15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

OfficialreprintfromUpToDate
www.uptodate.com.scihub.cc2016UpToDate

Preeclampsia:Managementandprognosis
Authors: ErrolRNorwitz,MD,PhD,MBA,JohnTRepke,MD
SectionEditor: CharlesJLockwood,MD,MHCM
DeputyEditor: VanessaABarss,MD,FACOG

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Sep2016.|Thistopiclastupdated:Aug24,2016.
INTRODUCTIONPreeclampsiareferstothenewonsetofhypertensionandeitherproteinuriaorendorgan
dysfunctionafter20weeksofgestationinapreviouslynormotensivewoman(table1).Itisamultisystem,
progressivedisorderwithadiseasespectrumthatrangesfrommildtosevere.Progressiontoseveredisease
(table2)maybegradualorrapid.Deliveryresultsinresolutionofthedisease.
GENERALPRINCIPLESAkeyaspectofroutineprenatalcareismonitoringpregnanciesforsignsand
symptomsofpreeclampsia.Ifthediagnosisismade,thedefinitivetreatmentisdeliverytopreventdevelopmentof
maternalorfetalcomplicationsfromdiseaseprogression(see"Preeclampsia:Clinicalfeaturesanddiagnosis",
sectionon'Burdenofdisease').Whentoinitiatedeliveryisbasedupongestationalage,theseverityofthe
disease,andmaternalandfetalcondition.Patientswithpreeclampsiaat37weeksofgestationaredelivered
however,beforeterm,therisksofserioussequelaefromdiseaseprogressionneedtobebalancedwiththerisks
ofpretermbirth.Evidenceofseriousmaternalendorgandysfunctionorindeterminatetestsoffetalwellbeing
maybeindicationsforpromptdeliveryatanygestationalage.Ontheotherhand,whenmotherandfetusare
stableandwithoutfindingsofseriousendorgandysfunction,aconservativeapproachwithclosemonitoringfor
evidenceofprogressiontoseverefeaturesofthedisease(table2)isreasonableinordertoachievefurtherfetal
growthandmaturity.
APPROACHBASEDONDISEASESEVERITY
PreeclampsiawithfeaturesofseverediseasePreeclampsiawithfeaturesofseveredisease(alsocalled
severepreeclampsia)(table2)isgenerallyregardedasanindicationfordeliveryinthefollowingsettings:
Beforefetalviability

At340/7thsweeksofgestation
Whenthematernalorfetalconditionisunstable,regardlessofgestationalage
Deliveryminimizestheriskofdevelopmentofseriousmaternalandfetalcomplications(eg,cerebralhemorrhage,
hepaticrupture,renalfailure,pulmonaryedema,seizure,bleedingrelatedtothrombocytopenia,fetalgrowth
restriction,abruptioplacentae)[14].Withtheexceptionoffetalgrowthrestriction,anyoftheseadverseevents
canoccursuddenlyinawomanwithseveredisease.Afterfetalviabilityandbefore34weeksofgestation,when
themotherandfetusarestable,prolongationofpregnancyinatertiarycaresettingorinconsultationwitha
maternalfetalmedicinespecialistisreasonabletoreducemorbidityfrompretermbirth.Candidatesforthis
approachandmanagementofthesepregnanciesarediscussedseparately.(See"Expectantmanagementof
preeclampsiawithseverefeatures".)
Observationaldatasuggestthatthedecisiontoexpeditedeliveryinthesettingofseverepreeclampsiadoesnot
mandateimmediatecesareanbirth[46].Cervicalripeningagentscanbeusedpriortoinductionifthecervixis
http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selected

1/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

notfavorable[7].However,wefeelthataprolongedinductionandinductionswithalowlikelihoodofsuccessare
bestavoided.Cesareandeliveryisreasonableforwomenwithseverepreeclampsia/eclampsiawhoareunder
about32weeksofgestationandhavealowBishopscore,giventhehighfrequencyofindeterminatefetalheart
ratetracingsandfailureofthecervixtodilateinthissetting[79].Lessthanonethirdofpreterminductionsinthis
settingresultinvaginalbirth.
PreeclampsiawithoutfeaturesofseverediseaseExpertsconsistentlyrecommenddeliveryofwomenwith
preeclampsiaat37weeksofgestation,evenintheabsenceoffeaturesofseveredisease(previouslycalled
mildpreeclampsia)[3,4,1012].Cervicalripeningagentsshouldbeusedinwomenwithunfavorablecervices.
Thebenefitsoflaborinductionat37weeksofgestationwereillustratedinamulticentertrial(HYPITAT)that
randomlyassigned756womenwithmildpreeclampsiaorgestationalhypertension>360/7weekstoinduction
oflabororexpectantmanagementwithmaternal/fetalmonitoring[13].Routineinductionwasassociatedwith
asignificantreductionincompositeadversematernaloutcome(relativerisk[RR]0.71,95%CI0.590.86
absoluteriskreduction12.76percent),whichwasprimarilydrivenbyareductioninpatientswhodeveloped
severehypertensionandwasnotsignificantforwomenat360to366weeks.Theinducedgroupdelivered,on
average,1.2weeksearlierthanthecontrolgroupandhadasignificantlylowerrateofcesareandelivery(14
versus19percent).Therewerenosignificantdifferencesbetweengroupsinneonataloutcome.

Thistrialshowedthatpreeclampticwomenbenefitedfromearlyintervention,withoutincurringanincreased
riskofoperativedeliveryorneonatalmorbidity.Thetrialwasnotlargeenoughtodeterminewhethersmall
differencesinnewbornoutcomesorinductionbetween36and37weeksmightbestatisticallysignificant.A
followupeconomicanalysisofthistrialconcludedinductionwasalsolesscostlyoverallthanexpectant
managementwithmonitoring[14].Otherfollowupanalysesshowedthatanunfavorablecervixwasnota
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
reasontoavoidinduction[15,16].InasecondaryanalysisofdatafromthistrialandDIGITAT(pregnancies
URL,DOI,
complicatedbyfetalgrowthrestriction),inductionoflaboratterminwomenwithamedianBishopscoreof3
(range1to6)wasnotassociatedwithahigherrateofcesareandeliverythanexpectantmanagement,and
approximately85percentofwomeninbothgroupsachievedavaginaldelivery[16].Prostaglandinsora
ballooncatheterwasusedforcervicalripening.

SciHub

Theoptimummanagementforwomenwithpreeclampsiawithoutfeaturesofseverediseaseandstablematernal
andfetalconditionsat340/7to360/7weeksisuncertain.Althoughthereareseriousmaternalriskswithexpectant
management,webelieveexpectantmanagementisreasonableinfullyinformedpatientsbecausetheabsolute
maternalriskofanadverseoutcomeislowandtheneonatalbenefitsofdeliveryattermaresubstantial.Data

fromtherandomizedHYPITATIItrialandobservationalstudiesindicatethatmostpatientswithlateonset
diseasewillreachtermwithoutdevelopinganadversematernaloutcome(thromboembolicdisease,pulmonary
edema,eclampsia,HELLPsyndrome[Hemolysis,ElevatedLiverenzymes,LowPlateletcount],placental
abruption,maternaldeath).InHYPITATII,atleastoneoftheseadverseoutcomesoccurredin2/165(1.2
percent)ofwomenwithpreeclampsiawithoutseverefeaturesrandomlyassignedtotheimmediatedeliverygroup
versus4/159(2.5percent)ofthoseassignedtotheexpectantmanagementgroup,buttherewerenomaternal
deathsorcasesofpulmonaryedema[17].Newbornsbenefitedfromtheextratimeinutero:Respiratorydistress
syndromewasdiagnosedin5.7percentofneonatesintheimmediatedeliverygroupversus1.7percentof
neonatesintheexpectantmonitoringgroup(RR3.3,95%CI1.48.2).
Forpatientsmanagedexpectantly,deliveryisindicatedat37weeksofgestationorassoonastheydevelop
preeclampsiawithseverefeatures(table2)oreclampsia,whetherornotthecervixisfavorable.
Priorto340/7weeks,guidelinesfrommajormedicalorganizationsgenerallyrecommendexpectantmanagement
ofpreeclampsiawithoutfeaturesofseveredisease,basedonexpertopinion,giventhehighriskofcomplications

http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selected

2/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

ofprematurity[3,4,12].(See"Shorttermcomplicationsofthepreterminfant"and"Longtermcomplicationsofthe
preterminfant"and"Incidenceandmortalityofthepreterminfant".)
EXPECTANTANTEPARTUMMANAGEMENTOFPREECLAMPSIAWITHOUTFEATURESOFSEVERE
DISEASEWomenwithpreterm(<37weeksofgestation)preeclampsiawithoutfeaturesofseverediseaseare
managedexpectantly,withclosematernalandfetalmonitoringandwithoutantihypertensivetherapy.
InpatientversusoutpatientcareClosematernalmonitoringupondiagnosisofpreeclampsiaisimportantto
establishdiseaseseverityandtherateofprogression.Hospitalizationisusefulformakingtheseassessmentsand
facilitatesrapidinterventionintheeventofrapidprogression.Aftertheinitialdiagnosticevaluation,outpatient
careisacosteffectiveoptionforwomenwithstablenonseverepreeclampsia[1822].Outpatientcarecanbe
providedinthepatientshomeor,whereavailable,atanantenataldaycareunit[23].
Therearelimiteddataonoutcomeofoutpatientmanagementofpreeclampticwomen.Anobservationalstudy
andarandomizedtrialreportedgoodoutcomes,butthesestudieshadtoofewsubjectstodetectclinically
significantdifferencesinoutcomebetweeninpatientandoutpatientmanagement[19,20].Asystematicreviewof
threetrialswithatotalof504womenwithvariouscomplicationsofpregnancyobservednomajordifferencesin
clinicaloutcomesformothersorbabiesbetweenantenataldayunitsorhospitaladmission[23].

Patientsofferedoutpatientmonitoringshouldbeabletocomplywithfrequentmaternalandfetalevaluations
(everyonetothreedays)andshouldhavereadyaccesstomedicalcare.Restrictedactivitymaybe
recommendedsincebloodpressureislowerinrestedpatientshowever,thereisnoevidencethatbedrest
improvespregnancyoutcomeordelaysprogressionofdisease[24].Furthermore,bedrestinthehospital
increasestheriskofvenousthromboembolism[25].Restintheleftlateraldecubituspositioncanaugment
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
uteroplacentalflow,whichmaybenefitsomepregnancies.Avoidingthesupinesleeppositionisprudent[26].If
signsorsymptomsofdiseaseprogressionarenoted,hospitalizationformoreintensivemonitoringandpossible
URL,DOI,
deliveryisindicated.

