What is the recommended medication regimen for a pregnant woman with Systemic Lupus Erythematosus (SLE) and a history of antiphospholipid syndrome (APS)?

Recommended Medication Regimen for Pregnant Women with SLE and APS

For a pregnant woman with SLE and antiphospholipid syndrome, prescribe: (1) hydroxychloroquine 200-400 mg daily continued throughout pregnancy, (2) low-dose aspirin 81 mg daily starting in the first trimester, and (3) prophylactic-dose low-molecular-weight heparin (LMWH) throughout pregnancy and for 6-12 weeks postpartum. 1

Core Medication Regimen

Hydroxychloroquine (Essential for All SLE Pregnancies)

• Continue or initiate hydroxychloroquine 200-400 mg daily throughout pregnancy 1, 2
• If already taking HCQ, strongly continue it; if not taking it, start it unless contraindicated (allergy, adverse effects, or intolerance) 1
• HCQ reduces disease activity, prevents flares, and improves obstetrical outcomes with no increased risk of birth defects, miscarriage, or fetal toxicity 3, 4
• Hydroxychloroquine readily crosses the placenta but no retinal toxicity, ototoxicity, cardiotoxicity, or developmental abnormalities have been observed in exposed children 3

Low-Dose Aspirin (For Preeclampsia Prevention)

• Prescribe aspirin 81-100 mg daily starting in the first trimester (ideally by 16 weeks gestation) and continue until delivery 1, 2
• SLE patients, especially those with lupus nephritis or positive antiphospholipid antibodies, are at high risk for preeclampsia 1
• HCQ treatment itself reduces preeclampsia risk by approximately 90% (OR 0.106) 5

Anticoagulation for APS (Critical for Thrombosis Prevention)

• For obstetric APS: prescribe prophylactic-dose LMWH plus low-dose aspirin throughout pregnancy 1
• Continue prophylactic-dose anticoagulation for 6-12 weeks postpartum 1
• The combination of low-dose aspirin and heparin is strongly recommended to decrease adverse pregnancy outcomes in women with SLE-associated APS 1
• Consider adding HCQ to the prophylactic-dose heparin/LMWH and aspirin regimen, as recent studies suggest HCQ may decrease complications in APS pregnancies 1

Additional Safe Immunosuppressive Options (If Active Disease Requires Treatment)

Glucocorticoids

• Use oral glucocorticoids at the lowest effective dose, ideally ≤7.5 mg/day prednisone equivalent 2, 6
• Prednisone, azathioprine, ciclosporin A, and tacrolimus can be used to prevent or manage SLE flares during pregnancy 1
• Moderate-to-severe flares can be managed with intravenous glucocorticoid pulse therapy, intravenous immunoglobulin, or plasmapheresis 1

Steroid-Sparing Agents

• Azathioprine is safe throughout pregnancy for maintenance therapy 2, 6
• Calcineurin inhibitors (ciclosporin A, tacrolimus) are also safe options 1

Medications to AVOID

• Absolutely avoid mycophenolic acid, cyclophosphamide, leflunomide, and methotrexate during pregnancy 1
• Discontinue ACE inhibitors and ARBs immediately upon pregnancy confirmation due to first-trimester teratogenic effects; switch to nifedipine or labetalol 2, 6

Supplementation

• Prescribe calcium, vitamin D, and folic acid supplementation as in the general population 1
• Consider measuring vitamin D levels after pregnancy is confirmed 1

Monitoring Requirements

Maternal Disease Activity Monitoring

• Assess disease activity at least once per trimester with clinical history, examination, and laboratory tests 1, 7
• Laboratory monitoring should include: complete blood count with differential, urinalysis with protein:creatinine ratio, serum creatinine, complement levels (C3/C4), and anti-dsDNA antibody titers 1, 7
• Increase monitoring frequency based on individual disease activity and medication requirements 7

Antiphospholipid Antibody Testing

• Test once before or early in pregnancy for lupus anticoagulant, anticardiolipin antibodies, and anti-β2GPI antibodies 1
• Do NOT repeat these tests during pregnancy 1

Fetal Surveillance

• Perform supplementary fetal surveillance with Doppler ultrasonography and biometric parameters, particularly in the third trimester, to screen for placental insufficiency and small-for-gestational-age fetuses 1
• If positive anti-Ro/SSA or anti-La/SSB antibodies, perform serial fetal echocardiography from weeks 16-26 to monitor for congenital heart block 7

Critical Pitfalls to Avoid

Do NOT Discontinue Hydroxychloroquine

• Stopping HCQ during pregnancy increases lupus activity, flare rates, and requires higher prednisone doses 8
• Women who stopped HCQ had significantly higher lupus activity during pregnancy without improvement in fetal outcomes 8
• Withdrawal of HCQ at pregnancy onset may result in SLE exacerbation detrimental to both mother and fetus 9, 10

Do NOT Underdose Anticoagulation in APS

• The combination of aspirin AND heparin is essential—aspirin alone is insufficient for obstetric APS 1
• Prophylactic-dose anticoagulation must continue for 6-12 weeks postpartum when thrombosis risk remains elevated 1

Do NOT Forget Postpartum Surveillance

• Close surveillance for renal flare postpartum is essential, as this is a high-risk period for disease exacerbation 2
• All prescribed medications (hydroxychloroquine, prednisone, azathioprine) are compatible with breastfeeding 2, 3