Longitudinal profiling of antiphospholipid antibodies reveals pre-conception levels as a key predictor of live birth in women with recurrent pregnancy loss

Introduction: Studies indicate that approximately 15-20% of patients with recurrent pregnancy loss (RPL) test positive for antiphospholipid antibodies (aPL). However, the dynamic changes in aPL from pre-conception to early pregnancy in the RPL population and their relationship with pregnancy outcomes remain unclear. This study aimed to longitudinally analyze the dynamic changes of aPL profiles in RPL patients and evaluate their predictive value for pregnancy outcomes. Methods: 100 patients diagnosed with RPL between March 2022 and December 2023 were enrolled. Serum levels of anticardiolipin antibody (aCL) and anti-β2-glycoprotein I antibody (aβ2GPI) isotypes (IgA, IgM, and IgG) were measured via chemiluminescence immunoassay at three timepoints: pre-conception, post-conception, and 3 months post-conception, with subsequent pregnancy outcomes tracked. Results: A total of 61 patients (61%) tested positive for at least one aPL subtype at one or more timepoints; however, only one met the 2006 Sydney classification criteria for antiphospholipid syndrome. Longitudinal analysis revealed that post-conception levels of aβ2GPI-IgM, aCL-IgA, and aCL-IgG were significantly elevated compared to pre-conception levels (all p < 0.05). Regarding outcomes, the live birth rate was significantly lower in pre-conception aPL-positive patients compared to those who were negative (44.8% vs 66.2%, p = 0.048), while the early pregnancy loss rate was significantly higher (51.7% vs 26.8%, p = 0.017). Multivariate logistic regression analysis identified three independent risk factors for subsequent pregnancy loss: higher number of previous pregnancy losses (OR = 1.871, 95% CI: 1.102-3.175, p = 0.020), elevated post-conception aCL-IgG level (OR = 1.336, 95% CI: 1.039-1.718, p = 0.024), and higher number of pre-conception aPL types positive (OR = 2.730, 95% CI: 1.039-7.173, p = 0.042). This model demonstrated fair discrimination with an area under the receiver operating characteristic curve (AUC) of 0.733 (95% CI: 0.631-0.835, p < 0.001). Conclusion: aPL levels increase significantly after conception in women with RPL and are independently associated with adverse pregnancy outcomes. Our findings suggest that aPL screening should be performed both before pregnancy and in early pregnancy in RPL patients to enable timely intervention and improve pregnancy outcomes. Pre-conception aPL testing may hold greater predictive value than in early pregnancy.