Modifying Predictors of Adverse Maternal and Obstetric Outcomes in SLE

Pregnancy is associated with significant maternal and fetal risks in those with systemic lupus erythematosus (SLE), including loss of pregnancy. Careful planning to avoid active stages of disease during pregnancy and management of risk during the course of the pregnancy are essential for good outcomes.^1,2

Risks of pregnancy in SLE

An estimated 4500 women in the United States with SLE become pregnant each year.³ A recent study of 13,555 pregnancies in women with SLE reported a 20-fold increase in risk, including maternal mortality and morbidity associated with cesarean section, preterm labor, and preeclampsia.⁴ One-third of women with SLE undergo cesarean section, and one-third of babies born to mothers with SLE are preterm. Complications from preeclampsia have been estimated to occur in 13% to 35% of mothers with SLE compared with 5% to 8% of mothers without SLE.^3,5-7

The most common factor predicting poor outcome in those with SLE is disease activity at the time of conception.^1,6,8,9 A 2010 worldwide meta-analysis of 29 studies that included a total of 2751 pregnant women with SLE found high rates of fetal mortality and morbidity in this population, including premature birth (39.4%), spontaneous abortion (16%), intrauterine growth restriction (12.7%), stillbirth (3.6%), and neonatal death (2.5%).⁹

Poor pregnancy outcomes in those with SLE are the result of various factors that manifest at different times during the pregnancy. During the first trimester, proteinuria, antiphospholipid antibody syndrome, thrombocytopenia, and hypertension can result in loss of the fetus.¹⁰

Risks to the mother, most prominently preeclampsia and SLE flares, can also be significant. The overlapping condition of lupus nephritis in particular is associated with 2 to 3 times higher risk for disease flares.¹¹ Additionally, women with SLE appear to have a genetic predisposition to preeclampsia. This finding was supported by the PROMISSE trial, in which 7 of 40 women with SLE were found to have heterozygous mutations in member cofactor protein and complement factor I that correlated with preeclampsia.¹²

Importance of pregnancy timing

By far, the best way to ensure the health of both a mother with SLE and her child is careful timing of the pregnancy, as the majority of complications occur in women who conceive during an active period of SLE or lupus nephritis.^13-15

Conversely, inactive disease during the previous 6 months before conception has been associated with good pregnancy outcomes in women with SLE. Disease flares are less likely to occur during these pregnancies than in women who have mild to moderate disease at conception (8% vs 58%, respectively).³ A more recent review reported good outcomes in women with inactive disease 4 months prior to conception.²

Despite these risks, studies indicate that patterns of contraceptive use are highly irregular among women with SLE, and that when contraception is used, it is often one of the less effective barrier methods.^16-18 In a survey of 97 women with SLE, 55% reported having occasional unprotected sex and 23% reported frequent unprotected sex.¹⁷ Another observational study of 86 women with SLE at risk for pregnancy found that 59% had no contraceptive counseling in the previous year.¹⁹ These practices are found even in women taking teratogenic medications for SLE, suggesting an unmet need for contraceptive counseling to prevent complications of pregnancy and childbirth in these women.