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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