy15percentforsamesextwins(assume30percentare
monochorionic[150])and30percentforthosewithdifferentsexes[153].Thelowerthresholdforrisk
withsamesextwinsmayberelatedtocomplicationsinmonochorionictwinning,whereasoppositesex
twinsare,withveryrareexception,dichorionic.
ThereisnoconvincingevidencethatDopplervelocimetryhasbenefitsfordetectionofgrowthrestrictionover
theuseofultrasoundalonetherefore,routineuseofDopplervelocimetryintwingestationsisnot
recommended[154,155].However,Dopplerultrasoundisusefulformonitoringpregnanciesinwhichthe
diagnosisofgrowthrestriction,discordance,orfetalanemiahasbeenmade.
AssessmentoffetalwellbeingThereisnoprovenbenefitfromroutineuseofantepartumfetaltesting
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(nonstresstest[NST],biophysicalprofile[BPP],amnioticfluidvolumedetermination,orDopplervelocimetry)
inuncomplicatedtwinpregnancies.However,antepartumfetalmonitoringintwinsiswidelypracticedbeginning
at32weeksofgestationbecauseoftheincreasedriskofstillbirthintwins,particularlymonochorionictwins
[156].Webeginweeklytestingroutinelyat32weeksofgestationinalltwinpregnancies,butearlierand/or
morefrequentlyifcomplications,suchasfetalgrowthrestriction,develop.Indichorionictwinpregnancies,the
AmericanCollegeofObstetriciansandGynecologistssuggestsreservingantenataltestingforgestations
complicatedbymaternalorfetaldisordersthatrequireantepartumtesting,suchasfetalgrowthrestriction
[157].
BothNSTsandBPPsarereliableintwingestations[158160].(See"Nonstresstestandcontractionstress
test"and"Thefetalbiophysicalprofile".)
Thebesttechniquetoassessamnioticfluidvolumeindiamniotictwingestationsisuncertain.Subjective
assessmentofthevolumeofamnioticfluidineachsacappearstobeasaccurateasquantitativeassessment.
(See"Assessmentofamnioticfluidvolume",sectionon'AFVassessmentintwins'.)
Chorionicitybasedfollowup
MonochorionictwinsOurapproachtomonitoringmonochorionictwinsisoutlinedinthealgorithm
(algorithm1).Wesuggestmonitoringmonochorionic/diamnioticpregnanciesbeginningat16to18weeksby
assessmentofamnioticfluidvolumeandfetalbladderinbothtwinsforearlydetectionofTTTSwebegin
measurementofmiddlecerebralarterypeaksystolicvelocity(MCAPSV)inbothfetusesat26to28weeksfor
earlydetectionoftwinanemiapolycythemiasequence(TAPS)[161,162],althoughthereisnoconsensusabout
routineperformanceofmiddlecerebralarteryDopplertoassessforTAPS[15,163].Thereareinadequatedata
todeterminetheoptimalfrequencyofmonitoring,butmeasurementeverytwotothreeweeksisreasonable,
withmorefrequentmonitoringifabnormalitiesaredetected.ThediagnosisofTTTSisbasedonthe
sonographicfindingofoligohydramnios(maximalverticalpocket<2cm)andpolyhydramnios(maximalvertical
pocket>8cmbefore20weeksand>10cmafter20weeks)(see"Twintwintransfusionsyndrome:
Pathogenesisanddiagnosis",sectionon'Clinicalmanifestationsanddiagnosis'and"Twintwintransfusion
syndrome:Pathogenesisanddiagnosis",sectionon'MonitoringforTTTS').ThediagnosisofTAPSisbasedon
MCAPSVgreaterthan1.5multiplesofmedian(MoM)inonetwinandlessthan0.8MoMintheothertwin.
(See"Twintwintransfusionsyndrome:Pathogenesisanddiagnosis",sectionon'TAPS'.)
FetalgrowthisevaluatedeverytwotofourweekswhenultrasoundisperformedtomonitorforTTTSand
TAPS.Monochorionicplacentationisasignificantriskfactorfordiscordantgrowth(see'Evaluationoffetal
growth'above)duetounequalsharingoftheplacentaorTTTS[6,164166].Monochorionicplacentationalso
appearstohaveasmallindependentadverseeffectonintrauterinegrowthcomparedwithdichorionic
placentation[167].
