Download - Preeclampsia_ Management and Prognosis UpToDate

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



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].

0/7

0 6

0/7 0/7

0/7



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



examinationisnormal,werepeattheultrasoundexaminationeverythreeweeks.Managementofthegrowthrestrictedfetusisreviewedseparately.(See"Fetalgrowthrestriction:Evaluationandmanagement",sectionon'Serialfetalweightassessment'and"Dopplerultrasoundoftheumbilicalarteryforfetalsurveillance".)

AntenatalcorticosteroidsAlthoughpreeclampsiamayacceleratefetallungmaturation,neonatalrespiratorydistressremainscommoninprematureneonatesofpreeclampticpregnancies[33,34].Antenatalcorticosteroids(betamethasone)topromotefetallungmaturityshouldbeadministeredtowomen



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



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



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]



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.



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


http://aplicacionesbiblioteca.udea.edu.co:4560/contents/preeclampsiamanagementandprognosis?topicKey=OBGYN%2F6825&elapsedTimeMs=0&view=p 10/23

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(



UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

REFERENCES

1. HeardAR,DekkerGA,ChanA,etal.HypertensionduringpregnancyinSouthAustralia,part1:pregnancyoutcomes.AustNZJObstetGynaecol200444:404.

2. HauthJC,EwellMG,LevineRJ,etal.Pregnancyoutcomesinhealthynulliparaswhodevelopedhypertension.CalciumforPreeclampsiaPreventionStudyGroup.ObstetGynecol200095:24.

3. Hypertensioninpregnancy:themanagementofhypertensivedisordersduringpregnancy.NICEClinicalGuideline.http://www.guideline.gov/content.aspx?id=24122(AccessedonJanuary11,2012).

4. AmericanCollegeofObstetriciansandGynecologists,TaskForceonHypertensioninPregnancy.Hypertensioninpregnancy.ReportoftheAmericanCollegeofObstetriciansandGynecologistsTaskForceonHypertensioninPregnancy.ObstetGynecol2013122:1122.

5. CoppageKH,PolzinWJ.Severepreeclampsiaanddeliveryoutcomes:isimmediatecesareandeliverybeneficial?AmJObstetGynecol2002186:921.

6. RedmanCW,SacksGP,SargentIL.Preeclampsia:anexcessivematernalinflammatoryresponsetopregnancy.AmJObstetGynecol1999180:499.

7. NassarAH,AdraAM,ChakhtouraN,etal.Severepreeclampsiaremotefromterm:laborinductionorelectivecesareandelivery?AmJObstetGynecol1998179:1210.

8. SibaiBM.Diagnosisandmanagementofgestationalhypertensionandpreeclampsia.ObstetGynecol2003102:181.

9. AlexanderJM,BloomSL,McIntireDD,LevenoKJ.Severepreeclampsiaandtheverylowbirthweightinfant:isinductionoflaborharmful?ObstetGynecol199993:485.

10. SpongCY,MercerBM,D'altonM,etal.Timingofindicatedlatepretermandearlytermbirth.ObstetGynecol2011118:323.

11. AmericanCollegeofObstetriciansandGynecologists.ACOGcommitteeopinionno.560:Medicallyindicatedlatepretermandearlytermdeliveries.ObstetGynecol2013121:908.

12. MageeLA,PelsA,HelewaM,etal.Diagnosis,evaluation,andmanagementofthehypertensivedisordersofpregnancy:executivesummary.JObstetGynaecolCan201436:416.

13. KoopmansCM,BijlengaD,GroenH,etal.Inductionoflabourversusexpectantmonitoringforgestationalhypertensionormildpreeclampsiaafter36weeks'gestation(HYPITAT):amulticentre,openlabelrandomisedcontrolledtrial.Lancet2009374:979.

14. VijgenSM,KoopmansCM,OpmeerBC,etal.Aneconomicanalysisofinductionoflabourandexpectantmonitoringinwomenwithgestationalhypertensionorpreeclampsiaatterm(HYPITATtrial).BJOG2010117:1577.

