Dudding Tracy E, Attia John
Hunter Genetics, PO Box 84 Waratah, 2289, NSW, Australia.
Thromb Haemost. 2004 Apr;91(4):700-11. doi: 10.1160/TH03-10-0637.
The conclusions of studies to date which evaluate a possible association between factor V Leiden and adverse pregnancy outcome have been conflicting. This study was undertaken to further investigate this association. Our objective was to evaluate the association between adverse pregnancy outcomes and maternal factor V Leiden genotype by meta-analysis. Inclusion criteria were: (a) cohort or case control design; (b) outcomes clearly defined as one of the following: first or second/ third trimester miscarriage or intrauterine death, preeclampsia, fetal growth retardation, or placental abruption; (c) both the case and control mothers tested for the factor V Leiden mutation; (d) sufficient data for calculation of an odds ratio. Both fixed and random effect models were used to pool results and heterogeneity and publication bias were checked. For first trimester fetal loss, the pooled odds ratio was heterogeneous (p=0.06) and no dose-response curve could be found. For second/third trimester fetal loss, there was a consistent and graded increase in risk: the odds ratio was 2.4 (95% CI 1.1-5.2) for isolated (non-recurrent) third trimester fetal loss, rising to 10.7 (95% CI 4.0-28.5) for those with 2 or more second/third trimester fetal losses. Factor V Leiden is associated with a 2.9 fold (95% CI 2.0-4.3) increased risk of severe preeclampsia, and a 4.8 fold (95% CI 2.4-9.4) increased risk of fetal growth retardation. These results support factor V Leiden testing for women with recurrent fetal loss in the second/third trimester. Women with only 1 event may also warrant testing if the fetal loss occurred in the third trimester. Conversely, in those women known to have the factor V Leiden mutation, monitoring for adverse pregnancy outcomes is warranted; whether this means increased vigilance or anti-coagulant prophylaxis is still contentious.
迄今为止，评估凝血因子V莱顿突变与不良妊娠结局之间可能存在关联的研究结论一直相互矛盾。开展本研究是为了进一步探究这种关联。我们的目标是通过荟萃分析评估不良妊娠结局与母亲凝血因子V莱顿基因型之间的关联。纳入标准为：(a)队列研究或病例对照研究设计；(b)结局明确界定为以下之一：孕早期或孕中/晚期流产或宫内死亡、子痫前期、胎儿生长受限或胎盘早剥；(c)病例组和对照组母亲均检测凝血因子V莱顿突变；(d)有足够数据用于计算比值比。采用固定效应模型和随机效应模型汇总结果，并检查异质性和发表偏倚。对于孕早期胎儿丢失，汇总的比值比具有异质性(p = 0.06)，且未发现剂量反应曲线。对于孕中/晚期胎儿丢失，风险呈一致且分级增加：孤立性（非复发性）孕晚期胎儿丢失的比值比为2.4(95%可信区间1.1 - 5.2)，有2次或更多次孕中/晚期胎儿丢失者的比值比升至10.7(95%可信区间4.0 - 28.5)。凝血因子V莱顿突变与重度子痫前期风险增加2.9倍(95%可信区间2.0 - 4.3)以及胎儿生长受限风险增加4.8倍(95%可信区间2.4 - 9.4)相关。这些结果支持对孕中/晚期复发性胎儿丢失妇女进行凝血因子V莱顿突变检测。如果胎儿丢失发生在孕晚期，仅有1次事件的妇女也可能需要检测。相反，对于已知有凝血因子V莱顿突变的妇女，有必要监测不良妊娠结局；这是否意味着提高警惕或进行抗凝预防仍存在争议。