DichorionictwinsClosefetalmonitoringforTTTSandTAPSisunnecessaryindichorionictwins.
Weperformanultrasoundexaminationeveryfourtosixweeksafter20weeksofgestationtomonitorfetal
growth,asfetalgrowthdecelerationleadingtodiscordancyisoptimallydetectedbetween20and28weeksof
gestation[164].Manytwinfetuseswithgrowthabnormalitiescanbeidentifiedby20to24weeks,soifthereis
noevidenceofgrowthabnormalityatthattime,thenfrequentscanningmightnotbenecessary[168]however,
wecontinueserialultrasoundassessmentuntildelivery.Scanningeverytwoweeksdetectedmore
abnormalitiesthatpromptedearlydeliveryinonestudy,butwhetherthisresultedinbetterperinataloutcomes
wasnotdetermined[169].
PREVENTIONANDMANAGEMENTOFSELECTEDPREGNANCYCOMPLICATIONS
DeathofonetwinSinglefetaldeathintwinpregnanciesisnotrare.Inoneseriesof3621twinpregnancies
withtwolivefetusesatthenuchaltranslucencyscanatabout12weeksofgestation,singlefetaldeathbefore
22weeksofgestationoccurredin0.7percentofdichorionictwinpregnanciesand0.9percentofmonochorionic
diamniotictwinpregnancies[58].Singlefetaldeathat22weeksoccurredin0.6percentofdichorionictwin
pregnanciesand1.7percentofmonochorionicdiamniotictwinpregnancies.Obviously,thefrequencyofsingle
fetaldemiseishigherifearlylosses(before12weeks)areincluded.
Becauseoftheplacentalvascularanastomosesbetweenmonochorionictwins,theintrauterinedeathofone
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twininamonochorionicpregnancycancauseacutehypotension,anemia,andischemiainthecotwindueto
exsanguinationintothelowpressurevascularsystemofthedeceasedtwin,resultinginmorbidityordeathof
thecotwin.Inadichorionicpregnancy,deathofonetwinmayreflectanadverseintrauterineenvironmentthat
couldalsoplacethecotwinatrisk,buttheriskismuchlower.
Thetypeandmagnitudeoftheseriskswereillustratedina2011systematicreviewof22studiesthatevaluated
theprognosisofthecotwinfollowingasingletwindeathinvariousclinicalsettings[170].Following
intrauterinedemiseofonetwin:
Theratesoffetaldemiseofthecotwininmonochorionicanddichorionicpregnancieswere15and3
percent,respectively(oddsratio[OR]5.24,95%CI1.7515.73).
Theratesofpretermbirthinmonochorionicanddichorionicpregnancieswere68and54percent,
respectively(OR1.10,95%CI0.343.51).
Theratesofabnormalpostnatalcranialimaginginmonochorionicanddichorionicpregnancieswere34
and16percent,respectively(OR3.25,95%CI0.6616.1).
Theratesofneurodevelopmentalimpairmentofthecotwininmonochorionicanddichorionicpregnancies
were26and2percent,respectively(OR4.81,95%CI1.3916.64).
Whiletherisktothesurvivingcotwininamonochorionicpregnancyisclearwhendeathofonetwinoccurs
lateinpregnancy,theriskwithdeathofonetwininthefirsttrimesterisunclear.Ithasbeenhypothesizedthat
congenitalanomaliesandcerebralpalsymaybeattributabletoearlyfetallossofoneconceptusinatwin
gestation[171].AretrospectivestudyusingdatafromthepopulationbasedNorthernMultiplePregnancy
RegisterandNorthernCongenitalAbnormalitySurveyintheUnitedKingdomprovidedsupportforthistheory.
Theriskofacongenitalanomalyinthesurvivorfollowinglossofacoconceptusbefore16weeksofgestation
wasmorethantwicethatintwinbirths[172].Thesedatamayreflect,atleastinpart,theknownincreasedrisk
ofconcordantanddiscordantcongenitalanomaliesinmonozygotictwins,whichmayleadtoearlyinutero
deathofonetwiniftheanomalyissevere.Prospectivestudiesareneededtoclarifytheserelationships.
