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3/4/2015 Preeclampsia:Managementandprognosis
http://aplicacionesbiblioteca.udea.edu.co:4560/contents/preeclampsiamanagementandprognosis?topicKey=OBGYN%2F6825&elapsedTimeMs=0&view=pri 1/23
OfficialreprintfromUpToDate www.uptodate.com2015UpToDate
AuthorsErrolRNorwitz,MD,PhDJohnTRepke,MD
SectionEditorCharlesJLockwood,MD,MHCM
DeputyEditorVanessaABarss,MD,FACOG
Preeclampsia:Managementandprognosis
Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.Literaturereviewcurrentthrough:Mar2015.|Thistopiclastupdated:Mar05,2015.
INTRODUCTIONPreeclampsiareferstothenewonsetofhypertensionandeitherproteinuriaorendorgandysfunctionafter20weeksofgestationinapreviouslynormotensivewoman(table1).Itisamultisystem,progressivedisorderwithadiseasespectrumthatrangesfrommildtosevere.Progressiontoseveredisease(table2)maybegradualorrapid.Deliveryresultsinresolutionofthedisease.
GENERALPRINCIPLESAkeyaspectofroutineprenatalcareismonitoringpregnanciesforsignsandsymptomsofpreeclampsia.Ifthediagnosisismade,thedefinitivetreatmentisdeliverytopreventdevelopmentofmaternalorfetalcomplicationsfromdiseaseprogression.(See"Preeclampsia:Clinicalfeaturesanddiagnosis",sectionon'Burdenofdisease'.)Whentoinitiatedeliveryisbasedupongestationalage,theseverityofthedisease,andmaternalandfetalcondition.Patientswithpreeclampsiaat37weeksofgestationaredeliveredhowever,beforeterm,therisksofserioussequelaefromdiseaseprogressionneedtobebalancedwiththerisksofpretermbirth.Evidenceofseriousmaternalendorgandysfunctionorindeterminatetestsoffetalwellbeingmaybeindicationsforpromptdeliveryatanygestationalage.Ontheotherhand,whenmotherandfetusarestableandwithoutfindingsofseriousendorgandysfunction,aconservativeapproachwithclosemonitoringforevidenceofprogressiontoseverefeaturesofthedisease(table2)isreasonableinordertoachievefurtherfetalgrowthandmaturity.
APPROACHBASEDONDISEASESEVERITY
PreeclampsiawithfeaturesofseverediseasePreeclampsiawithfeaturesofseveredisease(alsocalledseverepreeclampsia)(table2)isgenerallyregardedasanindicationfordeliveryinthefollowingsettings:
Deliveryminimizestheriskofdevelopmentofseriousmaternalandfetalcomplications(eg,cerebralhemorrhage,hepaticrupture,renalfailure,pulmonaryedema,seizure,bleedingrelatedtothrombocytopenia,fetalgrowthrestriction,abruptioplacentae)[14].Withtheexceptionoffetalgrowthrestriction,anyoftheseadverseeventscanoccursuddenlyinawomanwithseveredisease.Afterfetalviabilityandbefore34weeksofgestation,whenthemotherandfetusarestable,prolongationofpregnancyinatertiarycaresettingorinconsultationwithamaternalfetalmedicinespecialistisreasonabletoreducemorbidityfrompretermbirth.Candidatesforthisapproachandmanagementofthesepregnanciesarediscussedseparately.(See"Expectantmanagementofpreeclampsiawithseverefeatures".)
Observationaldatasuggestthatthedecisiontoexpeditedeliveryinthesettingofseverepreeclampsiadoesnotmandateimmediatecesareanbirth[46].Cervicalripeningagentscanbeusedpriortoinductionifthecervixisnotfavorable[7].However,wefeelthataprolongedinductionandinductionswithalowlikelihoodofsuccessarebestavoided.Cesareandeliveryisreasonableforwomenwithseverepreeclampsia/eclampsiawhoareunderabout32weeksofgestationandhavealowBishopscore,giventhehighfrequencyofindeterminatefetalheartratetracingsandfailureofthecervixtodilateinthissetting[79].Lessthanonethirdofpreterminductionsinthissettingresultinvaginalbirth.
Beforefetalviability
At34 weeksofgestation 0/7ths
Whenthematernalorfetalconditionisunstable,regardlessofgestationalage
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PreeclampsiawithoutfeaturesofseverediseaseExpertsconsistentlyrecommenddeliveryofwomenwithpreeclampsiaat37weeksofgestation,evenintheabsenceoffeaturesofseveredisease(previouslycalledmildpreeclampsia)[3,4,1012].Cervicalripeningagentsshouldbeusedinwomenwithunfavorablecervices.
Theoptimummanagementforwomenwithpreeclampsiawithoutfeaturesofseverediseaseandstablematernalandfetalconditionsat34 to36 weeksremainsuncertainnorandomizedtrialshavebeenperformedinthispopulation.Thesepregnanciesaregenerallymanagedexpectantlytoenablefurtherfetalgrowthandmaturation.Progressionofthediseaseisgenerallyslowandobservationaldatashowthatmanypatientswithlateonsetdiseasewillreachtermwithoutprogressiontoseveredisease.Forpatientsmanagedexpectantly,deliveryisindicatedassoonastheydevelopsignsorsymptomsofseverepreeclampsia/eclampsia(table2)orat37weeksofgestationifthediseasedoesnotprogresstotheseverestage.
