The Association Between Anti-beta2 Glycoprotein 1 Antibodies and Adverse Pregnancy Outcomes.

The Sapporo criteria include anti-β2 glycoprotein1 (anti-B2GP1) antibodies among antiphospholipid antibodies used to diagnose the antiphospholipid syndrome (APS). Although pre-eclampsia, intra-uterine growth restriction (IUGR), late fetal loss and placental abruption, collectively termed “placenta mediated complications”, are recognized as clinical criteria for the APS, strong evidence to support their association with anti-B2GP1 antibodies is lacking.

This study aims to assess the association between anti-B2GP1 antibodies and placenta mediated complications.

We performed a nested case-control study from a prospective cohort of 7000 mother baby pairs whereby women and their fetuses were recruited between 12-20 weeks gestation. Five hundred cases were randomly selected amongst women who experienced one of the following adjudicated adverse pregnancy outcomes: pre-eclampsia (BP ≥140/90 with proteinuria), placental abruption (antepartum bleeding with objective evidence of placental thrombus), late pregnancy loss (≥ 12 weeks gestation) and IUGR (birth weight less than the 10th percentile of normal population). Random selection of 500 controls was performed amongst women who did not experience the above mentioned adverse pregnancy outcomes. Stored blood samples were analyzed for the presence of anti-B2GP1 IgG and IgM antibodies by enzyme-linked immunosorbent assay. Titers ≥ than 20 G or M units were considered positive. This study has an 80% power to detect an odds ratio of 2.25 at the 5% level of significance based on an estimated 4 % prevalence of anti-B2GP1 IgG and/or IgM antibodies in titers ≥ 20 G/M units in our cohort of pregnant women.

Anti-B2GP1 IgG and/or IgM antibodies in titers ≥ 20 G/M units were present in 24/497 (4.8%) controls and 33/503 (6.6%) cases. The presence of anti-B2GP1 IgG and/or IgM in titers ' 20 G/M units was not significantly associated with a composite outcome of pre-eclampsia, IUGR, late fetal loss and placental abruption (OR 1.38; 95%CI 0.8-2.37 p=0.18). This combination of antibodies and titers only demonstrated a weak association with IUGR (OR 1.86; 95%CI 1.09-3.18 p=0.02). The presence of anti-B2GP1 IgG and/or IgM antibodies in titers ≥ 40 G/M units also failed to show an association with a composite outcome of pre-eclampsia, IUGR, late fetal loss and placental abruption (OR 2.65; 95%CI 0.7-10.04 p=0.15). However, stronger associations were observed with placental abruption (OR 4.87; 95%CI 1.02-23.25 p=0.047) and IUGR (OR 3.53; 95%CI 1.03-12.15 p=0.045).

The presence of anti-B2GP1 IgG and/or IgM antibodies in titers 20 ≥ G/M units during pregnancy is only associated with an increased risk of IUGR. Anti-B2GP1 antibodies in titers ' 40 G/M units, as suggested in the Sapporo diagnostic criteria for the APS, are associated with IUGR and placental abruption and possibly other placenta mediated complications. Larger adequately powered studies will be required to provide definitive answers.

No relevant conflicts of interest to declare.