Summary
Background: Women with familial thrombophilia have an increased risk of still 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 least one episode of late unexplained foetal
loss and in control women with successful pregnancies. Partners of cases and controls
were also studied. Written conclusions of the pathological examination of the placentas,
when available, were also reviewed. Results: We found at least one positive biological 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 (95%CI) [3.4-9.0]. No difference was found between partners of cases and controls (5.2%
and 4.7%). Using conditional logistic regression analysis, 4 adjusted risk factors
for still birth remained: protein S deficiency, positive anti β2 glycoprotein I IgG antibodies, positive anticardiolipin IgG antibodies and the factor
V Leiden mutation. 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 associations, still births always occurred
in absence of folic acid supplementation during pregnancy. Available conclusions of
pathological analysis of placentas were found to have a very high proportion of “maternal
vascular disease of the placenta” in patients with at least one positive risk marker
for thromboembolism, specially in case of association with the C677T MTHFR homozygous
genotype, compared to patients with negative markers (p <10–4). Conclusions: Late foetal loss, through placenta thrombosis, may sometimes be the consequence of
a maternal multifactorial prothrombotic state associating traditional heritable or
acquired thrombosis risk factors to conditions predisposing to an acute mild hyperhomocysteinaemia
(coexistence of a genetic predisposition with late pregnancy-related increased folate
needs).
