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SLE and Pregnancy
Syed Atiqul HaqProfessor of Medicine-RheumatologyBSM Medical University, Dhaka, &
APLAR-COPCORD Coordinator
Major DivisionsMajor Divisions
Background
Management
BackgroundBackground
●● Effects of SLE on fertilityEffects of SLE on fertility
●● Effects of SLE on pregnancyEffects of SLE on pregnancy
●● Effects of pregnancy on SLEEffects of pregnancy on SLE
Effects On FertilityEffects On FertilityFertility of SLE patients usually unaltered
Factors lowering fertility
– Renal failure
– Cyclophosphamide
– Very active disease
– Anti-phospholipid antibodies (aPLs) in high titers
– High dose steroid/NSAIDs
On Fetal Outcome
On Maternal Outcome
Effects on Pregnancy
Fetal OutcomeFetal Outcome
EffectsEffects Risk FactorsRisk Factors
Abortions (6%-35%)Abortions (6%-35%)
Stillbirths (4%-22%)Stillbirths (4%-22%)
●●Active lupus nephritisActive lupus nephritis
●●Previous history of fetal deathPrevious history of fetal death
●●TheThe presence of the aPLspresence of the aPLs
IUGR (9-35%)IUGR (9-35%) Hypertension, pre-eclampsia, Hypertension, pre-eclampsia, steroidsteroid
Prematurity (40-50%)Prematurity (40-50%) Hypertension, pre-eclamsiaHypertension, pre-eclamsia
PROMPROM Steroid treatmentSteroid treatment
NLE syndrome (5%)NLE syndrome (5%)
CHB (1.7%)CHB (1.7%)
Anti-Ro, anti-LaAnti-Ro, anti-La
Maternal OutcomeMaternal Outcome
EffectsEffects Risk FactorsRisk Factors
ToxemiasToxemias DiabetesDiabetesLN (30%)LN (30%)HypertensionHypertensionToxemia in previous pregnancyToxemia in previous pregnancyThrombocytopeniaThrombocytopeniaaPLsaPLs
HypertensionHypertensionDiabetesDiabetesInfections, UTIInfections, UTI
Steroid treatmentSteroid treatment
Maternal death (1%, Maternal death (1%, in ’60s 20%)in ’60s 20%)
LNLN
Pulmonary hypertensionPulmonary hypertension
CardiomyopathyCardiomyopathy
Causes of Maternal DeathCauses of Maternal Death
Severe renal flareSevere renal flare
Pulmonary hypertensionPulmonary hypertension
CardiomyopathyCardiomyopathy
Pulmonary embolusPulmonary embolus
HELLP syndromeHELLP syndrome
Effects of Pregnancy on SLEEffects of Pregnancy on SLE
● ● Disease flare
● Permanent loss of renal function in
a small proportion
● No change in the long term course
Flare During Pregnancy..Flare During Pregnancy..
