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By
MD
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Mostautoimmunediseaseisfemalepredominate InSLEfemale:maleis~10:1SLEaffectsmostlyinyoungfemalesinchildbearing
age(20-40yr).
TheimportantismostautoimmunediseasesincludeSLEdosenotimpairedfertilityability.
CerveraR,BalaschJ.Bidirectionaleffectsonautoimmunityandreproduction.HumReprodUpdate2008;14:359e66.
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PathogenesisofSLE(Harrisons17
th
Edion)
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Scope1. EffectofpregnancyonSLE.2. EffectofSLEonpregnancy.3. FlareofSLE4. Lupusnephritis5. Lupusanticoagulant6. Neonatallupus7. Managementanddrugsuseduringpregnancy
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EffectofpregnancyonSLEPossibilityfactorsthatinfluencetheSLE;diseaseflareduringpregnancy.
Sexhormones Dramaticofestrogensandprogesterone.
Immunologicalchanges aTh2-dominatedstateinlateGA. (aTh1-dominatedrequiredforimplantationand
vascular,tissueremodelingoftheutinearyGA)
AndreaT.Borchers,StanleyM.Theimplicationsofautoimmunityandpregnancy.JournalofAutoimmunity34(2010)J287eJ299
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FLAREOFSLE
EffectofpregnancyonSLE
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ChallengesofSLEinPregnancy Normalmanifestationsofpregnancy
VS SLEsymptoms
1. CommoncomplicationsofpregnancysuchaspreeclampsiamaymimicexacerbationsofSLE.
2. Laboratoryinterprete
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ClinicalmimicSLEFlareEdemaArthralgia,arthritisAnemiaPregnancyinducehypertensionHEELPLab:
CBC;anemiaANA,ESR Complement
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LupusnephrisvsPre-eclampsia
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TimingofflaresinSLE
duringpregnancyTheriskofflaredependonthelevelofmaternaldiseaseactivityinthe612monthsbeforeconception.
Rateofflare 7-33%inwomenwhoremissionforatleast6mos 61-67%inwomenwhoactivedz.atthetimeof
conception.
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ConclusionofSLEFlareTherearebothpositiveandnegativestudies.CurrentconceptagreementwithnooverallincreaseinSLEflarepregnancy.
Diseaseflarecanoccuratanytimeduringpregnancyandpostpartumwithoutanyclearpattern.
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HighRiskLupusPregnancy
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EffectofSLEonpregnancy
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EffectofSLEonpregnancy PregnancyofSLEpatientscanbecomplicatedbyanumberofobstetricandneonatalproblems
Obstetriccomplications. Pre-eclampsia/eclampsiaseemstobethemostcommon
Fetalcomplications. Pregnancylosses(spontaneousabortionorintrauterinefetaldeath),isthemostcommon Prematurebirth IUGR
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JMedAssocThai2007;90(10):1981-5
68
61(89.7) 27(39.7) 15(22.1) 7(10.3)
20(29.4)
785
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Autoanbodieshighlyassociatedwithfetal
damage.1. aPLsarethemajorriskfactorforpregnancylossin
patientswithSLEandinthosewithprimaryAPS.
2. anti-Ro/SS-Aandanti-La/SSBantibodies,responsibleforneonatallupus
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ANTIPHOSPHOLIPIDSYNDROMEAPSmaybeprimaryorsecondarywithotherconnectivetissuediseases
Approximately30-40%ofwomenwithSLEhaveaPLantibodies Inpregnancy,aPLarespecificallyassociatedwith
Recurrentmiscarriage IUGR Olygohydramnios Pre-eclampsia, HELLPsyndrome Placentalabruption Fetaldeath
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AnphospholipidAbandnormalpregnancy Inhealthynon-pregnanthave5%ofnonspecific
antiphospholipidabinlowtiter
Innormalpregnancyhave4.7%ofnonspecificantiphospholipidab(thesameofnormalnonpregnantindividual)
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ClinicalOneormoreepisodesofvenous,arterial,orsmallvesselthrombosisand/ormorbiditywithpregnancy.