SciHub

Outpatientsshouldbeawareofthesignsandsymptomsofpreeclampsiaandtheyshouldmonitorfetal
movementsdaily[4].Theyshouldbetoldtocalltheirhealthcareproviderimmediatelyiftheydevelopsevereor
persistentheadache,visualchanges,shortnessofbreath,orrightupperquadrantorepigastricpain.Aswithany
pregnancy,decreasedfetalmovement,vaginalbleeding,abdominalpain,ruptureofmembranes,oruterine
contractionsshouldbereportedimmediately,aswell.
LaboratoryfollowupTheminimumlaboratoryevaluationshouldincludeplateletcount,serumcreatinine,

andliverenzymes.Thesetestsshouldberepeatedatleastweeklyinwomenwithnonseverepreeclampsiato

assessfordiseaseprogression,andmoreoftenifclinicalsignsandsymptomssuggestworseningdisease[4].
Thevalueofothertestsislessclearlydefined.Arisinghematocritcanbeusefultolookforhemoconcentration,
whichsuggestscontractionofintravascularvolumeandprogressiontomoreseveredisease,whileafalling
hematocritmaybeasignofhemolysis.Anelevatedserumindirectbilirubinconcentrationisabettersignof
hemolysis,althoughanelevatedLDHmayalsobeamarkerofseverediseaseorHELLPsyndrome.Hemolysis
canbeconfirmedbyobservationofschistocytesandhelmetcellsonabloodsmear(picture1AB).(See"HELLP
syndrome".)
Sinceseveralclinicalstudieshaveshownthatneithertherateofincreasenortheamountofproteinuriaaffects
maternalorperinataloutcomeinthesettingofpreeclampsia[2730],repeated24hoururinaryprotein
estimationsarenotusefuloncethethresholdof300mg/24hoursorprotein/creatinineratio0.3mg/dL/mg/dLfor
thediagnosisofpreeclampsiahasbeenexceeded.Serumcreatininealonecanbeusedtomonitorrenalfunction.
(See"Expectantmanagementofpreeclampsiawithseverefeatures".)

http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selected

3/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

TreatmentofhypertensionBloodpressureshouldbeassessedatleasttwiceweekly.Theuseof
antihypertensivedrugstocontrolmildhypertensioninthesettingofpreeclampsiadoesnotalterthecourseofthe
diseaseordiminishperinatalmorbidityormortality,andshouldbeavoidedinmostpatients.Theindicationsfor
startingantihypertensivetherapy,thechoiceofdrug,andbloodpressuregoalsarediscussedseparately.(See
"Managementofhypertensioninpregnantandpostpartumwomen",sectionon'Preeclampsia'.)
Sodiumrestrictionbelowtherecommendeddailyintakeanddiureticshavenoroleinroutinetherapy[3133].
Althoughintravascularvascularvolumeisreduced,arandomizedtrialshowedthatplasmavolumeexpansiondid
notimprovematernalorfetaloutcome[34].
AssessmentoffetalwellbeingTherearenodatafromrandomizedtrialsonwhichtobase
recommendationsfortheoptimaltypeandfrequencyoffetalbiophysicalmonitoring.Wesuggestdailyfetal
movementcountsandtwiceweeklyfetalnonstresstestingwithassessmentofamnioticfluidvolume,ortwice
weeklybiophysicalprofiles.Testingisrepeatedimmediatelyifthereisanabruptchangeinmaternalcondition.
(See"Nonstresstestandcontractionstresstest"and"Thefetalbiophysicalprofile".)

EvaluationofumbilicalarteryDopplerindicesisalsousefuliffetalgrowthrestrictionissuspected,astheresults
helpinoptimaltimingofdelivery.Inametaanalysisof16randomizedtrialsinhighriskpregnancies,knowledge
ofumbilicalarteryDopplervelocimetryresultswasassociatedwitha29percentreductioninperinataldeath(RR
0.71,95%CI0.520.98,10,225babies,1.2versus1.7percentnumberneededtotreat203,95%CI1034352),
primarilyinpregnanciescomplicatedbypreeclampsiaand/orgrowthrestriction.Thefrequencyofassessment
dependsonthefindingsweeklyassessmentisreasonablewhenDopplerindicesarenormal.(See"Doppler
ultrasoundoftheumbilicalarteryforfetalsurveillance",sectionon'Clinicaleffectiveness'and"Dopplerultrasound
oftheumbilicalarteryforfetalsurveillance",sectionon'Guidelinesforclinicalpractice'.)
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s

SciHub

AssessmentoffetalgrowthEarlyfetalgrowthrestrictionmaybethefirstmanifestationofpreeclampsiaand
URL,DOI,
isasignofsevereuteroplacentalinsufficiency.Wesuggestperformingsonographicestimationoffetalweightto
evaluateforgrowthrestrictionandoligohydramniosatthetimeofdiagnosisofpreeclampsia.Iftheinitial
examinationisnormal,werepeattheultrasoundexaminationeverythreeweeks.Managementofthegrowth
restrictedfetusisreviewedseparately.(See"Dopplerultrasoundoftheumbilicalarteryforfetalsurveillance".)
AntenatalcorticosteroidsAlthoughpreeclampsiamayacceleratefetallungmaturation,neonatalrespiratory
distressremainscommoninprematureneonatesofpreeclampticpregnancies[35,36].Antenatalcorticosteroids
(betamethasone)topromotefetallungmaturityshouldbeadministeredtowomen<34weeksofgestationsince
theyareatincreasedriskofprogressiontoseverediseaseandpretermdelivery.Useofsteroidsafter34weeksis

morecomplicatedanddiscussedseparately.(See"Antenatalcorticosteroidtherapyforreductionofneonatal
morbidityandmortalityfrompretermdelivery",sectionon'Gestationalageatadministration'.)
INTRAPARTUMMANAGEMENT
IntrapartummonitoringContinuousmaternalfetalmonitoringisindicatedintrapartumtoidentifyworsening
hypertension,deterioratingmaternalhepatic,renal,cardiopulmonary,neurological,orhematologicfunction,as
wellasabruptioplacentaeoranabnormalorindeterminatefetalheartratetracing.Therearenoevidencebased
standardsfortheoptimalapproach.
FluidsFluidbalanceshouldbemonitoredcloselytoavoidexcessiveadministration,sincewomenwithsevere
diseaseareatriskofpulmonaryedemaandsignificantthirdspacing.Maintenancefluidsof80mL/hourareoften
adequateintheabsenceofongoingfluidloss,suchasbleeding.Oliguriathatdoesnotrespondtoamodesttrial
ofincreasedfluidsshouldbetolerated.Diureticsareonlyindicatedfortreatmentofpulmonaryedema.
ManagementofhypertensionSeverehypertensioninlaborshouldbetreatedwithintravenouslabetalolor
hydralazineororalnifedipinetopreventstroke.Antihypertensivemedicationsdonotpreventeclampsia.(See
http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selected

4/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

"Managementofhypertensioninpregnantandpostpartumwomen",sectionon'Acutetherapy'.)
ManagementofthrombocytopeniaForseverelythrombocytopenicpatients,bothauthorshaveplatelets
readilyavailablefortransfusionincaseexcessivebleedingdevelopsatvaginaldeliveryorexcessiveoozingis
observedatthetimeofskinincisionatcesarean.Thedecisionforprophylacticplatelettransfusioninwomenwith
severepreeclampsiarelatedthrombocytopeniabutnoexcessivebleedingdependsonpatientspecificfactors
consultationwiththehematologyservicemaybehelpful.Patientspecificfactorsthatmayinfluencetheauthors'
decisiontoinitiateprophylacticplatelettransfusionincludearapidlyfallingplateletcount,recentuseoflowdose
aspirin,coexistentabruption,andseverehypertensionbecauseallofthesefactorsmayimpacttheriskofclinical
bleedingorcerebrovascularaccident.
TheAmericanCollegeofObstetriciansandGynecologistshasnotmadeaspecificrecommendation[37],but
citesanAABBguidelinethatrecommendsplatelettransfusiontoincreasethematernalplateletcountto>50x
109/Lbeforemajorelectivenonneuraxialsurgery(weakrecommendationbasedonverylowqualityevidence)
[38].
Theminimumcountbeforeaneuraxialprocedureiscontroversial,dependsonfactorsinadditiontoplatelet
concentration,andisinstitutiondependent.(See"Adverseeffectsofneuraxialanalgesiaandanesthesiafor
obstetrics",sectionon'Neuraxialanalgesiaandlowplatelets'.)
Glucocorticoidtherapydoesnotappeartobeeffectiveforsignificantlyraisingtheplateletcountinwomenwith
preeclampsia[39],butavailabledatainwomenwithpreeclampsiaorHELLPsyndrome[40]arelimitedbythe
smallnumberofsubjectsinthetrials.

SciHub

AnesthesiaNeuraxialtechniquesaregenerallysafeandeffectiveinpreeclampticwomen[4,41].In
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
preeclampsia,thetwomajoranesthesiarelatedconcernswithuseofneuraxialtechniquesare(1)thepotential
URL,DOI,
foralargedropinbloodpressureduetodepletedintravascularvolumeandsympatheticblockadeand(2)
periduralhematomainwomenwithseverethrombocytopenia.Theformercanbeminimizedbyappropriate
adjustmentsinprehydration,drugchoice,drugdosing,anddrugdeliverybytheanesthesiologisthowever,alow
plateletcountmayprecludeneuraxialanesthesia.(See"Adverseeffectsofneuraxialanalgesiaandanesthesia
forobstetrics",sectionon'Hypotension'and"Adverseeffectsofneuraxialanalgesiaandanesthesiafor
obstetrics",sectionon'Neuraxialanalgesiaandlowplatelets'.)
Themajorconcernsassociatedwithgeneralanesthesia(forcesareandelivery)areatransientspikeinblood
pressureduringintubation(responsetonoxiousstimuli),hypotension(fromreductionincardiacoutputand

systemicvascularresistance),anddifficultorfailedintubationbecauseoforopharyngealedema.(See"Airway

managementofthepregnantpatientatdelivery".)
Giventheseissues,earlypatientassessmentbytheanesthesiateamisdesirable.
InvasivehemodynamicmonitoringAlthoughnotroutinelyrecommendedeveninthesettingofsevere
preeclampsia[4],invasivehemodynamicmonitoringcanbeusefulincomplicatedpatients,suchasthosewith
severecardiacdisease,severerenaldisease,severeoliguria,refractoryhypertension,orpulmonaryedema.
However,mostwomencanbemanagedwithoutthesetoolsandshouldnotbeexposedtotherisksassociated
witharterialandcentralvenouscatheterization.Randomizedtrialshavenotbeenperformed[42].(See
"Pulmonaryarterycatheterization:Indications,contraindications,andcomplicationsinadults"and"Complications
ofcentralvenouscathetersandtheirprevention".)
SeizureprophylaxisBasedupondatafromrandomizedtrials,weadministerintrapartumandpostpartum
magnesiumsulfateseizureprophylaxistoallwomenwithpreeclampsia.Althoughseizureanddeatharerare
outcomeswhenmagnesiumsulfateisomittedinwomenwhodonothaveseverehypertensionorpreeclampsia
symptoms,wefeelthebenefitoftreatmentisjustifiablegiventhelowcostandtoxicityofmagnesiumsulfateand
http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selected