Priorto34 weeks,guidelinesfrommajormedicalorganizationsgenerallyrecommendexpectantmanagementofpreeclampsiawithoutfeaturesofseveredisease,basedonexpertopinion,giventhehighriskofcomplicationsofprematurity[3,4,12].(See"Shorttermcomplicationsoftheprematureinfant"and"Longtermcomplicationsoftheprematureinfant"and"Incidenceandmortalityoftheprematureinfant".)
EXPECTANTANTEPARTUMMANAGEMENTOFPREECLAMPSIAWITHOUTFEATURESOFSEVEREDISEASEWomenwithpreterm(36 weekstoinductionoflabororexpectantmanagementwithmaternal/fetalmonitoring[13].Routineinductionwasassociatedwithasignificantreductionincompositeadversematernaloutcome(RR0.71,95%CI0.590.86absoluteriskreduction12.76percent),whichwasprimarilydrivenbyareductioninpatientswhodevelopedseverehypertensionandwasnotsignificantforwomenat36 to36 weeks.Theinducedgroupdelivered,onaverage,1.2weeksearlierthanthecontrolgroupandhadasignificantlylowerrateofcesareandelivery(14versus19percent).Therewerenosignificantdifferencesbetweengroupsinneonataloutcome.
Thistrialshowedthatpreeclampticwomenbenefitedfromearlyintervention,withoutincurringanincreasedriskofoperativedeliveryorneonatalmorbidity.Thetrialwasnotlargeenoughtodeterminewhethersmalldifferencesinnewbornoutcomesorinductionbetween36and37weeksmightbestatisticallysignificant.Afollowupeconomicanalysisofthistrialconcludedinductionwasalsolesscostlyoverallthanexpectantmanagementwithmonitoring[14].Anotherfollowupanalysisshowedthatanunfavorablecervixwasnotareasontoavoidinduction[15].
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benefitsomepregnancies.Avoidingthesupinesleeppositionisprudent[24].Ifsignsorsymptomsofdiseaseprogressionarenoted,hospitalizationformoreintensivemonitoringandpossibledeliveryisindicated.
Outpatientsshouldbeawareofthesignsandsymptomsofpreeclampsiaandtheyshouldmonitorfetalmovementsdaily[4].Theyshouldbetoldtocalltheirhealthcareproviderimmediatelyiftheydevelopsevereorpersistentheadache,visualchanges,shortnessofbreath,orrightupperquadrantorepigastricpain.Aswithanypregnancy,decreasedfetalmovement,vaginalbleeding,abdominalpain,ruptureofmembranes,oruterinecontractionsshouldbereportedimmediately,aswell.
LaboratoryfollowupTheminimumlaboratoryevaluationshouldincludeplateletcount,serumcreatinine,andliverenzymes.Thesetestsshouldberepeatedatleastweeklyinwomenwithnonseverepreeclampsiatoassessfordiseaseprogression,andmoreoftenifclinicalsignsandsymptomssuggestworseningdisease[4].
Thevalueofothertestsislessclearlydefined.Arisinghematocritcanbeusefultolookforhemoconcentration,whichsuggestscontractionofintravascularvolumeandprogressiontomoreseveredisease,whileafallinghematocritmaybeasignofhemolysis.Anelevatedserumindirectbilirubinconcentrationisabettersignofhemolysis,althoughanelevatedLDHmayalsobeamarkerofseverediseaseorHELLPsyndrome.Hemolysiscanbeconfirmedbyobservationofschistocytesandhelmetcellsonabloodsmear(picture1AB).(See"HELLPsyndrome".)
Sinceseveralclinicalstudieshaveshownthatneithertherateofincreasenortheamountofproteinuriaaffectsmaternalorperinataloutcomeinthesettingofpreeclampsia[2528],repeated24hoururinaryproteinestimationsarenotusefuloncethethresholdof300mg/24hoursorprotein/creatinineratio0.3mg/dL/mg/dLforthediagnosisofpreeclampsiahasbeenexceeded.Serumcreatininealonecanbeusedtomonitorrenalfunction.(See"Expectantmanagementofpreeclampsiawithseverefeatures".)
TreatmentofhypertensionBloodpressureshouldbeassessedatleasttwiceweekly.Theuseofantihypertensivedrugstocontrolmildhypertensioninthesettingofpreeclampsiadoesnotalterthecourseofthediseaseordiminishperinatalmorbidityormortality,andshouldbeavoidedinmostpatients.Theindicationsforstartingantihypertensivetherapy,thechoiceofdrug,andbloodpressuregoalsarediscussedseparately.(See"Managementofhypertensioninpregnantandpostpartumwomen",sectionon'Preeclampsia'.)
Sodiumrestrictionbelowtherecommendeddailyintakeanddiureticshavenoroleinroutinetherapy[2931].Althoughintravascularvascularvolumeisreduced,arandomizedtrialshowedthatplasmavolumeexpansiondidnotimprovematernalorfetaloutcome[32].
AssessmentoffetalwellbeingTherearenodatafromrandomizedtrialsonwhichtobaserecommendationsfortheoptimaltypeandfrequencyoffetalbiophysicalmonitoring.Wesuggestdailyfetalmovementcountsandtwiceweeklyfetalnonstresstestingwithassessmentofamnioticfluidvolume,ortwiceweeklybiophysicalprofiles.Testingisrepeatedimmediatelyifthereisanabruptchangeinmaternalcondition.(See"Nonstresstestandcontractionstresstest"and"Thefetalbiophysicalprofile".)
