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SLE and Pregnancy
Syed Atiqul HaqProfessor of Medicine-RheumatologyBSM Medical University, Dhaka, &
APLAR-COPCORD Coordinator
Basic Layout
Background
Management
Background
Effects on fertility
Effects of SLE on pregnancy
Effects of pregnancy on SLE
Effects On Fertility
• Fertility of SLE patients usually unaltered
• Factors lowering fertility– Renal failure– Cyclophosphamide– Very active disease– Anti-phospholipid antibodies (aPLs) in high titers
– High dose steroid
On Fetal Outcome
On Maternal Outcome
Fetal Outcome
Effects Risk Factors
Abortions (6%-35%)
Stillbirths (4%-22%)
•Active lupus nephritis•Previous history of fetal death•The presence of the aPLs
IUGR (9-35%) Hypertension, pre-eclampsia, steroid
Prematurity (40-50%) Hypertension, pre-eclamsia
PROM Steroid treatment
NLE syndrome (5%)
CHB (1.7%)
Anti-Ro, anti-La
Maternal Outcome
Effects Risk Factors
Toxemias DiabetesLN (30%)HypertensionToxemia in previous pregnancyThrombocytopeniaaPLs
HypertensionDiabetesInfections, UTI
Steroid treatment
Maternal death (1%, in ’60s 20%)
LN
Pulmonary hypertension
Cardiomyopathy
Effects of Pregnancy on SLE
• Flare of disease activity during
– Any trimester of pregnancy (≈ 60%)
– Postpartum
– Commonly mild
– Severe renal flare if LN active during conception
• Permanent loss of renal function in a small proportion
• No change in the long term course
Management
Family planning & contraception
Patient in remission
Active disease & flares
Delivery
Puerperium and Lactation
Family Planning
• The best time for conception: after a 6-
12 months of cytotoxic-free remission
• Incidence of a flare with conception
after remission is 10% or less
Contraception
• Mechanical barrier methods are safe
and effective, albeit less so than OCPs
• Intrauterine devices controversial
– Infections: endometritis, PID
– Perforation
– Menorrhagia
• Low estrogen contraceptive pills
Oral Contraceptives• Contraindications:
– aPL, other thromboembolic diseases
– Highly active disease
– Migraine
– Raynaud’s phenomenon
– FH of breast cancer
• Specific indication:
– Cyclophosphamide therapy
• Mitigates against gonadotoxicity
Evaluation
Treatment
Follow-up Schedule
• Monthly up to 28 weeks
• Fortnightly 28 to 32 weeks
• Weekly afterwards
• More often in patients with active disease
Evaluation at First Visit
Initial visit: Thorough evaluation of disease activity-
• A full history and examination, BP
• Routine urinalysis
• CBC and platelet count
• Serum creatinine
• A 24 hour urinary total protein, CCr
• Anti-ds-DNA, anti-Ro and –La, aPLs
• Fasting blood glucose if at high risk
Evaluation at Subsequent Visits
• History and examination: detect flares, BP
• Routine urinalyses
• Blood counts incl. platelet, Hb%, ESR
• From 28 weeks biophysical profile (BPP) scoring
Additional Tests at End of Each Trimester
Urine culture
Urine protein:creatinine ratio
Serum creatinine
Anti-ds-DNA
aCL
Anti-Ro/La Positive Mother
• FHR at each visit from 20 weeks
• Fetal echocardiography:
– Weekly 16 – 24 weeks
– Fortnightly 24 – 32 weeks
Sheet 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
• History in a previous pregnancy of
– Fetal loss after the 1st trimester
– IUGR
– Early onset pre-eclampsia requiring delivery before 32 weeks
• Nephritis
• aPLs
• (Aspirin may be continued throughout pregnancy and delivery if there is
H/O MI/stroke.)