5/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

therelativelylownumberofpatientsthatneedtobetreatedtopreventoneseizure.Inarandomizedplacebo
controlledtrialincluding10,000women(MAGPIE[magnesiumsulfateforpreventionofeclampsiatrial]),about
100womenwithmildpreeclampsiaandabout60womenwithseverepreeclampsiawouldneedtobetreatedto
preventoneseizure[43].Thisrecommendationisincontrasttothe2013AmericanCollegeofObstetriciansand
Gynecologistsrecommendations,whichstatethatforwomenwithpreeclampsiawithsystolicbloodpressureof
lessthan160mmHgandadiastolicbloodpressurelessthan110mmHgandnomaternalsymptoms,itis
suggestedthatmagnesiumsulfatenotbeadministereduniversallyforthepreventionofeclampsia[4].
Itisimportanttoemphasizethatseizureprophylaxisdoesnotpreventprogressionofdiseaseunrelatedto
convulsions.Approximately10to15percentofwomeninlaborwithnonseverepreeclampsiawilldevelopsignsof
severepreeclampsia(eg,severehypertension,severeheadache,visualdisturbance,epigastricpain,laboratory
abnormalities)orabruptioplacenta,whetherornottheyreceivemagnesiumtherapy[44,45].
Wedonotadministerseizureprophylaxistowomenwithonlygestationalhypertension(pregnancyrelated
hypertensionwithoutproteinuriaorendorgandysfunction),astheseizureriskinthelattergroupislessthan0.1
percent[46].(See"Gestationalhypertension".)

MagnesiumsulfateversusotheranticonvulsantsMajormedicalorganizationsworldwideconsistently
recommendmagnesiumsulfateasthedrugofchoiceforthepreventionofeclampsia[4,12,47].Inrandomized
trials[43,48,49]andlargeobservationalseries[50],magnesiumsulfatewasmoreeffectiveforpreventionofafirst
seizurethanphenytoin[48]oranantihypertensivedrugalone(nimodipine)[49]orplacebo[50].Asanexample,a
trialthatrandomlyassigned2138preeclampticpatientsadmittedtoLaborandDeliveryatParklandHospitalto
seizureprophylaxiswithmagnesiumsulfateorphenytoinreportedeclampticseizuresin10of1089women
assignedtophenytoincomparedtononeof1049womenassignedtomagnesiumsulfate[48].Maternaland
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
neonataloutcomesweresimilarinbothgroups.

SciHub

URL,DOI,

Inmetaanalysesofrandomizedtrialsineclampticwomen,magnesiumsulfatewassaferandmoreeffectivefor
preventionofrecurrentseizuresthanphenytoin,diazepam,orlyticcocktail(ie,chlorpromazine,promethazine,
andpethidine).Thesedataprovideadditionalindirectevidenceofitseffectivenessinpreeclampsia.(See
"Eclampsia",sectionon'Preventionofrecurrentseizures'.)
MagnesiumregimenandmonitoringThereisnoconsensusontheoptimalmagnesiumregimen,whenit
shouldbestartedandterminated,orrouteofadministration[51].Thedrugisusuallyinitiatedattheonsetoflabor
orinduction,orpriortoacesareandelivery[4,52,53].Itisusuallynotgiventostableantepartumpatientsoffthe
laborunit,butissometimesusedinwomenwithseverepreeclampsiabeingconsideredforexpectant

management.Prolongedantepartumtherapy(morethanfivetosevendays)inwomenwithpretermlaborhas
beenassociatedwithadverseeffectsonfetalbones[54].(See"Expectantmanagementofpreeclampsiawith
severefeatures".)
DosingAlthoughpublisheddosageregimensformagnesiumsulfatevarywidely(loadingdoseof4to6
gramsintravenouslyandmaintenancedoseof1to3gramsperhour),themostcommonregimen,andtheone
thatweuse,isaloadingdoseof6gramsintravenouslyover15to20minutesfollowedby2gramsperhourasa
continuousinfusion[4,45,50,53].Analternativeregimenis5gramsintramuscularlyintoeachbuttock(totalof10
grams)followedby5gramsintramuscularlyeveryfourhours.Theseregimensgenerallyresultinsimilar
magnesiumlevelshowever,intramuscularadministrationresultsinmorefluctuationandisassociatedwithmore
sideeffects,particularlypainattheinjectionsite[55].
Theredoesnotappeartobeaclearthresholdconcentrationforinsuringthepreventionofconvulsions,although
atherapeuticrangeof4.8to8.4mg/dL(2.0to3.5mmol/L)hasbeenrecommendedbasedonretrospectivedata
[56].Loadingdoseslessthan6gramsaremorelikelytoresultinsubtherapeuticmagnesiumlevels(lessthan4.5
mg/dL)[50,57].Highermaternalweightincreasesthetimerequiredtoreachsteadystatelevels[58].
http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selected

6/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

Sincemagnesiumsulfateisexcretedbythekidneys,dosingshouldbeadjustedinwomenwithrenalinsufficiency
(definedasaserumcreatininegreaterthan1.0mg/dL).Suchwomenshouldreceiveastandardloadingdose
(sincetheirvolumeofdistributionisnotaltered),butareducedmaintenancedose(1gramperhourorno
maintenancedoseiftheserumcreatinineisgreaterthan2.5mg/dL)andclosemonitoringoftheirserum
magnesiumleveleverysixhoursorbyclinicalassessmenteveryonetotwohours.
Themaintenancephaseisgivenonlyifapatellarreflexispresent(lossofreflexesbeingthefirstmanifestationof
symptomatichypermagnesemia),respirationsexceed12perminute,andtheurineoutputexceeds100mLper
fourhours.(See"Symptomsofhypermagnesemia".)Followingserummagnesiumlevelsisnotrequiredifthe
woman'sclinicalstatusiscloselymonitoredforevidenceofpotentialmagnesiumtoxicity(see'Complicationsand
sideeffects'below).Themaintenancedoseshouldbedecreasedifthereisclinicalevidenceofmagnesium
toxicity.
DurationoftherapyMagnesiumsulfateisusuallycontinuedfor24hourspostpartum[53].Timingof
drugdiscontinuationhasbeenarbitrarytherearenohighqualitydatatoguidetherapy.Inwomenwhohave
nonseverepreeclampsia,discontinuationoftherapyafter12hoursmaybesafe[59].Inwomenwithsevere
preeclampsiaoreclampsia,seizureprophylaxisisgenerallycontinuedfor24to48hourspostpartum,afterwhich
theriskofrecurrentseizuresislow.

Itisprobablyreasonabletoextendthedurationofmagnesiumsulfatetherapyinwomenwhosediseasehasnot
beguntoimprovepostpartumandshortenthedurationoftherapyinwomenwhoareclearlyimprovingclinically
(eg,diuresisof100mL/hourfortwoconsecutivehours,absenceofsymptoms[headache,visualchanges,
epigastricpain],andabsenceofseverehypertension)[6063].Diuresis(greaterthan4L/day)isbelievedtobe
themostaccurateclinicalindicatorofresolutionofpreeclampsia/eclampsia,butisnotaguaranteeagainstthe
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
developmentofseizures[64].Inwomenwithpersistentrenalimpairmentpostpartum,itisimportanttobe
URL,DOI,
cautiouswhenadministeringaprolongedmagnesiumsulfateinfusiontopreventtheoccurrenceofmagnesium
toxicity.

SciHub

ComplicationsandsideeffectsRapidinfusionofmagnesiumsulfatecausesdiaphoresis,flushing,and
warmth,probablyrelatedtoperipheralvasodilationandadropinbloodpressure.Nausea,vomiting,headache,
muscleweakness,visualdisturbances,andpalpitationscanalsooccur.Dyspneaorchestpainmaybesymptoms
ofpulmonaryedema,whichisararesideeffect.(See"Symptomsofhypermagnesemia".)
Magnesiumtoxicityisuncommoninwomenwithgoodrenalfunction[65].Toxicityisrelatedtoserummagnesium
concentration: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)
[66].Calciumgluconate(1gramintravenouslyover5to10minutes)shouldbeadministeredonlytocounteract
lifethreateningsymptomsofmagnesiumtoxicity(suchascardiorespiratorycompromise).
Magnesiumsulfateiscontraindicatedinwomenwithmyastheniagravissinceitcanprecipitateasevere
myastheniccrisis(see"Managementofmyastheniagravisinpregnancy").Neuromuscularblockadeand
hypotensionduetoconcurrentuseofmagnesiumsulfateandcalciumchannelblockershavebeendescribedin
casereports,buttheriskappearstobeminimal[67].
Althoughmagnesiumsulfateisaweaktocolytic,labordurationdoesnotappeartobeaffectedbymagnesium
sulfateadministration[68].Theriskofpostpartumhemorrhage,possiblyrelatedtouterineatonyfrom
magnesium'stocolyticeffects,wasslightlyincreasedinonetrial[49].
Magnesiumfreelycrossestheplacentaasaresult,thecordbloodconcentrationapproximatesthematernal
serumconcentration.Maternaltherapycausesadecreaseinbaselinefetalheartrate,whichgenerallyremains
http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selected

7/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

withinthenormalrange,andadecreaseinfetalheartratevariability,whichmaybeabsentorminimal[69].
Antenatalfetalassessmenttestresults(eg,biophysicalprofilescoreandnonstresstestreactivity)arenot
significantlyaltered[70].
Magnesiumtherapyresultsinatransientreductionoftotalandionizedserumcalciumconcentrationduetorapid
suppressionofparathyroidhormonerelease[71].Rarely,hypocalcemiabecomessymptomatic(myoclonus,
delirium,ECGabnormalities).(See"Symptomsofhypermagnesemia",sectionon'Hypocalcemia'.)Cessationof
magnesiumtherapywillrestorenormalserumcalciumlevels.However,calciumadministrationmayberequiredif
symptomsarepresent(calciumgluconate1gramintravenouslyover5to10minutes).(See"Causesand
treatmentofhypermagnesemia".)
MechanismofanticonvulsantactionThemechanismfortheanticonvulsanteffectsofmagnesium
sulfatehasnotbeenclearlydefined.Theprimaryeffectisthoughttobecentral.Hypothesesincluderaisingthe
seizurethresholdbyitsactionatthenmethyldaspartate(NMDA)receptor,membranestabilizationinthecentral
nervoussystemsecondarytoitsactionsasanonspecificcalciumchannelblocker,aswellasdecreasing
acetylcholineinmotornerveterminals[72,73].Anothertheoryisthatitpromotesvasodilatationofconstricted
cerebralvesselsbyopposingcalciumdependentarterialvasospasm,therebyreducingcerebralbarotrauma[74].
POSTPARTUMMANAGEMENTNonsteroidalantiinflammatorydrugs(NSAIDs)forpaincontrolshouldbe
avoidedinwomenwithpoorlycontrolledhypertension,oliguria,renalinsufficiency,orthrombocytopenia.(See
"NonselectiveNSAIDs:Overviewofadverseeffects".)