EvaluationofumbilicalarteryDopplerindicesisalsouseful,astheresultshelpinoptimaltimingofdelivery.Inametaanalysisof16randomizedtrialsinhighriskpregnancies,knowledgeofumbilicalarteryDopplervelocimetryresultswasassociatedwitha29percentreductioninperinataldeath(RR0.71,95%CI0.520.98,10,225babies,1.2versus1.7percentnumberneededtotreat203,95%CI1034352),primarilyinpregnanciescomplicatedbypreeclampsiaand/orgrowthrestriction.ThefrequencyofassessmentdependsonthefindingsweeklyassessmentisreasonablewhenDopplerindicesarenormal.(See"Dopplerultrasoundoftheumbilicalarteryforfetalsurveillance",sectionon'Clinicaleffectiveness'and"Dopplerultrasoundoftheumbilicalarteryforfetalsurveillance",sectionon'Guidelinesforclinicalpractice'.)
AssessmentoffetalgrowthEarlyfetalgrowthrestrictionmaybethefirstmanifestationofpreeclampsiaandisasignofsevereuteroplacentalinsufficiency.Wesuggestperformingsonographicestimationoffetalweighttoevaluateforgrowthrestrictionandoligohydramniosatthetimeofdiagnosisofpreeclampsia.Iftheinitial
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examinationisnormal,werepeattheultrasoundexaminationeverythreeweeks.Managementofthegrowthrestrictedfetusisreviewedseparately.(See"Fetalgrowthrestriction:Evaluationandmanagement",sectionon'Serialfetalweightassessment'and"Dopplerultrasoundoftheumbilicalarteryforfetalsurveillance".)
AntenatalcorticosteroidsAlthoughpreeclampsiamayacceleratefetallungmaturation,neonatalrespiratorydistressremainscommoninprematureneonatesofpreeclampticpregnancies[33,34].Antenatalcorticosteroids(betamethasone)topromotefetallungmaturityshouldbeadministeredtowomen
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controlledtrialincluding10,000women(MAGPIE[magnesiumsulfateforpreventionofeclampsiatrial]),about100womenwithmildpreeclampsiaandabout60womenwithseverepreeclampsiawouldneedtobetreatedtopreventoneseizure[37].Thisrecommendationisincontrasttothe2013AmericanCollegeofObstetriciansandGynecologistsrecommendations,whichstatethatforwomenwithpreeclampsiawithsystolicbloodpressureoflessthan160mmHgandadiastolicbloodpressurelessthan110mmHgandnomaternalsymptoms,itissuggestedthatmagnesiumsulfatenotbeadministereduniversallyforthepreventionofeclampsia[4].
Itisimportanttoemphasizethatseizureprophylaxisdoesnotpreventprogressionofdiseaseunrelatedtoconvulsions.Approximately10to15percentofwomeninlaborwithnonseverepreeclampsiawilldevelopsignsofseverepreeclampsia(eg,severehypertension,severeheadache,visualdisturbance,epigastricpain,laboratoryabnormalities)orabruptioplacenta,whetherornottheyreceivemagnesiumtherapy[38,39].
Wedonotadministerseizureprophylaxistowomenwithonlygestationalhypertension(pregnancyrelatedhypertensionwithoutproteinuriaorendorgandysfunction),astheseizureriskinthelattergroupislessthan0.1percent[40].(See"Gestationalhypertension".)
MagnesiumsulfateversusotheranticonvulsantsMajormedicalorganizationsworldwideconsistentlyrecommendmagnesiumsulfateasthedrugofchoiceforthepreventionofeclampsia[4,12,41].Inrandomizedtrials[37,42,43]andlargeobservationalseries[44],magnesiumsulfatewasmoreeffectiveforpreventionofafirstseizurethanphenytoin[42]oranantihypertensivedrugalone(nimodipine)[43]orplacebo[44].Asanexample,atrialthatrandomlyassigned2138preeclampticpatientsadmittedtoLaborandDeliveryatParklandHospitaltoseizureprophylaxiswithmagnesiumsulfateorphenytoinreportedeclampticseizuresin10of1089womenassignedtophenytoincomparedtononeof1049womenassignedtomagnesiumsulfate[42].Maternalandneonataloutcomesweresimilarinbothgroups.
Inmetaanalysesofrandomizedtrialsineclampticwomen,magnesiumsulfatewassaferandmoreeffectiveforpreventionofrecurrentseizuresthanphenytoin,diazepam,orlyticcocktail(ie,chlorpromazine,promethazine,andpethidine).Thesedataprovideadditionalindirectevidenceofitseffectivenessinpreeclampsia.(See"Eclampsia",sectionon'Preventionofrecurrentseizures'.)
MagnesiumregimenandmonitoringThereisnoconsensusontheoptimalmagnesiumregimen,whenitshouldbestartedandterminated,orrouteofadministration[45].Thedrugisusuallyinitiatedattheonsetoflabororinduction,orpriortoacesareandelivery[4,46,47].Itisusuallynotgiventostableantepartumpatientsoffthelaborunit,butissometimesusedinwomenwithseverepreeclampsiabeingconsideredforexpectantmanagement.Prolongedantepartumtherapy(morethanfivetosevendays)inwomenwithpretermlaborhasbeenassociatedwithadverseeffectsonfetalbones[48].(See"Expectantmanagementofpreeclampsiawithseverefeatures".)
DosingAlthoughpublisheddosageregimensformagnesiumsulfatevarywidely(loadingdoseof4to6gramsintravenouslyandmaintenancedoseof1to3gramsperhour),themostcommonregimen,andtheonethatweuse,isaloadingdoseof6gramsintravenouslyover15to20minutesfollowedby2gramsperhourasacontinuousinfusion[4,39,44,47].Analternativeregimenis5gramsintramuscularlyintoeachbuttock(totalof10grams)followedby5gramsintramuscularlyeveryfourhours.However,thismethodisassociatedwithmoresideeffects,particularlypainattheinjectionsite.