15. TajikP,vanderTuukK,KoopmansCM,etal.Shouldcervicalfavourabilityplayaroleinthedecisionforlabourinductioningestationalhypertensionormildpreeclampsiaatterm?AnexploratoryanalysisoftheHYPITATtrial.BJOG2012119:1123.

16. BartonJR,IstwanNB,RheaD,etal.Costsavingsanalysisofanoutpatientmanagementprogramforwomenwithpregnancyrelatedhypertensiveconditions.DisManag20069:236.

Magnesiumtoxicityisuncommoninwomenwithgoodrenalfunction.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).Calciumgluconate(1gramintravenouslyover5to10minutes)shouldbeadministeredtocounteractlifethreateningsymptomsofmagnesiumtoxicity.(See'Complicationsandsideeffects'above.)

Thereisanincreasedriskofpreeclampsiarecurrenceinsubsequentpregnanciesandpossiblelongtermrisksofcardiovasculardiseaseandprematuredeath.Earlyonsetpreeclampsiawithseverefeatureshasahigherriskofrecurrencethanmilderdiseasewithonsetatterm.(See'Prognosis'above.)



17. BartonJR,StanzianoGJ,SibaiBM.Monitoredoutpatientmanagementofmildgestationalhypertensionremotefromterm.AmJObstetGynecol1994170:765.

18. TurnbullDA,WilkinsonC,GerardK,etal.Clinical,psychosocial,andeconomiceffectsofantenataldaycareforthreemedicalcomplicationsofpregnancy:arandomisedcontrolledtrialof395women.Lancet2004363:1104.

19. WaughJ,BosioP,ShennanA,HalliganA.Inpatientmonitoringonanoutpatientbasis:managinghypertensivepregnanciesinthecommunityusingautomatedtechnologies.JSocGynecolInvestig20018:14.

20. HelewaM,HeamanM,RobinsonMA,ThompsonL.Communitybasedhomecareprogramforthemanagementofpreeclampsia:analternative.CMAJ1993149:829.

21. DowswellT,MiddletonP,WeeksA.Antenataldaycareunitsversushospitaladmissionforwomenwithcomplicatedpregnancy.CochraneDatabaseSystRev2009:CD001803.

22. GoldenbergRL,CliverSP,BronsteinJ,etal.Bedrestinpregnancy.ObstetGynecol199484:131.23. AbdulSultanA,WestJ,TataLJ,etal.Riskoffirstvenousthromboembolisminpregnantwomenin

hospital:populationbasedcohortstudyfromEngland.BMJ2013347:f6099.24. GordonA,RaynesGreenowC,BondD,etal.Sleepposition,fetalgrowthrestriction,andlatepregnancy

stillbirth:theSydneystillbirthstudy.ObstetGynecol2015125:347.25. SchiffE,FriedmanSA,KaoL,SibaiBM.Theimportanceofurinaryproteinexcretionduringconservative

managementofseverepreeclampsia.AmJObstetGynecol1996175:1313.26. HallDR,OdendaalHJ,SteynDW,GrovD.Urinaryproteinexcretionandexpectantmanagementofearly

onset,severepreeclampsia.IntJGynaecolObstet200277:1.27. vonDadelszenP,PayneB,LiJ,etal.Predictionofadversematernaloutcomesinpreeclampsia:

developmentandvalidationofthefullPIERSmodel.Lancet2011377:219.28. LindheimerMD,KanterD.Interpretingabnormalproteinuriainpregnancy:theneedforamore

pathophysiologicalapproach.ObstetGynecol2010115:365.29. UngerC,BiedermannK,SzlobodaJ,etal.[Sodiumconcentrationandpreeclampsia:issaltrestrictionof

value?].ZGeburtshilfeNeonatol1998202:97.30. NabeshimaK.[Effectofsaltrestrictiononpreeclampsia].NihonJinzoGakkaiShi199436:227.31. MattarF,SibaiBM.Preventionofpreeclampsia.SeminPerinatol199923:58.32. GanzevoortW,RepA,BonselGJ,etal.Arandomisedcontrolledtrialcomparingtwotemporising

managementstrategies,onewithandonewithoutplasmavolumeexpansion,forsevereandearlyonsetpreeclampsia.BJOG2005112:1358.

