Dr. Evelyn Vinet
CHICAGO—Women with systemic lupus erythematosus (SLE) are at higher risk of maternal and fetal complications than those in the general population. These risks are shared to varying degrees by other systemic autoimmune rheumatic diseases, such as Sjögren’s disease. At a session of ACR Convergence 2025, Evelyn Vinet, MD, PhD, associate professor in the Division of Rheumatology at McGill University Health Centre, Montreal, discussed management considerations to optimize outcomes in pregnant patients with SLE.
Initial Risk Stratification
Preconception counseling and risk stratification are important aspects of care, noted Dr. Vinet, although sometimes these patients may not present until after conception. She explained that for women with SLE, clinicians should assess levels of disease activity, extent of disease damage and comorbidities. Positive antibodies for Sjögren’s-syndrome-related antigen A (anti-Ro/SSA), for Sjögren’s-syndrome-related antigen B (anti-La/SSB) or for antiphospholipid antibodies (aPL) also increase risk.
The latter should also be tested in women with suggestive clinical findings who have other rheumatic diseases because they may indicate antiphospholipid syndrome (APS).1 These antibodies are required but not sufficient for diagnosis of the systemic autoimmune syndrome, recently redefined by the 2023 ACR/EULAR classification criteria; APS increases the risk of thrombosis and other factors affecting pregnancy morbidity and fetal loss.2
Current ACR guidelines recommend prenatal or early pregnancy testing for anti-Ro/SSA and anti-La/SBB antibodies not just in patients with SLE, but also in patients with systemic sclerosis, rheumatoid arthritis and Sjögren’s disease.1 Although most commonly positive in the latter group, the presence of these antibodies may trigger neonatal lupus syndrome in any patient with rheumatic disease who is positive for these antibodies, and sometimes even in antibody-positive females without a previously diagnosed autoimmune rheumatic condition.3
Dr. Peter Izmirly
Another presenter at the session, Peter Izmirly, MD, a rheumatologist and professor of medicine at New York University Grossman School of Medicine, New York, discussed the poorly named neonatal lupus syndrome, which does not cause true SLE in the child. The transfer of anti-Ro/SSA or anti-La/SBB antibodies across the placenta leads to lupus-like symptoms in the infant, such as rash.
Although symptoms are sometimes mild and temporary, congenital heart block is a potentially permanent and serious complication. In patients positive for these antibodies, the risk of neonatal lupus with cardiac involvement is about 2%, with recurrence rates in subsequent pregnancies at about 6 to 10 times this rate.4
Disease Activity & Treatment Approaches
Dr. Vinet stressed that treatment should aim for remission or low-disease activity before, during and after pregnancy. Although complete remission is ideal, achieving a lupus low disease activity state (LLDAS) can reduce adverse pregnancy outcomes by about 50%, she noted.5 Ideally, pregnancy should be postponed during active disease until manifestations are optimally controlled.
Treatment of rheumatic diseases during pregnancy requires special considerations. Poorly controlled disease leads to worse outcomes, and patients are at risk of postpartum disease flare, yet medication safety is sometimes uncertain, and some medications are clearly contraindicated.
Low-Dose Aspirin
The ACR strongly recommends that all pregnant patients with SLE take low-dose aspirin, in line with non-rheumatology medical society recommendations for patients at high risk of preeclampsia.1 Low-dose aspirin is also advised for patients who are high risk because of aPL positivity, regardless of underlying rheumatic disease diagnosis. Dr. Vinet noted that aspirin should be started early in pregnancy (<16 weeks) and continued all the way to delivery.
Glucocorticoids
Although not associated with major risk of birth defects, glucocorticoids carry some other dose-related risks to the mother, and they also increase the risk of preterm birth and fetuses who are small for their gestational age. Current pregnancy guidelines from both the ACR and EULAR aim for lower doses of prednisone than used in the past by using pregnancy-compatible conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic DMARDs.1,6
The 2020 ACR guideline recommends continuing low-dose steroids during pregnancy if clinically indicated (≤10 mg of prednisone daily). The 2024 EULAR guideline relies on more recent data to recommend an even lower threshold (≤5 mg of prednisone daily), withdrawing completely if possible.1,6
Dr. Vinet emphasized, however, that higher doses can sometimes be critically important in managing very severe or life-threatening flares, for example, through intravenous high-dose methylprednisolone.