Therearenoevidencebasedstandardsfortheoptimalapproachtopostpartummonitoringandfollowup.We
monitorvitalsignseverytwohourswhilethepatientremainsonmagnesiumsulfateandwerepeatlaboratory
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
testsuntiltwoconsecutivesetsofdataarenormal.

SciHub

URL,DOI,

Severehypertensionshouldbetreatedsomepatientswillhavetobedischargedonantihypertensive
medications,whicharediscontinuedwhenbloodpressurereturnstonormal.(See"Managementofhypertension
inpregnantandpostpartumwomen",sectionon'Postpartumhypertension'.)
Patientsshouldbefollowedcloselyasoutpatients.TheAmericanCollegeofObstetriciansandGynecologists
suggestsmonitoringbloodpressureinhospitalorathomeforthefirst72hourspostpartumandagain7to10
dayspostdelivery[4].Somepatientswillrequirelongermonitoringcontinuedfollowupisneededuntilallofthe
signsandsymptomsofpreeclampsiahaveresolved.Alternativediagnosesshouldbesoughtinthosewith
persistentabnormalfindingsafterthreetosixmonths[75].(See"Overviewofhypertensioninadults".)

PostpartumonsetofpreeclampsiaInwomenwhoareinitiallydiagnosedwithpreeclampsiaafterdelivery,
magnesiumsulfateshouldbeadministeredtothoseatincreasedriskofdevelopingseizures[4]:
Womenwithnewonsethypertensionandheadacheorblurredvision,or
Womenwithseverehypertension
Antihypertensivetherapyshouldalsobeinitiated.TheAmericanCollegeofObstetriciansandGynecologists
suggeststreatmentofsystolicbloodpressure150mmHgordiastolicbloodpressure100mmHgontwo
occasionsfourtosixhoursapart[4].Treatmentshouldbeinitiatedwithinonehourifsystolicbloodpressureis
160mmHgordiastolicbloodpressureis110mmHg.
GUIDELINESFROMSELECTEDORGANIZATIONSAnumberofmedicalorganizationshavepublished
guidelinesformanagementofpreeclampsia.Theseguidelinesaregenerallyconsistentwiththe
recommendationsinthistopicreview.
AmericanCollegeofObstetriciansandGynecologists(ACOG).HypertensioninPregnancy[4]
http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selected

8/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

NationalInstituteforHealthandClinicalExcellence(NICE).Hypertensioninpregnancy:Themanagementof
hypertensivedisordersduringpregnancy[3]
SocietyofObstetriciansandGynaecologistsofCanada(SOGC).Diagnosis,evaluation,andmanagementof
thehypertensivedisordersofpregnancy[12]
PROGNOSISPrognosticissuesincludetheriskofrecurrentpreeclampsiaandrelatedcomplicationsin
subsequentpregnanciesandlongtermmaternalhealthrisks.
RecurrenceA2015metaanalysisofindividualpatientdatafromover75,000womenwithpreeclampsiawho
becamepregnantagainfoundthat20percentdevelopedhypertensioninasubsequentpregnancyand16
percentdevelopedrecurrentpreeclampsia[76].
Therecurrenceriskvarieswiththeseverityandtimeofonsetoftheacuteepisode[77].Womenwithearlyonset,
severepreeclampsiaareatgreatestriskofrecurrence(ashighas25to65percent)[7880].Theriskismuch
lower(5to7percent)inwomenwhohadnonseverepreeclampsiaduringthefirstpregnancy,versuslessthan1
percentinwomenwhohadanormotensivefirstpregnancy(doesnotapplytoabortions)[78,8186].Inaseriesof
125womenwithseveresecondtrimesterpreeclampsiafollowedforfiveyears,65percentdevelopedrecurrent
preeclampsiaand35percentwerenormotensiveintheirsubsequentpregnancy[78].Ofthepreeclampticgroup,
approximatelyonethirddevelopedthediseaseat27weeks,onethirdat28to36weeks,andonethirdat37
weeks.Thus,21percentofsubsequentpregnancieswerecomplicatedbyseverepreeclampsiainthesecond
trimester.

Recurrentpreeclampsiaismorelikelyfollowingapreeclampticsingletonpregnancythanapreeclamptictwin
pregnancy[87].TherecurrenceriskinwomenwithHELLPsyndrome(whomaydevelopeitherHELLPor
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
preeclampsiainasubsequentpregnancy)isdiscussedseparately.(See"HELLPsyndrome",sectionon
URL,DOI,
'Recurrenceinsubsequentpregnancies'.)

SciHub

PreventionPreventivetherapy(lowdoseaspirin)isreviewedelsewhere.(See"Preeclampsia:
Prevention".)
RiskofrelatedobstetricalcomplicationsPreeclampsia,growthrestriction,pretermdelivery,abruptio
placentae,andstillbirthcanallbesequelaeofimpairedplacentalfunction.Womenwithpregnanciescomplicated
byoneofthesedisordersareatincreasedriskofdevelopingoneoftheotherdisordersinfuturepregnancies.
Earlyonsetpreeclampsiaismorelikelytobeassociatedwithoneoftheseadverseeventsinasubsequent

pregnancy,evenifnormotensive,thanlateonsetpreeclampsia[88,89].

Longtermmaternalrisksofpregnancyassociatedhypertension
CardiovasculardiseaseCasecontrolandcohortstudiesconsistentlyreportthatpreeclampsiais
predictiveoffuturecardiovascularandcerebrovasculardiseaseandthatearlyonsetofpreeclampsiaincreases
thewomanslongtermriskforcardiovasculardisease.Theserelationshipsweresummarizedintwosystematic
reviewsofcontrolledstudiesthatevaluatedtheriskoflatecardiovasculareventsinwomenwithandwithouta
historyofpreeclampsia[90,91]:
Comparedwithwomenwithnohistoryofthedisease,womenwithpreeclampsiawereatincreasedriskof
developinghypertension(RR3.70,95%CI2.705.05atmeanfollowupof14years),ischemicheartdisease
(RR2.16,95%CI1.862.52atmeanfollowupof11.7years),stroke(RR1.81,95%CI1.452.27atmean
followupof10.4years),andvenousthromboembolism(RR1.79,95%CI1.372.33atmeanfollowupof4.7
years)[90].Theabsoluteriskthatawomanwithorwithoutahistoryofpreeclampsiawoulddeveloponeof
thesecardiovasculareventsatage50to59yearswasestimatedtobe17.8and8.3percent,respectively.
http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selected

9/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

Inaddition,agradedrelationshipwasobservedbetweenseverityofpreeclampsiaandriskoffuturecardiac
disease(mildpreeclampsiaRR2.00,95%CI1.832.19moderatepreeclampsiaRR2.99,95%CI2.513.58
severepreeclampsiaRR5.36,95%CI3.967.27),aswellasacorrelationbetweenpreeclampsiaandfuture
peripheralarterydisease(RR1.87,95%CI0.943.73)[91].Theauthorsdefinedpreeclampsiaas'mild'ifthe
pregnancyhadanuncomplicatedcourse,'moderate'ifpreeclampsiawascomplicatedbyfetalgrowth
restrictionormaternalseizuresand'severe'ifpreeclampsiawascomplicatedbypretermdeliveryorfetal
demise.
Prospectivecohortstudiespublishedafterthesereviewshavereportedsimilarfindings[9295].Oneofthese
studieshad30yearsoffollowupandreportedthat,comparedwithwomenwithnohistoryofpreeclampsia,the
riskofdeathfromcardiovasculardiseasewasincreasedtwofoldinwomenwithpreeclampsiaonset>34weeksof
gestationandincreased9to10foldinwomenwithpreeclampsiaonset<34weeks[94].
Aretrospectivepopulationbasedcohortstudyalsonotedthatwomenwithahistoryofpreeclampsiaor
gestationalhypertensionhadasmallincreaseinriskofcardiomyopathythatpersisted>5yearsafterdelivery
comparedwithwomenwithoutsuchahistory[96].Elevenpercentofallcardiomyopathyeventsinthecohort
occurredamongwomenwithahistoryofpreeclampsiaorgestationalhypertensionandabout50percentofthe
associationwasrelatedtopostpregnancychronichypertension.However,theabsoluteriskofcardiomyopathy
wassmall,14.6to17.3cases/100000personyears.

Thefutureriskofcardiovascularmorbidityandmortalityappearstoberelatedtoboththeseverityof
preeclampsiaandthenumberofepisodesofpreeclampsia[97].Womenwithearlyonset/severepreeclampsia
withpretermdeliveryareathighestriskofcardiovasculardiseaselaterinlife,includingduringthepremenopausal
period(table3).Intwolargestudies,thesewomenhadaneighttoninefoldincreasedriskofdeathfrom
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
cardiovascularcausescomparedwithwomenwithoutahistoryofpreeclampsia[94,98].Incontrast,mild
URL,DOI,
preeclampsiaoccurringlateingestationdoesnotappeartobeassociatedwithahighriskofremote
cardiovasculardisease[99].Thestrongerassociationbetweencardiovasculardiseaseandpretermpreeclampsia
suggeststhatthepathogenesisofearlyversuslatepreeclampsiamaybedifferent.

