Pregnancy Complications Avoidable in SLE and APS

November 4, 2013

ACR2013: Biomarkers can predict pregnancy complications in lupus and antiphospholipid syndrome patients, and with some difficulty they also succeed at IVF.

In-vitro fertilization can succeed for women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS), but may increase the risk of flares or blood clots if they do not adhere to treatment.regimens, according to one of several studies on pregnancy problems among women with these conditions reported at the 2013 annual meeting of the American College of Rheumatology.

The retrospective study of 34 women with SLE and/or APS who underwent at least one cycle of IVF in France shows 92% had successful pregnancies. However, 10% had hormone-related flares or thromboses, often due to poor treatment adherence, researchers said.

Among a total of 82 cycles of IVF between 2003 and 2012 (at a mean age 34.7), one case of SLE and one case of primary APS were diagnosed during IVF. Inability to conceive was due to mixed or male-related causes in 58% of cases. Of the 24 resulting pregnancies, there were 22 live births, one miscarriage and one medical termination (for trisomy 13). Eight women became pregnant spontaneously during followup.

Eight IVF cycles resulted in complications: One SLE flare in a woman undiagnosed prior to IVF; two flares and two thromboses attributed to poor adherence or the absence of treatment. New IVF protocols using GnRH antagonists may further decrease the risk of complications, the researchers conclude.

Two other reports at the ACR meeting presented biomarkers that may prove useful in predicting pregnancy complications among women with these conditions. Spanish researchers say that three novel markers -- mean pulsatility index in the uterine arteries (mPI-UtA), sFlt-1/PlGF ratio, and endoglin levels -- may not only help predict preeclampsia (PE) but may also differentiate it from disease activity.

These researchers studied 34 patients with SLE and/or APS seen in the high-risk pregnancy unit at the Hospital Universitario in Madrid during pregnancy, at delivery, and postpartum (five had not delivered when the study was written). Twenty-nine of the women had SLE (four of with secondary APS), three had primary APS, and two had antiphospholipid antibodies without clinical criteria for APS.

Data analysis included demographics, cardiovascular risk factors such as high blood pressure (HBP) and smoking, obstetrical history, last SLE flare, as well as previous and current treatments. The women had blood tests, including complement and a-dsDNA antibody levels, along with ELISA levels of sFlt-1, PlGF, and maternal serum endoglin.

Among women with no complications, biomarker values were within normal limits during pregnancy. In contrast, among SLE patients with elevated levels of these markers, 10 had early pregnancy loss (<12 wks), one had mild PE and intrauterine growth restriction (IUGR) after 32 weeks, one patient with SLE developed HBP before delivery, another had premature rupture of membranes at term, and 3 SLE patients had a preterm delivery at 28, 32 and 36 weeks, respectively.

“Elevated levels of these markers are early predictors of preeclampsia in both healthy pregnancies and in lupus patients and should be assessed,” concluded lead author Esther Rodriguez-Almaraz MD. “Elevated MPI in the maternal umbilical artery is another marker for preeclampsia in lupus and also should be assessed.”

A different study of pregnant women with SLE/APS suggests that anti-prothrombin antibodies (aPT) may predict second- and third-trimester complications, particularly recurrent early miscarriage.

In this study, researchers from Pisa, Italy, collected serum from 60 patients (52 with SLE, 18 with APS), among whom  76 pregnancies had lasted more than 10 weeks. The women were tested in the first trimester for aPT (n=16) anticardiolipin antibodies (aCL, n=25), lupus anticoagulant (LA, n=17), and anti-B2GPI antibodies (n=6) and occurrences recorded during pregnancy for PE, eclampsia, preterm delivery, IUGR, and intrauterine fetal death.

Obstetric complications turned out to be strongly associated with aPTs -- with late obstetric complications significantly linked to aPT as well as to positive aCL, anti-B2GPI and/or LA.

“These include intrauterine fetal death, eclampsia, preeclampsia, and intrauterine fetal growth restriction,” commented lead author Tiana Chairi MD. “Our data are unique because we added anti-phosphoglycerin to the assay and, if confirmed, it could be an additional tool to assess pregnancy outcomes.”