Pregnancy in SLE: Advances in management and outcomes

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Reference: June 2026 | Issue 6 | Vol 12 | Page 25

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Systemic lupus erythematosus (SLE) is a complex chronic multisystem autoimmune disease characterised by dysregulated immune activation and chronic inflammation affecting multiple organ systems. SLE predominately affects women of reproductive age, making reproductive health and pregnancy management central aspects of long-term care.

Clinical presentations of SLE disease can vary from mucocutaneous to severe renal, haematological, neurological, and cardiopulmonary manifestations. Despite advances in immunosuppressive therapy and improvements in multidisciplinary care, pregnancy in women with SLE remains high risk due to increased maternal and foetal complications.^1,2 Particular care is required in patients with concomitant SLE and anti-phospholipid syndrome (APS), due to an increased risk of adverse obstetric outcomes.^1,2

Historically, pregnancy was discouraged in SLE patients due to high maternal and foetal risk. Therapeutic options were limited, particularly due to concerns regarding prolonged corticosteroid exposure and clinicians faced significant challenges balancing maternal disease activity and foetal safety.

Pregnancy in SLE patients is now increasingly recognised as feasible and successful when managed during disease quiescence, within a collaborative multidisciplinary framework.

Today, many women with SLE can achieve successful, safe pregnancies. Over the last decade, major advances in the management of SLE have transformed the management of pregnancy in women with SLE.

Contemporary recommendations from the European Alliance of Associations for Rheumatology (EULAR) and American College of Rheumatology (ACR) now advocate a treat-to-target approach emphasising remission, low disease activity, prevention of organ damage, and minimisation of glucocorticoid toxicity.^3,4

Modern guidelines emphasise optimising pre-conception disease control, the continuation of pregnancy-compatible therapies, and early combined obstetric-rheumatology care.^3,4

Pre-conception counselling and management

A major development in SLE and pregnancy, is the increasing emphasis on pre-conception planning and counselling. Pregnancy in patients with SLE requires comprehensive planning and multidisciplinary input. Pregnancy should be planned during sustained disease remission and periods of disease quiescence lasting more than six months.^3,4

EULAR reproductive health recommendations and ACR reproductive health guidelines both emphasise the importance of pre-conception disease control, patient risk stratification, hydroxychloroquine continuation, and avoidance of corticosteroid exposure in advance of conception.^3,4

Active SLE disease at the point of conception is associated with poorer pregnancy outcomes and a significantly increased risk of maternal disease flares, preterm delivery, miscarriage, and pre-eclampsia.^1,3

Factors such as lupus nephritis, major organ involvement, and uncontrolled hypertension further increase the risk of foetal and maternal morbidity.^1,5 Consequently, comprehensive pre-pregnancy assessments have become integral aspects of modern SLE care.

All patients with SLE should be risk stratified and assessed for significant organ involvement prior to conception. Investigations should include an assessment of renal function, blood pressure, complement levels, anti-dsDNA antibodies, antiphospholipid antibodies, anti-Ro/SSA, and anti-La/SSB antibodies.^3,4

In Ireland, specialist SLE and pregnancy care is generally delivered through tertiary referral centres and combined obstetric-rheumatology clinics such as at the National Maternity Hospital, Rotunda Hospital, and the Coombe Hospital.

Monitoring

Women with SLE require close maternal and foetal surveillance during pregnancy, tailored according to disease severity and organ involvement. Patients should be risk stratified according to organ involvement, obstetric risk factors, and disease severity. Foetal monitoring commonly includes serial growth scans, doppler studies, placental assessment, and foetal echocardiography when indicated.

Maternal monitoring should include regular assessment of disease activity, blood pressure, urinalysis, renal function, complement levels, and anti-dsDNA antibodies.^1,3 The risk of disease flare is increased in the postpartum period; therefore, close monitoring is required.

Medications, thromboprophylaxis, and disease activity should be monitored closely during this period. Modern postpartum care in SLE emphasises early recognition of disease flares, thrombotic risk modification, and blood pressure surveillance with close multidisciplinary follow-up.

Psychological welfare should also be thoroughly evaluated as postpartum depression is common and may be mistaken for neuropsychiatric SLE. Blood pressure monitoring is particularly important in the postpartum period due to the risk of hypertensive complications and pre-eclampsia, this risk may persist post-delivery.

Guidelines from the EULAR and ACR emphasise that the postpartum period is high risk for both lupus flares and thrombosis, particularly in the first six-12 weeks.^3,4

Hydroxychloroquine, azathioprine, and low-dose prednisolone are generally compatible with breastfeeding and can be continued in the post-partum period.^3,4 Individualised medication management is required to optimise both maternal and neonatal outcomes.