SciHub

Severalstudieshavedemonstratedthatwomenwithahistoryofpreeclampsiaorsevereearlyonsetfetalgrowth
restrictionexhibitimpairedendothelialfunctionandvasodilatationremotefrompregnancy[100103].Womenwith
ahistoryofhypertensivedisordersinpregnancyhavehigherlevelsofglucose,insulin,andunfavorablelipidsthan
womenwithahistoryofnormotensivepregnancy[104].Datafromsomeepidemiologicstudiessuggestthatthe
increasedriskoflatecardiovascularmorbidityinpreviouslypreeclampticwomenreflectsanunderlying

predispositioninthesewomenforbothdisorders(geneticfactors,sharedriskfactors),butitisalsopossiblethat

preeclampsiaresultsinpermanentarterialchangesleadingtolatecardiovasculardisease[105108].Some
investigatorshavehypothesizedthatincreasedinsulinresistance,sympatheticoveractivity,proinflammatory
activity,endothelialdysfunction,andtheabnormallipidprofileinpreeclampticwomenconstituteanearly
manifestationofmetabolicsyndromeandthatthesechangespersistafterpregnancy,therebyputtingaffected
womanatincreasedriskofcardiovasculardisease[109113].Womenwithbothpreeclampsiaandagrowth
restrictednewbornappeartobeathighestrisk.Inonestudy,20percentofsuchwomenmetcriteriaformetabolic
syndromewhenevaluatedseveralmonthspostpartum[114].Onegroupestimatedthatlifestyleinterventionsafter
preeclampsiawoulddecreasecardiovasculardiseaseriskby4to13percent[115].
TheAmericanHeartAssociationconsidersahistoryofpreeclampsia,gestationaldiabetes,orpregnancyinduced
hypertensionamajorriskfactorfordevelopmentofcardiovasculardisease[116].Assessmentofcardiovascular
riskfactors,typeandfrequencyofpatientmonitoring,andriskreductionstrategiesarereviewedseparately.(See
"Overviewofprimarypreventionofcoronaryheartdiseaseandstroke".)
DiabetesmellitusInapopulationbasedretrospectivecohortstudyincludingoveronemillionwomen,
preeclampsiaorgestationalhypertensionintheabsenceofgestationaldiabetesmellitus(GDM)wasassociated
http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

10/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

withatwofoldincreaseintheincidenceofdiabetesduring16.5yearsofpostdeliveryfollowup,aftercontrolling
forseveralconfoundingvariables(butnotobesity)[117].Inwomenwhohadpreeclampsiaorgestational
hypertensionandGDM,theriskoffuturediabeteswasincreased16to18fold,whichwasabovethealready
elevated13foldincreaseinriskassociatedwithGDMalone.Thesefindings,andthosefrompreviousreports
[118120],suggestthatcliniciansshouldinformwomenwithahistoryofpreeclampsiaorgestationalhypertension
thattheymaybeatincreasedriskofdevelopingdiabeteshowever,theavailableevidencedoesnotsupporta
changeinstandardscreeningguidelines.(See"Screeningfortype2diabetesmellitus",sectionon'Screening
recommendationsbyexpertgroups'.)
EndstagerenaldiseaseWomenwithpreeclampsiamaybeatincreasedriskofdevelopingendstage
renaldisease(ESRD)laterinlife,buttheabsoluteriskissmall.Astudythatlinkedfourdecadesofdatafromthe
NorwegiannationalbirthandESRDregistriesfoundthatwomenwithpreeclampsiaintheirfirstpregnancyhada
fourfoldincreaseinriskofESRDcomparedwithwomenwithoutpreeclampsia(RR4.7,95%CI3.66.1)after
adjustingforknownconfounders,buttheabsoluteriskofESRDwaslessthan1percentwithin20years[121].
Similarly,astudyusingclaimsdatafromtheTaiwanNationalHealthInsuranceProgramnotedthatwomenwith
preeclampsia/eclampsiawereatsignificantlyhigherriskofdevelopingESRDovertimethanwomenwithout
hypertensivedisordersduringpregnancy(incidence5.33versus0.34per10,000personyears)[122].
AlthoughwomenwhowentontodevelopESRDmayhavehadsubclinicalrenaldiseaseduringpregnancy,itis
alsopossiblethatasyetundefinedriskfactorspredisposedthesewomentobothpreeclampsiaandESRD.Itis
lesslikelythatpreeclampsiadamagesthekidney,therebyinitiatingaprocessofchronicdeterioration.

SubclinicalhypothyroidismAnestedcasecontrolstudyfoundthatnulliparouswomenwhodeveloped
preeclampsiaweretwiceaslikelytodevelopsubclinicalhypothyroidismduringpregnancyandlongafterdelivery
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
thanmatchednormotensivecontrols[123].Theriskwasstrongestinwomenwithrecurrentpreeclampsiaand
URL,DOI,
withoutthyroidperoxidaseantibodies,suggestingthatanautoimmunemediatedmechanismofhypothyroidism
wasnotinvolved.Inastudyincluding25,000pregnantwomen,womenwithsubclinicalhypothyroidismidentified
duringpregnancywereatincreasedriskofdevelopingseverepreeclampsiacomparedwitheuthyroidwomen(OR
1.6,95%CI1.12.4),afteradjustmentforriskfactorsforpreeclampsia[124].Abnormallevelsofthyroid
hormonesappeartodamageendothelialcells,potentiallyleadingtopreeclampsiaandlongtermcardiovascular
sequelae.

SciHub

CancerAntiangiogenesisisakeycharacteristicofpreeclampsia.Becauseantiangiogenesisisalso
importantforrestrictingtumorgrowth,ithasbeenhypothesizedthatwomenwithpreeclampsiamaybeat

reducedriskoffuturedevelopmentofsolidcancers.However,asystematicreviewofprospectiveand

retrospectivecohortstudiesfoundnosignificantassociationbetweenpreeclampsiaandlaterdevelopmentof
cancer[90].
OtherAsingleretrospectivestudyobservedanassociationbetweenhypertensivediseaseofpregnancy
anddeathfromAlzheimerdisease[125].Thisobservationrequiresfurtherstudygiventhemethodologic
limitationsofthestudy,whichreviewedbirthanddeathcertificatedataforwomenwhodeliveredbetween1939
and2012andlivedinUtahforatleastoneyearafterdelivery.
INFORMATIONFORPATIENTSUpToDateofferstwotypesofpatienteducationmaterials,TheBasicsand
BeyondtheBasics.TheBasicspatienteducationpiecesarewritteninplainlanguage,atthe5thto6thgrade
readinglevel,andtheyanswerthefourorfivekeyquestionsapatientmighthaveaboutagivencondition.These
articlesarebestforpatientswhowantageneraloverviewandwhoprefershort,easytoreadmaterials.Beyond
theBasicspatienteducationpiecesarelonger,moresophisticated,andmoredetailed.Thesearticlesarewritten
atthe10thto12thgradereadinglevelandarebestforpatientswhowantindepthinformationandare
comfortablewithsomemedicaljargon.
http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selected 11/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

Herearethepatienteducationarticlesthatarerelevanttothistopic.Weencourageyoutoprintoremailthese
topicstoyourpatients.(Youcanalsolocatepatienteducationarticlesonavarietyofsubjectsbysearchingon
patientinfoandthekeyword(s)ofinterest.)
Basicstopics(see"Patienteducation:Preeclampsia(TheBasics)"and"Patienteducation:Highblood
pressureandpregnancy(TheBasics)"and"Patienteducation:HELLPsyndrome(TheBasics)")
BeyondtheBasicstopics(see"Patienteducation:Preeclampsia(BeyondtheBasics)")
SUMMARYANDRECOMMENDATIONS
Thedefinitivetreatmentofpreeclampsiaisdeliverytopreventdevelopmentofmaternalorfetalcomplications
fromdiseaseprogression.Timingofdeliveryisbasedupongestationalage,theseverityofpreeclampsia,
andmaternalandfetalcondition.(See'Generalprinciples'above.)
Preeclampsiawithfeaturesofseveredisease(table2)isgenerallyregardedasanindicationfordelivery,
regardlessofgestationalage,giventhehighriskofseriousmaternalmorbidity.However,prolonged
antepartummanagementinatertiarycaresettingorinconsultationwithamaternalfetalmedicinespecialist
isanoptionforselectedwomenremotefromterm(<34weeksofgestation).(See'Preeclampsiawith
featuresofseveredisease'above.)
Forwomenwithpreeclampsiawithoutfeaturesofseveredisease,wesuggestexpectantmanagementwith
deliveryat37weeksofgestation(Grade2B).(See'Preeclampsiawithoutfeaturesofseveredisease'
above.)

SciHub

https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
Expectantmanagementofwomenwithpreeclampsiawithoutfeaturesofseverediseaseconsistsoffrequent
laboratorymonitoring(plateletcount,liverandrenalfunctiontests),assessmentofmaternalbloodpressure
URL,DOI,
andsymptoms,andevaluationoffetalgrowthandwellbeing.Inmostpatients,antihypertensivetherapyis
notindicatedforsystolicbloodpressure<160mmHgordiastolicbloodpressure<110mmHg.(See
'Expectantantepartummanagementofpreeclampsiawithoutfeaturesofseveredisease'above.)

Forwomenwithaviablefetusandpreeclampsia<34weeksofgestation,werecommendacourseof
antenatalglucocorticoids(betamethasone)(Grade1A).(See"Antenatalcorticosteroidtherapyforreduction
ofneonatalmorbidityandmortalityfrompretermdelivery".)
Forwomenwithpreeclampsiaandfeaturesofseveredisease,werecommendintrapartumandpostpartum

seizureprophylaxis(Grade1A).Thebenefitofseizureprophylaxisislessclearinwomenwithoutsevere

hypertensionorpreeclampsiasymptomshowever,wealsosuggestintrapartumandpostpartumprophylaxis
forthesewomen(Grade2B).Werecommendtheuseofmagnesiumsulfateasafirstlineagentforseizure
prophylaxisinpreeclampsia(Grade1A).(See'Seizureprophylaxis'above.)
Wegivealoadingdoseof6gramsmagnesiumsulfateintravenouslyover15to20minutesfollowedby2
gramsperhourasacontinuousinfusion.Themaintenancedose(butnottheloadingdose)shouldbe
adjustedinwomenwithrenalinsufficiency.(See'Magnesiumregimenandmonitoring'above.)
Magnesiumtoxicityisuncommoninwomenwithgoodrenalfunction.Toxicityisrelatedtoserummagnesium
concentration:lossofdeeptendonreflexesoccursat7to10mEq/L(8.5to12mg/dLor3.5to5.0mmol/L),
respiratoryparalysisat10to13mEq/L(12to16mg/dLor5.0to6.5mmol/L),cardiacconductionisaltered
at>15mEq/L(>18mg/dLor>7.5mmol/L),andcardiacarrestoccursat>25mEq/L(>30mg/dLor>12.5
mmol/L).Calciumgluconate(1gramintravenouslyover5to10minutes)shouldbeadministeredto
counteractlifethreateningsymptomsofmagnesiumtoxicity.(See'Complicationsandsideeffects'above.)

http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

12/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

Forseverelythrombocytopenicpatients,wehaveplateletsreadilyavailablefortransfusionincaseexcessive
bleedingdevelopsatvaginaldeliveryorexcessiveoozingisobservedatthetimeofskinincisionatcesarean.
Thedecisionforprophylacticplatelettransfusioninwomenwithseverepreeclampsiarelated
thrombocytopeniabutnoexcessivebleedingdependsonpatientspecificfactorsconsultationwiththe
hematologyservicemaybehelpful.(See'Managementofthrombocytopenia'above.)
Thereisanincreasedriskofpreeclampsiarecurrenceinsubsequentpregnancies.Earlyonsetpreeclampsia
withseverefeatureshasahigherriskofrecurrencethanmilderdiseasewithonsetatterm.(See'Prognosis'
above.)
TheAmericanHeartAssociationconsidersahistoryofpreeclampsiaorpregnancyinducedhypertensiona
majorriskfactorfordevelopmentofcardiovasculardisease(see'Cardiovasculardisease'above).Routine
wellwomancareshouldincludeassessmentofcardiovascularriskfactors,withappropriatepatient
monitoringandriskreductioninterventions,whenindicated.(See"Overviewofprimarypreventionof
coronaryheartdiseaseandstroke".)
UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.
REFERENCES
1.HeardAR,DekkerGA,ChanA,etal.HypertensionduringpregnancyinSouthAustralia,part1:pregnancy
outcomes.AustNZJObstetGynaecol200444:404.