Theredoesnotappeartobeaclearthresholdconcentrationforinsuringthepreventionofconvulsions,althoughatherapeuticrangeof4.8to8.4mg/dL(2.0to3.5mmol/L)hasbeenrecommendedbasedonretrospectivedata[49].Loadingdoseslessthan6gramsaremorelikelytoresultinsubtherapeuticmagnesiumlevels(lessthan4.5mg/dL)[44,50].
Sincemagnesiumsulfateisexcretedbythekidneys,dosingshouldbeadjustedinwomenwithrenalinsufficiency(definedasaserumcreatininegreaterthan1.0mg/dL).Suchwomenshouldreceiveastandardloadingdose(sincetheirvolumeofdistributionisnotaltered),butareducedmaintenancedose(1gramperhourornomaintenancedoseiftheserumcreatinineisgreaterthan2.5mg/dL)andclosemonitoringoftheirserum
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magnesiumleveleverysixhoursorbyclinicalassessmenteveryonetotwohours.
Themaintenancephaseisgivenonlyifapatellarreflexispresent(lossofreflexesbeingthefirstmanifestationofsymptomatichypermagnesemia),respirationsexceed12perminute,andtheurineoutputexceeds100mLperfourhours.(See"Symptomsofhypermagnesemia".)Followingserummagnesiumlevelsisnotrequiredifthewoman'sclinicalstatusiscloselymonitoredforevidenceofpotentialmagnesiumtoxicity(see'Complicationsandsideeffects'below).Themaintenancedoseshouldbedecreasedifthereisclinicalevidenceofmagnesiumtoxicity.
DurationoftherapyMagnesiumsulfateisusuallycontinuedfor24hourspostpartum[47].Timingofdrugdiscontinuationhasbeenarbitrarytherearenohighqualitydatatoguidetherapy.Inwomenwhohavenonseverepreeclampsia,discontinuationoftherapyafter12hoursmaybesafe[51].Inwomenwithseverepreeclampsiaoreclampsia,seizureprophylaxisisgenerallycontinuedfor24to48hourspostpartum,afterwhichtheriskofrecurrentseizuresislow.
Itisprobablyreasonabletoextendthedurationofmagnesiumsulfatetherapyinwomenwhosediseasehasnotbeguntoimprovepostpartumandshortenthedurationoftherapyinwomenwhoareclearlyimprovingclinically(eg,diuresisof100mL/hourfortwoconsecutivehours,absenceofsymptoms[headache,visualchanges,epigastricpain],andabsenceofseverehypertension)[5255].Diuresis(greaterthan4L/day)isbelievedtobethemostaccurateclinicalindicatorofresolutionofpreeclampsia/eclampsia,butisnotaguaranteeagainstthedevelopmentofseizures[56].Inwomenwithpersistentrenalimpairmentpostpartum,itisimportanttobecautiouswhenadministeringaprolongedmagnesiumsulfateinfusiontopreventtheoccurrenceofmagnesiumtoxicity.
ComplicationsandsideeffectsRapidinfusionofmagnesiumsulfatecausesdiaphoresis,flushing,andwarmth,probablyrelatedtoperipheralvasodilationandadropinbloodpressure.Nausea,vomiting,headache,muscleweakness,visualdisturbances,andpalpitationscanalsooccur.Dyspneaorchestpainmaybesymptomsofpulmonaryedema,whichisararesideeffect.(See"Symptomsofhypermagnesemia".)
Magnesiumtoxicityisuncommoninwomenwithgoodrenalfunction[57].Toxicityisrelatedtoserummagnesiumconcentration:lossofdeeptendonreflexesoccursat7to10mEq/L(8.5to12mg/dLor3.5to5.0mmol/L),respiratoryparalysisat10to13mEq/L(12to16mg/dLor5.0to6.5mmol/L),cardiacconductionisalteredat>15mEq/L(>18mg/dLor>7.5mmol/L),andcardiacarrestoccursat>25mEq/L(>30mg/dLor>12.5mmol/L)[58].Calciumgluconate(1gramintravenouslyover5to10minutes)shouldbeadministeredonlytocounteractlifethreateningsymptomsofmagnesiumtoxicity(suchascardiorespiratorycompromise).
Magnesiumsulfateiscontraindicatedinwomenwithmyastheniagravissinceitcanprecipitateaseveremyastheniccrisis(see"Managementofmyastheniagravisinpregnancy").Neuromuscularblockadeandhypotensionduetoconcurrentuseofmagnesiumsulfateandcalciumchannelblockershavebeendescribedincasereports,buttheriskappearstobeminimal[59].
Althoughmagnesiumsulfateisaweaktocolytic,labordurationdoesnotappeartobeaffectedbymagnesiumsulfateadministration[60].Theriskofpostpartumhemorrhage,possiblyrelatedtouterineatonyfrommagnesium'stocolyticeffects,wasslightlyincreasedinonetrial[43].
Magnesiumfreelycrossestheplacentaasaresult,thecordbloodconcentrationapproximatesthematernalserumconcentration.Maternaltherapycausesadecreaseinbaselinefetalheartrate,whichgenerallyremainswithinthenormalrange,andadecreaseinfetalheartratevariability,whichmaybeabsentorminimal[61].Antenatalfetalassessmenttestresults(eg,biophysicalprofilescoreandnonstresstestreactivity)arenotsignificantlyaltered[62].
