Lupus Anticoagulant is Main Predictor of Poor Pregnancy Outcomes in SLE

Systemic lupus erythematosus (SLE) predominantly affects women of childbearing age. Compared with healthy pregnant women, pregnancy in women with SLE is associated with a higher risk of complications, including  a 2- to 4-fold increased rate of obstetric complications including preterm labor, unplanned cesarean delivery, fetal growth restriction, preeclampsia, and eclampsia.¹  

Several predictors of adverse pregnancy outcomes (APOs) among women with SLE have been identified, including active SLE disease, use of antihypertensive agents, history of prior lupus nephritis, thrombocytopenia, and lupus anticoagulant (LAC). ^2,3 The antiphospholipid syndrome (APS) is characterized by the occurrence of venous or arterial thrombosis during pregnancy, in the presence of laboratory evidence of antiphospholipid antibodies (aPL). APLs include LAC, immunoglobulin G (IgG)/IgM anticardiolipin ( aCL] antibodies, and IgG/ IgM anti-beta2-glycoprotein (aβ2GPI).² 

To confirm LAC as the main predictor of APO in aPL-positive patients, Yelnik and colleagues conducted a large multicenter, observational study of pregnancy outcomes (the PROMISSE Study: Predictors of Pregnancy Outcome Biomarkers in Antiphospholipid Antibody Syndrome and Systemic Lupus Erythematosus). A total of 44 aPL-positive patients were followed monthly until delivery, and aPL was tested at the first, second, and third trimesters of pregnancy, as well as at 12 weeks postpartum.⁴

Of the 44 aPL-positive patients, 13 were found to have APOs, defined as  fetal death after 12 weeks of gestation, neonatal death, delivery prior to 36 weeks of gestation due to pre-eclampsia or placental insufficiency, or small-for-gestational age (birth weight less than the fifth percentile).  LAC was found in 69% of the patients with APOs, compared to 27% of patients without APOs.  

The investigators found no statistically significant association between aCL or anti-β2 glycoprotein I antibodies (aβ2GPI) and APOs.  There was a high association between APOs and definitive antiphospholipid syndrome in aPL-positive patients, as indicated by a history of thrombosis or pregnancy morbidity.

The authors conclude that LAC, and not aCL or aβ2GPI, was predictive of APOs after 12 weeks of pregnancy.

Summary and Clinical Applicability

Pregnancy in women with SLE carries a higher maternal and fetal risk compared with pregnancy in healthy women.  The presence of LAC appears to be most predictive of poor pregnancy outcomes; therefore, women who test positive for poor prognostic indicators may require more frequent maternal and fetal monitoring.⁵  A multidisciplinary approach with close medical, obstetric, and neonatal assessment is necessary to optimize both maternal and fetal outcomes.

References

1.  Clowse ME, Magder LS, Witter F, et al. The impact of increased lupus activity on obstetric outcomes. Arthritis Rheum. 2005;52:514-521.

2. Buyon JP, Kim MY, Guerra MM, et al. Predictors of pregnancy outcomes in patients with lupus: a cohort study. Ann Intern Med. 2015;163:153-163.

3. Borella E, Lojacono A, Gatto M, et al. Predictors of maternal and fetal complications in SLE patients: a prospective study. Immunol Res. 2014;60:170-176.

4. Yelnik CM, Laskin CA, Porter TF, et al. Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL-positive patients: validation of PROMISSE study results. Lupus Sci Med. 2016 Jan 12;3(1):e000131. doi: 10.1136/lupus-2015-000131. eCollection 2016.

5. Yasmeen S, Wilkins EE, Field NT, et al. Pregnancy outcomes in women with systemic lupus erythematosus. J Matern Fetal Med. 2001;10:91-96.