SciHub

https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
2.HauthJC,EwellMG,LevineRJ,etal.Pregnancyoutcomesinhealthynulliparaswhodeveloped
hypertension.CalciumforPreeclampsiaPreventionStudyGroup.ObstetGynecol200095:24.
URL,DOI,

3.Hypertensioninpregnancy:themanagementofhypertensivedisordersduringpregnancy.NICEClinical
Guideline.http://www.guideline.gov.scihub.cc/content.aspx?id=24122(AccessedonJanuary11,2012).
4.AmericanCollegeofObstetriciansandGynecologists,TaskForceonHypertensioninPregnancy.
Hypertensioninpregnancy.ReportoftheAmericanCollegeofObstetriciansandGynecologistsTaskForce
onHypertensioninPregnancy.ObstetGynecol2013122:1122.
5.CoppageKH,PolzinWJ.Severepreeclampsiaanddeliveryoutcomes:isimmediatecesareandelivery
beneficial?AmJObstetGynecol2002186:921.

6.RedmanCW,SacksGP,SargentIL.Preeclampsia:anexcessivematernalinflammatoryresponseto

pregnancy.AmJObstetGynecol1999180:499.

7.NassarAH,AdraAM,ChakhtouraN,etal.Severepreeclampsiaremotefromterm:laborinductionor
electivecesareandelivery?AmJObstetGynecol1998179:1210.
8.SibaiBM.Diagnosisandmanagementofgestationalhypertensionandpreeclampsia.ObstetGynecol2003
102:181.
9.AlexanderJM,BloomSL,McIntireDD,LevenoKJ.Severepreeclampsiaandtheverylowbirthweight
infant:isinductionoflaborharmful?ObstetGynecol199993:485.
10.SpongCY,MercerBM,D'altonM,etal.Timingofindicatedlatepretermandearlytermbirth.Obstet
Gynecol2011118:323.
11.AmericanCollegeofObstetriciansandGynecologists.ACOGcommitteeopinionno.560:Medically
indicatedlatepretermandearlytermdeliveries.ObstetGynecol2013121:908.
12.MageeLA,PelsA,HelewaM,etal.Diagnosis,evaluation,andmanagementofthehypertensivedisorders
ofpregnancy:executivesummary.JObstetGynaecolCan201436:416.
http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

13/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

13.KoopmansCM,BijlengaD,GroenH,etal.Inductionoflabourversusexpectantmonitoringforgestational
hypertensionormildpreeclampsiaafter36weeks'gestation(HYPITAT):amulticentre,openlabel
randomisedcontrolledtrial.Lancet2009374:979.
14.VijgenSM,KoopmansCM,OpmeerBC,etal.Aneconomicanalysisofinductionoflabourandexpectant
monitoringinwomenwithgestationalhypertensionorpreeclampsiaatterm(HYPITATtrial).BJOG2010
117:1577.
15.TajikP,vanderTuukK,KoopmansCM,etal.Shouldcervicalfavourabilityplayaroleinthedecisionfor
labourinductioningestationalhypertensionormildpreeclampsiaatterm?Anexploratoryanalysisofthe
HYPITATtrial.BJOG2012119:1123.
16.BernardesTP,BroekhuijsenK,KoopmansCM,etal.Caesareansectionratesandadverseneonatal
outcomesafterinductionoflabourversusexpectantmanagementinwomenwithanunripecervix:a
secondaryanalysisoftheHYPITATandDIGITATtrials.BJOG2016123:1501.
17.BroekhuijsenK,vanBaarenGJ,vanPampusMG,etal.Immediatedeliveryversusexpectantmonitoringfor
hypertensivedisordersofpregnancybetween34and37weeksofgestation(HYPITATII):anopenlabel,
randomisedcontrolledtrial.Lancet2015385:2492.
18.BartonJR,IstwanNB,RheaD,etal.Costsavingsanalysisofanoutpatientmanagementprogramfor
womenwithpregnancyrelatedhypertensiveconditions.DisManag20069:236.
19.BartonJR,StanzianoGJ,SibaiBM.Monitoredoutpatientmanagementofmildgestationalhypertension
remotefromterm.AmJObstetGynecol1994170:765.

20.TurnbullDA,WilkinsonC,GerardK,etal.Clinical,psychosocial,andeconomiceffectsofantenataldaycare
forthreemedicalcomplicationsofpregnancy:arandomisedcontrolledtrialof395women.Lancet2004
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
363:1104.

SciHub

URL,DOI,

21.WaughJ,BosioP,ShennanA,HalliganA.Inpatientmonitoringonanoutpatientbasis:managing
hypertensivepregnanciesinthecommunityusingautomatedtechnologies.JSocGynecolInvestig2001
8:14.
22.HelewaM,HeamanM,RobinsonMA,ThompsonL.Communitybasedhomecareprogramforthe
managementofpreeclampsia:analternative.CMAJ1993149:829.
23.DowswellT,MiddletonP,WeeksA.Antenataldaycareunitsversushospitaladmissionforwomenwith
complicatedpregnancy.CochraneDatabaseSystRev2009:CD001803.
24.GoldenbergRL,CliverSP,BronsteinJ,etal.Bedrestinpregnancy.ObstetGynecol199484:131.

25.AbdulSultanA,WestJ,TataLJ,etal.Riskoffirstvenousthromboembolisminpregnantwomeninhospital:
populationbasedcohortstudyfromEngland.BMJ2013347:f6099.
26.GordonA,RaynesGreenowC,BondD,etal.Sleepposition,fetalgrowthrestriction,andlatepregnancy
stillbirth:theSydneystillbirthstudy.ObstetGynecol2015125:347.
27.SchiffE,FriedmanSA,KaoL,SibaiBM.Theimportanceofurinaryproteinexcretionduringconservative
managementofseverepreeclampsia.AmJObstetGynecol1996175:1313.
28.HallDR,OdendaalHJ,SteynDW,GrovD.Urinaryproteinexcretionandexpectantmanagementofearly
onset,severepreeclampsia.IntJGynaecolObstet200277:1.
29.vonDadelszenP,PayneB,LiJ,etal.Predictionofadversematernaloutcomesinpreeclampsia:
developmentandvalidationofthefullPIERSmodel.Lancet2011377:219.
30.LindheimerMD,KanterD.Interpretingabnormalproteinuriainpregnancy:theneedforamore
pathophysiologicalapproach.ObstetGynecol2010115:365.

http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

14/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

31.UngerC,BiedermannK,SzlobodaJ,etal.[Sodiumconcentrationandpreeclampsia:issaltrestrictionof
value?].ZGeburtshilfeNeonatol1998202:97.
32.NabeshimaK.[Effectofsaltrestrictiononpreeclampsia].NihonJinzoGakkaiShi199436:227.
33.MattarF,SibaiBM.Preventionofpreeclampsia.SeminPerinatol199923:58.
34.GanzevoortW,RepA,BonselGJ,etal.Arandomisedcontrolledtrialcomparingtwotemporising
managementstrategies,onewithandonewithoutplasmavolumeexpansion,forsevereandearlyonset
preeclampsia.BJOG2005112:1358.
35.ChangEY,MenardMK,VermillionST,etal.Theassociationbetweenhyalinemembranediseaseand
preeclampsia.AmJObstetGynecol2004191:1414.
36.LangenveldJ,RavelliAC,vanKaamAH,etal.Neonataloutcomeofpregnanciescomplicatedby
hypertensivedisordersbetween34and37weeksofgestation:a7yearretrospectiveanalysisofanational
registry.AmJObstetGynecol2011205:540.e1.
37.PracticeBulletinNo.166:ThrombocytopeniainPregnancy.ObstetGynecol2016128:e43.
38.KaufmanRM,DjulbegovicB,GernsheimerT,etal.Platelettransfusion:aclinicalpracticeguidelinefromthe
AABB.AnnInternMed2015162:205.
39.PourratO,DoreyM,RagotS,etal.HighDoseMethylprednisolonetoPreventPlateletDeclinein
Preeclampsia:ARandomizedControlledTrial.ObstetGynecol2016128:153.
40.WoudstraDM,ChandraS,HofmeyrGJ,DowswellT.CorticosteroidsforHELLP(hemolysis,elevatedliver
enzymes,lowplatelets)syndromeinpregnancy.CochraneDatabaseSystRev2010:CD008148.

SciHub

41.WallaceDH,LevenoKJ,CunninghamFG,etal.Randomizedcomparisonofgeneralandregional
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
anesthesiaforcesareandeliveryinpregnanciescomplicatedbyseverepreeclampsia.ObstetGynecol1995
URL,DOI,
86:193.
42.LiYH,NovikovaN.Pulmonaryarteryflowcathetersfordirectingmanagementinpreeclampsia.Cochrane
DatabaseSystRev2012:CD008882.
43.AltmanD,CarroliG,DuleyL,etal.Dowomenwithpreeclampsia,andtheirbabies,benefitfrom
magnesiumsulphate?TheMagpieTrial:arandomisedplacebocontrolledtrial.Lancet2002359:1877.
44.LivingstonJC,LivingstonLW,RamseyR,etal.Magnesiumsulfateinwomenwithmildpreeclampsia:a
randomizedcontrolledtrial.ObstetGynecol2003101:217.
45.WitlinAG,SibaiBM.Magnesiumsulfatetherapyinpreeclampsiaandeclampsia.ObstetGynecol1998

92:883.
46.CoetzeeEJ,DommisseJ,AnthonyJ.Arandomisedcontrolledtrialofintravenousmagnesiumsulphate
versusplacebointhemanagementofwomenwithseverepreeclampsia.BrJObstetGynaecol1998
105:300.
47.RobertsJM,VillarJ,ArulkumaranS.Preventingandtreatingeclampticseizures.BMJ2002325:609.
48.LucasMJ,LevenoKJ,CunninghamFG.Acomparisonofmagnesiumsulfatewithphenytoinforthe
preventionofeclampsia.NEnglJMed1995333:201.
49.BelfortMA,AnthonyJ,SaadeGR,etal.Acomparisonofmagnesiumsulfateandnimodipineforthe
preventionofeclampsia.NEnglJMed2003348:304.
50.AlexanderJM,McIntireDD,LevenoKJ,CunninghamFG.Selectivemagnesiumsulfateprophylaxisforthe
preventionofeclampsiainwomenwithgestationalhypertension.ObstetGynecol2006108:826.
51.DuleyL,MatarHE,AlmerieMQ,HallDR.Alternativemagnesiumsulphateregimensforwomenwithpre
eclampsiaandeclampsia.CochraneDatabaseSystRev2010:CD007388.

