Preconception antiphospholipid antibodies and risk of subsequent early pregnancy loss

Objectives: To prospectively estimate the association of preconception antiphospholipid antibodies (aPL) with subsequent pregnancy loss using a cohort design. aPL have been associated with recurrent early pregnancy loss (EPL) prior to 10 weeks in previous case-control studies. Prospective ascertainment of pregnancy loss is challenging, as most women do not seek care prior to EPL. Methods: Secondary analysis of the Effects of Aspirin in Gestation and Reproduction trial of preconception low-dose aspirin. Preconception anticardiolipin (aCL) and anti-β2-glycoprotein-I (a-β2-I) were assessed in 1208 women with one or two prior pregnancy losses and no more than two prior live births. Comparison cohorts were defined by positive aPL (+aPL) or negative aPL (–aPL) status. All women were followed for six menstrual cycles while trying to conceive; if successful, they underwent an ultrasound at 6–7 weeks’ gestation. EPL was defined as loss prior to 10 weeks’ gestation; embryonic loss was loss after visualization of an embryo but prior to 10 weeks; clinical loss was any loss after visualization of an embryo (with or without fetal cardiac activity detected). Results: In total, 14/1208 (1%) tested positive for +aPL. 786/1208 (65%) women had positive human chorionic gonadotropin during the study period, of which 9/786 (1%) had +aPL. Of the 786 pregnant women, 589 (75%) had live births and 24% had pregnancy losses. Women with +aPL experienced EPL at similar rates as women with –aPL, 44% vs 21% (aRR 2.4, 95% confidence interval (CI) 0.5–10.9). Embryonic loss was more common in women with +aCL IgM (aRR 4.8, 95% CI 1.0–23.0) and in women with two positive aPL. Clinical pregnancy loss was more common in women with positive a-β2-I IgM (50% vs 16.5%, aRR 3.7, 95% CI 1.3–10.8). Conclusion: Positive levels of aPL are rare in women with one or two prior pregnancy losses and are not clearly associated with an increased rate of subsequent loss. Clinical trial registration: The original source study was registered at ClinicalTrials.gov (#NCT00467363).