Magnesiumtherapyresultsinatransientreductionoftotalandionizedserumcalciumconcentrationduetorapidsuppressionofparathyroidhormonerelease[63].Rarely,hypocalcemiabecomessymptomatic(myoclonus,delirium,ECGabnormalities).(See"Symptomsofhypermagnesemia",sectionon'Hypocalcemia'.)Cessationofmagnesiumtherapywillrestorenormalserumcalciumlevels.However,calciumadministrationmayberequiredifsymptomsarepresent(calciumgluconate1gramintravenouslyover5to10minutes).(See"Causesand
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treatmentofhypermagnesemia".)
MechanismofanticonvulsantactionThemechanismfortheanticonvulsanteffectsofmagnesiumsulfatehasnotbeenclearlydefined.Theprimaryeffectisthoughttobecentral.Hypothesesincluderaisingtheseizurethresholdbyitsactionatthenmethyldaspartate(NMDA)receptor,membranestabilizationinthecentralnervoussystemsecondarytoitsactionsasanonspecificcalciumchannelblocker,aswellasdecreasingacetylcholineinmotornerveterminals[64,65].Anothertheoryisthatitpromotesvasodilatationofconstrictedcerebralvesselsbyopposingcalciumdependentarterialvasospasm,therebyreducingcerebralbarotrauma[66].
POSTPARTUMMANAGEMENTNonsteroidalantiinflammatorydrugs(NSAIDs)forpaincontrolshouldbeavoidedinwomenwithpoorlycontrolledhypertension,oliguria,renalinsufficiency,orthrombocytopenia.(See"NonselectiveNSAIDs:Overviewofadverseeffects".)
Therearenoevidencebasedstandardsfortheoptimalapproachtopostpartummonitoringandfollowup.Wemonitorvitalsignseverytwohourswhilethepatientremainsonmagnesiumsulfateandwerepeatlaboratorytestsuntiltwoconsecutivesetsofdataarenormal.
Severehypertensionshouldbetreatedsomepatientswillhavetobedischargedonantihypertensivemedications,whicharediscontinuedwhenbloodpressurereturnstonormal.(See"Managementofhypertensioninpregnantandpostpartumwomen",sectionon'Postpartumhypertension'.)
Patientsshouldbefollowedcloselyasoutpatients.TheAmericanCollegeofObstetriciansandGynecologistssuggestsmonitoringbloodpressureinhospitalorathomeforthefirst72hourspostpartumandagain7to10dayspostdelivery[4].Somepatientswillrequirelongermonitoringcontinuedfollowupisneededuntilallofthesignsandsymptomsofpreeclampsiahaveresolved.Alternativediagnosesshouldbesoughtinthosewithpersistentabnormalfindingsafterthreetosixmonths[67].(See"Overviewofhypertensioninadults".)
PostpartumonsetofpreeclampsiaInwomenwhoareinitiallydiagnosedwithpreeclampsiaafterdelivery,magnesiumsulfateshouldbeadministeredtothoseatincreasedriskofdevelopingseizures[4]:
Antihypertensivetherapyshouldalsobeinitiated.TheAmericanCollegeofObstetriciansandGynecologistssuggeststreatmentofsystolicbloodpressure150mmHgordiastolicbloodpressure100mmHgontwooccasionsfourtosixhoursapart[4].Treatmentshouldbeinitiatedwithinonehourifsystolicbloodpressureis160mmHgordiastolicbloodpressureis110mmHg.
GUIDELINESFROMSELECTEDORGANIZATIONSAnumberofmedicalorganizationshavepublishedguidelinesformanagementofpreeclampsia.Theseguidelinesaregenerallyconsistentwiththerecommendationsinthistopicreview.
PROGNOSISPrognosticissuesincludetheriskofrecurrentpreeclampsiaandrelatedcomplicationsinsubsequentpregnanciesandlongtermmaternalhealthrisks.
RecurrenceA2015metaanalysisofindividualpatientdatafromover75,000womenwithpreeclampsiawhobecamepregnantagainfoundthat20percentdevelopedhypertensioninasubsequentpregnancyand16percentdevelopedrecurrentpreeclampsia[68].
Womenwithnewonsethypertensionandheadacheorblurredvision,orWomenwithseverehypertension
AmericanCollegeofObstetriciansandGynecologists(ACOG).HypertensioninPregnancy[4]
NationalInstituteforHealthandClinicalExcellence(NICE).Hypertensioninpregnancy:Themanagementofhypertensivedisordersduringpregnancy[3]
SocietyofObstetriciansandGynaecologistsofCanada(SOGC).Diagnosis,evaluation,andmanagementofthehypertensivedisordersofpregnancy[12]
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Therecurrenceriskvarieswiththeseverityandtimeofonsetoftheacuteepisode[69].Womenwithearlyonset,severepreeclampsiaareatgreatestriskofrecurrence(ashighas25to65percent)[7072].Theriskismuchlower(5to7percent)inwomenwhohadnonseverepreeclampsiaduringthefirstpregnancy,versuslessthan1percentinwomenwhohadanormotensivefirstpregnancy(doesnotapplytoabortions)[70,7378].Inaseriesof125womenwithseveresecondtrimesterpreeclampsiafollowedforfiveyears,65percentdevelopedrecurrentpreeclampsiaand35percentwerenormotensiveintheirsubsequentpregnancy[70].Ofthepreeclampticgroup,approximatelyonethirddevelopedthediseaseat27weeks,onethirdat28to36weeks,andonethirdat37weeks.Thus,21percentofsubsequentpregnancieswerecomplicatedbyseverepreeclampsiainthesecondtrimester.