33. ChangEY,MenardMK,VermillionST,etal.Theassociationbetweenhyalinemembranediseaseandpreeclampsia.AmJObstetGynecol2004191:1414.

34. LangenveldJ,RavelliAC,vanKaamAH,etal.Neonataloutcomeofpregnanciescomplicatedbyhypertensivedisordersbetween34and37weeksofgestation:a7yearretrospectiveanalysisofanationalregistry.AmJObstetGynecol2011205:540.e1.

35. WallaceDH,LevenoKJ,CunninghamFG,etal.Randomizedcomparisonofgeneralandregionalanesthesiaforcesareandeliveryinpregnanciescomplicatedbyseverepreeclampsia.ObstetGynecol199586:193.

36. LiYH,NovikovaN.Pulmonaryarteryflowcathetersfordirectingmanagementinpreeclampsia.CochraneDatabaseSystRev2012:CD008882.

37. AltmanD,CarroliG,DuleyL,etal.Dowomenwithpreeclampsia,andtheirbabies,benefitfrommagnesiumsulphate?TheMagpieTrial:arandomisedplacebocontrolledtrial.Lancet2002359:1877.

38. LivingstonJC,LivingstonLW,RamseyR,etal.Magnesiumsulfateinwomenwithmildpreeclampsia:arandomizedcontrolledtrial.ObstetGynecol2003101:217.

39. WitlinAG,SibaiBM.Magnesiumsulfatetherapyinpreeclampsiaandeclampsia.ObstetGynecol199892:883.

40. CoetzeeEJ,DommisseJ,AnthonyJ.Arandomisedcontrolledtrialofintravenousmagnesiumsulphateversusplacebointhemanagementofwomenwithseverepreeclampsia.BrJObstetGynaecol1998105:300.

41. RobertsJM,VillarJ,ArulkumaranS.Preventingandtreatingeclampticseizures.BMJ2002325:609.



42. LucasMJ,LevenoKJ,CunninghamFG.Acomparisonofmagnesiumsulfatewithphenytoinforthepreventionofeclampsia.NEnglJMed1995333:201.

43. BelfortMA,AnthonyJ,SaadeGR,etal.Acomparisonofmagnesiumsulfateandnimodipineforthepreventionofeclampsia.NEnglJMed2003348:304.

44. AlexanderJM,McIntireDD,LevenoKJ,CunninghamFG.Selectivemagnesiumsulfateprophylaxisforthepreventionofeclampsiainwomenwithgestationalhypertension.ObstetGynecol2006108:826.

45. DuleyL,MatarHE,AlmerieMQ,HallDR.Alternativemagnesiumsulphateregimensforwomenwithpreeclampsiaandeclampsia.CochraneDatabaseSystRev2010:CD007388.

46. HallDR,OdendaalHJ,SmithM.Istheprophylacticadministrationofmagnesiumsulphateinwomenwithpreeclampsiaindicatedpriortolabour?BJOG2000107:903.

47. SibaiBM.Magnesiumsulfateprophylaxisinpreeclampsia:Lessonslearnedfromrecenttrials.AmJObstetGynecol2004190:1520.

48. FDARecommendsAgainstProlongedUseofMagnesiumSulfatetoStopPretermLaborDuetoBoneChangesinExposedBabieshttp://www.fda.gov/downloads/Drugs/DrugSafety/UCM353335.pdf(AccessedonMay30,2013).

49. SibaiBM,LipshitzJ,AndersonGD,DiltsPVJr.ReassessmentofintravenousMgSO4therapyinpreeclampsiaeclampsia.ObstetGynecol198157:199.

50. TaberEB,TanL,ChaoCR,etal.Pharmacokineticsofionizedversustotalmagnesiuminsubjectswithpretermlaborandpreeclampsia.AmJObstetGynecol2002186:1017.