Comparedwithpregnanciesconceivedassingletons,additionalriskstothesurvivorafterdemiseofonetwin
includea120gramreductioninmeanbirthweight,anincreasedriskofsmallforgestationalagebirth,andan
increasedriskofpretermbirth[45].
ManagementTheoptimalmanagementofpregnanciesinwhichtwinislikelytodieorhasdiedis
unclear.
DichorionictwinsIndichorionictwins,deathofonetwinisnot,byitself,astrongindicationfor
deliveryofthesurvivingtwin.However,ifaconditionaffectingbothtwinsispresent(eg,preeclampsia,
chorioamnionitis),thenclosesurveillanceandtimelydeliveryofthesurvivingtwinareindicatedtoprevent
asecondfetalloss.
MonochorionictwinsAsdiscussedabove,deathofonetwinofamonochorionicpairmayhavedirect
harmfuleffectsonthesurvivorbecauseofintertwinvascularanastomoses.Thehemodynamicchanges
thatoccurupondeathofonetwinareimmediatetherefore,promptdeliveryafterdeathtopreventdamage
tothesurvivorappearstobefutile[173].Whenonetwindiespriortoviability,ourpracticeistodiscuss
theoptionofpregnancytermination,although,asstatedabove,therisktothecotwinisnotclearwhen
thedeathoccursinthefirsttrimester.Ultrasoundandmagneticresonanceevaluationofthesurvivingco
twincanidentifysignsofbraininjury,suchaswhitematterlesionsorintracranialhemorrhage,which
developovertime.However,theabilityofimagingstudiestopredictorexcludefetalbraininjuryinthis
settingisunknown.
Iffetalassessmentafter26weeksofgestationsuggestsimpendingdeathratherthandemiseofonetwin
ofamonochorionicpair,wesuggestpromptdeliveryofbothtwinsratherthanexpectantmanagement
giventhehighriskofneurologicimpairmentinthesurvivingcotwin.
Itisnotnecessarytomonitorformaternalcoagulopathysinceitisrare,althoughaplateletcountand
fibrinogenlevelaredesirablepriortodelivery.Maternalhypofibrinogenemiaordisseminatedintravascular
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coagulationfollowingdeathofonefetusofamultiplegestationhasbeendescribedinonlyafewcase
reports[174178].Althoughsomeexpertshavetreatedthesewomenwithashortcourseofheparin,
spontaneousresolutionofhypofibrinogenemiaoccurswithouttherapy.Weonlyconsiderheparintherapyif
thereisactivehypofibrinogemiarelatedbleedingorhypofibrinogemiarelatedriskofactivebleeding(eg,
placentaprevia,impendinglabor),oriftherearethromboticcomplications.Wehavenotseenclinical
bleedingwithhypofibrinogenemiainthissetting.(See"Clinicalfeatures,diagnosis,andtreatmentof
disseminatedintravascularcoagulationinadults".)
AntiDimmuneglobulinprophylaxisisrecommendedforRh(D)negativewomen.(See"PreventionofRh(D)
alloimmunizationinpregnancy".)
PretermlaboranddeliveryThemajorsourceofperinatalmorbidityandmortalityintwingestationsis
spontaneouspretermbirth.Theincreasedriskofspontaneouspretermbirthintwinsversussingletonsmaybe
related,atleastinpart,todifferencesinmyometrialcontractilityrelatedtoincreasedmyometrialdistension
[179,180].IntheUnitedStates,thepretermdeliveryrateintwinsis59percentbefore37completedweeksof
gestationand11percentbefore32completedweeks(55percentoftwinsarelowbirthweight[<2500g]and10
percentareverylowbirthweight[<1500g]),althoughnotallofthepretermdeliveriesarespontaneous[34].
Interestingly,malemaletwinpairsseemtobeathighestriskofpretermbirth[181183].Otherriskfactorsfor
pretermbirth,includingtherelationshipbetweenpriorpretermbirthandpretermbirthinthecurrentpregnancy,
arereviewedseparately.(See"Pretermbirth:Riskfactorsandinterventionsforriskreduction",sectionon
'Historyofspontaneouspretermbirth'.)
