What is the recommended treatment for Systemic Lupus Erythematosus (SLE) in pregnancy?

Treatment of Systemic Lupus Erythematosus in Pregnancy

All women with SLE should continue or start hydroxychloroquine during pregnancy, combined with low-dose aspirin (81-100 mg daily) beginning in the first trimester, with additional heparin therapy if antiphospholipid antibodies are present. 1

Core Pharmacologic Management

Hydroxychloroquine: The Foundation of Treatment

• If already taking HCQ, strongly continue it throughout pregnancy without interruption, as discontinuation significantly increases lupus flares and disease activity 1
• If not currently on HCQ, start it immediately unless there is a specific contraindication (allergy, intolerance, or adverse effects) 1
• HCQ reduces SLE flares by approximately 90%, prevents poor obstetrical outcomes, and decreases preeclampsia risk (odds ratio 0.106) 1, 2
• HCQ reduces intrauterine growth restriction from 32% to 10% and extends gestational age at delivery 3
• The drug readily crosses the placenta but causes no retinal toxicity, ototoxicity, cardiotoxicity, or developmental abnormalities in exposed children 4, 5, 6

Low-Dose Aspirin: Universal Prophylaxis

• Start aspirin 81-100 mg daily in the first trimester (ideally preconceptionally or no later than gestational week 16) for all SLE patients 1
• This prevents or delays preeclampsia in high-risk SLE patients 1
• Doses above 100 mg daily lack evidence of superiority 1
• Discontinuation timing before delivery should be determined by the obstetrician and anesthesiologist based on individual circumstances 1

Antiphospholipid Antibody Management

• Test for lupus anticoagulant, anticardiolipin, and anti-β2GPI antibodies once before or early in pregnancy—do not repeat during pregnancy 1
• For obstetric antiphospholipid syndrome (prior pregnancy losses), use combination therapy: low-dose aspirin PLUS prophylactic-dose heparin (preferably LMWH for practical reasons, though unfractionated heparin has stronger RCT evidence) 1
• For thrombotic APS with prior thrombosis, therapeutic anticoagulation with LMWH is required throughout pregnancy 1

Glucocorticoids and Immunosuppressives

Safe Medications During Pregnancy

• Prednisone and other non-fluorinated glucocorticoids are safe and can be used for disease control, but minimize to the lowest effective dose 1, 7
• Azathioprine is safe throughout pregnancy for maintenance therapy or active disease 1, 7
• For active lupus nephritis requiring induction therapy, glucocorticoids combined with azathioprine can be used (mycophenolate and cyclophosphamide must be avoided) 1, 7

Absolutely Contraindicated Medications

• Mycophenolate mofetil must be stopped before conception—it causes major birth defects 1, 7
• Cyclophosphamide must be avoided during pregnancy 1, 7
• Methotrexate is absolutely contraindicated 1, 7

Monitoring Strategy

Disease Activity Surveillance

• Monitor SLE disease activity at least once per trimester with clinical history, physical examination, and laboratory tests 1
• Check complete blood count, urinalysis with protein-to-creatinine ratio, anti-dsDNA, C3, and C4 levels 1
• Abnormalities may indicate SLE flare or preeclampsia even without clinical symptoms 1
• Patients with lupus nephritis or positive antiphospholipid antibodies require more intensive monitoring for hypertensive complications and preeclampsia 1

Fetal Monitoring

• For anti-Ro/SSA or anti-La/SSB positive patients, perform fetal echocardiography if fetal dysrhythmia or myocarditis is suspected 1
• The cost-effectiveness of intensive weekly/biweekly surveillance between 16-26 weeks for all anti-Ro/La positive women remains unestablished given the low 0.7-2% risk of congenital heart block 1
• Fluorinated steroids (dexamethasone, betamethasone) have not shown established efficacy for preventing or treating complete congenital heart block in large cohorts 1

Adjunctive Therapies

• Supplement with calcium, vitamin D, and folic acid for all SLE pregnancies, particularly those receiving glucocorticoids or heparin due to bone mass effects 1
• Focus supplementation on patients with low 25-OH vitamin D levels in the first trimester 1

Critical Pitfalls to Avoid

The most dangerous error is discontinuing hydroxychloroquine due to pregnancy concerns—this precipitates disease flares that harm both mother and fetus more than the medication itself 5, 6, 8. One study documented that even temporary one-month discontinuation caused clinically and serologically confirmed flares 6. Women who stopped HCQ had significantly higher lupus activity scores and flare rates throughout pregnancy 5.

Do not delay aspirin initiation—it must start by gestational week 16 at the latest, though preconceptional initiation is preferable 1.

Do not use high-dose aspirin (>100 mg) without evidence of benefit, as comparative studies showing superiority are lacking 1.