51. EhrenbergHM,MercerBM.Abbreviatedpostpartummagnesiumsulfatetherapyforwomenwithmildpreeclampsia:arandomizedcontrolledtrial.ObstetGynecol2006108:833.

52. AscarelliMH,JohnsonV,MayWL,etal.Individuallydeterminedpostpartummagnesiumsulfatetherapywithclinicalparameterstosafelyandcosteffectivelyshortentreatmentforpreeclampsia.AmJObstetGynecol1998179:952.

53. IslerCM,BarrilleauxPS,RinehartBK,etal.Repeatpostpartummagnesiumsulfateadministrationforseizureprophylaxis:isthereapatientprofilepredictiveofneedforadditionaltherapy?JMaternFetalNeonatalMed200211:75.

54. IslerCM,BarrilleauxPS,RinehartBK,etal.Postpartumseizureprophylaxis:usingmaternalclinicalparameterstoguidetherapy.ObstetGynecol2003101:66.

55. FontenotMT,LewisDF,FrederickJB,etal.Aprospectiverandomizedtrialofmagnesiumsulfateinseverepreeclampsia:useofdiuresisasaclinicalparametertodeterminethedurationofpostpartumtherapy.AmJObstetGynecol2005192:1788.

56. MilesJFJr,MartinJNJr,BlakePG,etal.Postpartumeclampsia:arecurringperinataldilemma.ObstetGynecol199076:328.

57. SmithJM,LoweRF,FullertonJ,etal.Anintegrativereviewofthesideeffectsrelatedtotheuseofmagnesiumsulfateforpreeclampsiaandeclampsiamanagement.BMCPregnancyChildbirth201313:34.

58. LuJF,NightingaleCH.Magnesiumsulfateineclampsiaandpreeclampsia:pharmacokineticprinciples.ClinPharmacokinet200038:305.

59. MageeLA,MiremadiS,LiJ,etal.Therapywithbothmagnesiumsulfateandnifedipinedoesnotincreasetheriskofseriousmagnesiumrelatedmaternalsideeffectsinwomenwithpreeclampsia.AmJObstetGynecol2005193:153.

60. SzalSE,CroughanMinihaneMS,KilpatrickSJ.Effectofmagnesiumprophylaxisandpreeclampsiaonthedurationoflabor.AmJObstetGynecol1999180:1475.

61. DuffyCR,OdiboAO,RoehlKA,etal.Effectofmagnesiumsulfateonfetalheartratepatternsinthesecondstageoflabor.ObstetGynecol2012119:1129.

62. GraySE,RodisJF,LettieriL,etal.Effectofintravenousmagnesiumsulfateonthebiophysicalprofileofthehealthypretermfetus.AmJObstetGynecol1994170:1131.

63. CholstIN,SteinbergSF,TropperPJ,etal.Theinfluenceofhypermagnesemiaonserumcalciumandparathyroidhormonelevelsinhumansubjects.NEnglJMed1984310:1221.

64. HallakM.Effectofparenteralmagnesiumsulfateadministrationonexcitatoryaminoacidreceptorsintheratbrain.MagnesRes199811:117.



65. CottonDB,HallakM,JanuszC,etal.CentralanticonvulsanteffectsofmagnesiumsulfateonNmethylDaspartateinducedseizures.AmJObstetGynecol1993168:974.

66. BelfortMA,ClarkSL,SibaiB.Cerebralhemodynamicsinpreeclampsia:cerebralperfusionandtherationaleforanalternativetomagnesiumsulfate.ObstetGynecolSurv200661:655.

67. BerksD,SteegersEA,MolasM,VisserW.Resolutionofhypertensionandproteinuriaafterpreeclampsia.ObstetGynecol2009114:1307.

68. vanOostwaardMF,LangenveldJ,SchuitE,etal.Recurrenceofhypertensivedisordersofpregnancy:anindividualpatientdatametaanalysis.AmJObstetGynecol2015.

