Gris J C, Quéré I, Monpeyroux F, Mercier E, Ripart-Neveu S, Tailland M L, Hoffet M, Berlan J, Daurès J P, Marès P
Consultation et Laboratoire d'Hématologie, University Hospital, Nîmes, France.
Thromb Haemost. 1999 Jun;81(6):891-9.
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.
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.
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 beta2 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)).
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).
患有家族性血栓形成倾向的女性死产风险增加。我们推测静脉血栓形成的无症状危险因素可能是晚期胎儿丢失的一个危险因素。
我们对至少有一次晚期不明原因胎儿丢失的患者以及妊娠成功的对照女性进行了一项病例对照研究，以调查遗传性血栓形成缺陷、抗磷脂相关标志物以及亚甲基四氢叶酸还原酶（MTHFR）基因C677T突变的患病率。病例组和对照组的配偶也纳入研究。如有胎盘病理检查的书面结论，也进行了回顾。
我们发现21.1%的患者和3.9%的对照者至少有一项静脉血栓形成的阳性生物学危险因素（p < 10⁻⁴）。在女性中，与任何静脉血栓形成阳性生物学危险因素相关的死产粗比值比为5.5，95%置信区间（95%CI）[3.4 - 9.0]。病例组和对照组的配偶之间未发现差异（5.2%和4.7%）。使用条件逻辑回归分析，仍有4个死产的校正危险因素：蛋白S缺乏、抗β2糖蛋白I IgG抗体阳性、抗心磷脂IgG抗体阳性以及因子V Leiden突变。MTHFR基因的C677T突变不是个体危险因素，但纯合基因型与前4个危险因素密切相关（患者中占16.8%，对照者中占0.9%）。在有这些关联的女性中，死产总是发生在孕期未补充叶酸的情况下。与阴性标志物的患者相比，在至少有一项血栓栓塞阳性风险标志物的患者中，尤其是与C677T MTHFR纯合基因型相关的患者，胎盘病理分析的现有结论显示“胎盘母体血管疾病”的比例非常高（p < 10⁻⁴）。
晚期胎儿丢失有时可能是由于母体多因素血栓前状态导致胎盘血栓形成，这种状态将传统的遗传性或获得性血栓形成危险因素与易导致急性轻度高同型半胱氨酸血症的情况（遗传易感性与妊娠晚期叶酸需求增加并存）联系起来。
