Case-control study of the frequency of thrombophilic disorders in couples with late foetal loss and no thrombotic antecedent - The nimes obstetricians and haematologists study (NOHA)

Background: Women with familial thrombophilia have an increased risk of sti ll birth. We postulated that the presence of asymptomatic risk factors for venous thrombosis might be a risk factor for late foetal loss. Methods: We performed a case-control study on the prevalence of heritable thrombophilic defects, of antiphospholipid-related markers and of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with at le ast one episode of late unexplained foetal loss and in control women with s uccessful pregnancies. Partners of cases and controls were also studied. Wr itten conclusions of the pathological examination of the placentas, when av ailable, were also reviewed. Results: We found at least one positive biolog ical risk factor for venous thrombosis in 21.1% of the patients and in 3.9% of the controls (p <10(-4). In women, the crude odds ratio for still birth associated with any positive biological risk factor for venous thrombosis was 5.5, 95% confidence interval (Cl-95%) [3.4-9.0]. No difference was foun d between partners of cases and controls (5.2% and 4.7%). Using conditional logistic regression analysis, 4 adjusted risk factors for still birth rema ined: protein S deficiency, positive anti beta(2) glycoprotein I IgG antibo dies, positive anticardiolipin Ige antibodies and the factor V Leiden mutat ion. The C677T mutation in the MTHFR gene was not an individual risk factor but an homozygous genotype was strongly associated with the former 4 risk factors (16.8% of patients vs. 0.9% of controls). In women with such associ ations, still births always occurred in absence of folic acid supplementati on during pregnancy. Available conclusions of pathological analysis of plac entas were found to have a very high proportion of "maternal vascular disea se of the placenta" in patients with at least one positive risk marker for thromboembolism, specially in case of association with the C677T MTHFR homo zygous genotype, compared to patients with negative markers (p <10(-4)). Co nclusions: Late foetal loss, through placenta thrombosis, may sometimes be the consequence of a maternal multifactorial prothrombotic state associatin g traditional heritable or acquired thrombosis risk factors to conditions p redisposing to an acute mild hyperhomocysteinaemia (coexistence of a geneti c predisposition with late pregnancy-related increased folate needs).