Any trimester of pregnancy (≈ 60%)
Postpartum
Commonly mild
Severe renal flare if LN active during
conception
Flare During PregnancyFlare During Pregnancy
Usually mild with arthritis and rashUsually mild with arthritis and rash
Major organ flares may occur Major organ flares may occur
– Kidneys 40%: in LN patientsKidneys 40%: in LN patients
50-60% if active during conception50-60% if active during conception
7-10% if quiescent during conception7-10% if quiescent during conception
– Central nervous system 5%Central nervous system 5%
Counseling Target: patient and familyTarget: patient and family IssuesIssues
Chances of flareChances of flareFetal lossFetal lossPrematurityPrematurity IUGRIUGRHypertensionHypertensionPreeclampsiaPreeclampsiaNeed for rigorous follow-up Need for rigorous follow-up
ManagementManagement
●● Family planning & contraceptionFamily planning & contraception
●● Patient in remissionPatient in remission
●● Active disease & flaresActive disease & flares
●● DeliveryDelivery
●● Puerperium and LactationPuerperium and Lactation
Desired State During ConceptionDesired State During Conception
≥6-month full remission on HCQ– In grumbling lupus
± ≈0.125 mg/kg prednisolone± AZT 1 to 2 mg/kg in desperate circumstances
No Cyclophosphamide, MTX, MMF Higher dose prednisolone NSAID
ContraceptionContraception
● ● Mechanical barrier methods are safe Mechanical barrier methods are safe
and effective, albeit less so than OCPsand effective, albeit less so than OCPs
● ● Intrauterine devices controversialIntrauterine devices controversial
– Infections: endometritis, PIDInfections: endometritis, PID
– PerforationPerforation
– MenorrhagiaMenorrhagia
● ● Low estrogen contraceptive pillsLow estrogen contraceptive pills
Oral ContraceptivesOral Contraceptives●●Contraindications:Contraindications:
– aPL, other thromboembolic diseasesaPL, other thromboembolic diseases
– Highly active diseaseHighly active disease
– MigraineMigraine
– RaynaudRaynaud’’s phenomenons phenomenon
– Family history of breast cancerFamily history of breast cancer
●●Specific indication:Specific indication:
– Cyclophosphamide therapyCyclophosphamide therapy
Mitigates against gonadotoxicityMitigates against gonadotoxicity
Anti-resorptive, anti-atherogenicAnti-resorptive, anti-atherogenic
Monitoring & EvaluationMonitoring & Evaluation
TreatmentTreatment
Follow-up Schedule
Monthly up to 28 weeksMonthly up to 28 weeks
Fortnightly 28 to 32 weeksFortnightly 28 to 32 weeks
Weekly afterwardsWeekly afterwards
More often in patients with active diseaseMore often in patients with active disease
Evaluation at First VisitEvaluation at First Visit
Initial visit: Initial visit: Thorough evaluation of disease activity-Thorough evaluation of disease activity-
▪ ▪ A full history and examination, BPA full history and examination, BP
▪ ▪ Routine urinalysisRoutine urinalysis
▪ ▪ CBC and platelet countCBC and platelet count
▪ ▪ Serum creatinineSerum creatinine
▪ ▪ A 24 hour urinary total protein, CA 24 hour urinary total protein, CCrCr
▪ ▪ Anti-ds-DNA, Anti-ds-DNA, anti-Ro and anti-Ro and ––La, aPLsLa, aPLs
▪▪ Fasting blood glucose if at high riskFasting blood glucose if at high risk
Evaluation at Subsequent VisitsEvaluation at Subsequent Visits
History and examination: detect flares, BPHistory and examination: detect flares, BP
Routine urinalysesRoutine urinalyses
Blood counts incl. platelet, Hb%, ESRBlood counts incl. platelet, Hb%, ESR
FBG/Modified OGTT 24 to 28 weeksFBG/Modified OGTT 24 to 28 weeks
Biophysical profile (BPP) scoring from 28 weeks Biophysical profile (BPP) scoring from 28 weeks
Additional Tests at End of Each TrimesterAdditional Tests at End of Each Trimester
▪ ▪ Urine cultureUrine culture
▪ ▪ Urine protein:creatinine ratioUrine protein:creatinine ratio
▪ ▪ Serum creatinineSerum creatinine
▪ ▪ Anti-ds-DNAAnti-ds-DNA
▪ ▪ aCL aCL
Anti-Ro/La Positive MotherAnti-Ro/La Positive Mother
FHR at each visit from 20 weeksFHR at each visit from 20 weeks
Fetal echocardiography:Fetal echocardiography:
– Weekly 16 – 24 weeksWeekly 16 – 24 weeks
– Fortnightly 24 – 32 weeksFortnightly 24 – 32 weeks
Biophysical Profile ScoringBiophysical Profile Scoring
Non-stress test (CTG)Non-stress test (CTG)
Fetal breathing movementsFetal breathing movements
Fetal toneFetal tone
Amniotic fluid volumeAmniotic fluid volume
Fetal movementFetal movement
Sheet AnchorSheet Anchor Patient and family education & counseling
Drugs:
– Folic acid 400 µg/d during first trimester
– HCQ: 4 to 6 mg/kg/d throughout pregnancy
– Aspirin: 75 mg/d up to 38 weeks aPLs Nephritis History in a previous pregnancy of
– Fetal loss after the 1st trimester
– IUGR
– Early onset pre-eclampsia requiring delivery before 32 weeks
– Flare prophylaxis with universal use of low dose prednisolone throughout pregnancy – does more harm!
