Freedman Alexa A, Hogue Carol J, Dudley Donald J, Silver Robert M, Stoll Barbara J, Pinar Halit, Goldenberg Robert L, Drews-Botsch Carolyn
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, United States.
Department of Obstetrics and Gynecology, School of Medicine, University of Virginia, Charlottesville, Virginia, United States.
TH Open. 2017 Jun 28;1(1):e43-e55. doi: 10.1055/s-0037-1603925. eCollection 2017 Jun.
Pregnancy results in alterations in coagulation processes, which may increase the risk of thrombosis. Inherited thrombophilia mutations may further increase this risk, possibly through alterations in the placenta, which may result in pregnancy complications such as poor fetal growth. The purpose of our study is to evaluate the association of fetal growth, approximated by birth weight for gestational age percentile, with genetic markers of thrombophilia and placental characteristics related to vascular malperfusion. We analyzed data from the Stillbirth Collaborative Research Network's population-based case-control study conducted in 2006-2008. Study recruitment occurred in five states: Rhode Island and counties in Massachusetts, Georgia, Texas, and Utah. The analysis was restricted to singleton, nonanomalous live births ≤42 weeks' gestation with a complete placental examination and successful testing for ≥1 thrombophilia marker (858 mothers, 902 infants). Data were weighted to account for oversampling, differential consent, and availability of placental examination. We evaluated five thrombophilia markers: factor V Leiden, factor II prothrombin, methylenetetrahydrofolate reductase A1298C and C677T, and plasminogen activator inhibitor type 1 in both maternal blood and placenta/cord blood. We modeled maternal and fetal thrombophilia markers separately using linear regression. Maternal factor V Leiden mutation was associated with a 13.16-point decrease in adjusted birth weight percentile (95% confidence interval: -25.50, -0.82). Adjustment for placental abnormalities related to vascular malperfusion did not affect the observed association. No other maternal or fetal thrombophilia markers were significantly associated with birth weight percentile. Maternal factor V Leiden may be associated with fetal growth independent of placental characteristics.
怀孕会导致凝血过程发生改变，这可能会增加血栓形成的风险。遗传性血栓形成倾向突变可能会进一步增加这种风险，可能是通过胎盘的改变，这可能导致诸如胎儿生长受限等妊娠并发症。我们研究的目的是评估以出生体重相对于胎龄百分位数来估算的胎儿生长与血栓形成倾向的基因标志物以及与血管灌注不良相关的胎盘特征之间的关联。我们分析了2006 - 2008年进行的死产协作研究网络基于人群的病例对照研究的数据。研究招募在五个州进行：罗德岛州以及马萨诸塞州、佐治亚州、德克萨斯州和犹他州的部分县。分析仅限于单胎、非畸形活产且妊娠≤42周、胎盘检查完整且至少成功检测一种血栓形成倾向标志物的情况（858名母亲，902名婴儿）。数据进行了加权处理，以考虑过采样、不同的同意率以及胎盘检查的可获得性。我们评估了五种血栓形成倾向标志物：母亲血液和胎盘/脐带血中的凝血因子V莱顿突变、凝血因子II凝血酶原、亚甲基四氢叶酸还原酶A1298C和C677T以及纤溶酶原激活物抑制剂1型。我们分别使用线性回归对母亲和胎儿的血栓形成倾向标志物进行建模。母亲的凝血因子V莱顿突变与校正后的出生体重百分位数下降13.16点相关（95%置信区间：-25.50，-0.82）。对与血管灌注不良相关的胎盘异常进行校正后，并未影响观察到的关联。没有其他母亲或胎儿的血栓形成倾向标志物与出生体重百分位数有显著关联。母亲的凝血因子V莱顿突变可能与胎儿生长有关，且独立于胎盘特征。