69. BartonJR,SibaiBM.Predictionandpreventionofrecurrentpreeclampsia.ObstetGynecol2008112:359.70. SibaiBM,MercerB,SarinogluC.Severepreeclampsiainthesecondtrimester:recurrenceriskandlong

termprognosis.AmJObstetGynecol1991165:1408.71. vanRijnBB,HoeksLB,BotsML,etal.Outcomesofsubsequentpregnancyafterfirstpregnancywithearly

onsetpreeclampsia.AmJObstetGynecol2006195:723.72. BramhamK,BrileyAL,SeedP,etal.Adversematernalandperinataloutcomesinwomenwithprevious

preeclampsia:aprospectivestudy.AmJObstetGynecol2011204:512.e1.73. SibaiBM,elNazerA,GonzalezRuizA.Severepreeclampsiaeclampsiainyoungprimigravidwomen:

subsequentpregnancyoutcomeandremoteprognosis.AmJObstetGynecol1986155:1011.74. CampbellDM,MacGillivrayI,CarrHillR.Preeclampsiainsecondpregnancy.BrJObstetGynaecol1985

92:131.75. XiongX,FraserWD,DemianczukNN.Historyofabortion,preterm,termbirth,andriskofpreeclampsia:a

populationbasedstudy.AmJObstetGynecol2002187:1013.76. SibaiBM,SarinogluC,MercerBM.Eclampsia.VII.Pregnancyoutcomeaftereclampsiaandlongterm

prognosis.AmJObstetGynecol1992166:1757.77. MostelloD,KallogjeriD,TungsiripatR,LeetT.Recurrenceofpreeclampsia:effectsofgestationalageat

deliveryofthefirstpregnancy,bodymassindex,paternity,andintervalbetweenbirths.AmJObstetGynecol2008199:55.e1.

78. McDonaldSD,BestC,LamK.Therecurrenceriskofseveredenovopreeclampsiainsingletonpregnancies:apopulationbasedcohort.BJOG2009116:1578.

79. TrogstadL,SkrondalA,StoltenbergC,etal.Recurrenceriskofpreeclampsiaintwinandsingletonpregnancies.AmJMedGenetA2004126A:41.

80. ChangJJ,MugliaLJ,MaconesGA.Associationofearlyonsetpreeclampsiainfirstpregnancywithnormotensivesecondpregnancyoutcomes:apopulationbasedstudy.BJOG2010117:946.

81. WikstrmAK,StephanssonO,CnattingiusS.Previouspreeclampsiaandrisksofadverseoutcomesinsubsequentnonpreeclampticpregnancies.AmJObstetGynecol2011204:148.e1.

82. BellamyL,CasasJP,HingoraniAD,WilliamsDJ.Preeclampsiaandriskofcardiovasculardiseaseandcancerinlaterlife:systematicreviewandmetaanalysis.BMJ2007335:974.

83. McDonaldSD,MalinowskiA,ZhouQ,etal.Cardiovascularsequelaeofpreeclampsia/eclampsia:asystematicreviewandmetaanalyses.AmHeartJ2008156:918.

84. FraserA,NelsonSM,MacdonaldWallisC,etal.Associationsofpregnancycomplicationswithcalculatedcardiovasculardiseaseriskandcardiovascularriskfactorsinmiddleage:theAvonLongitudinalStudyofParentsandChildren.Circulation2012125:1367.

85. HermesW,FranxA,vanPampusMG,etal.Cardiovascularriskfactorsinwomenwhohadhypertensivedisorderslateinpregnancy:acohortstudy.AmJObstetGynecol2013208:474.e1.

86. MongrawChaffinML,CirilloPM,CohnBA.Preeclampsiaandcardiovasculardiseasedeath:prospectiveevidencefromthechildhealthanddevelopmentstudiescohort.Hypertension201056:166.

87. SmithGN,PudwellJ,WalkerM,WenSW.Tenyear,thirtyyear,andlifetimecardiovasculardiseaseriskestimatesfollowingapregnancycomplicatedbypreeclampsia.JObstetGynaecolCan201234:830.

88. KessousR,ShohamVardiI,ParienteG,etal.Longtermmaternalatheroscleroticmorbidityinwomenwithpreeclampsia.Heart2015101:442.

