Our aim was to elucidate prospectively whether beta 2-glycoprotein I-dependent anticardiolipin antibodies (beta 2GPI-dependent aCL; autoimmune type) can predict an adverse pregnancy outcome in healthy pregnant women and whether beta 2GPI-dependent aCL should be applied for routine screening of the pregnant population. A prospective cohort study was performed on 1600 healthy pregnant women from whom blood samples were obtained at about week 10 of gestation. We used a modified enzyme-linked immunosorbent assay with which to divide the subjects into three study groups: beta 2GPI-independent aCL positive, beta 2GPI-dependent aCL positive and aCL negative. Their subsequent pregnancy outcomes were ascertained and the three study groups were compared statistically for the following poor pregnancy outcomes: intrauterine fetal death (IUFD) after 12 gestational weeks, intrauterine growth retardation (IUGR) and pre-eclampsia. The total number of patients eligible for this study was 1125. The prevalence of beta 2GPI-dependent aCL positive was eight (0.7%), beta 2GPI-independent aCL positive was 17 (1.5%) and aCL negative was 1100 (97.8%). Beta 2-GPI-dependent aCL positivity was significantly associated with poor pregnancy outcome: 25.0% of beta 2GPI-dependent aCL-positive and 0.5% of aCL-negative patients experienced IUFD [relative risk 52.4; 95% confidence interval (CI), 12.7-216.3; P = 0.0009]; 37.5% of beta 2GPI-dependent aCL-positive and 2.9% of aCL-negative patients experienced IUGR (relative risk 18.4; 95% CI, 4.6-74.0; P = 0.001); and 50.0% of beta 2GPI-dependent aCL-positive and 4.0% aCL-negative patients experienced pre-eclampsia (relative risk 22.1; 95% CI, 5.7-85.7; P = 0.0002). In contrast, beta 2GPI-independent aCL did not show any significant association with such adverse pregnancy outcomes. beta 2GPI-dependent aCL are significantly highly associated with adverse pregnancy outcomes in healthy pregnant women and can be used for prediction purposes, whereas beta 2GPI-independent aCL cannot. Our results suggest that routine screening for beta 2GPI-dependent aCL should be introduced for the general pregnant population.

Anticardiolipin antibodies (aCL) were found to recognize beta 2glycoprotein I (beta 2GPI) structure altered by its interaction with an oxygen modified solid phase surface by gamma-ray radiation. Lupus anticoagulant (LA) has been reported to comprise anti prothrombin antibodies, anti factor X antibodies and anti beta 2GPI antibodies. The present study focuses on the possible association between antibodies against the altered beta 2GPI structure (anti beta 2GPI antibodies) and LA in patients with recurrent pregnancy loss. Moreover, the clinical significance of both subgroups of so-called antiphospholipid antibodies were investigated to cast light on the controversy of whether aCL and LA are risk factors for pregnancy losses. One hundred and ninety five women with a history of two or more unexplained consecutive miscarriages and 100 control pregnant women were tested. Lupus anticoagulant was detected by the dilute phospholipid activated partial thromboplastin time. Anti beta 2GPI antibodies were measured by the ELISA method using commercially oxygenated microtiter plates. Twenty two (11.3%) and 19 (9.7%) of the 195 recurrent aborters were, respectively, positive for LA and anti beta 2GPI antibodies. Seven (3.6%) of the aborters had both of them. None of the control pregnant women had LA. Three of the control pregnant women had anti beta 2GPI antibodies. Nine (40.9%) of 22 aborters with positive-LA had a history of miscarriages in the second trimester as compared to 8 (4.6%) of 173 aborters with negative-LA. (P = 0.000007, Odds ratio = 14.3). None of the 12 aborters with anti beta 2GPI antibodies but no LA had a history of second trimester-fetal loss. These results support the hypothesis that aCL and LA define two distinct but partly related populations and that aCL include two subtypes of antibodies, with and without LA activity. LA and anti beta 2GPI antibodies appear to be associated with pregnancy loss, with LA being linked not only to abortions in the first trimester but also to miscarriages in the second trimester.

Allergic granulomatosis and angiitis was first reported as a disease entity separate from polyarteritis nodosa in 1951 by Churg and Strauss. It is characterized by bronchial asthma, eosinophilia, and vasculitis and is especially rare in women of reproductive age, though, when present, may be associated with fetal mortality in pregnancy. We report a successful pregnancy in a patient who previously experienced intrauterine fetal death at 30 weeks of gestation.

The live birth rate in patients strongly positive for aPL is lower than that in patients with moderate aPL production even if treatment is performed during pregnancy. However, ASA is useful to treat cases with moderate aPL so that distinction of the two groups is warranted.

A 29-year-old woman experienced unexplained intrauterine fetal death (IUFD) three times, at 16, 27 and 27 gestational weeks. She was found to be protein C-deficient and the existence of infarction in the placenta was suspected at 20 weeks' gestation during her fourth pregnancy. Both heparin and antithrombin III were administered until delivery of a small-for-dates but live baby. Massive infarction in the placenta was evident at term. Anticoagulation with heparin is a useful treatment approach for cases of recurrent IUFD with protein C deficiency.