Low expression of soluble human leukocyte antigen G in early gestation and subsequent placenta-mediated complications of pregnancy.

AIM: Abnormal placentation is a common pathogenic mechanism of many placenta-mediated complications of late pregnancy, including pre-eclampsia, fetal growth restriction, stillbirth, and placental abruption. During successful placentation, the trophoblast (which is a semi-allograft) is not rejected by decidual immune cells because of maternal immune tolerance, mainly induced by human leukocyte antigen G (HLA-G). Deficient HLA-G expression seems to be associated with the development of complications of pregnancy. The aim of this study was to determine whether low soluble HLA-G (sHLA-G) levels in maternal blood at the beginning of pregnancy may be associated with subsequent placenta-mediated complications. METHODS: For this retrospective case-control study, 117 cases of placenta-mediated complications of pregnancy and 234 controls with uneventful pregnancy were selected. Plasma sHLA-G levels were measured at 11-13 weeks' gestation by the enzyme-linked immunosorbent assay method in blood samples previously obtained at first-trimester prenatal screening for chromosomal fetal abnormalities. RESULTS: Women who subsequently developed placenta-mediated complications had significantly lower sHLA-G levels at the beginning of pregnancy (median, 43.08 IU/mL) than controls (median, 49.10 IU/mL; P = 0.008). An sHLA-G level lower than 43.50 IU/mL at the end of the first trimester was associated with a twofold increased risk of developing a pregnancy complication (odds ratio, 1.82; 95% confidence interval, 1.22-2.73). The strongest association, although only moderately strong, was observed with severe pre-eclampsia (odds ratio, 2.66; 95% confidence interval, 1.08-6.56). CONCLUSION: Placenta-mediated complications of pregnancy may be associated with low sHLA-G levels in the first trimester, suggesting a potential role of sHLA-G in the early stages of placentation.

Biochemistry of HELLP syndrome.

The HELLP syndrome is a serious complication of pregnancy characterized by hemolysis (H), elevated liver (EL) enzymes, and low platelet (LP) count that occurs in 0.2-0.6% of all pregnancies and in 10-20% of cases with severe preeclampsia and frequently leads to adverse maternal and perinatal outcome. The exact pathobiology of HELLP syndrome has not been clearly defined. As it is considered a form or a complication of severe preeclampsia, it likely has its origin in aberrant placental development and function resulting in ischemia-producing oxidative stress. However, there is still a debate on whether HELLP must be considered a severe form of preeclampsia or a separate disease entity. It can be described as a placenta-induced disease, as is preeclampsia itself, but with a more acute and predominant inflammatory process typically targeting the liver and with a greater activation of the coagulation system. This occurs during a disordered immunologic process and may be due to a genetic predisposition. In this review, we discuss the main biochemical characteristics of HELLP syndrome, particularly focusing on molecular aspects of placental involvement and maternal systemic responses.

Anti-prothrombin antibodies are associated with adverse pregnancy outcome.

PROBLEM: Women with antiphospholipid antibodies (aPL) such as lupus anticoagulant, anticardiolipin antibodies, and anti-ß(2) glycoprotein-1 antibodies are at high risk of late pregnancy complications, such as severe pre-eclampsia, placental insufficiency, and fetal loss. It has been observed that aPL consists of a heterogeneous group of antibodies targeting several phospholipid-binding plasma proteins, including also anti-prothrombin (anti-PT), anti-protein S (anti-PS), and anti-protein C (anti-PC) antibodies. Their potential role in late pregnancy complications is not known. The aim of this work was to investigate the association between those autoantibodies and histories for adverse pregnancy outcome. METHOD OF STUDY: Anti-PT, anti-PS, and anti-PC antibodies were evaluated in 163 patients with previous severe pre-eclampsia, fetal death, and/or placental abruption and in as many women with previous uneventful pregnancies, negative for aPL. RESULTS: The prevalence of anti-PT antibodies was higher in cases than in controls (OR, 95% CI: 10.92, 4.52-26.38). The highest prevalence was observed in subjects with fetal death. CONCLUSION: Anti-PT antibodies appear to be associated with adverse pregnancy outcome, irrespectively of aPL.

Coagulation disorders in pregnancy: acquired and inherited thrombophilias.

Both acquired and inherited thrombophilias are associated with an increased risk of pregnancy-related venous thromboembolism (VTE) as well as with adverse pregnancy outcome. However, the extension of attributable risk for each thrombophilia and outcome is still a question of debate. Thrombophilias have been investigated in connection with VTE and pregnancy complications such as: recurrent and nonrecurrent early pregnancy loss, late fetal death, placental abruption, fetal growth restriction, and preeclampsia. This review discusses the evidence of association between thrombophilias and pregnancy outcome together with issues as to clinical management and preventive strategies.

Response to activated protein C decreases throughout pregnancy.

BACKGROUND: The possibility that changes in activated protein C anticoagulant activity may contribute to the hemostatic changes associated with pregnancy has been previously investigated, but the results of the studies are still controversial. METHODS: Nine hundred and sixty-one healthy nonpregnant and 711 normal pregnant women who were noncarriers of factor V Leiden at different weeks' gestation were included in a cross-sectional trial. Moreover, the APC ratio was repeatedly measured in 45 women throughout pregnancy. The activated protein C ratio was tested using the modified activated partial thromboplastin time-based assay. RESULTS: A significantly lower APC ratio was observed at 20-28 and 32-38 (p = 0.0001) weeks' gestation compared with nonpregnant values. The decrease in the APC ratio throughout pregnancy showed a significant trend (p = 0.014). In none of the subjects did the APC ratio reach the cut-off values for APC resistance. CONCLUSIONS: Our data confirm a reduction in the APC ratio throughout pregnancy. In our series, an APC ratio of less than 2.0 according to the cut-off point of our laboratory).