Management during pregnancy

Pharmacologic management during pregnancy has evolved over the last decade. A significant update is the strong recommendation to continue hydroxychloroquine during pregnancy. Current evidence-based guidelines recommend hydroxychloroquine as a cornerstone therapy in patients with SLE, including in pregnancy.^3,4 The benefits of this medication include a reduction in flares, improved survival, and steroid sparing effects.^1,3

Hydroxychloroquine should be continued throughout pregnancy as this medication reduces the risk of neonatal lupus and congenital heart block.^3,6 Conversely, cessation of hydroxychloroquine is associated with an increased risk of disease flares.¹ The recommended dose of hydroxychloroquine is less than <5mg/kg/day and retinal screening is recommended when prescribing this medication long term.⁷

Careful review of medication is essential due to the risk of teratogenicity associated with several medications used to manage SLE.

Current guidelines recommend the continuation of pregnancy-compatible medications to minimise the risk of disease flares and maintain maternal disease control.^3,4 Medications such as hydroxychloroquine, azathioprine, low-dose corticosteroids, and tacrolimus are compatible with pregnancy. Low-dose aspirin is commonly recommended to reduce pre-eclampsia risk in all SLE patients.³

Corticosteroids may be necessary in the event of lupus flares during pregnancy. However, the lowest effective dose is recommended as placental metabolism limits foetal exposure to corticosteroids.³ The use of high-dose, prolonged courses of corticosteroids confer risks of infection, hypertension, gestational diabetes, and premature rupture of membranes.³ Modern guidelines therefore recommend the minimisation of corticosteroid use whenever possible.^3,4

In contrast, medications – such as methotrexate, cyclophosphamide, mycophenolate mofetil, and ACE inhibitors/ARBs – are contraindicated during pregnancy and breastfeeding. These medications should be stopped prior to conception.^3,4 NSAIDS should be stopped after 20 weeks’ gestation due to the risk of premature closure of the ductus arteriosus. Recommended anti-hypertensive agents during pregnancy include labetalol, nifedipine, and methyldopa.

Mycophenolate should be stopped at least six weeks prior to conception, while methotrexate should be stopped three months prior to conception.^2,3 SLE patients on biologic therapy, rituximab, belimumab, and abatacept can be continued until conception and resumed during lactation.^2,3,4 These medications should generally be stopped during pregnancy. Medication cessation and therapeutic transition should be managed in conjunction with the relevant tertiary specialists.^2,3

Positive anti-Ro/SSA and anti-La/SSB antibodies

All women of childbearing age with SLE should be tested for anti-Ro and anti-La antibodies prior to conception. Anti-Ro and anti-La antibodies are associated with an increased risk of neonatal lupus and congenital foetal heart block. In the event these antibodies are positive, serial foetal echocardiography and close obstetric monitoring are required due to placental antibody transfer.^3,6

Management of these findings include pre-conception counselling, recommendation to continue hydroxychloroquine, and serial foetal surveillance. In some instances, pregnancy complications such as foetal congenital heart block may lead to the first diagnosis of previously unrecognised maternal lupus.⁶

Approximately 1-2 per cent of patients with anti-Ro/SSA antibodies during pregnancy are complicated by congenital heart block during a first pregnancy.⁶ This risk is substantially increased in women with a previous child affected by congenital heart block. Congenital foetal heart block typically manifests between 16 and 26 weeks of gestation.

Additional neonatal manifestations may include cytopenias, liver derangement, and cutaneous neonatal SLE. Current guidelines recommend the continuation of hydroxychloroquine to reduce the risk of congenital heart block and neonatal disease.^3,6 Cutaneous lesions can occur after severe weeks and generally resolve spontaneously, paediatric input may be required in some cases.

Antiphospholipid syndrome

Antiphospholipid syndrome (APS) frequently coexists with lupus and contributes significantly to pregnancy outcomes. Women of childbearing age with SLE should be screened for APS due to the risk of recurrent pregnancy loss and thrombotic complications.^2,8

Pregnant women with SLE and concomitant APS require intensive multidisciplinary management due to increased risks of recurrent miscarriage, placental insufficiency, thrombosis, pre-eclampsia, and foetal growth restriction.^3,8 Diagnosis is based on both clinical and laboratory criteria. Diagnostic laboratory testing includes lupus anticoagulant, anticardiolipin antibodies, anti-β2 glycoprotein antibodies that are persistently positive (≥12 weeks apart).⁸