1. ThrombosisUnequivocalimagingorhistologicevidenceofthrombosisinanytissueororgan,OR
2. Pregnancymorbidity 1unexplainedfetaldeathGA>10wk 3spontaneusabortionGA
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Laboratorycriteria**1.Lupusanticoagulant(LA)presentinplasma2
occasionsatleast12wksapart
2.Anticardiolipin(aCL)antibodyofIgGand/orIgMserumorplasma,inmediumorhightiter(i.e.>40GPLorMPL,or>the99thpercentile),2occasions,atleast
12wksapart,
3.Anti-b2glycoprotein-IantibodyofIgGand/orIgMserumorplasma(intiter>the99thpercentile),2
occasions,atleast12weeksapart,
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PreviousHxisanimportantpredictoroffutureobstetricperformance.
Pregnancylosses>50%ofwomenwithmediumorhightiterIgGanticardiolipin(aCL)
IgM,IgA-positiveorLowpositiveIgGaCLarelessassociatedwithpregnancycomplications
ANTIPHOSPHOLIPIDSYNDROME
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Thromboticocclusionofplacentalvesselsandplacentalinfarctionarefrequentlyreported.
ThromboticComplications 70%ofthromboticeventsoccurinthevenoussystem
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ObstetricComplicaonsofAPSinPregnancy GESTATIONALHYPERTENSION/PREECLAMPSIA
32% Preeclampsiamaydevelopasearlyas15to17weeks'
gestation
UTEROPLACENTALINSUFFICIENCYANDPRETERMBIRTH
IUGRapproaches30%
Earlyrecurrentpregnancyloss
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TreatmentforAnphospholipid
SyndromeduringPregnancy IdealtreatmentforAPSduringpregnancy1.
Improvementinmaternalandfetal-neonataloutcomebypreventingpregnancyloss,preeclampsiaplacentalinsufficiencypretermbirth
2.Reductionoreliminationoftheriskofthromboembolism
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PrepregnancyPreconceptionalcousellingDiscussriskthrombosis,pregnancyloss,preterm
delivery,preeclampsia,UPI
Informedrisk/benefitofheparinLab
CBC,Plt,UA,urinefortotalprotein&Crfor24hr
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APSwithoutpreviousthrombosis 1.Low-doseaspirinshouldbetakenbyallwomenwithaPL,(ifpossible)
beforeconceptiontodecreasetheriskof Miscarriage Preeclampsia
2.Recurrentearlymiscarraige(
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APSwithoutpreviousthrombosis3. Fetaldeath(>10wk)or previousearlydelivery(
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LabourandDelivery Offheparin12hrbeforeinductionlabour IfplanSB->offheparin24hrfromlastdose
Incaseextremelythromboembolism offheparin2-4hrbeforelabour
addbackheparin 6hrafterVgdelivery 12hrafterC/S
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Lupusnephris
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LupusnephrisActivenephritishasbeenshowntobeanindependentfactorforfetalmortality
Overall,thisgrouphasahighrateoffetalloss.
TheriskofflareishigherifLNisactiveatthetimeofconception.
Diseaseactivityinthe6monthspriortopregnancyisanimportantpredictor
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Twostudiescarriedouton102pregnanciesin75SLEpatientswithpriorLNbutinremissionbeforeconceptus.
Proteinuricflarerangingbetween45%and50% Worseningofrenalfunctionin1721%
Lupusnephris
TandonA,IbanezD,GladmanDD,UrowitzMB.Theeffectofpregnancyonlupusnephritis.ArthritisRheum2004
SoubassiL,HaidopoulosD,SindosMetal.Pregnancyoutcomeinwomenwithpreexistinglupusnephritis.JObsGynaecol2004
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Pre-existingrenalimpairmentisassociatedwithapoorfetaloutcome.1
SerumCr>140mmol/Lassociatedwitha50%pregnancyloss SerumCr>400mmol/Lassociatedwitha80%pregnancyloss
Nephroticrangeproteinuriahavetendencytodeliverprematurely.2
EffectofLNonpregnancy
1) BurkettG.Lupusnephropathyandpregnancy.ClinObstetGynecol19852) LimaF,BuchananNM,KhamashtaMAetal.Obstetricoutcomeinsystemiclupuserythematosus.