Cleft palateIUGRPROM
DMHT
Toxemia
Flare prevention
Anti-phospholipid Ab Syndrome... Anti coagulation LMWH or UFH: up to 13th wk
▪Women with prior pregnancy complications but no
thrombosis LMWH (0.5mg/kg twice daily) or UFH (10,000 IU twice daily)
▪Women with previous history of thrombosis LMWH (1mg/kg twice daily) or UFH (Adjusted dose to prolong
the APTT to twice control)
14th to 34 wk: Warfarin INR 2-3 Switched to UFH or LMWH if necessary
Anti-phospholipid Ab Syndrome
Low dose aspirin
Calcium supplement (1.5 gm daily)
Axial exercise
Prednisolone has no added benefit
Sheet AnchorSheet Anchor
Counseling and reassuranceCounseling and reassurance Prednisone/prednisolonePrednisone/prednisolone
– Dose as per severityDose as per severity
– Start tapering 1 week after remissionStart tapering 1 week after remission
– Speed depends onSpeed depends onSeveritySeverityResponse rateResponse rate
Maximize HCQ to 6 to 6.5 mg/kg/dMaximize HCQ to 6 to 6.5 mg/kg/d
Flare controlImprovement of fetal & maternal outcomes
Cleft palateIUGRPROMDMHTToxemia
Classification of FlaresClassification of Flares
Mild
Moderate
Severe
Mild Flares Prednisone/prednisolone: 0.1 – 0.3 mg/kg/dayPrednisone/prednisolone: 0.1 – 0.3 mg/kg/day
– Tapered off if full remission achieved quicklyTapered off if full remission achieved quickly
Flares in 1Flares in 1stst trimester & mildest flares: may be trimester & mildest flares: may be
treated treated initiallyinitially with with
– SunscreenSunscreen
– topical steroidtopical steroid
– paracetamol paracetamol
– NSAIDs (late first and second trimesters)NSAIDs (late first and second trimesters)
Moderate FlareModerate Flare
Prednisone/Prednisolone: ≈0.5 mg/kgPrednisone/Prednisolone: ≈0.5 mg/kg
– Attempt slow taper after full remissionAttempt slow taper after full remission
AZT or Cys AAZT or Cys A
– Flare recurs with pred Flare recurs with pred ≤≤7.5-10 mg/d7.5-10 mg/d
Severe Flare Prednisone/Prednisolone: 1 mg/kg/dayPrednisone/Prednisolone: 1 mg/kg/day
– May be preceded by pulse MPMay be preceded by pulse MP
Azathioprine: 1.5 to 2 mg/kg/day or Azathioprine: 1.5 to 2 mg/kg/day or
Cyclosporin A 3 -- 4 mg/kg/dayCyclosporin A 3 -- 4 mg/kg/day
Maintenance Steroid Till Term
Patients taking maintenance steroid Patients taking maintenance steroid
during conceptionduring conception
All with severe flaresAll with severe flares
Majority with moderate flaresMajority with moderate flares
Recurrent mild flaresRecurrent mild flares
CyclophosphamideCyclophosphamide
Indications:Indications:
– Alveolar heamorrage Alveolar heamorrage
– Acute anuric renal failureAcute anuric renal failure
– Refractory class IV nephritisRefractory class IV nephritis
Amniocentesis and karyotypingAmniocentesis and karyotyping
High risk of spontaneous abortionHigh risk of spontaneous abortion
Indications for Elective AbortionIndications for Elective Abortion
Severe compromise of function of
Kidneys
Myocardium
Lungs
Chromosomal anomaly after cyclop
Delivery SettingDelivery Setting
In a hospital with neonatal ICUIn a hospital with neonatal ICU
Vaginal route preferredVaginal route preferred
Routine caesarian delivery Routine caesarian delivery notnot recommended recommended
Indications for caesarian sectionIndications for caesarian section
