Systemic lupus erythematosus (SLE), often seen in women of childbearing age, is an autoimmune disease that affects multiple organ systems. To ensure optimal maternal and fetal health outcomes, proper disease management is key when caring for this high-risk population. Ideally, providers and patients should work together to plan a pregnancy when the disease is in remission. Adequate disease control is crucial as the risk for a flare seems to relate to the level of maternal disease activity in the 6 to 12 months before conception.1
Healthcare providers should be well versed in pertinent issues related to SLE management throughout pregnancy because of the increased risk for disease-related mortality and morbidity. Immunologic and hormonal changes related to pregnancy may lead to increased frequency of SLE flares; however, the severity of symptoms remains unchanged. Increases in cortisol, progesterone, and estradiol during pregnancy may lead to Th1/Th2 cytokine shifts.1 With SLE being a predominantly Th2-driven disease, some researchers believe these shifts contribute to symptomatic relapse during pregnancy.
One of the major risks for women with SLE during pregnancy is preeclampsia, marked by elevated blood pressure and proteinuria. Mothers are approximately 30% more likely to develop preeclampsia during pregnancy compared with 5% in the general population.2 Although lowering the risk for preeclampsia can be challenging, a recent review pertaining to the use of low-dose aspirin during SLE pregnancy suggests a 20% risk reduction for preeclampsia in patients with lupus.
Additional risks during SLE pregnancies include preterm birth, hypertension, premature rupture of membranes, diabetes mellitus, antiphospholipid syndrome, retina damage or detachment, deep vein thrombosis, and stroke. All SLE pregnancies are considered high risk, and labs should be obtained as soon as pregnancy is confirmed: 24-hour urine protein, urinalysis, complete blood count, creatinine, liver function test, antideoxyribonucleic acid, anti-SSA/Ro and anti-SSB/La antibodies, and antiphospholipid antibodies.
Antibody screening is an important predictor of potentially harmful maternal and fetal complications, including antiphospholipid syndrome (APS) and neonatal lupus. APS is an autoimmune thrombolytic syndrome with clinical manifestations that include recurrent miscarriage, fetal prematurity, maternal and/or fetal thrombosis, HELLP syndrome (H, hemolysis; EL, elevated liver enzymes; LP, low platelet count), fetal distress, and intrauterine growth restrictions.3 The preferred treatment regimen includes low-dose aspirin and heparin in combination with frequent prenatal visits for necessary monitoring. With appropriate management, >70% of patients will deliver a viable, live baby.
Infants born to SLE mothers with positive anti-SSA/Ro and anti-SSB/La antibodies are at risk for symptoms associated with neonatal lupus. Maternal antibodies begin crossing the placenta as early as 11 weeks and can lead to rash, various blood or liver abnormalities, and permanent cardiac abnormalities in the infant.4 Congenital heart block develops in approximately 2% of infants and requires
frequent fetal echocardiograms throughout the pregnancy to help determine if pacemaker implantation will be warranted postdelivery.
Common medications in the treatment of SLE include combinations of methotrexate, hydroxychloroquine, leflunomide, azathioprine, mycophenolate, corticosteroids, various nonsteroidal anti-inflammatory drugs, and belimumab. Careful consideration should be taken when educating patients on the teratogenic effects of specific medications associated with the management of SLE. In particular, methotrexate must be discontinued at least 3 to 6 months prior to conception, and leflunomide should be stopped at least 2 years prior to pregnancy.5 Ideally, patients should discuss pregnancy options with their healthcare providers because of the delicate balance of maintaining low-disease activity and the discontinuation of potentially teratogenic medications. Although corticosteroids are considered a Category C medication, low doses up to 15 mg daily are considered safe throughout pregnancy, and are often used to lessen the severity of SLE symptoms.5
Hydroxychloroquine—although compatible with pregnancy—is still considered Category C because of associated congenital malformations seen with chloroquine. Intravenous belimumab is a b-lymphocyte-specific inhibitor used to treat adult patients with moderate-to-severe SLE who are also on a combination of disease maintenance medications. Providers should discuss the potential risks versus benefits of continuing belimumab (Category C) therapy with patients as there are no human studies or pregnancy data available.
Another teaching point for both providers and patients is the availability of pregnancy exposure registries. The Organization of Teratology Information Specialists is dedicated to providing evidence-based information to mothers, healthcare providers, and the general public about medication exposures during pregnancy.
Ms Owens is Director, Infusion and Clinical Services, Low Country Rheumatology, Charleston, SC; and Member, Board of Directors, Rheumatology Nurses Society.
1. Doria A, Incani A, Lockshin M. Challenges of lupus pregnancies. Rheumatology (Oxford). 2008;47(suppl 3): iii9-12.
2. Stanhope TJ, White WM, Moder KG, et al. Obstetric nephrology: lupus and lupus nephritis in pregnancy. Clin J Am Soc Nephrol. 2012;7:2089-2099.
3. Fosca D, Valenti O, Hyseni E, et al. Antiphospholipid syndrome during pregnancy: the state of the art.
J Prenat Med. 2011;5:41-63.
4. Capone C, Buyon J, Friedman D, et al. Cardiac manifestations of neonatal lupus: a review of autoantibody- associated congenital heart block and its impact in an adult population. Cardiol Rev. 2012;20:72-76.
5. Hazes JM, Coulie PG, Geenen V, et al. Rheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological considerations for drug use. Rheumatology (Oxford). 2011;50:1955-1968.