Prevalence and Laboratory-associated Variability of Non-criteria Antiphospholipid Antibodies in Women with Pregnancy Loss: A Cross-sectional Study

ABSTRACT Background Non-criteria antiphospholipid antibodies (NC-aPLs) may supplement criteria antiphospholipid antibody testing in women with pregnancy loss, but their prevalence, laboratory-associated variability, and susceptibility to pregnancy status remain incompletely characterized. Methods This cross-sectional study included 1,897 women with a history of pregnancy loss who underwent testing for 10 NC-aPLs at three independent commercial laboratories. Positivity was defined using laboratory-specific manufacturer reference ranges. We compared positivity across laboratories and by criteria aPL status, pregnancy status at testing, and number of previous losses. Multivariable logistic regression evaluated associations between pregnancy status and individual NC-aPL positivity. Results Overall, 55.5% of women had at least one positive NC-aPL; 54.6% of those negative for criteria aPLs remained positive for at least one NC-aPL. Positivity differed across laboratories for 8 of 10 markers, with marked variation for aAnxA5-IgG (8.6%-29.8%) and aPE-IgG (4.8%-24.3%). After adjustment, pregnancy at testing was associated with higher odds of aAnxA5-IgG positivity, whereas no significant associations were observed for the other nine markers. NC-aPL positivity showed no significant trend with the number of previous pregnancy losses. Conclusions NC-aPLs were common in women with pregnancy loss, including those negative for criteria aPLs. Substantial laboratory-associated variability highlights a barrier to clinical interpretation and the need for assay standardization. The association between pregnancy status and aAnxA5-IgG positivity warrants longitudinal evaluation.