http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

15/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

52.HallDR,OdendaalHJ,SmithM.Istheprophylacticadministrationofmagnesiumsulphateinwomenwith
preeclampsiaindicatedpriortolabour?BJOG2000107:903.
53.SibaiBM.Magnesiumsulfateprophylaxisinpreeclampsia:Lessonslearnedfromrecenttrials.AmJObstet
Gynecol2004190:1520.
54.FDArecommendsagainstprolongeduseofmagnesiumsulfatetostoppretermlaborduetobonechanges
inexposedbabies.http://www.fda.gov.scihub.cc/downloads/Drugs/DrugSafety/UCM353335.pdf(Accessed
onMay30,2013).
55.OkusanyaBO,OladapoOT,LongQ,etal.Clinicalpharmacokineticpropertiesofmagnesiumsulphatein
womenwithpreeclampsiaandeclampsia.BJOG2016123:356.
56.SibaiBM,LipshitzJ,AndersonGD,DiltsPVJr.ReassessmentofintravenousMgSO4therapyin
preeclampsiaeclampsia.ObstetGynecol198157:199.
57.TaberEB,TanL,ChaoCR,etal.Pharmacokineticsofionizedversustotalmagnesiuminsubjectswith
pretermlaborandpreeclampsia.AmJObstetGynecol2002186:1017.
58.BrookfieldKF,SuF,ElkomyMH,etal.Pharmacokineticsandplacentaltransferofmagnesiumsulfatein
pregnantwomen.AmJObstetGynecol2016214:737.e1.
59.EhrenbergHM,MercerBM.Abbreviatedpostpartummagnesiumsulfatetherapyforwomenwithmild
preeclampsia:arandomizedcontrolledtrial.ObstetGynecol2006108:833.
60.AscarelliMH,JohnsonV,MayWL,etal.Individuallydeterminedpostpartummagnesiumsulfatetherapy
withclinicalparameterstosafelyandcosteffectivelyshortentreatmentforpreeclampsia.AmJObstet
Gynecol1998179:952.

SciHub

https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s

61.IslerCM,BarrilleauxPS,RinehartBK,etal.Repeatpostpartummagnesiumsulfateadministrationfor
URL,DOI,
seizureprophylaxis:isthereapatientprofilepredictiveofneedforadditionaltherapy?JMaternFetal
NeonatalMed200211:75.
62.IslerCM,BarrilleauxPS,RinehartBK,etal.Postpartumseizureprophylaxis:usingmaternalclinical
parameterstoguidetherapy.ObstetGynecol2003101:66.

63.FontenotMT,LewisDF,FrederickJB,etal.Aprospectiverandomizedtrialofmagnesiumsulfateinsevere
preeclampsia:useofdiuresisasaclinicalparametertodeterminethedurationofpostpartumtherapy.AmJ
ObstetGynecol2005192:1788.
64.MilesJFJr,MartinJNJr,BlakePG,etal.Postpartumeclampsia:arecurringperinataldilemma.Obstet

Gynecol199076:328.

65.SmithJM,LoweRF,FullertonJ,etal.Anintegrativereviewofthesideeffectsrelatedtotheuseof
magnesiumsulfateforpreeclampsiaandeclampsiamanagement.BMCPregnancyChildbirth201313:34.
66.LuJF,NightingaleCH.Magnesiumsulfateineclampsiaandpreeclampsia:pharmacokineticprinciples.Clin
Pharmacokinet200038:305.
67.MageeLA,MiremadiS,LiJ,etal.Therapywithbothmagnesiumsulfateandnifedipinedoesnotincrease
theriskofseriousmagnesiumrelatedmaternalsideeffectsinwomenwithpreeclampsia.AmJObstet
Gynecol2005193:153.
68.SzalSE,CroughanMinihaneMS,KilpatrickSJ.Effectofmagnesiumprophylaxisandpreeclampsiaonthe
durationoflabor.AmJObstetGynecol1999180:1475.
69.DuffyCR,OdiboAO,RoehlKA,etal.Effectofmagnesiumsulfateonfetalheartratepatternsinthesecond
stageoflabor.ObstetGynecol2012119:1129.
70.GraySE,RodisJF,LettieriL,etal.Effectofintravenousmagnesiumsulfateonthebiophysicalprofileofthe
healthypretermfetus.AmJObstetGynecol1994170:1131.
http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

16/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

71.CholstIN,SteinbergSF,TropperPJ,etal.Theinfluenceofhypermagnesemiaonserumcalciumand
parathyroidhormonelevelsinhumansubjects.NEnglJMed1984310:1221.
72.HallakM.Effectofparenteralmagnesiumsulfateadministrationonexcitatoryaminoacidreceptorsintherat
brain.MagnesRes199811:117.
73.CottonDB,HallakM,JanuszC,etal.CentralanticonvulsanteffectsofmagnesiumsulfateonNmethylD
aspartateinducedseizures.AmJObstetGynecol1993168:974.
74.BelfortMA,ClarkSL,SibaiB.Cerebralhemodynamicsinpreeclampsia:cerebralperfusionandthe
rationaleforanalternativetomagnesiumsulfate.ObstetGynecolSurv200661:655.
75.BerksD,SteegersEA,MolasM,VisserW.Resolutionofhypertensionandproteinuriaafterpreeclampsia.
ObstetGynecol2009114:1307.
76.vanOostwaardMF,LangenveldJ,SchuitE,etal.Recurrenceofhypertensivedisordersofpregnancy:an
individualpatientdatametaanalysis.AmJObstetGynecol2015212:624.e1.
77.BartonJR,SibaiBM.Predictionandpreventionofrecurrentpreeclampsia.ObstetGynecol2008112:359.
78.SibaiBM,MercerB,SarinogluC.Severepreeclampsiainthesecondtrimester:recurrenceriskandlong
termprognosis.AmJObstetGynecol1991165:1408.
79.vanRijnBB,HoeksLB,BotsML,etal.Outcomesofsubsequentpregnancyafterfirstpregnancywithearly
onsetpreeclampsia.AmJObstetGynecol2006195:723.
80.BramhamK,BrileyAL,SeedP,etal.Adversematernalandperinataloutcomesinwomenwithprevious
preeclampsia:aprospectivestudy.AmJObstetGynecol2011204:512.e1.

SciHub

81.SibaiBM,elNazerA,GonzalezRuizA.Severepreeclampsiaeclampsiainyoungprimigravidwomen:
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
subsequentpregnancyoutcomeandremoteprognosis.AmJObstetGynecol1986155:1011.
URL,DOI,

82.CampbellDM,MacGillivrayI,CarrHillR.Preeclampsiainsecondpregnancy.BrJObstetGynaecol1985
92:131.
83.XiongX,FraserWD,DemianczukNN.Historyofabortion,preterm,termbirth,andriskofpreeclampsia:a
populationbasedstudy.AmJObstetGynecol2002187:1013.
84.SibaiBM,SarinogluC,MercerBM.Eclampsia.VII.Pregnancyoutcomeaftereclampsiaandlongterm
prognosis.AmJObstetGynecol1992166:1757.
85.MostelloD,KallogjeriD,TungsiripatR,LeetT.Recurrenceofpreeclampsia:effectsofgestationalageat
deliveryofthefirstpregnancy,bodymassindex,paternity,andintervalbetweenbirths.AmJObstet

Gynecol2008199:55.e1.
86.McDonaldSD,BestC,LamK.Therecurrenceriskofseveredenovopreeclampsiainsingleton
pregnancies:apopulationbasedcohort.BJOG2009116:1578.
87.TrogstadL,SkrondalA,StoltenbergC,etal.Recurrenceriskofpreeclampsiaintwinandsingleton
pregnancies.AmJMedGenetA2004126A:41.
88.ChangJJ,MugliaLJ,MaconesGA.Associationofearlyonsetpreeclampsiainfirstpregnancywith
normotensivesecondpregnancyoutcomes:apopulationbasedstudy.BJOG2010117:946.
89.WikstrmAK,StephanssonO,CnattingiusS.Previouspreeclampsiaandrisksofadverseoutcomesin
subsequentnonpreeclampticpregnancies.AmJObstetGynecol2011204:148.e1.
90.BellamyL,CasasJP,HingoraniAD,WilliamsDJ.Preeclampsiaandriskofcardiovasculardiseaseand
cancerinlaterlife:systematicreviewandmetaanalysis.BMJ2007335:974.
91.McDonaldSD,MalinowskiA,ZhouQ,etal.Cardiovascularsequelaeofpreeclampsia/eclampsia:a
systematicreviewandmetaanalyses.AmHeartJ2008156:918.

http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

17/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

92.FraserA,NelsonSM,MacdonaldWallisC,etal.Associationsofpregnancycomplicationswithcalculated
cardiovasculardiseaseriskandcardiovascularriskfactorsinmiddleage:theAvonLongitudinalStudyof
ParentsandChildren.Circulation2012125:1367.
93.HermesW,FranxA,vanPampusMG,etal.Cardiovascularriskfactorsinwomenwhohadhypertensive
disorderslateinpregnancy:acohortstudy.AmJObstetGynecol2013208:474.e1.
94.MongrawChaffinML,CirilloPM,CohnBA.Preeclampsiaandcardiovasculardiseasedeath:prospective
evidencefromthechildhealthanddevelopmentstudiescohort.Hypertension201056:166.
95.SmithGN,PudwellJ,WalkerM,WenSW.Tenyear,thirtyyear,andlifetimecardiovasculardiseaserisk
estimatesfollowingapregnancycomplicatedbypreeclampsia.JObstetGynaecolCan201234:830.
96.BehrensI,BasitS,LykkeJA,etal.AssociationBetweenHypertensiveDisordersofPregnancyandLater
RiskofCardiomyopathy.JAMA2016315:1026.
97.KessousR,ShohamVardiI,ParienteG,etal.Longtermmaternalatheroscleroticmorbidityinwomenwith
preeclampsia.Heart2015101:442.
98.IrgensHU,ReisaeterL,IrgensLM,LieRT.Longtermmortalityofmothersandfathersafterpreeclampsia:
populationbasedcohortstudy.BMJ2001323:1213.
99.ChesleyLC,AnnittoJE,CosgroveRA.Theremoteprognosisofeclampticwomen.Sixthperiodicreport.Am
JObstetGynecol1976124:446.
100.ChambersJC,FusiL,MalikIS,etal.Associationofmaternalendothelialdysfunctionwithpreeclampsia.
JAMA2001285:1607.

SciHub

101.AgatisaPK,NessRB,RobertsJM,etal.Impairmentofendothelialfunctioninwomenwithahistoryof
https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
preeclampsia:anindicatorofcardiovascularrisk.AmJPhysiolHeartCircPhysiol2004286:H1389.
URL,DOI,

102.LampinenKH,RnnbackM,KaajaRJ,GroopPH.Impairedvasculardilatationinwomenwithahistoryof
preeclampsia.JHypertens200624:751.
103.YinonY,KingdomJC,OdutayoA,etal.Vasculardysfunctioninwomenwithahistoryofpreeclampsiaand
intrauterinegrowthrestriction:insightsintofuturevascularrisk.Circulation2010122:1846.
104.HermesW,KetJC,vanPampusMG,etal.Biochemicalcardiovascularriskfactorsafterhypertensive
pregnancydisorders:asystematicreviewandmetaanalysis.ObstetGynecolSurv201267:793.
105.MagnussenEB,VattenLJ,LundNilsenTI,etal.Prepregnancycardiovascularriskfactorsaspredictorsof
preeclampsia:populationbasedcohortstudy.BMJ2007335:978.
106.MagnussenEB,VattenLJ,SmithGD,RomundstadPR.Hypertensivedisordersinpregnancyand
subsequentlymeasuredcardiovascularriskfactors.ObstetGynecol2009114:961.