89. IrgensHU,ReisaeterL,IrgensLM,LieRT.Longtermmortalityofmothersandfathersafterpreeclampsia:populationbasedcohortstudy.BMJ2001323:1213.



90. ChesleySC,AnnittoJE,CosgroveRA.Theremoteprognosisofeclampticwomen.Sixthperiodicreport.AmJObstetGynecol1976124:446.

91. ChambersJC,FusiL,MalikIS,etal.Associationofmaternalendothelialdysfunctionwithpreeclampsia.JAMA2001285:1607.

92. AgatisaPK,NessRB,RobertsJM,etal.Impairmentofendothelialfunctioninwomenwithahistoryofpreeclampsia:anindicatorofcardiovascularrisk.AmJPhysiolHeartCircPhysiol2004286:H1389.

93. LampinenKH,RnnbackM,KaajaRJ,GroopPH.Impairedvasculardilatationinwomenwithahistoryofpreeclampsia.JHypertens200624:751.

94. YinonY,KingdomJC,OdutayoA,etal.Vasculardysfunctioninwomenwithahistoryofpreeclampsiaandintrauterinegrowthrestriction:insightsintofuturevascularrisk.Circulation2010122:1846.

95. HermesW,KetJC,vanPampusMG,etal.Biochemicalcardiovascularriskfactorsafterhypertensivepregnancydisorders:asystematicreviewandmetaanalysis.ObstetGynecolSurv201267:793.

96. MagnussenEB,VattenLJ,LundNilsenTI,etal.Prepregnancycardiovascularriskfactorsaspredictorsofpreeclampsia:populationbasedcohortstudy.BMJ2007335:978.

97. MagnussenEB,VattenLJ,SmithGD,RomundstadPR.Hypertensivedisordersinpregnancyandsubsequentlymeasuredcardiovascularriskfactors.ObstetGynecol2009114:961.

98. RomundstadPR,MagnussenEB,SmithGD,VattenLJ.Hypertensioninpregnancyandlatercardiovascularrisk:commonantecedents?Circulation2010122:579.

99. BytautieneE,BulayevaN,BhatG,etal.LongtermalterationsinmaternalplasmaproteomeaftersFlt1inducedpreeclampsiainmice.AmJObstetGynecol2013208:388.e1.

100. KaajaRJ,PyhnenAlhoMK.Insulinresistanceandsympatheticoveractivityinwomen.JHypertens200624:131.

101. KaajaRJ,GreerIA.Manifestationsofchronicdiseaseduringpregnancy.JAMA2005294:2751.102. StekkingerE,ZandstraM,PeetersLL,SpaandermanME.Earlyonsetpreeclampsiaandtheprevalenceof

postpartummetabolicsyndrome.ObstetGynecol2009114:1076.103. ZandstraM,StekkingerE,vanderVlugtMJ,etal.Cardiacdiastolicdysfunctionandmetabolicsyndromein

youngwomenafterplacentalsyndrome.ObstetGynecol2010115:101.104. vanRijnBB,NijdamME,BruinseHW,etal.Cardiovasculardiseaseriskfactorsinwomenwithahistoryof

earlyonsetpreeclampsia.ObstetGynecol2013121:1040.105. BerksD,HoedjesM,RaatH,etal.Riskofcardiovasculardiseaseafterpreeclampsiaandtheeffectof

lifestyleinterventions:aliteraturebasedstudy.BJOG2013120:924.106. FeigDS,ShahBR,LipscombeLL,etal.Preeclampsiaasariskfactorfordiabetes:apopulationbased

cohortstudy.PLoSMed201310:e1001425.107. LykkeJA,LanghoffRoosJ,SibaiBM,etal.Hypertensivepregnancydisordersandsubsequent

cardiovascularmorbidityandtype2diabetesmellitusinthemother.Hypertension200953:944.108. CallawayLK,LawlorDA,O'CallaghanM,etal.Diabetesmellitusinthe21yearsafterapregnancythatwas

complicatedbyhypertension:findingsfromaprospectivecohortstudy.AmJObstetGynecol2007197:492.e1.