Anti-phospholipid Ab Syndrome
• Low dose aspirin
• LMWH or UFH– 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)
• Calcium supplement (1.5 gm daily)
• Axial exercise
• Prednisolone has no added benefit
Classification of Flares
Mild
Moderate
Severe
Mild Flares
• Maximizing dose of HCQ to 6 to 6.5 mg/kg
• Prednisone/prednisolone: 0.1 – 0.3 mg/kg/day
– Tapered off if full remission achieved quickly
– Avoided or used in low dose in 1st trimester
• Mildest flares: may be treated initially with
– Sunscreen
– topical steroid
– paracetamol
– NSAIDs (late first and second trimesters)
Moderate Flare
• Maximizing dose of HCQ
• Prednisone/Prednisolone: 0.3 – 0.5 mg/kg
– Attempt at gradual taper after full remission
• AZT or Cys A
– Flare recurrence with prednisone <7.5 mg/d
Severe Flare
• Prednisone/Prednisolone: 1 mg/kg/day
– May be preceded by pulse MP
• Azathioprine: 1.5 to 2 mg/kg/day or
cyclosporin A 3 -- 4 mg/kg/day
Steroid Maintenance Till Term
• Patients requiring maintenance
steroid before conception
• Recurrent mild flares
• Moderate to severe flares
Cyclophosphamide
• Indications:
– Acute anuric renal failure
– Alveolar heamorrage
– Refractory class IV nephritis
• Amniocentesis and karyotyping
• High risk of spontaneous abortion
Delivery Setting
• In a hospital with neonatal ICU
• Vaginal route preferred
• Routine caesarian delivery not recommended
• Indications for caesarian section
– As for women without lupus
– High incidence of non-reassuring BPP score leading to
caesarian delivery
Steroid Stress Coverage: Indication
• Treatment with systemic steroid within 2
years of the anticipated delivery
Steroid Stress Coverage: Protocol
• Day of delivery: Hydrocortisone 100 mg I/V just prior to onset of delivery and 8 hourly
• 2nd day: 50 mg 8 hourly
• Day 3 onwards:– No steroid if not on steroid before delivery
– Restart oral dose used before delivery
• If on more than 75 mg of prednisone daily– appropriate hydrocortisone equivalent for days 2 and 3
– then resume previous oral dose
Post-partum Flare
• Risk groups:– Active disease at conception
– Significant end-organ damage
• Detection:– Focused history & examination
– Lab tests:• Urinalysis
• blood counts
• Serum creatinine
• Urine protein/creatinine ratio
• Anti-dsDNA
Lactation• Safe drugs:
– short acting NSAIDs (not aspirin)
– prednisolone <15 mg/d
• Higher dose: after morning feed and next feed after 4 hrs
– HCQ
– Warfarin
– Heparin
• Drugs to be avoided
– AZT
– CysA
– MTX
– Cylophosphamide
Conclusion
Safe motherhood possible with
• Increased awareness of the potential problems for mother and fetus
• Meticulous multidisciplinary follow up
• Effective disease control
Neonatal Lupus Syndrome (NLE)
• Congenital heart block (CHB) – 1.7%
– CCHB carries 15 to 30% mortality
• Transient cutaneous lupus lesions
• Cytopenias
• Hepatic, and other systemic manifestations
Causes of Maternal Death
Pulmonary hypertension
Pulmonary embolus
HELLP syndrome
Cardiomyopathy
Severe renal flare
Flare During Pregnancy
• Usually mild with arthritis and rash
• Major organ flares may occur
– Kidneys 40%: in LN patients
• 50-60% if active during conception
• 7-10% if quiescent during conception
– Central nervous system 5%
Counselling
• Target: patient and family• Issues
• Chances of flare• Fetal loss• Prematurity• IUGR• Hypertension• Preeclampsia• Need for rigorous follow-up
Indications for Elective Abortion
Severe compromise of function of
• Kidneys
• Myocardium
• Lungs
Mild Moderate
Muco-cutaneous Butterfly rash
Photosensitivity
Maculopapular
Mild oral ulcer
Mild DLE
Severe oral ulcer
Severe DLE
Diffuse SCLE
Lupus profundus
Skin vasculitis
Articular Arthralgia, mild polyartritis
Disabling polyarthritis
Therapeutic Classification
Mild Moderate Severe
Renal Class I, IIa Class IIb, LN Class III, IV LN
Neuro-psychiatric
Lupus headache
ChoreaPeripheral neuropathy
Delirium
Encephalitis
Psychosis
Coma
Myelopathy
Therapeutic Classification (contd.)
Mild Moderate Severe
Hematological Platelet30 to 100,000
Platelet
15 to 30,000 (preg: 30 to 100,000)
Hemolytic anemia
Lupus adenitis
Platelet <15,000
(preg: <30,000)
Cardiopulmonary Pleurisy Pleural effusion
Pneumonitis
Pericarditis
Mild myocarditis
Severe pneumonitis
Pulmonary hemorrhage
Cardiac tamponade
Severe myocarditis
Therapeutic Classification (contd.)
Mild Moderate Severe
Gastro-intestinal
Mild hepatitis
Pancreatitis
Peritonitis
Severe hepatitis
Colitis
Protein-losing enteropathy
Mesenteric vasculitis
Miscellaneous Responsive fever
Fatigue
Myalgia
Refractory/high fever
Therapeutic Classification (contd.)
Pre-eclampsia vs. Renal Flare
Feature Pre-eclampsia Lupus flare
Arthritis, rash -- +
Active sediment in urine
C3, C4 ↓ ↑
Anti-dsDNA = ↑
Uric acid, liver enzymes ↑ =
Urinary calcium ↓ =
Treatment of Heart Block
• Dexamethasone 4 mg/day– Partial:
• If reverts or doesn’t progress: till delivery• If progresses to complete: taper
– Complete:• If reverts to partial: till delivery• If doesn’t revert after 6 weeks: taper