Recurrentpreeclampsiaismorelikelyfollowingapreeclampticsingletonpregnancythanapreeclamptictwinpregnancy[79].TherecurrenceriskinwomenwithHELLPsyndrome(whomaydevelopeitherHELLPorpreeclampsiainasubsequentpregnancy)isdiscussedseparately.(See"HELLPsyndrome",sectionon'Recurrenceinsubsequentpregnancies'.)
PreventionPreventivetherapy(lowdoseaspirin)isreviewedelsewhere.(See"Preeclampsia:Prevention".)
RiskofrelatedobstetricalcomplicationsPreeclampsia,growthrestriction,pretermdelivery,abruptioplacentae,andstillbirthcanallbesequelaeofimpairedplacentalfunction.Womenwithpregnanciescomplicatedbyoneofthesedisordersareatincreasedriskofdevelopingoneoftheotherdisordersinfuturepregnancies.Earlyonsetpreeclampsiaismorelikelytobeassociatedwithoneoftheseadverseeventsinasubsequentpregnancy,evenifnormotensive,thanlateonsetpreeclampsia[80,81].
Longtermmaternalrisks
CardiovasculardiseaseCasecontrolandcohortstudiesconsistentlyreportthatpreeclampsiaispredictiveoffuturecardiovascularandcerebrovasculardisease.Thisriskwassummarizedintwosystematicreviewsofcontrolledstudiesthatevaluatedtheriskoflatecardiovasculareventsinwomenwithandwithoutahistoryofpreeclampsia[82,83]:
Prospectivecohortstudiespublishedafterthesereviewshavereportedsimilarfindings[8487].
Thefutureriskofcardiovascularmorbidityandmortalityappearstoberelatedtoboththeseverityofpreeclampsiaandthenumberofepisodesofpreeclampsia[88].Womenwithearlyonset/severepreeclampsiawithpretermdeliveryareathighestriskofcardiovasculardiseaselaterinlife,includingduringthepremenopausalperiod(table3).Intwolargestudies,thesewomenhadaneighttoninefoldincreasedriskofdeathfromcardiovascularcausescomparedwithwomenwithoutahistoryofpreeclampsia[86,89].Incontrast,mildpreeclampsiaoccurringlateingestationdoesnotappeartobeassociatedwithahighriskofremotecardiovasculardisease[90].Thestrongerassociationbetweencardiovasculardiseaseandpretermpreeclampsiasuggeststhatthepathogenesisofearly
Comparedwithwomenwithnohistoryofthedisease,womenwithpreeclampsiawereatincreasedriskofdevelopinghypertension(RR3.70,95%CI2.705.05atmeanfollowupof14years),ischemicheartdisease(RR2.16,95%CI1.862.52atmeanfollowupof11.7years),stroke(RR1.81,95%CI1.452.27atmeanfollowupof10.4years),andvenousthromboembolism(RR1.79,95%CI1.372.33atmeanfollowupof4.7years)[82].Theabsoluteriskthatawomanwithorwithoutahistoryofpreeclampsiawoulddeveloponeofthesecardiovasculareventsatage50to59yearswasestimatedtobe17.8and8.3percent,respectively.
Inaddition,agradedrelationshipwasobservedbetweenseverityofpreeclampsiaandriskoffuturecardiacdisease(mildpreeclampsiaRR2.00,95%CI1.832.19moderatepreeclampsiaRR2.99,95%CI2.513.58severepreeclampsiaRR5.36,95%CI3.967.27),aswellasacorrelationbetweenpreeclampsiaandfutureperipheralarterydisease(RR1.87,95%CI0.943.73)[83].Theauthorsdefinedpreeclampsiaas'mild'ifthepregnancyhadanuncomplicatedcourse,'moderate'ifpreeclampsiawascomplicatedbyfetalgrowthrestrictionormaternalseizuresand'severe'ifpreeclampsiawascomplicatedbypretermdeliveryorfetaldemise.
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versuslatepreeclampsiamaybedifferent.
Severalstudieshavedemonstratedthatwomenwithahistoryofpreeclampsiaorsevereearlyonsetfetalgrowthrestrictionexhibitimpairedendothelialfunctionandvasodilatationremotefrompregnancy[9194].Womenwithahistoryofhypertensivedisordersinpregnancyhavehigherlevelsofglucose,insulin,andunfavorablelipidsthanwomenwithahistoryofnormotensivepregnancy[95].Datafromsomeepidemiologicstudiessuggestthattheincreasedriskoflatecardiovascularmorbidityinpreviouslypreeclampticwomenreflectsanunderlyingpredispositioninthesewomenforbothdisorders(geneticfactors,sharedriskfactors),butitisalsopossiblethatpreeclampsiaresultsinpermanentarterialchangesleadingtolatecardiovasculardisease[9699].Someinvestigatorshavehypothesizedthatincreasedinsulinresistance,sympatheticoveractivity,proinflammatoryactivity,endothelialdysfunction,andtheabnormallipidprofileinpreeclampticwomenconstituteanearlymanifestationofmetabolicsyndromeandthatthesechangespersistafterpregnancy,therebyputtingaffectedwomanatincreasedriskofcardiovasculardisease[100104].Onegroupestimatedthatlifestyleinterventionsafterpreeclampsiawoulddecreasecardiovasculardiseaseriskby4to13percent[105].
