Adverse Pregnancy Outcomes Within the Lupus in Pregnancy (Legacy) Cohort: Anti-Phosphatidylserine/Prothrombin IgG Antibodies Are Stronger Predictors Than Lupus Anticoagulant

Objectives Adverse pregnancy outcomes (APO) are a major concern in SLE, particularly with antiphospholipid antibodies. While lupus anticoagulant (LAC) is the strongest predictor of APO, emerging evidence suggests anti-phosphatidylserine/prothrombin antibodies (aPS/PT) may also indicate increased risk. We examined whether aPS/PT predict APO and how they compare to LAC in the multicenter prospective LEGACY cohort. Methods LEGACY includes Systemic Lupus International Collaborating Clinics in Canada, South Korea, Peru, and Mexico. Pregnant SLE women are consecutively enrolled <17 weeks’ gestation and followed at predefined visits throughout pregnancy and postpartum. At enrollment, plasma was tested for aPS/PT, using ELISA (Werfen, San Diego), with positivity cutoffs for IgG and IgM as >30 chemiluminescent units. LAC testing was performed at each site using validated assays. The present analysis includes the first 98 pregnancies with aPS/PT results. APO were a composite outcome of either: (1) fetal death >20 weeks, (2) neonatal death, (3) placenta-mediated preterm delivery <36 weeks, and/or 4) small for gestational age (<5th percentile). We performed multivariable hazards models with frailties and gestational age as the time axis to assess associations between APO and aPS/PT IgG and/or IgM vs LAC. Maternal covariates at enrollment included age, body mass index, prior nephritis, SLE Pregnancy Disease Activity Index, and medications. We used Harrell’s C-index to assess model discrimination. Results Among 98 SLE pregnancies, 9 (9%) were aPS/PT IgG-positive, 25 (26%) were aPS/PT IgM-positive, and 11 (11%) were LAC-positive (Table 1). Eight pregnancies (8%) were positive for both aPS/PT (IgG and/or IgM) and LAC. Thirteen pregnancies (13%) experienced APO, including 5/9 (56%) in the aPS/PT IgG-positive group and 5/11 (46%) in the LAC-positive group. In multivariable analysis, aPS/PT IgG positivity was strongly associated with APO (HR 12.2, 95% CI 1.7-87.2), whereas IgM and/or overall aPS/PT positivity showed nonsignificant trends [HR 1.9 (95% CI 0.3-11.2) and HR 2.2 (95% CI 0.4-11.2), respectively]. LAC positivity was also associated with a substantially higher APO risk (HR 7.8, 95% CI 1.7-35.1), though less strongly than aPS/PT IgG. Discriminative performance was slightly higher for aPS/PT IgG (adjusted C-index 0.80, 95% CI 0.65-0.95) compared with LAC, aPS/PT IgM, and combined aPS/PT IgG and/or IgM models (0.78, 95% CI 0.68-0.89; 0.72, 95% CI 0.59-0.85; and 0.73, 95% CI 0.61-0.86, respectively). Table 1. Maternal characteristics at baseline and pregnancy outcomes (n=98) Conclusion In this preliminary analysis of the LEGACY cohort, aPS/PT IgG demonstrated a stronger independent association with APO and slightly better discriminative performance than LAC. These findings suggest that aPS/PT IgG may outperform LAC in predicting APO and could improve risk stratification in SLE pregnancies. Supported by a CIORA grant.