Severalstudieshavereportedthatneonataloutcomeissimilarforsingletons,twins,andtripletswhoare
matchedforgestationalage[184,185].However,actualoutcomesarenotequivalentbecausetheaverage
lengthofgestationforsingletons,twins,andtripletsisapproximately39,35,and32weeksofgestation,
respectively.
Multiplegestationsthatexperiencespontaneousreductiondeliverearlierthannonreducedpregnancieswiththe
samenumberoffetuses.Inonelargeseries,tripletpregnanciesthatspontaneouslyreducedtotwinshad
significantlymorepretermbirths<32weeksthantwinsthatdidnotoriginatefromatripletpregnancy(27versus
12percentOR3.09,95%CI1.635.87),andthelengthofgestationwasonaverage1.5weeksshorter[186].
Thedifferencebetweengroupsindelivery<37weekswasnotstatisticallysignificant(83percentversus73
percentintwinswithoutspontaneousreduction).
PredictionofpretermlaboranddeliveryWedonotroutinelyperformanytestsinanattemptto
identifyasymptomatictwinpregnanciesathighestriskforpretermlaboranddelivery.Althoughanelevated
fetalfibronectinlevel[187189]orshortcervicallengthonultrasoundexamination[190,191]maypredict
pregnanciesatparticularlyincreasedriskofpretermdelivery,nointerventionhasbeenproventobeeffectivein
reducingpretermbirthratesandthepredictivevalueislowinasymptomaticpatients(table4).Homeuterine
activitymonitoring(HUAM)effectivelydetectscontractionshowever,therearenoconvincingdatathatuseof
HUAMresultsinanimprovementanymeasureofneonataloutcome[192].(See"Secondtrimesterevaluation
ofcervicallengthforpredictionofspontaneouspretermbirth",sectionon'Multiplegestation'.)
UnproveninterventionstopreventordelaypretermlaborTheauthorsdonotuseanyofthefollowing
interventionsintheroutinemanagementoftwinpregnanciesasnonehasbeenproventobeeffective.Allhave
beenevaluatedaspotentialmethodsforreducingtheriskofpretermdeliveryinasymptomatictwingestations.
SupplementalprogesteroneTheevidencedoesnotsupportroutineuseofprogesterone
supplementationtoreducetheriskofpretermdeliveryordeathintwinpregnancies.Thesedataare
reviewedseparately.(See"Progesteronesupplementationtoreducetheriskofspontaneouspreterm
birth",sectionon'Twinpregnancy'.)
Whetherprogesteronesupplementalimprovespregnancyoutcomeinselectedtwinpregnancies,suchas
thosewithashortcervix,isunderinvestigation.Ina2015metaanalysisofindividualpatientdatafrom13
trialsofwomenwithtwingestationsrandomlyassignedtoreceiveprogesteronesupplementation
(intramuscularorvaginal)ornotreatment/placebo,thesubgroupoftwinpregnancieswithashortcervix
(25mm)before24weekstreatedwithvaginalprogesteronehadasignificantreductioninadverse
perinataloutcome(relativerisk[RR]0.56,95%CI0.420.7514/52[27percent]versus21/56[38
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percent])[193].Ifthesefindingsareconfirmedinlargerandomizedtrialsfocusedonthispopulation,we
wouldconsiderroutinecervicallengthscreeningintwinpregnanciesandprogesteronesupplementationin
thosewithashortcervix.(See"Secondtrimesterevaluationofcervicallengthforpredictionof
spontaneouspretermbirth",sectionon'Multiplegestation'.)
BedrestSystematicreviewsofrandomizedtrialsofhospitalizationorbedrestintwinpregnancieshave
failedtoshowthateitherinterventionincreasesgestationalageatdelivery[194,195].Bedrestmaybe
harmful:Apopulationbasedcohortstudyofpregnantwomenreportedthatantepartumhospitalization
unrelatedtodeliverywasassociatedwithanincreasedtheriskofvenousthromboembolismduring
hospitalizationandinthe28daysafterdischarge[196].
