Pregnancy Among Patients with Lupus: Progress, Problems, and Promise

Over the last several decades, we have made progress in the management of pregnant patients with lupus. Pregnancy is no longer prohibited in this patient population, and many patients have successful pregnancies without complications. We also have more knowledge about this disease and have more treatment options. We know that lupus disease activity should be quiescent for at least 6 months prior to conception (1). Individuals with prior kidney involvement, even with partial or complete remission, have a higher risk of developing active nephritis and additional pregnancy complications (2). Hypocomplementemia, including low C4, has been associated with renal flare during pregnancy (2).

Medications such as hydroxychloroquine have been associated with a reduced risk of developing high disease activity during pregnancy and pregnancy-related lupus flare, potentially improving long-term kidney outcomes (3) (Table 1). Low-dose aspirin use has also been associated with a reduced risk of preeclampsia in patients at high risk of preeclampsia, such as those with lupus (4). At many medical centers within the United States, interdisciplinary teams composed of nephrologists, rheumatologists, perinatologists, advanced practice providers, nurses, and other medical professionals provide care for pregnant people with lupus. The advancement in therapeutic options for lupus has also provided unique opportunities for treatment during pregnancy. For example, the Belimumab (Benlysta®) Pregnancy Registry (GSK study BEL114256; NCT01532310) has been established to evaluate pregnancy outcomes among pregnant patients exposed to belimumab. However, enrollment for this prospective study has been low—with only 55 participants reportedly recruited from a goal of 500 participants—over the course of 10 years (5).

Table 1.

Safety of medications for SLE and blood pressure management in pregnancy and lactation

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Although there have been advances in the care for pregnant patients with lupus, many challenges still remain. Changes in immunosuppressant therapy may result in lupus flares in previously stable patients. Medications such as mycophenolate mofetil are discontinued during pregnancy due to their teratogenicity (6), with patients switching to azathioprine or tacrolimus as an alternative therapy. Pregnant patients with lupus still experience high rates of adverse pregnancy outcomes.

A recent study evaluating adverse pregnancy outcomes among patients prospectively enrolled in lupus pregnancy cohorts at tertiary and quaternary academic medical centers in North America found that at least two of five pregnant patients with lupus experienced an adverse pregnancy outcome. Patients with lupus nephritis had double the odds of preeclampsia (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.01–4.13) and fetal loss (OR, 1.90; 95% CI, 1.10–3.56) compared with individuals without a history of lupus nephritis (7). Those with active lupus nephritis (defined by at least >500 mg/g on a spot urinary protein-to-creatinine ratio) had a sixfold higher odds of fetal loss (OR, 6.29; 95% CI, 2.52–15.70) and a threefold higher odds of poor pregnancy outcome (OR, 3.08; 95% CI, 1.31–7.23) compared with individuals without a history of lupus nephritis (7). Similar findings have been reported in other prospective lupus pregnancy cohorts around the globe. Pregnant patients with lupus continue to experience higher odds of adverse outcomes compared with the general population (8). Additionally, distinguishing between active lupus nephritis and preeclampsia during pregnancy may be difficult for even well-trained clinicians. Although kidney biopsies may offer a definitive diagnosis, performing this procedure during pregnancy is not without risk (9). Circulating angiogenic factors, such as soluble fms-like tyrosine kinase 1 (sFlt 1) and placental growth factor (PlGF), have shown promise as biomarkers (10) but are not widely available in the United States.

To continue to improve outcomes for pregnant patients with lupus and their offspring, rigorous prospective cohort studies and pragmatic clinical trials will need to be conducted. Moreover, a biopsychosocial approach should be adopted to address the sociopolitical context of our patients and understand the structural barriers that may impact health outcomes. Finally, there is still more investigation needed to facilitate the identification of novel biomarkers, therapeutics, development of risk-stratification tools, and incorporation of the sFlt1/PlGF ratio as a screening test for preeclampsia into clinical practice to ensure even greater success for pregnant patients with lupus.