Stroke recurrence in pregnancy: Experience at a regional referral center

Stroke

recurrence

in

pregnancy:

Experience

at

a

regional

referral

center

Adeeb

Khalifeh

,

Andrea

Berghella

,

Sindy

Moreno

,

Kathryn

Corelli

,

Emily

Leubner

,

Gabriele

Saccone

*,

Badih

Daou

,

Pascal

Jabbour

a_{DivisionofMaternalFetalMedicine,DepartmentofObstetricsandGynecology,EinsteinMedicalCenter,Philadelphia,PA,UnitedStates} b_{DepartmentofObstetricsandGynecology,SidneyKimmelMedicalCollegeatThomasJeffersonUniversity,Philadelphia,PA,UnitedStates} c

BrownUniversity,Providence,RI,UnitedStates

d

DepartmentofObstetricsandGynecology,FlushingHospitalMedicalCenter,Flushing,NY,UnitedStates

e

DepartmentofNeuroscience,ReproductiveSciencesandDentistry,SchoolofMedicine,UniversityofNaplesFedericoII,Naples,Italy

f

DepartmentofNeurosurgery,UniversityofMichigan,AnnArbor,MI,UnitedStates

g

DepartmentofNeurologicalSurgery,SidneyKimmelMedicalCollegeatThomasJeffersonUniversity,Philadelphia,PA,UnitedStates

ARTICLE INFO

Articlehistory:

Received17December2018

Receivedinrevisedform28February2019 Accepted4March2019 Availableonlinexxx Keywords: Stroke Pregnancy NICU Neonataloutcome Cesareandelivery ABSTRACT

Background:Althoughstrokeismorecommonwithadvancingage,especiallyintheelderly,womenof reproductive age may still suffer from stroke, and from itsdeleterious consequences. Women of reproductive agewhosufferastrokemay doso eitherduetoaspecific predisposition,ordueto pregnancy-relatedhypertensiveemergencies.

Objective:Toassesstheriskofstrokerecurrenceinpregnancyandthepostpartumperiodinwomenwho havesufferedastrokebeforepregnancy.

Studydesign:ThiswasaretrospectivecohortstudyconductedatThomasJeffersonUniversityHospital fromJanuary2005toDecember2015.Thisisatertiaryreferralcenterforhigh-riskobstetricsandoneof thelargeststrokereferralcentersforneurosurgery.Allconsecutivepregnantwomenthathadaviable pregnancy(24weeksofgestation)andahistoryofstrokepriortopregnancywereidentified.The primaryoutcomeofthisstudywasstrokerecurrenceinpregnancyorthepostpartumperioddefinedas6 weeksafterdelivery.

Results:Forty-eightpregnancieswithahistoryofstrokebeforepregnancywereidentifiedin24women. Thirty-onepregnancies(64.6%)hadahistoryofanischemicstroke,11(22.9%)hadahistoryoftransient ischemicattack,and6(12.5%)hadahistoryofahemorrhagicstroke.Therewasnostrokerecurrence duringpregnancyorthepostpartumperiodforthethreegroupsofstroke.Intheischemicstrokegroup,8 (25.8%)hadrecurrenceinthenon-pregnantstatecomparedtononeintheTIAandthehemorrhagic strokegroup.

Conclusion:Therewasnostrokerecurrenceduringpregnancyorthepostpartumperiodforthethree groupsofstroke.

©2019PublishedbyElsevierB.V.

Introduction

Although stroke is more common with advancing age, especially in theelderly, women of reproductive agemay still suffer from stroke, and from its deleterious consequences [1]. Womenofreproductiveagewhosufferastrokemaydosoeither due toa speci_fic predisposition,suchasa brainaneurysm ora specificclottingdisorder,ordue topregnancy-related hyperten-siveemergencies[2].

Hypertensivedisordersinpregnancyremainamajorcauseof maternalmorbiditymortalityintheUnitedStates[3].Stroke in pregnancyandtheperipartumperiodisaknowncomplicationof hypertensiveemergencies,andcontinuestobea seriousclinical challenge despite national safety bundles to minimize the deleteriouseffectsofsuchacuteemergencies[4].

Fortunately,manywomenofreproductiveagewhosuffereda stroke,haveagood prognosis[5]. Theyoftenpresenteither for prenatalorpreconceptioncounselingtoassessthematernalrisks to help in their decision-making whether tostart, continue or terminate a pregnancy. While counseling women who have suffered a strokemay be guided by the patient’spredisposing riskfactors,itremainschallengingtocounselpatientsaboutthe possibilityofstrokerecurrenceinpregnancy.