Management of APS during pregnancy in patients with SLE requires extensive input from rheumatology, obstetrics, maternal-foetal specialists, and haematology. SLE patients with a history of prior thrombosis, triple positive antibodies, active SLE, and renal disease are at higher risk during pregnancy and necessitate closer monitoring.⁸

Current guidelines support the use of low-dose aspirin (75-150mg once daily) in combination with low molecular weight heparin.^3,8 Low-dose aspirin is generally commenced pre-conception or early in the pregnancy course in all patients with SLE regardless of APS status.³ The benefits of this medication include a reduced risk of pre-eclampsia, reduced placental thrombosis, and improved outcomes for the neonate.³

The choice between prophylactic or therapeutic dosing of low molecular weight heparin is determined by a patient’s prior thrombotic history.⁸ In the event of no prior history of thrombosis, prophylactic dosing will typically suffice.⁸ Extensive maternal and foetal monitoring is essential in high-risk anti-phospholipid antibody profile pregnancies.

Anticoagulation should continue for at least six weeks postpartum as the thrombotic risk remains significantly elevated during this period.^3,8 Warfarin therapy can be commenced in the post-partum setting and is compatible with breastfeeding but is contraindicated during pregnancy due to teratogenicity.

Lupus nephritis in pregnancy

Active lupus nephritis is a strong predictor of adverse pregnancy outcomes. Lupus nephritis can increase the risk of pre-eclampsia, foetal growth restriction, preterm delivery, and worsening maternal renal function.^5,9

Management of active renal nephritis requires combined input between nephrology, rheumatology, and maternal-foetal specialists.⁵

Mycophenolate mofetil, a commonly used first-line agent for lupus nephritis, is contraindicated during pregnancy due to teratogenicity.^2,3 Medications such as azathioprine are commonly used as maintenance therapy during pregnancy in patients with SLE and lupus nephritis.

Tacrolimus and cyclosporin may also be considered in patients with persistent proteinuria or active disease.^2,3 Medications should be transitioned to pregnancy compatible medications prior to conception and lupus nephritis should be quiescent for six months following medication change.^2,3

A challenging aspect of managing patients with lupus nephritis is the difficulty in differentiating a lupus nephritis flare from pre-eclampsia. Lupus nephritis flares will typically demonstrate active urinary sediment, rising anti-dsDNA antibody titres,and hypocomplementaemia. Pre-eclampsia is more commonly associated with an elevated uric acid, placental dysfunction, and late gestational hypertension.^5,9

Contraception

Contraceptive counselling is an important component of care in women with SLE due to the risk of teratogenic medications, high-risk pregnancy complications, and adverse maternal and foetal outcomes.⁴ Management should be individualised according to disease activity, thrombotic risk profile, and anti-phospholipid status.^3,4

Effective and reliable contraception is essential in women receiving mycophenolate mofetil, methotrexate, and cyclophosphamide. These medications are teratogenic and require pre-pregnancy counselling.

Contraceptive counselling is particularly important in women with systemic SLE and APS. The choice of contraceptive should be individualised with factors such as anti-phospholipid antibody status, thrombotic risk, and disease activity taken into account.

Oestrogen-containing contraceptives should be avoided in women with APS and in patients with positive antiphospholipid antibodies.^3,8 SLE patients with APS have an increased risk of venous thrombosis, arterial thrombosis, and cerebrovascular events, thus oestrogen should be avoided due to the increased thrombotic risk.⁸

Progestogen-only contraceptive methods are generally preferred, and intrauterine (IUD) devices are often considered to be a safer alternative in this patient group. Methods such as the copper IUD and levonorgestrel-releasing intrauterine system (IUS) are both highly effective options, offering long-acting reversible contraception. These agents are suitable in APS and confer low systemic hormone exposure.^3,4

Conclusion

Pregnancy in patients with SLE remains high risk; however, pregnancy outcomes have improved greatly in women with SLE through optimisation of disease activity prior to conception, pre-pregnancy counselling, and combined obstetric-rheumatology models of care.^1,3

Close foetal and maternal monitoring during pregnancy and during the post-partum period are essential aspects of care delivery within tertiary specialist centres. Particular attention is required in SLE pregnancies complicated by lupus nephritis, APS, and anti-Ro/SSA or anti-La/SSB antibodies.^5,6,8

Disease activity at conception remains one of the strongest predictors of pregnancy outcomes, highlighting the importance of disease quiescence prior to conception. Optimal management includes pre-conception disease optimisation and continuation of pregnancy-compatible medications.

Modern recommendations emphasise risk stratification and  individualised care, with early referral to the relevant multidisciplinary specialist.^3,4 These strategies have significantly improved pregnancy outcomes in women with SLE.