– As for women without lupusAs for women without lupus
– Non-reassuring BPP score leading to caesarian Non-reassuring BPP score leading to caesarian
delivery – more frequentdelivery – more frequent
Steroid Stress Coverage: IndicationSteroid Stress Coverage: Indication
Treatment with systemic steroid Treatment with systemic steroid
within 2 years of the anticipated within 2 years of the anticipated
deliverydelivery
Steroid Stress Coverage: ProtocolSteroid Stress Coverage: Protocol
● ● Day of delivery: Hydrocortisone 100 mg I/V just Day of delivery: Hydrocortisone 100 mg I/V just prior to onset of delivery and 8 hourlyprior to onset of delivery and 8 hourly
● ● 22ndnd day: 50 mg 8 hourly day: 50 mg 8 hourly
● ● Day 3 onwards:Day 3 onwards:
– No steroid if not on steroid before deliveryNo steroid if not on steroid before delivery
– Restart oral dose used before deliveryRestart oral dose used before delivery
● ● If on more than 75 mg of prednisone dailyIf on more than 75 mg of prednisone daily
– appropriate hydrocortisone equivalent for days 2 and 3appropriate hydrocortisone equivalent for days 2 and 3
– then resume previous oral dosethen resume previous oral dose
Neonatal Lupus Syndrome (NLE)Neonatal Lupus Syndrome (NLE)
Congenital heart block (CHB) Congenital heart block (CHB) –– 1.7% 1.7%
– CCHB carries 15 to 30% mortalityCCHB carries 15 to 30% mortality
Transient cutaneous lupus lesionsTransient cutaneous lupus lesions
CytopeniasCytopenias
Hepatic, and otherHepatic, and other systemic manifestationssystemic manifestations
NLENLE Neonatal screeningNeonatal screening
– Clinical examinationClinical examination* Annular erythema or arcuate macules in Annular erythema or arcuate macules in
scalp and periorbital areasscalp and periorbital areas* Heart rate: bradycardiaHeart rate: bradycardia* Blood pressure: born to mothers treated Blood pressure: born to mothers treated
with fluorinated steroidswith fluorinated steroids
ECGECG
Treatment: Treatment: PPM in patients with 2PPM in patients with 2ndnd & 3 & 3rdrd degree blocksdegree blocks
Post-partum FlarePost-partum Flare
Risk groups:Risk groups:– Active disease at conceptionActive disease at conception
– Significant end-organ damageSignificant end-organ damage
Detection:Detection:– Focused history & examinationFocused history & examination
– Lab tests:Lab tests: UrinalysisUrinalysis blood countsblood counts Serum creatinineSerum creatinine Urine protein/creatinine ratio Urine protein/creatinine ratio Anti-dsDNAAnti-dsDNA
Lactation: Safe Drugs …
Short acting NSAIDs (not aspirin)
HCQ
Warfarin
Heparin: started 6 hrs after vaginal & 12 hrs
after CS
Prednisolone <15 mg/d
– Higher dose: after morning feed and next feed
after 4 hrs
Lactation: Drugs to be avoided
AZT
CysA
MTX
Cylophosphamide
Take Home Messages……
Low estrogen contraceptives are not forbidden
≥6-month remission on HCQ before conception
HCQ should probably be continued throughout
pregnancy
No evidence supporting flare prophylaxis with
LDGC
Mainstay of flare suppression: steroid in
appropriate doses
Minimum or no steroid in 1st trimester
NSAIDs avoided in early 1st & 3rd trimesters
Vaginal delivery
Steroid stress coverage
ConclusionConclusion
