Risk and Protective Factors of Disease Flare During Pregnancy in Systemic Lupus Erythematosus: a Systematic Review and Meta-analysis

To synthesize available evidence on predictive factors associated with systemic lupus erythematosus (SLE) flares during pregnancy, we systematically searched MEDLINE, Embase, and the Cochrane Library through January 2024 for observational studies on risk and protective factors of SLE flares during pregnancy. Odds ratios (OR) and mean differences (MD), as well as their 95% confidence intervals (CI) were used to quantify effect sizes. We employed fixed-effect or random-effect models based on heterogeneity assessments (I statistics). Sensitivity analyses were performed using the leave-one-out method, and publication bias was assessed through Egger's test. Thirty-two studies were included in the meta-analysis. Significant baseline SLE characteristics associated with higher risks for flares during pregnancy were identified: thrombocytopenia (with OR [95%CI], 2.29 [1.14-4.58]), hypocomplementemia (1.70 [1.28-2.27]), anti-dsDNA positivity (1.43 [1.16-1.77]), and a history of lupus nephritis (2.34 [1.70-3.21]). Protective factors included achieving remission before pregnancy (0.32 [0.20-0.49]) and antimalarial use at baseline (0.71 [0.55-0.92]) and during pregnancy (0.44 [0.33-0.58]). Additional risk factors included baseline glucocorticoid usage (1.51 [1.17-1.94]), glucocorticoid administration during pregnancy (3.39 [1.90-6.06]), use of other immunosuppressive drugs at baseline (1.46 [1.00-2.12]), and hypertension (2.16 [1.45-3.23]). Furthermore, individuals in the flare group were younger, had higher baseline disease activity, and lower C3/C4 levels compared to the non-flare group. This study highlighted the critical role of managing SLE disease activity prior to pregnancy to minimize flare risks, and identified significant risk and protective factors associated with flares. These evidences facilitate better clinical management strategies for pregnant women with SLE. Key Points • Synthesizes existing evidence on the risk and protective factors associated with SLE flares during pregnancy. • Highlights the critical importance of effectively managing disease activity prior to conception. • Provides insights to enhance risk stratification and management strategies for pregnancies in patients with SLE.