109. EngelandA,BjrgeT,DaltveitAK,etal.Riskofdiabetesaftergestationaldiabetesandpreeclampsia.Aregistrybasedstudyof230,000womeninNorway.EurJEpidemiol201126:157.

110. VikseBE,IrgensLM,LeivestadT,etal.Preeclampsiaandtheriskofendstagerenaldisease.NEnglJMed2008359:800.

111. WangIK,MuoCH,ChangYC,etal.Associationbetweenhypertensivedisordersduringpregnancyandendstagerenaldisease:apopulationbasedstudy.CMAJ2013185:207.

112. LevineRJ,VattenLJ,HorowitzGL,etal.Preeclampsia,solublefmsliketyrosinekinase1,andtheriskofreducedthyroidfunction:nestedcasecontrolandpopulationbasedstudy.BMJ2009339:b4336.

113. WilsonKL,CaseyBM,McIntireDD,etal.Subclinicalthyroiddiseaseandtheincidenceofhypertensioninpregnancy.ObstetGynecol2012119:315.

114. ArnadottirGA,GeirssonRT,ArngrimssonR,etal.Cardiovasculardeathinwomenwhohadhypertensioninpregnancy:acasecontrolstudy.BJOG2005112:286.

115. MogrenI,StenlundH,HgbergU.Longtermimpactofreproductivefactorsontheriskofcervical,



endometrial,ovarianandbreastcancer.ActaOncol200140:849.116. CohnBA,CirilloPM,ChristiansonRE,etal.Placentalcharacteristicsandreducedriskofmaternalbreast

cancer.JNatlCancerInst200193:1133.117. VattenLJ,RomundstadPR,TrichopoulosD,SkjaervenR.Preeclampsiainpregnancyandsubsequentrisk

forbreastcancer.BrJCancer200287:971.118. PolednakAP,JanerichDT.Characteristicsoffirstpregnancyinrelationtoearlybreastcancer.Acase

controlstudy.JReprodMed198328:314.119. AagaardTilleryKM,StoddardGJ,HolmgrenC,etal.PreeclampsiaandsubsequentriskofcancerinUtah.

AmJObstetGynecol2006195:691.120. PaltielO,FriedlanderY,TiramE,etal.Cancerafterpreeclampsia:followupoftheJerusalemperinatal

studycohort.BMJ2004328:919.121. CalderonMargalitR,FriedlanderY,YanetzR,etal.Preeclampsiaandsubsequentriskofcancer:update

fromtheJerusalemPerinatalStudy.AmJObstetGynecol2009200:63.e1.

Topic6825Version58.0



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.

Graphic79977Version9.0



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.




Peripheralsmearinmicroangiopathichemolyticanemiashowingpresenceofschistocytes

Peripheralbloodsmearfromapatientwithamicroangiopathichemolyticanemiawithmarkedredcellfragmentation.Thesmearshowsmultiplehelmetcells(smallblackarrows),otherfragmentedredcells(largeblackarrow)microspherocytesarealsoseen(bluearrows).Theplateletnumberisreducedthelargeplateletinthecenter(redarrow)suggeststhatthethrombocytopeniaisduetoenhanceddestruction.

CourtesyofCarolavonKapff,SH(ASCP).


Normalperipheralbloodsmear

Highpowerviewofanormalperipheralbloodsmear.Severalplatelets(blackarrows)andanormallymphocyte(bluearrow)canalsobeseen.Theredcellsareofrelativelyuniformsizeandshape.Thediameterofthenormalredcellshouldapproximatethat



ofthenucleusofthesmalllymphocytecentralpallor(redarrow)shouldequalonethirdofitsdiameter.





Helmetcellsinmicroangiopathichemolyticanemia

Peripheralsmearsfromtwopatientswithmicroangiopathichemolyticanemia,showinganumberofredcellfragments(ie,schistocytes),someofwhichtaketheformofcombat(redarrow),bicycle(thickblackarrow),orfootball(bluearrow)"helmets."Microspherocytesarealsoseen(thinblackarrows),alongwithanucleatedredcell(greenarrow).





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.




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