* Correspondingauthor.

E-mailaddress:gabriele.saccone.1990@gmail.com(G.Saccone).

https://doi.org/10.1016/j.ejogrb.2019.03.005

0301-2115/©2019PublishedbyElsevierB.V.

EuropeanJournalofObstetrics&GynecologyandReproductiveBiology236(2019)75–78

ContentslistsavailableatScienceDirect

European

Journal

of

Obstetrics

&

Gynecology

and

Reproductive

Biology

Thus, theaimof this study was toassessthe risk of stroke recurrenceinpregnancyandthepostpartumperiodinwomenwho havesufferedastrokebeforepregnancy.

Materialsandmethods

This was a retrospective cohort study conductedat Thomas JeffersonUniversityHospitalfromJanuary2005toDecember2015. Thisisatertiaryreferralcenterforhigh-riskobstetricsandoneof thelargeststrokereferralcentersforneurosurgery.Thisstudywas approvedbytheInstitutionalReviewBoardofThomasJefferson University.

Allconsecutivepregnantwomenthathadaviablepregnancy (24weeksofgestation)andahistoryofstrokepriortopregnancy wereidentified.Onlywomenwithconfirmeddocumentationof strokebyestablishedcriteriawereincluded.Thiswasdonefirstby identifyingpatientswhohadahistoryofastrokeandpresentedto theObstetricsandGynecologyDepartment for prenatalcareor preconceptioncounseling.Second,thedatabaseofthe neurosur-gerydepartmentwasaccessedtoidentifyallwomenof reproduc-tiveage(18–45)whowereadmittedandtreatedforastroke.These patients’ medical records were reviewed; patients were also subsequentlyreachedand interviewedoverthephonefor their detailedobstetricalandmedicalhistory.

Informationonmaternalcharacteristicssuchasmaternalage, gravidity and parity, BMI, pregnancy-associated hypertensive disordersandgestationalagefordeliverywasrecorded.Adetailed history about each patient’s stroke was collected. The type of strokewasclassifiedaccordingtotheAmericanStrokeAssociation: ischemic,hemorrhagicortransientischemicattack(TIA)[6].Any predisposingfactorforastrokewasrecorded.Iftherewereany neurological deficits after the stroke, a detailed neurological historywastaken.

The primaryoutcomeofthis studywasstrokerecurrencein pregnancy or the postpartum period defined as 6 weeks after delivery.Secondaryoutcomesincludedpregnancyoutcomes.

StatisticalanalysiswasperformedusingStatisticalPackagefor SocialSciences(SPSS)v.19.0(IBMInc.,Armonk,NY,USA).Dataare shownasmeansstandarddeviation(SD),orasmedians(range), orasnumbers(percentage). Univariatecomparisonsof dichoto-mousdatawereperformedwiththeuseofthechi-square with continuity correction. Comparisons between groups were

performedwiththeuseof thet-testtotest groupmeanswith SDbyassumingequalwithin-groupvariances,andwiththeuseof theMann-WhitneyUtesttocalculategroupmedianswithrange.A p-value<0.05wasconsideredtoindicatestatisticalsignificance. Results

Forty-eight pregnancies with a history of stroke before pregnancy wereidentifiedin 24 women.The primaryoutcome ofstrokerecurrenceofthesepatientswasavailableforallpatients. Obstetricaloutcomeincludingmodeofdeliverywasavailablefor 42pregnancies.

Thirty-onepregnancies (64.6%)had ahistory of anischemic stroke,11(22.9%)hadahistoryoftransientischemicattack,and6 (12.5%)hadahistoryofahemorrhagicstroke.

Baselinecharacteristicsofthethreegroupsofstrokeareshown inTable1.

AfricanAmericanracewassignificantlymorecommon(70.8%) comparedtowhite(20.8%)orHispanicrace(4.1%)(p<0.05).Five patients(16.1%)withahistoryofischemicstrokehadprophylactic anticoagulationwithlowmolecularweightheparinatprophylactic dose;almosthalfofthewomenwereonlow-doseaspirin81mg Eleven women had chronic hypertension and five had hypertensive disorders of pregnancy (either preeclampsia or gestationalhypertension).Ninepatientsweresmokers.

