Is There Evidence to Support Serial aPL Testing in Pregnant Women?

Pregnancy outcomes were not associated with changes in antiphosphlipid (aPL) levels during pregnancy, according to data derived from a prospective, observational study of pregnancies of women, including a subset of those diagnosed with systemic lupus erythematosus (SLE).¹  Prior to this analysis, it was unclear whether repeat aPL testing throughout pregnancy were predictive of pregnancy complications.  

Cecile Yelnik, MD, of the University of Utah, Salt Lake City Utah, and colleagues analyzed data derived from the phase 3 trial entitled Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus and Antiphospholipid Syndrome (PROMISSE, ClinicalTrials.gov Identifier NCT00198068).  The PROMISSE study was an observational study of pregnant patients with SLE, concurrent SLE and aPL, or aPL alone conducted at 9 different clinical centers.

The PROMISSE study defined aPL positivity based on modifications to the revised Sapporo criteria: presence of anticardiolipin (aCL) and/or anti-β₂ glycoprotein I (anti-β₂GPI)  titers ≥40 IgG phospholipid (GPL) or IgM phospholipid (MPL) units and/or lupus anticoagulant (LAC)-positivity and aPL persistent positivity on repeat measurement at least 6 weeks later. 

A total of 152 women with singleton pregnancies were identified from the PROMISSE trial as being aPL-positive, of which 87 (57%) had clinical diagnoses of antiphospholipid syndrome (APS) and 54 (35%) carried met the American College of Rheumatology criteria for SLE.   

Baseline screening history and physical examinations, along with blood draws, were done in all women before 18 weeks of gestation.  After that, monthly follow-ups were conducted to assess medical and obstetric events. 

During the  course of pregnancy, adverse pregnancy outcomes including fetal death after 12 weeks gestation, neonatal death before hospital discharge, preterm delivery before 36 weeks secondary to gestational hypertension, preeclampsia, or placental insufficiency, or being small for gestational age.  

Serum aPL levels were repeated at 20-23 weeks gestation, 32-35 weeks gestation, and finally at 3 months postpartum.

Upon analysis, researchers found that as pregnancies progressed, serum titers of aCL and anti-β₂GPI decreased, but with small changes in magnitude, with 85% of patients retaining designation of high-positivity during the third trimester.  These titers appeared to return to baseline levels at 3 months postpartum. 

Levels of LAC similarly decreased during gestation, but  74% of patients remained LAC-positive in the second trimester and 50% in the third trimester, with levels returning to baseline 3 months postpartum. 

Adverse pregnancy outcomes were noted in 46 patients (30%). Of these patients, 67% had positive titers of IgG aCL ≥40 GPL units, 45% positive for anti-β₂GPI ≥40 GPL units, and 80% with LAC positivity. 

In women who converted from LAC negative to positive during their second trimester,  no significant increase in the frequency of adverse pregnancy outcomes were found compared to those who remained LAC negative ( P = .33). This was also true in women who converted from negative to positive in aCL or anti-β₂GPI  IgG status.

Summary and Clinical Applicability

“Although we observed modest decreases in levels of all aPL through patients’ pregnancies, these changes were not associated with adverse pregnancy outcomes. Conversely, among patients who were negative for a specific aPL in the first trimester, titers did not increase through pregnancy, and conversion from negative to positive  was not associated with adverse pregnancy outcomes,” the authors summarized.

“These findings provide evidence that it is not necessary to repeat aPL testing throughout pregnancy,” they concluded.

Limitations and Disclosures

• Patients included in PROMISSE were all enrolled at large tertiary centers which may have self-selected for a higher risk patient population

Reference

Yelnik CM, Porter TF, Branch DW, et al. Brief Report: Changes in Antiphospholipid Antibody Titers During Pregnancy: Effects on Pregnancy Outcomes. Arthritis Rheumatol. 2016;68(8):1964-9.

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