DiabetesmellitusInapopulationbasedretrospectivecohortstudyincludingoveronemillionwomen,preeclampsiaorgestationalhypertensionintheabsenceofgestationaldiabetesmellitus(GDM)wasassociatedwithatwofoldincreaseintheincidenceofdiabetesduring16.5yearsofpostdeliveryfollowup,aftercontrollingforseveralconfoundingvariables(butnotobesity)[106].InwomenwhohadpreeclampsiaorgestationalhypertensionandGDM,theriskoffuturediabeteswasincreased16to18fold,whichwasabovethealreadyelevated13foldincreaseinriskassociatedwithGDMalone.Thesefindings,andthosefrompreviousreports[107109],suggestthatcliniciansshouldinformwomenwithahistoryofpreeclampsiaorgestationalhypertensionthattheymaybeatincreasedriskofdevelopingdiabeteshowever,theavailableevidencedoesnotsupportachangeinstandardscreeningguidelines.(See"Screeningfortype2diabetesmellitus",sectionon'Screeningrecommendationsbyexpertgroups'.)
EndstagerenaldiseaseWomenwithpreeclampsiamaybeatincreasedriskofdevelopingendstagerenaldisease(ESRD)laterinlife,buttheabsoluteriskissmall.AstudythatlinkedfourdecadesofdatafromtheNorwegiannationalbirthandESRDregistriesfoundthatwomenwithpreeclampsiaintheirfirstpregnancyhadafourfoldincreaseinriskofESRDcomparedwithwomenwithoutpreeclampsia(RR4.7,95%CI3.66.1)afteradjustingforknownconfounders,buttheabsoluteriskofESRDwaslessthan1percentwithin20years[110].Similarly,astudyusingclaimsdatafromtheTaiwanNationalHealthInsuranceProgramnotedthatwomenwithpreeclampsia/eclampsiawereatsignificantlyhigherriskofdevelopingESRDovertimethanwomenwithouthypertensivedisordersduringpregnancy(incidence5.33versus0.34per10,000personyears)[111].
AlthoughwomenwhowentontodevelopESRDmayhavehadsubclinicalrenaldiseaseduringpregnancy,itisalsopossiblethatasyetundefinedriskfactorspredisposedthesewomentobothpreeclampsiaandESRD.Itislesslikelythatpreeclampsiadamagesthekidney,therebyinitiatingaprocessofchronicdeterioration.
SubclinicalhypothyroidismAnestedcasecontrolstudyfoundthatnulliparouswomenwhodevelopedpreeclampsiaweretwiceaslikelytodevelopsubclinicalhypothyroidismduringpregnancyandlongafterdeliverythanmatchednormotensivecontrols[112].Theriskwasstrongestinwomenwithrecurrentpreeclampsiaandwithoutthyroidperoxidaseantibodies,suggestingthatanautoimmunemediatedmechanismofhypothyroidismwasnotinvolved.Inastudyincluding25,000pregnantwomen,womenwithsubclinicalhypothyroidismidentifiedduringpregnancywereatincreasedriskofdevelopingseverepreeclampsiacomparedwitheuthyroidwomen(OR1.6,95%CI1.12.4),afteradjustmentforriskfactorsforpreeclampsia[113].Abnormallevelsofthyroidhormonesappeartodamageendothelialcells,potentiallyleadingtopreeclampsiaandlongtermcardiovascularsequelae.
OtherAsystematicreviewfoundnosignificantassociationbetweenpreeclampsiaandlaterdevelopmentofcancer[82].ObservationalstudiesfromtheUnitedStates,Sweden,andNorwayreportedthatwomenwithpreeclampsiawereatreducedriskorhadnoexcessriskofcancerwhenfollowed13to19yearspostpartum[89,114119].Incontrast,astudyfromIsraelreportedanincreasedriskofcancerinsuchwomen(hazardratio1.27,95%CI1.031.57)withamedianfollowupof29years[120,121].Sitespecificincreaseswerenotedfor
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cancerofthestomach,lungorlarynx,breast,andovary.Thediscordantresultsmaybeexplainedbyanumberoffactors,includingdifferencesinpatientpopulations,absenceoforinsufficientadjustmentforconfounders,differencesinlengthoffollowup,andincompleteascertainment.
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsandBeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5 to6 gradereadinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.Thesearticlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.BeyondtheBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewrittenatthe10 to12 gradereadinglevelandarebestforpatientswhowantindepthinformationandarecomfortablewithsomemedicaljargon.
Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthesetopicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingonpatientinfoandthekeyword(s)ofinterest.)
SUMMARYANDRECOMMENDATIONS
th th
th th
Basicstopics(see"Patientinformation:Preeclampsia(TheBasics)"and"Patientinformation:Highbloodpressureandpregnancy(TheBasics)"and"Patientinformation:HELLPsyndrome(TheBasics)")
BeyondtheBasicstopics(see"Patientinformation:Preeclampsia(BeyondtheBasics)")
Thedefinitivetreatmentofpreeclampsiaisdeliverytopreventdevelopmentofmaternalorfetalcomplicationsfromdiseaseprogression.Timingofdeliveryisbasedupongestationalage,theseverityofpreeclampsia,andmaternalandfetalcondition.(See'Generalprinciples'above.)