There was no stroke recurrence during pregnancy or the postpartumperiodforthethreegroupsofstroke.Intheischemic strokegroup,8(25.8%)hadrecurrenceinthenon-pregnantstate comparedtononeintheTIAandthehemorrhagicstrokegroup (Table2).

There was no difference in the incidence of hypertensive disordersinpregnancyorgestationalageatdeliveryamongthe three groups of stroke.The incidence ofcesarean delivery was significantlyhigherinthehemorrhagicstrokegroupcomparedto theischemicorTIAgroup(p<0.05)(Table3).

Discussion

Whiletheriskofstrokeislowamongwomenofreproductive age[6],thiscohortofwomendoespresentwithpregnanciesthat areclinicallychallengingintheirmanagementgiventheconcern forstrokerecurrenceduringpregnancy.Inourstudywefounda0%

Table1

Demographiccharacteristics.

IschemicStroken=31 TIAn=11 HemorrhagicStroken=6 pvalue

Race

Black 17(54.8) 11(100) 6(100) 0.14

White 10(32.3) – – –

Hispanic 2(6.5) – – –

Other 2(6.5) – – –

Maternalage(years) 31.35.4 26.75.4 30.56.6 0.47

Historyofsubstanceabuse 4(12.9) 0(0) 0(0) 0.95

HistoryofTobaccoabuse 9(29) 0(0) 0(0) 0.74

Dataarepresentedasnumber(percentage)orasmeanstandarddeviation.

Table2

PriorstrokedetailsandrelatedPregnancyManagement.

IschemicStrokeN=31 TIAN=11 HemorrhagicStrokeN=6 pvalue

Strokerecurrenceinnon-pregnantstate 8(25.8) 0(0) 0(0) –

Maternalageoffirststroke 23.97.6 22.53.0 268.3 0.41

Intervalstroketopregnancy(years) 6.74.7 4.34.1 4.53.1 0.75

Anticoagulationinpregnancy 5(16.1) 3(27.3) 0(0) 0.12

Aspirininpregnancy 13(41.9) 0(0) 2(3.3) <0.01

Dataarepresentedasnumber(percentage)orasmeanstandarddeviation.Boldfacedata,statisticallysignificant.

recurrencerateofstrokeduringpregnancy.Thisisconsistentwith other studies, such as a French study that reviewed 187 pregnancies with a history of ischemic stroke and found a recurrencerateof1%[7].

Amorerecentlargerstudy,thisonefromtheNetherlands,that reviewed213pregnantwomenwithahistoryofstrokealsofounda recurrencerateof0%duringpregnancy[8].Ourresults,however, were not consistent with a smaller study of 12 patients with thrombophilia,whichfounda27%rateofstrokerecurrence[9].

Unlike our study, which looked at all subtypes of strokes including history of hemorrhagic stroke, other studies either

includedonlywomenwithahistoryofischemicstrokeorTIA[7– 10]ordidnotatalldefinethesubtypesofstrokes[11].

Another interesting finding in our study was that even in patients that had strokerecurrence in the non-pregnant state, strokedidnotoccurinpregnancy.Thiswasconsistentwiththe recentDutchstudy[8].

AllwomenwithahistoryofanischemicstrokeoraTIAhada cesareandeliveryforobstetricalindications.However,thosewitha historyofahemorrhagicstrokehadplannedcaesareandeliveries despitethelackofconsensusonmode ofdeliveryevenintheabsence ofcerebrovascularmalformations,suchasbrainaneurysms.

Table3

Strokebeforepregnancyandsubsequentpregnancyoutcomes.

IschemicStroken=31 TIAn=11 HemorrhagicStroken=6 pvalue

Strokerecurrenceinpregnancy 0(0) 0(0) 0(0) –

Miscarriage 6(19.4) 0(0) 2(33.3) <0.01

Ectopic 1(3.2) 1(9.1) 0(0) 0.21

Hypertensivedisorderinpregnancy 3(9.7) 2(18.2) 0(0) 0.09

Gestationalageatdelivery(weeks) 37.91.9 38.51.3 38.31.5 0.45

Vaginaldelivery 15(62.5) 4(40) 0(0) 0.08

Cesareandelivery 6(25.0) 5(50) 4(100) <0.01

Dataarepresentedasnumber(percentage)orasmeanstandarddeviation.Boldfacedata,statisticallysignificant.

Table4

Priorstudiesofwomenwithpriorstrokeandsubsequentpregnancy.

