Lupus and Pregnancy: Counseling Strategies to Ensure Optimal Outcomes

Systemic lupus erythematosus (SLE) is the most common rheumatic condition requiring management during pregnancy.¹ The predominant group affected by SLE are women (10 times more likely than men), most frequently during childbearing years.^1-3 Effective management of SLE has raised the 10-year survival rate to 92% and improved quality of life for women who are considering pregnancy.¹ Today, greater attention to risk management of pregnancy in patients with SLE has led to strategies that can improve fetal and maternal outcomes.^2,3

As a consequence, counseling regarding pregnancy and fetal and maternal risk assessment have become major components of SLE diagnosis and management. According to recommendations from the European League Against Rheumatism (EULAR) published in 2017, pregnancy counseling should begin as soon as possible after diagnosis.³

Risks to mother and child during a pregnancy with SLE are considerable. Teng and colleagues⁴ reported that while normal outcomes are likely in 60% of pregnancies, complications such as preeclampsia occur in 1 of 5 cases, and 20% to 30% of women with SLE will deliver their infants prematurely. Recent studies of the interaction of SLE and pregnancy have provided important data that offer a more complete picture of what the patient can expect and help clinicians address the risks involved.

Impact of SLE on Fetal Outcomes

The primary risk is a disease flare of SLE occurring during pregnancy, reported at rates of 26% to 34% in the meta-analysis conducted by Teng et al; 80% of cases were considered mild and manageable.⁴ The remaining 20% of flares were severe, involving nephritis, pleurisy, arthritis, thrombocytopenia, cerebritis, myositis, and/or pericarditis.⁴ The influence of these types of flares on pregnancy outcomes was highly dependent on gestational term; specifically, Teng found that the majority occurred late in pregnancy, with 55% at 24 to 36 weeks, while 41% occurred after week 36. Late-stage flares were associated with significantly higher risks of preterm labor and perinatal mortality.⁴

A study by Clowse et al⁵ reported fetal loss rates (due to miscarriages and perinatal mortality) 3-times higher among women with SLE who experienced high disease activity during the first and second trimester compared with those with low or no disease activity. Disease flares occurring in the 6 months prior to conception were also found to be predictive of the risk of another occurrence during pregnancy, and outcomes were significantly improved if conception was delayed until 6 months after the disease was in remission.

Increased Maternal Risks Due to SLE

A number of risks for complications to pregnancy are significantly compounded by the comorbidity of SLE. An earlier study by Clowse and colleagues⁶ reported that, in general, women with SLE have a 20-fold higher risk of pregnancy-related mortality compared with pregnant women without SLE, including 10-fold higher risks of thromboembolic events such as stroke, deep vein thrombosis, or pulmonary embolism, along with an increased risk of infections. Risk of preeclampsia has been reported at rates of 16% to 23% in most studies, which Teng and coworkers calculated presents a 3-fold increased risk compared with the risk of preeclampsia in pregnant women without SLE.⁴ They also reported a moderate but significant preventive effect of daily aspirin on the risk of preeclampsia, preterm birth, and intrauterine growth restriction.⁴

Maternal-Fetal Transmission of SLE

A form of neonatal lupus erythematosus is observed in an estimated 5% to 10% of infants born to mothers with SLE, as a result of anti-Ro and anti-La antibodies associated with autoimmune disorders crossing the placenta.⁴ After birth, these infants will manifest symptoms of SLE, including abnormalities of liver and cardiac function and of blood enzymes resulting in anemia, neutropenia, and thrombocytopenia. Most of these symptoms will disappear in the first 3 to 6 months after birth, with the exception of congenital heart block, a rare (occurring in 1% to 3%) but serious condition associated with a 15% to 20% increased risk of mortality.⁴

Genetic Concerns

The question of whether SLE can be inherited is important for patients and clinicians alike. Although the analysis by Teng et al found several studies that reported an up to 14-fold increased risk of SLE in the offspring of parents with SLE, they suggested that on a population basis, these risks are actually quite low.^4,7 “Since the incidence of SLE in the general population is very low, the absolute risk for an SLE patient to conceive a child with SLE is negligible and patients can therefore be reassured on this matter during pre-pregnancy counseling,” the authors wrote.⁴

Risk Stratification

A number of successful strategies have been identified to minimize the risks of overlapping SLE and pregnancy. Discussion of the many compounding issues is recommended for any woman with SLE of childbearing age, hopefully before pregnancy occurs or is considered.

In a review of management strategies for pregnancy in patients with SLE, Knight and Nelson-Piercy¹ recommended that in the presence of disease activity, women should be advised of the risks and encouraged to postpone pregnancy to a quiescent period. Patients who do not wish to conceive should be counseled to use effective contraceptive measures to prevent unwanted pregnancies, particularly those occurring at times when they may be taking teratogenic therapies.³

Prepregnancy counseling should include a complete history of disease activity with a full exploration of potential organ damage and serologic profile, including anti-Ro and anti-La antibodies and antiphospholipid antibodies, and an anti-double-stranded DNA test to confirm the diagnosis of SLE.¹ Discussion of obstetric history as well as other medical disorders is important. Blood tests should include baseline levels for urea and electrolytes, creatinine, and liver function, and other tests may be important to assess cardiac and lung function. This information is invaluable for continuous monitoring of potential risks throughout the pregnancy.

References

1. Knight CL, Nelson-Piercy C. Management of systemic lupus erythematosus during pregnancy: challenges and solutions. Open Access Rheumatol. 2017;9:37-53.
2. Kavanaugh A, Cush JJ, Ahmed MS, et al. Proceedings from the American College of Rheumatology Reproductive Health Summit: the management of fertility, pregnancy, and lactation in women with autoimmune and systemic inflammatory diseases. Arthritis Care Res (Hoboken). 2015;67(3):313-325.
3. Andreoli L, Bertsias GK, Agmon-Levin N, et al. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2017;76(3):476-485.
4. Teng YKO, Bredewold EOW, Rabelink TJ, et al. An evidence-based approach to pre-pregnancy counselling for patients with systemic lupus erythematosus [published online November 20, 2017]. Rheumatology (Oxford). doi: 10.1093/rheumatology/kex374
5. Clowse ME, Magder LS, Witter F, Petri M. The impact of increased lupus activity on obstetric outcomes. Arthritis Rheum. 2005;52(2):514-521.
6. Clowse ME, Jamison M, Myers E, James AH. A national study of the complications of lupus in pregnancy. Am J Obstet Gynecol. 2008;199(2):127.e1-127.e6.
7. Somers EC, Antonsen S, Pedersen L, Sorensen HT. Parental history of lupus and rheumatoid arthritis and risk in offspring in a nationwide cohort study: does sex matter? Ann Rheum Dis. 2013;72(4):525-529.