Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome. The PREGNANTS study

Objective To assess the risk of obstetric complications in women with primary APS associated with specific antibody profile STUDY DESIGN: The PREGNANTS study is a multicenter, retrospective, cohort study. Diagnosis and classification of APS were based on the 2006 International revised criteria. All women included in the study had at least one clinical criteria for APS, were positive for at least one antiphospholipid antibodies (aCL, ab2GPI and/or LA), and were treated with low-dose aspirin and prophylactic low molecular weight heparin (LMWH) starting from the first trimester. Only singleton pregnancies with primary APS were included. The primary outcome was livebirth, defined as any delivery of a live infant after 22 weeks. The secondary outcomes were preeclampsia with and without severe features, intrauterine growth restriction (IUGR) and stillbirth. We planned to assess the outcomes associated with the various antibody profile (test result for LA, aCL and ab2GPI). RESULTS: There were 750 singleton pregnancies with primary APS in the study cohort. 54 (7.2%) were positive for LA only, 458 (61.0%) for aCL only, 128 (17.1%) for ab2GPI only; while 90 (12.0%) were double positive and LA negative and 20 (2.7%) were triple positive. The incidence of livebirth in each of these categories was 79.6%, 56.3%, 47.7%, 43.3%, and 30.0%, respectively. Compared to women with only one antibody positive test results, women with multiple antibody positive results had a significantly lower livebirth (40.9% vs 56.6%; aOR 0.71, 95% CI 0.51 to 0.90). Also, they were at increased risk of preeclampsia without (54.5% vs 34.8%; aOR 1.56, 95% CI 1.22 to 1.95) and with severe features (22.7% vs 13.8%, aOR 1.66, 95% CI 1.19 to 2.49), IUGR (53.6% vs 40.8%; aOR 2.31, 95% CI 1.17 to 2.61) and stillbirth (36.4% vs 21.7%; aOR 2.67, 95% CI 1.22 to 2.94). In women with only one positive test result, women with ab2GPI positivity present alone had a significantly lower livebirth (47.7% vs 56.3% vs 79.6%; p<0.01), and a significantly higher incidence of preeclampsia without (47.7% vs 34.1% vs 11.1%; p<0.01) and with severe features (17.2% vs 14.4% vs 0%; p=0.02), IUGR (48.4% vs 40.1% vs 25.9%; p<0.01) and stillbirth (29.7% vs 21.2% vs 7.4%; p<0.01) compared to women with aCL and to women with LA present alone, respectively. In the group of women with more than one antibody positivity, triple-positive women had lower livebirth (30% vs 43.3%; aOR 0.69, 95% CI 0.22 to 0.91), and higher incidence of IUGR (70.0% vs 50.0%; aOR 2.40, 95% CI 1.15 to 2.99) compared to double positive and LA negative women. CONCLUSION: In singleton pregnancies with primary APS, aCL is the most common sole antiphospholipid antibody present, but ab2GPI is the one associated with the lowest livebirth rate and highest incidence of preeclampsia, IUGR, and stillbirth, compared to presence of aCL or LA alone. Primary APS women have an increased risk of obstetric complications and lower livebirth when more than one antiphospholipid antibody is present. Despite therapy with low-dose aspirin and prophylactic LMWH, chance of a live-birth neonate is only 30% for triple-positive women