What is the recommended management of Systemic Lupus Erythematosus (SLE) in pregnancy?

Management of SLE in Pregnancy

All women with SLE should continue or initiate hydroxychloroquine during pregnancy, start low-dose aspirin (81-100 mg daily) in the first trimester, undergo antiphospholipid antibody testing early in pregnancy, and receive at least trimester-based disease activity monitoring to optimize maternal and fetal outcomes. 1

Pre-Pregnancy and Early Pregnancy Assessment

Essential Laboratory Testing

• Test once before or early in pregnancy for lupus anticoagulant (LAC), anticardiolipin antibodies (aCL), and anti-β2GPI antibodies—do not repeat these tests during pregnancy 1
• Test once for anti-Ro/SSA and anti-La/SSB antibodies before or early in pregnancy to assess risk of neonatal lupus and congenital heart block 1, 2
• Baseline assessment should include: complete blood count with differential, urinalysis with protein:creatinine ratio, serum creatinine, complement levels (C3, C4), and anti-dsDNA antibody titers 2

Risk Stratification

Pregnancy should be discouraged in patients with severe maternal risk factors including active nephritis, severe pulmonary/cardiac/renal/neurologic disease, recent stroke, or pulmonary hypertension 3

Pharmacologic Management

Hydroxychloroquine (HCQ) - Cornerstone Therapy

• If already taking HCQ: strongly continue throughout pregnancy 1
• If not taking HCQ: conditionally recommend starting if no contraindication 1
• Evidence supports: maternal and pregnancy benefit with low risk for mother and fetus; discontinuation increases lupus activity and flare rates during pregnancy 1, 4, 5
• FDA labeling confirms: no drug-associated risk of major birth defects, miscarriage, or adverse maternal/fetal outcomes based on prolonged clinical experience 6

Low-Dose Aspirin

• Start 81-100 mg daily in the first trimester and continue until delivery 1
• Rationale: SLE patients are at high risk for preeclampsia; aspirin prophylaxis is recommended by both ACR and ACOG 1, 3
• Doses up to 150 mg have been studied, but no comparative data show superiority over 100 mg daily 1

Antiphospholipid Antibody-Positive Patients

Treatment stratification based on APS status:

• Obstetric APS (no prior thrombosis): low-dose aspirin plus prophylactic heparin (LMWH or unfractionated heparin) 1, 3
• Thrombotic APS (history of thrombosis): low-dose aspirin plus therapeutic-dose heparin 1, 3
• Positive aPL antibodies without clinical APS: low-dose aspirin alone 3

Medications to Avoid

• Discontinue before pregnancy: methotrexate (1-3 months prior), mycophenolate mofetil/mycophenolic acid (at least 6 weeks prior) 1, 3
• Avoid during pregnancy: NSAIDs for prolonged use (>48 hours), COX-2 inhibitors, full-dose aspirin 3
• First trimester contraindication: cyclophosphamide due to high risk of fetal loss (OR 25.5); reserve only for life-threatening disease in second/third trimester 1

Pregnancy-Compatible Medications for Active Disease

• Oral glucocorticoids, azathioprine, calcineurin inhibitors (cyclosporine A, tacrolimus) have acceptable benefit/risk ratios 1
• For moderate-to-severe flares: high-dose glucocorticoids (including IV pulse therapy), IVIG, or plasmapheresis 1
• Active disease requiring therapy: strongly recommend initiating or continuing pregnancy-compatible steroid-sparing medication, as both active disease and continuous high-dose glucocorticoids cause maternal and fetal harm 1

Disease Activity Monitoring

Frequency and Parameters

• Monitor disease activity at least once per trimester with clinical history, examination, and laboratory tests 1, 2
• Laboratory monitoring should include: CBC with differential, urinalysis with protein:creatinine ratio, serum C3/C4 complement levels, anti-dsDNA antibody titers 2
• Increase monitoring frequency based on individual disease activity and medication requirements 1, 2

Distinguishing SLE Flare from Preeclampsia

• Serological markers help differentiate: declining C3/C4 levels (even within normal range) and/or rising anti-dsDNA titers suggest SLE flare rather than preeclampsia 1
• Renal monitoring is critical: urine protein excretion, urine sediment analysis (glomerular hematuria, urinary casts), and serum creatinine/GFR correlate with adverse pregnancy outcomes 1
• Common pitfall: pregnancy physiological changes can mimic SLE symptoms; awareness of these overlaps is essential 1

Fetal Surveillance

Anti-Ro/SSA and Anti-La/SSB Positive Patients

• Serial fetal echocardiography from weeks 16-26 for patients with positive anti-Ro/SSA or anti-La/SSB antibodies 1, 7
• Weekly fetal echocardiography if history of neonatal lupus in prior pregnancy 1
• Do NOT routinely perform serial PR interval assessments outside clinical trial settings 3

Management of Fetal Heart Block

• Brief course of dexamethasone if first or second-degree heart block detected 1
• Do NOT use dexamethasone for third-degree (complete) heart block—unproven benefit with known maternal and fetal risks 1, 3
• Do NOT use prednisone for fetal heart block prevention 1

General Fetal Monitoring

• Antenatal testing and serial growth scans are recommended due to increased risk of fetal growth restriction and stillbirth 3
• Routine ultrasonographic screening: first trimester (11-14 weeks), second trimester with Doppler (20-24 weeks) 1
• Third trimester monthly surveillance: Doppler of umbilical artery, uterine arteries, ductus venosus, and middle cerebral artery, particularly for early IUGR (<34 weeks) 1

Key Clinical Pearls

Active disease during pregnancy significantly affects maternal and pregnancy outcomes—maintaining disease control is paramount for both mother and fetus 1, 8, 7

Smaller increases in C3 levels from pregnancy onset to second/third trimester, along with serological activity, associate with increased risk for pregnancy loss, IUGR, and preterm birth 1

Vitamin D levels should be measured after pregnancy confirmation 2

Postpartum monitoring remains crucial as disease flares can occur in the postpartum period 7