107.RomundstadPR,MagnussenEB,SmithGD,VattenLJ.Hypertensioninpregnancyandlatercardiovascular
risk:commonantecedents?Circulation2010122:579.
108.BytautieneE,BulayevaN,BhatG,etal.LongtermalterationsinmaternalplasmaproteomeaftersFlt1
inducedpreeclampsiainmice.AmJObstetGynecol2013208:388.e1.
109.KaajaRJ,PyhnenAlhoMK.Insulinresistanceandsympatheticoveractivityinwomen.JHypertens2006
24:131.
110.KaajaRJ,GreerIA.Manifestationsofchronicdiseaseduringpregnancy.JAMA2005294:2751.
111.StekkingerE,ZandstraM,PeetersLL,SpaandermanME.Earlyonsetpreeclampsiaandtheprevalenceof
postpartummetabolicsyndrome.ObstetGynecol2009114:1076.
112.ZandstraM,StekkingerE,vanderVlugtMJ,etal.Cardiacdiastolicdysfunctionandmetabolicsyndromein
youngwomenafterplacentalsyndrome.ObstetGynecol2010115:101.
http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

18/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

113.vanRijnBB,NijdamME,BruinseHW,etal.Cardiovasculardiseaseriskfactorsinwomenwithahistoryof
earlyonsetpreeclampsia.ObstetGynecol2013121:1040.
114.HooijschuurMC,GhosseinDohaC,AlNasiryS,SpaandermanME.Maternalmetabolicsyndrome,
preeclampsia,andsmallforgestationalageinfancy.AmJObstetGynecol2015213:370.e1.
115.BerksD,HoedjesM,RaatH,etal.Riskofcardiovasculardiseaseafterpreeclampsiaandtheeffectof
lifestyleinterventions:aliteraturebasedstudy.BJOG2013120:924.
116.MoscaL,BenjaminEJ,BerraK,etal.Effectivenessbasedguidelinesforthepreventionofcardiovascular
diseaseinwomen2011update:aguidelinefromtheAmericanHeartAssociation.JAmCollCardiol2011
57:1404.
117.FeigDS,ShahBR,LipscombeLL,etal.Preeclampsiaasariskfactorfordiabetes:apopulationbased
cohortstudy.PLoSMed201310:e1001425.
118.LykkeJA,LanghoffRoosJ,SibaiBM,etal.Hypertensivepregnancydisordersandsubsequent
cardiovascularmorbidityandtype2diabetesmellitusinthemother.Hypertension200953:944.
119.CallawayLK,LawlorDA,O'CallaghanM,etal.Diabetesmellitusinthe21yearsafterapregnancythatwas
complicatedbyhypertension:findingsfromaprospectivecohortstudy.AmJObstetGynecol2007
197:492.e1.
120.EngelandA,BjrgeT,DaltveitAK,etal.Riskofdiabetesaftergestationaldiabetesandpreeclampsia.A
registrybasedstudyof230,000womeninNorway.EurJEpidemiol201126:157.
121.VikseBE,IrgensLM,LeivestadT,etal.Preeclampsiaandtheriskofendstagerenaldisease.NEnglJ
Med2008359:800.

SciHub

https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s

122.WangIK,MuoCH,ChangYC,etal.Associationbetweenhypertensivedisordersduringpregnancyand
URL,DOI,
endstagerenaldisease:apopulationbasedstudy.CMAJ2013185:207.

123.LevineRJ,VattenLJ,HorowitzGL,etal.Preeclampsia,solublefmsliketyrosinekinase1,andtheriskof
reducedthyroidfunction:nestedcasecontrolandpopulationbasedstudy.BMJ2009339:b4336.
124.WilsonKL,CaseyBM,McIntireDD,etal.Subclinicalthyroiddiseaseandtheincidenceofhypertensionin
pregnancy.ObstetGynecol2012119:315.
125.TheilenLH,FraserA,HollingshausMS,etal.AllCauseandCauseSpecificMortalityAfterHypertensive
DiseaseofPregnancy.ObstetGynecol2016128:238.
Topic6825Version71.0

http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

19/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

GRAPHICS
Criteriaforthediagnosisofpreeclampsia
Systolicbloodpressure140mmHgordiastolicbloodpressure90mmHgontwooccasionsatleastfourhoursapart
after20weeksofgestationinapreviouslynormotensivepatient
Ifsystolicbloodpressureis160mmHgordiastolicbloodpressureis110mmHg,confirmationwithinminutesis
sufficient
and
Proteinuria0.3gramsina24hoururinespecimenorprotein/creatinineratio0.3(mg/dL/mg/dL)
Dipstick1+ifaquantitativemeasurementisunavailable
Intheabsenceofproteinuria,newonsethypertensionwiththenewonsetofanyofthefollowing:
Plateletcount<100,000/microL
Serumcreatinine>1.1mg/dLordoublingofbaselineserumcreatininelevelintheabsenceofotherrenaldisease
Livertransaminasesatleasttwicethenormalconcentrations
Pulmonaryedema
Cerebralorvisualsymptoms
Adaptedfrom:AmericanCollegeofObstetriciansandGynecologists.Hypertensioninpregnancy:ReportoftheAmerican
CollegeofObstetriciansandGynecologists'taskforceonhypertensioninpregnancy.ObstetGynecol2013122:1122.
Graphic79977Version15.0

SciHub

https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
URL,DOI,

http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

20/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

Thepresenceofoneormoreofthefollowingindicatesadiagnosisof
"preeclampsiawithseverefeatures"
Symptomsofcentralnervoussystemdysfunction:
Newonsetcerebralorvisualdisturbance,suchas:
Photopsia,scotomata,corticalblindness,retinalvasospasm
Severeheadache(ie,incapacitating,"theworstheadacheI'veeverhad")orheadachethatpersistsandprogressesdespite
analgesictherapy
Alteredmentalstatus

Hepaticabnormality:
Severepersistentrightupperquadrantorepigastricpainunresponsivetomedicationandnotaccountedforbyanalternative
diagnosisorserumtransaminaseconcentration2timesnormal,orboth

Severebloodpressureelevation:
Systolicbloodpressure160mmHgordiastolicbloodpressure110mmHgontwooccasionsatleastfourhoursapartwhilethe
patientisonbedrest(unlessthepatientisonantihypertensivetherapy)

Thrombocytopenia:
<100,000platelets/microL

Renalabnormality:
Progressiverenalinsufficiency(serumcreatinine>1.1mg/dLordoublingofserumcreatinineconcentrationintheabsenceofother
renaldisease)

Pulmonaryedema

Incontrasttooldercriteria,the2013criteriadonotincludeproteinuria>5grams/24hoursandfetalgrowth
restrictionasfeaturesofseveredisease.

SciHub

https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s

Adaptedfrom:Hypertensioninpregnancy:ReportoftheAmericanCollegeofObstetriciansandGynecologists'TaskForceon
HypertensioninPregnancy.ObstetGynecol2013122:1122.

URL,DOI,

Graphic76975Version9.0

http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

21/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

Peripheralsmearinmicroangiopathichemolyticanemia
showingpresenceofschistocytes

Peripheralbloodsmearfromapatientwithamicroangiopathichemolyticanemia
withmarkedredcellfragmentation.Thesmearshowsmultiplehelmetcells
(arrows),otherfragmentedredcells(smallarrowhead)microspherocytesare
alsoseen(largearrowheads).Theplateletnumberisreducedthelargeplatelet
inthecenter(dashedarrow)suggeststhatthethrombocytopeniaisdueto
enhanceddestruction.
CourtesyofCarolavonKapff,SH(ASCP).

SciHub
Graphic70851Version7.0

https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
URL,DOI,

Normalperipheralbloodsmear

Highpowerviewofanormalperipheralbloodsmear.Severalplatelets
(arrows)andanormallymphocyte(arrowhead)canalsobeseen.Thered
cellsareofrelativelyuniformsizeandshape.Thediameterofthenormalred
cellshouldapproximatethatofthenucleusofthesmalllymphocytecentral
pallor(dashedarrow)shouldequalonethirdofitsdiameter.
CourtesyofCarolavonKapff,SH(ASCP).
Graphic59683Version4.0

http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

22/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

Helmetcellsinmicroangiopathichemolyticanemia

Peripheralsmearsfromtwopatientswithmicroangiopathichemolyticanemia,
showinganumberofredcellfragments(ie,schistocytes),someofwhichtakethe
formofcombat(arrow),bicycle(arrowhead),orfootball(shortarrow)"helmets."
Microspherocytesarealsoseen(dashedarrows),alongwithanucleatedredcell
(thickarrow).

SciHub

CourtesyofCarolavonKapff,SH(ASCP).
Graphic50715Version4.0

https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s

URL,DOI,

http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

23/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

Deathsfromcardiovascularcauses
Population

Relativehazardrate(95percentconfidenceinterval)

Nonpreeclamptic,termdelivery

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.
Graphic76674Version1.0

SciHub

https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
URL,DOI,

http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

24/25

15/10/2016

Preeclampsia:ManagementandprognosisUpToDate

ContributorDisclosures
ErrolRNorwitz,MD,PhD,MBA Consultant/AdvisoryBoards:Hologic[Pretermbirth(Fetalfibronectintestto
predictpretermbirth)]Natera[Fetalaneuploidytesting(NIPTasascreeningtestforfetalaneuploidy)]Seracare
[Fetalaneuploidytesting(DevelopingcontrolsforNIPTscreeningtestforfetalaneuploidy)].PatentHolder:Bayer
[Predictiontestforpreeclampsia(Useofurinaryangiogenicfactorstopredictpreeclampsia)]. JohnTRepke,
MD Nothingtodisclose CharlesJLockwood,MD,MHCM Consultant/AdvisoryBoards:Celula[Aneuploidy
screening(NocurrentproductsordrugsintheUS)]. VanessaABarss,MD,FACOG Nothingtodisclose
Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobe
providedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofallauthorsandmustconformto
UpToDatestandardsofevidence.
Conflictofinterestpolicy

SciHub

https://www.uptodate.com/contents/preeclampsiamanagementandprognosis?source=search_result&s
URL,DOI,

http://www.uptodate.com.secure.scihub.cc/contents/preeclampsiamanagementandprognosis/print?source=search_result&search=preeclampsia&selecte

25/25