PO:14:194 | The CORAL Study: Complement levels during pregnancy in prospectively followed systemic Lupus erythematosus patients

Irene Cecchi¹, Massimo Radin¹, Alice Barinotti¹, Francesca Crisafulli², Laura Andreoli², Cecilia Beatrice Chighizola³, Savino Sciascia¹, On Behalf Of The Coral Study Group¹ | ¹Università di Torino, Italy; ²Università di Brescia, Italy; ³Università di Milano, Italy

Aim. This study investigates the role of complement levels as biomarkers to predict disease flares and adverse pregnancy outcomes (APOs) in women with systemic lupus erythematosus (SLE) undergoing pregnancy. Despite improvements in SLE management, challenges remain in predicting maternal and fetal complications due to a lack of reliable biomarkers and validated clinical tools.

Methods. This multicenter, retrospective study analyzed 333 pregnancies in 264 SLE patients followed prospectively at international centers from preconception through postpartum. Complement levels (C3 and C4) were measured at defined time points alongside disease activity using the SLEDAI-2K index. Maternal, obstetric, and neonatal outcomes were collected, with statistical analysis correlating complement fluctations to clinical outcomes.

Results. The study revealed significant trends in complement fluctations during pregnancy. Complement levels consistently increased during the course of pregnancy when looking at the entire cohort, with peak levels during the third trimester (C3 114.4±28; C4 17.7±8.3), which were significantly higher when compared to the conception period (C3 97.7±25.4; C4 16.3±7.3; p<0.001)(Figure 1A). In the cohort, lower preconception C3 and C4 levels were strongly associated with higher rates of disease flares (18%) and APOs, including preeclampsia (6.3%), preterm births (21.9%), and intrauterine growth restriction (9.9%). Patients experiencing flares exhibited persistently low complement levels across all timepoints, with the majority of flares (91%) occurring between the second and third trimesters. Patients with late pregnancy complications demonstrated significant lower levels of complement during gestation. For instance, lower C3 levels during the third trimester (mean 96.7 vs. 115.5 mg/dL, p<0.001) and lower C4 levels (mean 14.2 vs. 18.3 mg/dL, p=0.018) were significant predictors of preeclampsia. Similarly, higher disease activity (SLEDAI-2K scores) during these periods correlated with APOs. Graphical representation of differences in complement levels according to presence of late pregnancy complications in the analyzed timepoints are illustrated in Figure 1B. Regression analysis identified third-trimester C3 levels as independent predictors for both flares (OR: 0.96, p<0.001) and APOs (OR: 0.98, p=0.003). Patients with high-titer anti-dsDNA antibodies and those treated with corticosteroids showed elevated risks for complications. Notably, a failure of expected complement increases was a distinguishing feature in patients with severe outcomes.

Conclusions. Monitoring complement levels during pregnancy in SLE patients offers valuable prognostic insights. Blunted complement increases and low baseline levels serve as markers for heightened maternal and fetal risk, emphasizing their utility in clinical surveillance. The findings suggest that preconception and gestational complement profiling should be integrated into routine care for SLE pregnancies to guide individualized risk stratification and therapeutic strategies.