CerclageA2014systematicreviewofrandomizedtrialscomparingcervicalcerclagewithnocervical
cerclageinmultiplegestationsdidnotprovideconvincingevidencethatcerclageisaneffective
interventionforpreventingpretermbirthandreducingperinataldeathorneonatalmorbidity[197].Because
ofthesmallnumberofpregnanciesinthereview,amodesteffectcannotbeexcluded(122twin
pregnanciesand6tripletpregnanciescerclagewasindicatedbyobstetrichistoryintwotrials[n=73
pregnancies]andtransvaginalultrasoundinthreetrials[n=55pregnancies]).
Aretrospectivestudylimitedtotwinpregnancieswithcervicallength25mmat16to24weeksreported
placementofanultrasoundindicatedcerclagedidnotincreasegestationalageatdeliveryorreducethe
rateofspontaneouspretermbirthcomparedwithnoplacementofanultrasoundindicatedcerclage[198].
Inthesubgroupwithcervicallength15mm,theintervalfromdiagnosistodeliverywassignificantly
longerinthecerclagegroup,withsignificantlyfewerspontaneouspretermbirthsat<34weeksanda
lowerrateofneonatalintensivecareunitadmission.Asthesubgroupincludedonly71pregnancies,data
fromlargerrandomizedtrialsarenecessarytodeterminetheappropriaterole,ifany,forultrasound
indicatedcerclageinmultiplepregnancy.
TocolyticsA2015systematicreviewofrandomized,placebocontrolledtrialsconcludedtherewasno
convincingevidencethatprophylacticoralbetamimeticsreducedpretermbirthinasymptomaticwomen
withtwinpregnancies(<37weeks:RR0.85,95%CI0.651.10<34weeks:RR0.47,95%CI0.151.50)
[199].
Useoftocolyticdrugsisindicatedforinhibitionofsymptomaticpretermlaborandisdiscussed
separately.(See"Inhibitionofacutepretermlabor".)
Womenwithtwinpregnanciesappeartobeathigherriskofpulmonaryedemaafteradministrationof
betaadrenergicagentsbecausetheyhaveahigherbloodvolumeandlowercolloidosmoticpressurethan
womencarryingsingletons.Therefore,thesedrugsshouldbeusedjudiciouslyinwomenwithmultiple
gestations.
PessaryinunselectedpregnanciesIntwomulticenter,randomizedtrialsthatincludedapproximately
2000unselectedwomenwithmultiplegestations,prophylacticplacementofacervicalpessarybetween
16and20weeks[200]or20and25weeks[201]ofgestationdidnotreducepretermbirthorpoor
perinataloutcomecomparedwithnopessaryuse.
Pessaryinpregnancieswithashortcervix(25mm)Useofapessarymayprolongpregnancyin
twinpregnancieswithashortcervix.InamulticenterrandomizedtrialinSpain,placementofapessary
intwinpregnancieswithashortcervixat18to22weeksreducedtherateofspontaneouspretermbirth
<34weeks:16.2percent(11/68)versus39.4percent(26/66)withexpectantmanagement(RR0.41,95%
CI0.220.76)[202].Thisreductionwasnotassociatedwithastatisticalreductioninneonatalmorbidity
(compositeadverseneonataloutcomes:5.9percent[8/68]versus9.1percent[12/66],RR0.64,95%CI
0.271.50).Useofacervicalpessaryisareasonableoptionintwinpregnancieswithashortcervix
however,wearenotadvisingourpatientstouseapessarybecauseasignificantimprovementin
compositeneonatalmorbidityhasnotbeenestablishedandfurtherstudyisneeded.
PretermprematureruptureofmembranesPrematureruptureofmembranestypicallyoccursinthe
presentingsacbutcandevelopinthenonpresentingtwin,especiallyafterinvasiveprocedures(eg,
amniocentesis).Severalstudieshavelookedatperinataloutcomeafterpretermprematureruptureof
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membranes(PPROM)intwinversussingletongestations[203205].Thelargestofthesewasaretrospective
cohortstudyof116twinpregnancieswithPPROM36weeksofgestationand116matchedsingleton
pregnancies[203].Perinatalandneonataloutcomesweresimilarinthetwogroupshowever,themedian
latencyperiodwasstatisticallyshorterintwins(11.4versus19.5hours).Inourseriesoftwinpregnancieswith
PPROM,53percentoftwinswithPPROM30weeksofgestationdeliveredwithintwodays,comparedwith
only29percentofpatientswithPPROM<30weeks[206].