N Typeofpriorstroke Numberofsubsequent

pregnancies

N/N(%)recurrenceof strokeinpregnancyor 6weekspost-partum

Lamyetal.[7] 441 373ischemicstroke;68cerebralvenousthrombosis 187 2/187(1%)

vanAlebeeketal.[8] 213 132ischemicstroke;81transientischemicattack 569 0/569(0%) Sorianoetal.[9] 12*

7ischemicstroke;3transientischemicattack;3 amaurosisfugax

15 4/15(27%)

Fischer-Betzetal.[11] 20* _{12ischemicstroke;8transientischemicattack 23 3/23(13%)}

CoppageetalAJOG2004[10] 23 6ischemicstroke;1cerebralvenousthrombosis;16 typenotidentified

35 0/35(0%)

Cruz-Herranzetal.[12] 102 64ischemicstroke;24transientischemicattack;12 cerebralvenousthrombosis;1intracranialhemorrhage

32 0/32(0%)

*

Allpatientswiththrombophiliapredisposingthemtothromboembolicevents.

Table5

Characteristicsofwomenwithstrokerecurrenceinpregnancy.

Case# Cerebrovascularevent Underlying thrombophilia

Situationinwhichstrokeoccurred Prophylactictreatment Other complicationsof pregnancy 1(Lamy

etal.)

Arterialischemicstroke Thrombocythemia Third-trimester,associatedwith preeclampsia

LMWHfordurationofpregnancy

2(Lamy etal.)

Arterialischemicstroke PrimaryAPS Afterspontaneousabortion None

3(Soriano etal.)

TIA ProteinS,C

deficiency

32weeksofpregnancy LMWHandASA100mg/daythroughat least6weekspostpartum

None

4(Soriano etal.)

TIA–Temporary paresthesiaoftheleftarm

APS LMWHandASA100mg/daythroughat

least6weekspostpartum

Preeclampsia withsevere features 5(Soriano

etal.)

TIA–Recurrentamaurosis fugax

APS LMWHandASA100mg/daythroughat

least6weekspostpartum

None

6(Soriano etal.)

TIA–Recurrentamaurosis fugax

APS LMWHandASA100mg/dailythrough

atleast6weekspostpartum

None

7 (Fischer-Betz etal.)

TIA–Slurredspeechand numbnessoflefthand

PrimaryAPS 34weeksofpregnancy LMWHandASA,aftereventASAdose increasedto300mg

None

8 (Fischer-Betz etal.)

TIA–Monocularvisionloss PrimaryAPS 4weekspostpartumaftercaesareansection at35weeksduetopreeclampsiaandIUGR

LMWHandASAthroughoutpregnancy, patientdiscontinuedASAafterdelivery

Preeclampsia andIUGR

9 (Fischer-Betz etal.)

Arterialischemicstroke– Paresthesiaoftheright hand

SecondaryAPS 1weekpostpartumaftercaesareansection at36weeksduetoHELPPsyndrome

LMWHand100mg/dayASA,switched towarfarin3weekspostpartum

HELLPsyndrome

APS-Antiphospholipidantibodysyndrome.

After reviewingthe literature,therewere 909 pregnancies that had a history of stroke before pregnancy. About 1% (9 patients)had stroke recurrencein pregnancy(Table 4). After reviewing all patients’ characteristics, the most common predisposing risk factor for stroke recurrence was antiphos-pholipid antibody syndrome (APS), occurring in 7 patients (Table5).Thisisanimportantfindingasthiswouldhelpguide the clinician’s counseling regarding the risks for stroke recurrence.

Our study’smainstrengthis thatitincludedpatientswitha historyofallsubtypesofstrokes,includinghemorrhagicstroke. The number of patients in this subcategory, however, remains small,makingit difficulttogeneralize pregnancymanagement. Also,ourstudycollectedallthedatainliteratureregardingstroke recurrenceinpregnancyandidentifiedtheindividual character-isticsofpatientswhohadastroke.

Nevertheless,ourstudyaddsfurtherevidencetotheliterature that pregnancy after a stroke without deleterious neurological consequenceshasaverylowriskofstrokerecurrencewithproper managementincludinganticoagulation.Thisfindingwillhelpwith patientcounselinginthepreconceptionandtheprenatalperiod. Disclosurestatement

Theauthorsreportnoconflictsofinterest Financialsupport

Nospecificfundingwasreceivedforthisstudy

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