University of Modena and Reggio Emilia, Mother-Infant Dept, Modena, Italy.
Early Hum Dev. 2012 Apr;88(4):251-4. doi: 10.1016/j.earlhumdev.2011.08.013. Epub 2011 Sep 25.
To investigate maternal thrombophilia in cases of Stillbirth (SB), also an uncertain topic because most case series were not characterised for cause/associated conditions of death.
In a consecutive, prospective, multicentre design, maternal DNA was obtained in 171 cases of antenatal SB and 326 controls (uneventful pregnancy at term, 1:2 ratio). Diagnostic work-up of SB included obstetric history, neonatologist inspection, placenta histology, autopsy, microbiology/chromosome evaluations. Results audited in each centre were classified by two of us by using CoDAC. Cases were subdivided into explained SB where a cause of death was identified and although no defined cause was detected in the remnants, 64 cases found conditions associated with placenta-vascular disorders (including preeclampsia, growth restriction and placenta abruption - PVD). In the remnant 79 cases, no cause of death or associated condition was found. Antithrombin activity, Factor V Leiden, G20210A Prothrombin mutation (FII mutation) and acquired thrombophilia were analysed.
Overall, the presence of a thrombophilic defect was significantly more prevalent in mothers with SBs compared to controls. In particular, SB mothers showed an increased risk of carrying Factor II mutation (OR=3.2, 95% CI: 1.3-8.3, p=0.01), namely in unexplained cases. Such mutation was significantly associated also with previous SB (OR=8.9, 95%CI 1.2-70.5). At multiple logistic regression, Factor II mutation was the only significantly associated variable with SB (adj OR=3.8, 95% CI: 1.3-13.5).
These data suggest that Factor II mutation is the only condition specifically associated with unexplained SB and could represents a risk of recurrence. PVD-associated condition is unrelated to thrombophilia.
研究死胎(Stillbirth,SB)病例中的母体血栓形成倾向,这也是一个不确定的问题,因为大多数病例系列并未对死因/相关死亡原因进行特征描述。
在连续的、前瞻性、多中心设计中,从 171 例产前 SB 病例和 326 例对照(足月无并发症妊娠,1:2 比例)中获得了母体 DNA。SB 的诊断工作包括产科史、新生儿科检查、胎盘组织学、尸检、微生物学/染色体评估。在每个中心进行审核的结果由我们中的两位使用 CoDAC 进行分类。病例分为有明确死因的可解释 SB 组和虽然在残留组织中未发现明确病因但存在与胎盘血管疾病相关的条件(包括子痫前期、生长受限和胎盘早剥-胎盘血管疾病,PVD)的 64 例。在剩余的 79 例病例中,未发现死因或相关疾病。分析了抗凝血酶活性、因子 V 莱顿、G20210A 凝血酶原突变(FII 突变)和获得性血栓形成倾向。
总体而言,SB 母亲的血栓形成缺陷发生率明显高于对照组。特别是,SB 母亲携带因子 II 突变的风险增加(OR=3.2,95%CI:1.3-8.3,p=0.01),特别是在不明原因的病例中。这种突变也与之前的 SB 显著相关(OR=8.9,95%CI 1.2-70.5)。在多元逻辑回归中,因子 II 突变是唯一与 SB 显著相关的变量(调整 OR=3.8,95%CI:1.3-13.5)。
这些数据表明,因子 II 突变是唯一与不明原因的 SB 具体相关的情况,可能代表着复发的风险。与血栓形成倾向无关的 PVD 相关疾病。