csDMARDs
Certain agents are believed to be safe in pregnancy due to sufficient experience in this population. These include the calcineurin inhibitors tacrolimus and cyclosporine, colchicine, azathioprine and hydroxychloroquine. Per ACR guidelines, the latter should be taken by all females with SLE during pregnancy, as randomized trials have shown that the low-risk agent decreases flares and improves pregnancy outcomes.1
Clinicians should also consider hydroxychloroquine for females with other autoimmune rheumatic diseases who are positive for anti-Ro/SSA antibodies, as it helps prevent complications from neonatal lupus.1,6 Dr. Izmirly shared results from studies by his group on heart block mediated by circulating maternal anti-SSA antibodies (neonatal lupus). In both a historical cohort study and a follow-up prospective study, hydroxychloroquine reduced the risk of heart block during subsequent pregnancies.4,7
In contrast, Janus kinase inhibitors should be avoided, due to insufficient data in this population, as should the calcineurin inhibitor voclosporin. Other agents should be discontinued during pregnancy due to clearly established teratogenicity, including methotrexate, mycophenolate mofetil (MMF) and cyclosporine.
“They are on a spectrum of teratogenicity,” Dr. Vinet explained. Correspondingly, methotrexate should ideally be held for four weeks prior to conception and MMF for six weeks. Cyclophosphamide should be held a full three months prior; however, cyclophosphamide may be employed for life-threatening manifestations during the second or third trimester if other options are not available.
Biologic DMARDs
Per EULAR guidelines, Dr. Vinet noted that belimumab can be used if needed to control disease throughout pregnancy.6 However, she explained that rituximab may cause B cell–depletion in neonates who are exposed during the second or third trimester. At present it’s unclear how significant the resulting infection risk might be, although B cells seem to fully recover within six months of birth. “So, we can use it in certain circumstances, but we need to be mindful of that and weigh the risks and benefits,” Dr. Vinet said.
Anifrolumab is an option if other agents cannot be used, Dr. Vinet explained, but because it is such a new therapy, little is known about its specific impact in pregnancy.
Considerations in Lupus Nephritis
Dr. Vinet discussed recent ACR guidelines on lupus nephritis, which recommend first-line triple therapy with glucocorticoids, MMF and a third agent (belimumab or a calcineurin inhibitor).8 However, a different approach is needed during a lupus nephritis flare during pregnancy due to teratogenicity concerns from MMF.
At Dr. Vinet’s institution, clinicians typically treat with intravenous glucocorticoids at 20 mg/daily or above (but with a rapid taper), along with azathioprine, tacrolimus and potentially belimumab (in addition to background low-dose aspirin and hydroxychloroquine). They might consider rituximab for inadequate response, escalating in rare circumstances to MMF or cyclophosphamide in a rapidly deteriorating patient, but only during the second or third trimester.
In a different setting, many non-flaring patients with previous lupus nephritis are kept on MMF as a maintenance therapy. Such patients need to be switched to a safer medication during pregnancy, and Dr. Vinet shared that clinicians often choose azathioprine in this situation.
Ruth Jessen Hickman, MD, a graduate of the Indiana University School of Medicine, is a medical and science writer in Bloomington, Ind.
References
- Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Care Res (Hoboken). 2020 Apr;72(4):461–488.
- Barbhaiya M, Zuily S, Naden R, et al. The 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Arthritis Rheumatol. 2023 Oct;75(10):1687–1702.
- Bankole A, Nwaonu J. A review of neonatal lupus syndrome. Sci Prog. 2024 Jul-Sep;107(3):368504241278476.
- Izmirly PM, Costedoat-Chalumeau N, Pisoni CN, et al. Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation. 2012 Jul 3;126(1):76–82.
- Tani C, Zucchi D, Haase I, et al. Are remission and low disease activity state ideal targets for pregnancy planning in systemic lupus erythematosus? A multicentre study. Rheumatology (Oxford). 2021 Dec 1;60(12):5610–5619.
- Rüegg L, Pluma A, Hamroun Set al. EULAR recommendations for use of antirheumatic drugs in reproduction, pregnancy, and lactation: 2024 update. Ann Rheum Dis. 2025 Jun;84(6):910–926.
- Izmirly P, Kim M, Friedman DM, et al. Hydroxychloroquine to prevent recurrent congenital heart block in fetuses of anti-SSA/Ro-positive mothers. J Am Coll Cardiol. 2020 Jul 21;76(3):292–302.
- Sammaritano LR, Askanase A, Bermas BL, et al. 2024 American College of Rheumatology (ACR) guideline for the screening, treatment, and management of lupus nephritis. Arthritis Rheumatol. 2025 Sep;77(9):1115–1135.