SeminarsinArthritisandRheumatism1995
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LupusnephrisvsPre-eclampsia
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NeonatallupusAssociatedwithmaternalanti-Roandanti-Laantibodies.
Evenifthemotherisasymptomatic.
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Neonatallupus Skinmanifestsas AnnularlesionssimilartothoseofadultSCLE, usuallyonthefaceandscalp,
appearaftersunorultravioletlightexposureinthefirst2weeksoflife.
Therashdisappearsspontaneouslywithin6months. Severecase
Residualhypopigmentationortelangiectasiamaypersistforupto2years
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NeonatallupusOtherrarerfeaturesofneonatalSLE
Abnormalliverfunctiontests Thrombocytopenia
Thesemanifestationsaretransient.
Resolvingbytheageof1year.Infantsareusuallyasymptomatic.
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CongenitalheartblockThemostseriouscomplication24%mortalityOccurs2%offetusesofwomenwithanti-RoAb.Occursbetween18-30weeks.Fetalechocardiographyshouldbeperformedoverthisperiodtoenableearlydetection.
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CongenitalheartblockCompleteheartblockcannotbereversed. Second-degreeheartblock1stdegreeblock
dexamethasone50%survivingchildrenrequirepacinginthe1styear
oflife.
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EffectofSLEonferlityability MostautoimmunediseasesincludeSLEdosenotimpairedfertilityability.
exceptwhen
1. Renalimpairment(creatinineclearance
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Themanagementshouldstartbeforeconception.Thediseaseisnotinitselfacontra-indicationto
pregnancy.
Diseaseshouldbeinactiveatleast6monthspriortoconception.
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ContraceponOralcontraceptivepillSLEflare.thromboembolisminAPS.
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Beforeconcepon Diseaseshouldbeinactiveatleast6monthspriortoconception.
Themedicationthatthepatientistakingtocontrolherdiseasewouldalsoneedtobereviewed. Drugsthatareconsideredtobesafeinpregnancyare:
Prednisolone
Azathioprine CyclosporinA Hydroxychloroquine.
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Recommendsaminimumof Q1movisitsuntil28weeks, Q2wksvisitsto36weeks Q1wksvisitsuntillabor.
Lab:CBC,complement,Anti-dsDNA,UADuringpregnancy,C3andC4mayriseto
supranormallevels.SLEflaremaynormallevelsofC3andC4.
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IfSLEflareduringpregnancyDrugsthatareconsideredinpregnancy:Corticosteroid ImmunosupressiveDMARDsNSAIDs
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Asystematicmeta-analysisofstudiesofwomenwhousedGCsduringpregnancyreported
anoveralloddsratioforbearingachildwithcleftpalateof3.4(95%CI1.97-5.69)
(=10/1)
Pred>20mg/dayriskpre-eclampsiaandGDM
Prednisolone(B)
Park-Wyllie,L,Mazzotta,P,Pastuszak,A,etal.Birthdefectsaftermaternalexposuretocorticosteroids:prospectivecohortstudyandmeta-analysisofepidemiologicalstudies.Teratology2000;62:385.
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CyclosporinA
A2001meta-analysisof15studiesofwomenwhoreceivedCSAduringpregnancyreported
majormalformationsin4.1%ofoffspring,aratesimilartothatofthegeneralpopulation
BarOz,B,Hackman,R,Einarson,T,Koren,G.Pregnancyoutcomeaftercyclosporinetherapyduringpregnancy:ameta-analysis.Transplantation2001;71:1051.
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Non-steroidalan-inflammatorydrugsGenerallysafeduring1st2ndtrimesterButshouldbeavoidedafter30weeksofgestation(duetoriskofprematureclosureoftheductusarteriosus)
Cyclo-oxygenase-2-specificinhibitors. Shouldbeavoided Thereareinadequatedataregardingsafetyin
pregnancy.
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Anhypertensives
Drugsthataresafeinpregnancy Methyldopa Labetalol Nifedipine
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Immunosuppressivedrugs
Methotrexate Mycophenolatemofetil Cyclophosphamide
Areteratogeniceffectdrugs.Shouldbestoppedatleast3monthspriortoconception.
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Post-partumandLactaon
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TheEnd
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