Anotherstudycomparedthefrequencyofchorioamnionitisinthenonpresentingandpresentingtwinsandby
placentation[207].Chorioamnionitisinthenonpresentingtwinwassignificantlylesscommonindichorionic
thaninmonochorionictwins.Advancedinflammation(definedaschorioamnionitiswithfunisitis)was
significantlylesscommoninthenonpresentingtwinthaninthepresentingtwin,butonlywhentheplacentas
weredichorionicandseparate.
GeneralissuesinmanagementofPPROMandPROMarediscussedseparately.(See"Pretermpremature
(prelabor)ruptureofmembranes"and"Managementofprematureruptureofthefetalmembranesatterm".)
AntenatalcorticosteroidsforpregnanciesatriskofpretermdeliveryWeuseastandarddosing
scheduleforantenatalcorticosteroidsforbothsingletonandmultiplegestationsbelievedtobeatincreasedrisk
forpretermdeliverywithinsevendays.(See"Antenatalcorticosteroidtherapyforreductionofneonatal
morbidityandmortalityfrompretermdelivery",sectionon'Multiplegestation'.)
Routineprophylacticadministrationtoalltwinpregnanciesshouldbeavoidedandmayhaveadverseeffects
[208].
GUIDELINESFROMNATIONALORGANIZATIONSNationalorganizationsthatprovideguidelinesfor
managementofmultiplegestationinclude:
NationalInstituteforHealthandClinicalExcellence(NICE)
AmericanCollegeofObstetriciansandGynecologistspracticebulletin[157]
NorthAmericanFetalTherapyNetwork[15,118,209]
FrenchCollegeofGynaecologistsandObstetricians[210]
Fetalimaging:ExecutiveSummaryofaJointEuniceKennedyShriverNationalInstituteofChildHealth
andHumanDevelopment,SocietyforMaternalFetalMedicine,AmericanInstituteofUltrasoundin
Medicine,AmericanCollegeofObstetriciansandGynecologists,AmericanCollegeofRadiology,Society
forPediatricRadiology,andSocietyofRadiologistsinUltrasoundFetalImagingWorkshop[211]
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasics
andBeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6th
gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagiven
condition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoread
materials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.
Thesearticlesarewrittenatthe10thto12thgradereadinglevelandarebestforpatientswhowantindepth
informationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
patientinfoandthekeyword(s)ofinterest.)
Basicstopics(see"Patientinformation:Havingtwins(TheBasics)")
SUMMARYANDRECOMMENDATIONS
Routineultrasoundexaminationinthefirstorearlysecondtrimesteristhebestmethodtoensureearly
diagnosisofatwinpregnancy,establishanaccurategestationalage,anddeterminechorionicity.(See
'Roleofearlyultrasoundexamination'above.)
Themostreliableindicatorsofdichorionictwinsareidentificationoftwoseparateplacentasandmaleand
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femalefetuses.Ifthereisasingleplacentalmass,chorionicityandamnionicityaredeterminedby
identificationofanintertwinmembraneandexaminationofthismembraneforthetwinpeakorlambda
sign,Tsign,thickness,andnumberoflayers.(See'Assessmentofchorionicity'above.)
Dizygotic(fraternal)twinsaremorecommonthanmonozygotic(identical)twins,approximately70and30
percentoftwins,respectively(intheabsenceofuseofassistedreproductivetechnology[ART]).The
prevalenceofdizygotictwinsvariesamongpopulationswhereastheprevalenceofmonozygotictwinsis
relativelystableworldwideat3to5per1000births.(See'Zygosityandchorionicity'aboveand
'Prevalenceandepidemiology'above.)
Spontaneousreductionofonesac(vanishingtwin)hasbeenreportedin27percentofpregnancies
diagnosedastwinspriorto7weeksofgestation.Ratesoflatefetalandinfantdeathareshowninthe
table(table1).Morbidityandmortalityintwinsissignificantlyhigherthaninsingletons(table2).(See
'Riskofearly,late,andpostnatalloss'aboveand'Comparativeoutcomesofsingleton,twin,andtriplet
pregnancy'above.)