Preeclampsiawithfeaturesofseveredisease(table2)isgenerallyregardedasanindicationfordelivery,regardlessofgestationalage,giventhehighriskofseriousmaternalmorbidity.However,prolongedantepartummanagementinatertiarycaresettingorinconsultationwithamaternalfetalmedicinespecialistisanoptionforselectedwomenremotefromterm(
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UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
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GRAPHICS
Criteriaforthediagnosisofpreeclampsia
Systolicbloodpressure140mmHgordiastolicbloodpressure90mmHgontwooccasionsatleastfourhoursapartafter20weeksofgestationinapreviouslynormotensivepatient
Ifsystolicbloodpressureis160mmHgordiastolicbloodpressureis110mmHg,confirmationwithinminutesissufficient
and
Proteinuria0.3gramsina24hoururinespecimenorprotein(mg/dL)/creatinine(mg/dL)ratio0.3
Dipstick1+ifaquantitativemeasurementisunavailable
Inpatientswithnewonsethypertensionwithoutproteinuria,thenewonsetofanyofthefollowingisdiagnosticofpreeclampsia:
Plateletcount1.1mg/dLordoublingofserumcreatinineintheabsenceofotherrenaldisease
Livertransaminasesatleasttwicethenormalconcentrations
Pulmonaryedema
Cerebralorvisualsymptoms
Adaptedfrom:Hypertensioninpregnancy:ReportoftheAmericanCollegeofObstetriciansandGynecologists'TaskForceonHypertensioninPregnancy.ObstetGynecol2013122:1122.
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Thepresenceofoneormoreofthefollowingindicatesadiagnosisof"preeclampsiawithseverefeatures"
Symptomsofcentralnervoussystemdysfunction:
Newonsetcerebralorvisualdisturbance,suchas:Photopsia,scotomata,corticalblindness,retinalvasospasmSevereheadache(ie,incapacitating,"theworstheadacheI'veeverhad")orheadachethatpersistsandprogressesdespiteanalgesictherapyAlteredmentalstatus
Hepaticabnormality:
Severepersistentrightupperquadrantorepigastricpainunresponsivetomedicationandnotaccountedforbyanalternativediagnosisorserumtransaminaseconcentrationtwicenormal,orboth
Severebloodpressureelevation:
Systolicbloodpressure160mmHgordiastolicbloodpressure110mmHgontwooccasionsatleastfourhoursapartwhilethepatientisonbedrest(unlessthepatientisonantihypertensivetherapy)
Thrombocytopenia:
1.1mg/dLordoublingofserumcreatinineconcentrationintheabsenceofotherrenaldisease)
Pulmonaryedema
Incontrasttooldercriteria,the2013criteriadonotincludeproteinuria>5grams/24hoursandfetalgrowthrestrictionasfeaturesofseveredisease.
Adaptedfrom:Hypertensioninpregnancy:ReportoftheAmericanCollegeofObstetriciansandGynecologists'TaskForceonHypertensioninPregnancy.ObstetGynecol2013122:1122.
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Peripheralsmearinmicroangiopathichemolyticanemiashowingpresenceofschistocytes
Peripheralbloodsmearfromapatientwithamicroangiopathichemolyticanemiawithmarkedredcellfragmentation.Thesmearshowsmultiplehelmetcells(smallblackarrows),otherfragmentedredcells(largeblackarrow)microspherocytesarealsoseen(bluearrows).Theplateletnumberisreducedthelargeplateletinthecenter(redarrow)suggeststhatthethrombocytopeniaisduetoenhanceddestruction.
CourtesyofCarolavonKapff,SH(ASCP).
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Normalperipheralbloodsmear
Highpowerviewofanormalperipheralbloodsmear.Severalplatelets(blackarrows)andanormallymphocyte(bluearrow)canalsobeseen.Theredcellsareofrelativelyuniformsizeandshape.Thediameterofthenormalredcellshouldapproximatethat
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ofthenucleusofthesmalllymphocytecentralpallor(redarrow)shouldequalonethirdofitsdiameter.
CourtesyofCarolavonKapff,SH(ASCP).
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Helmetcellsinmicroangiopathichemolyticanemia
Peripheralsmearsfromtwopatientswithmicroangiopathichemolyticanemia,showinganumberofredcellfragments(ie,schistocytes),someofwhichtaketheformofcombat(redarrow),bicycle(thickblackarrow),orfootball(bluearrow)"helmets."Microspherocytesarealsoseen(thinblackarrows),alongwithanucleatedredcell(greenarrow).
CourtesyofCarolavonKapff,SH(ASCP).
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Deathsfromcardiovascularcauses
Population Relativehazardrate(95percentconfidenceinterval)
Nonpreeclamptic,termdelivery
1
Nonpreeclamptic,pretermdelivery
2.95(2.12to4.11)
Preeclamptic,termdelivery 1.65(1.01to2.70)
Preeclamptic,pretermdelivery 8.12(4.31to15.33)
Datafrom:Irgens,HU,Reisaeter,L,Irgens,LM,Lie,RT.BMJ2001323:1213.
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Disclosures:ErrolRNorwitz,MD,PhDConsultant/AdvisoryBoards:Hologic[Pretermbirth(Fetalfibronectintesttopredictpretermbirth)]Natera[Fetalaneuploidyscreening(NIPTasascreeningtestforfetalaneuploidy)].PatentHolder:Bayer[Predictiontestforpreeclampsia(Useofurinaryangiogenicfactorstopredictpreeclampsia)].JohnTRepke,MDNothingtodisclose.CharlesJLockwood,MD,MHCMEquityOwnership/StockOptions:Celula[Aneuploidyscreening(PrenatalandcancerDNAscreeningtestsindevelopment)].VanessaABarss,MD,FACOGNothingtodisclose.Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseareaddressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobeprovidedtosupportthecontent.AppropriatelyreferencedcontentisrequiredofallauthorsandmustconformtoUpToDatestandardsofevidence.Conflictofinterestpolicy
Disclosures