Safe motherhood possible Safe motherhood possible withwith
● ● Increased awareness of the Increased awareness of the potential problems for potential problems for mother and fetusmother and fetus
● ● Meticulous multidisciplinary Meticulous multidisciplinary follow upfollow up
● ● Effective disease controlEffective disease control
SUNDARBAN
COX’S BAZAR
MildMild ModerateModerate
Muco-Muco-cutaneouscutaneous
Butterfly rashButterfly rash
PhotosensitivityPhotosensitivity
MaculopapularMaculopapular
Mild oral ulcerMild oral ulcer
Mild DLEMild DLE
Severe oral ulcerSevere oral ulcer
Severe DLESevere DLE
Diffuse SCLEDiffuse SCLE
Lupus profundusLupus profundus
Skin vasculitisSkin vasculitis
ArticularArticular Arthralgia, mild Arthralgia, mild polyartritispolyartritis
Disabling Disabling polyarthritispolyarthritis
Therapeutic ClassificationTherapeutic Classification
MildMild ModerateModerate SevereSevere
RenalRenal Class I, IIaClass I, IIa Class IIb, LNClass IIb, LN Class III, IV Class III, IV LNLN
Neuro-Neuro-psychipsychiatricatric
Lupus Lupus headacheheadache
ChoreaChoreaPeripheral Peripheral
neuropathyneuropathy
DeliriumDelirium
EncephalitisEncephalitis
PsychosisPsychosis
ComaComa
MyelopathyMyelopathy
Therapeutic Classification (contd.)Therapeutic Classification (contd.)
MildMild ModerateModerate SevereSevereHematologicalHematological PlateletPlatelet
30 to 30 to 100,000100,000
PlateletPlatelet
15 to 30,000 (preg: 15 to 30,000 (preg: 30 to 100,000) 30 to 100,000)
Hemolytic anemiaHemolytic anemia
Lupus adenitisLupus adenitis
Platelet Platelet <15,000<15,000
(preg: <(preg: <30,000)30,000)
Cardiopulmonary PleurisyPleurisy Pleural Pleural effusioneffusion
PneumonitisPneumonitis
PericarditisPericarditis
Mild Mild myocarditismyocarditis
Severe Severe pneumonitispneumonitis
Pulmonary Pulmonary hemorrhagehemorrhage
Cardiac Cardiac tamponadetamponade
Severe Severe myocarditismyocarditis
Therapeutic Classification (contd.)Therapeutic Classification (contd.)
MildMild ModeratModeratee
SevereSevere
Gastro-Gastro-intestinalintestinal
Mild Mild hepatitishepatitis
PancreatitisPancreatitis
PeritonitisPeritonitis
Severe Severe hepatitishepatitis
ColitisColitis
Protein-losing Protein-losing enteropathyenteropathy
MesenteriMesenteric c
vasculitisvasculitis
MiscellaneoMiscellaneousus
Responsive Responsive feverfever
FatigueFatigue
MyalgiaMyalgia
Refractory/Refractory/high feverhigh fever
Therapeutic Classification (contd.)Therapeutic Classification (contd.)
Pre-eclampsia vs. Renal FlarePre-eclampsia vs. Renal Flare
FeatureFeature Pre-eclampsia Lupus flare
Arthritis, rashArthritis, rash ---- ++
Active sediment in Active sediment in urineurine
CC33, C, C44 ↓↓ ↑↑
Anti-dsDNAAnti-dsDNA == ↑↑
Uric acid, liver Uric acid, liver enzymesenzymes
↑↑ ==
Urinary calciumUrinary calcium ↓↓ ==
Treatment of Heart BlockTreatment of Heart Block
Dexamethasone 4 mg/dayDexamethasone 4 mg/day– Partial:Partial:
If reverts or doesn’t progress: till If reverts or doesn’t progress: till deliverydelivery
If progresses to complete: taperIf progresses to complete: taper
– Complete:Complete: If reverts to partial: till deliveryIf reverts to partial: till delivery If doesn’t revert after 6 weeks: taperIf doesn’t revert after 6 weeks: taper