Alltwinpregnanciesareatincreasedriskofpretermdelivery,congenitalanomalies,andgrowthrestriction
comparedwithsingletonpregnancies,butlowerratesofposttermpregnancyandmacrosomia.
Monochorionictwinsareatsignificantlyhigherriskofadverseperinataloutcomethandichorionictwins.
Theyarealsoatriskforuniquepregnancycomplications,suchastwintwintransfusionsyndrome,twin
anemiapolycythemiasequence,twinreversedarterialperfusionsequence,andselectiveintrauterine
growthrestriction.Monoamniotictwinsareatriskforcordentanglementandconjoinedtwins.(See'Fetal
complications'above.)
TheInstituteofMedicinerecommends25to54poundstotalweightgainattermforwomencarrying
twins.Thelowerendofthisrangeisappropriateforobesewomen,themiddleoftherangeisappropriate
foroverweightwomen,andtheupperendoftherangeisappropriateforwomenofnormalweight.(See
'Gestationalweightgain'above.)
ForwomenwhochoosetoundergoscreeningforDownsyndrome,wepreferthefirsttrimestercombined
testoverotherserumscreeningtestsandnoninvasivescreeningusingcellfreeDNAinmaternalblood.
Thistestprovidesearly,fetusspecificriskassessmentwithalowerfalsepositiveratethansecond
trimestertests.Bothfetusesshouldbekaryotypedwhenkaryotypingisperformedsinceeven
monozygotictwinsmaybediscordant.(See'ScreeningforDownsyndrome'above.)
Theconcordancerateofmajorcongenitalmalformationsinmonozygotictwinsisapproximately20
percent.Inadditiontoasonographicanatomicsurvey,fetalechocardiographyissuggestedat18to22
weeksinmonochorionictwinsbecauseoftheirincreasedriskofcongenitalheartdisease.Eachtwinofa
dizygoticpairhasasimilarcongenitalanomalyrateasasingletonandanomalies,ifpresent,havealow
concordancerate.(See'Screeningforcongenitalanomalies'above.)
Growthrestrictionismorecommonintwinthaninsingletonpregnancyandcanbedefinedineitheroftwo
ways(see'Evaluationoffetalgrowth'above):
Estimatedfetalweightbelowthe10thpercentileusingsingletongrowthcurves,or
Presenceof20percentdiscordanceinestimatedfetalweightbetweenthelighterandheaviertwin.
Ourapproachtomonitoringmonochorionictwinpregnanciesisdescribedinthealgorithm(algorithm1).
(See'Monochorionictwins'above.)
Indichorionictwinpregnancies,weperformanultrasoundexaminationeveryfourtosixweeksafter20
weeksofgestationasfetalgrowthdecelerationleadingtodiscordancyisoptimallydetectedbetween20
and28weeksofgestation.(See'Dichorionictwins'above.)
Weperformweeklytestingwithnonstresstestsandamnioticfluidevaluationorbiophysicalprofile
scoringstartingat32weeksinalltwinpregnancies.Testingisperformedearlierand/ormorefrequentlyif
complications,suchasfetalgrowthrestriction,develop.(See'Assessmentoffetalwellbeing'above.)
Singlefetaldeathafter20weeksofgestationoccursinapproximately5percentoftwinpregnancies.
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Becauseofplacentalvascularanastomosesbetweenmonochorionictwins,theintrauterinedeathofone
twininamonochorionictwinpregnancycancauseacutehypotension,anemia,andischemiainitsco
twin,resultinginmorbidityordeathofthecotwin.Forthisreason,iffetalassessmentafter26weeksof
gestationsuggestsimpendingdeathofonetwin,wesuggestpromptdeliveryofmonochorionictwins
ratherthanexpectantmanagement(Grade2C).Promptdeliveryisunlikelytobenefitthesurvivorafter
deathofonetwinofadichorionicormonochorionicgestation.(See'Deathofonetwin'above.)
Anelevatedfetalfibronectinlevelorshortcervicallengthonultrasoundexaminationmaypredictwomen
atparticularlyincreasedriskofpretermdeliveryhowever,thepredictivevalueislowinasymptomatic
patients.Nointerventionhasbeenproventobeeffectiveinreducingpretermbirthratesintwin
pregnancies.(See'Pretermlaboranddelivery'above.)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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