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