Epidemiologic Study of Placental Abruption

在正常妊娠中，胎盘在出生后立即分离，而在妊娠合并早剥的情况下，胎盘开始较早分离。早产是导致早产和围产儿死亡的一个重要且有可能预防的原因。大约1%的妊娠合并胎盘早剥，但高达50%的早产可归因于这种情况。值得注意的是，一次妊娠中发生早孕会使随后怀孕的风险增加20-30倍。我们推测，这种非常高的复发风险反映了可能具有遗传易感性的生理异常，并与遗传性血栓形成有关。为了验证这些假设，我们提出了一项关于早孕的病例对照研究。我们将招募在分娩/分娩时发生早孕的妇女作为病例。对照将包括没有发生早孕的妇女，并将根据平等(0，1，2+)和种族/民族(高加索人、非裔美国人、西班牙裔人等)与病例(1：1)进行匹配。从新泽西州圣彼得大学医院(2002年4月至2006年9月)招募235名病例和235名对照人员，为期4.5年，将提供足够的数据来检验这一假设。同意的患者将在分娩后接受采访，以获得详细的社会、行为、生殖和产科病史。将为所有病例和对照妇女的分娩寻找医疗记录。来自病例和对照的胎盘将被检查组织学损害。患者和对照的血液将在面谈后立即采集(出院前)，从中提取DNA并进行基因突变和多态分析，包括因子V莱顿(1691G产生A)、凝血酶原基因(20210G产生A)、677C产生T和1298A产生C多态、5，10-亚甲基四氢叶酸还原酶(MTHFR)、蛋氨酸合成酶还原酶(MTR)66A产生G多态、甜菜碱-同型半胱氨酸甲基转移酶(BHMT)突变和高同型半胱氨酸血症。我们还将测试获得性(也许是暂时性)凝血异常，如狼疮抗凝剂和抗心磷脂抗体，以及其他遗传性血栓形成，包括蛋白C缺乏、活化蛋白C抵抗、凝血因子VIII和XI凝血异常。此外，我们还将评估两个MTHFR、MTRR和BHMT基因异常和叶酸代谢和维生素B12缺乏之间是否存在基因-环境相互作用，从而导致高同型半胱氨酸血症，从而导致胎盘血管病变。这项研究将提供可信的数据，这些数据对于为极高的复发风险建立遗传假说至关重要。它还将为几种遗传性血栓形成和早孕风险之间的关联增加大量新的证据。

In normal pregnancies, placental separation occurs immediately after birth, while in pregnancies complicated by abruption the placenta begins to detach earlier. Abruption is an important and potentially preventable cause of premature delivery and perinatal mortality. Placental abruption complicates approximately 1 percent of pregnancies, but up to 50 percent of premature births are attributable to this condition. Remarkably, the occurrence of abruption in one pregnancy confers a 20-30-fold increased risk in subsequent pregnancies. We hypothesize that this very high recurrence risk reflects physiological abnormalities that may have a genetic predisposition, and are associated with heritable thrombophilias. To test these hypotheses we propose a case-control study of abruption. We will enroll as cases women who develop abruption at the time of labor/delivery. Controls will comprise women who do not develop abruption, and will be matched to cases (1:1) based on parity (0, 1, 2+) and race/ethnicity (Caucasian, African-American, Hispanic, other). A proposed recruitment of 235 cases and 235 controls over 4.5 years from Saint Peter's University Hospital, NJ (April 2002 to September 2006) will provide adequate data to test the hypothesis. Consenting patients will be interviewed following their delivery to obtain detailed social, behavioral, reproductive and obstetric histories. Medical records will be sought for all deliveries of case and control women. Placentas from cases and controls will be examined for histologic lesions. Blood will be obtained from cases and controls immediately following the interview (prior to discharge from the hospital) from which DNA will be extracted and assayed for genetic mutations and polymorphisms, including those for factor V Leiden (1691G yields A), prothrombin gene (20210G yields A), the 677C yields T and 1298A yields C polymorphisms in 5,10- methylenetetrahydrofolate Reductase (MTHFR), methionine synthase reductase (MTRR) 66A yields G polymorphism, betaine-homocysteine methyltransferase (BHMT) mutation and hyperhomocysteinemia. We will also test for acquired (and perhaps transitory) coagulation abnormalities such as lupus anticoagulant and anticardiolipin antibodies, as well as other heritable thrombophilias including protein C deficiency, activated protein C resistance, factors VIII and XI coagulation abnormalities. In addition, we will also evaluate if there exists a gene-environment interaction between the two MTHFR , MTRR, and BHMT gene abnormalities and deficiencies of folate metabolism and vitamin B12, leading to hyperhomocysteinemia, and consequently, placental vasculopathy. This study will provide credible data that is critical to building a genetic hypothesis for the extraordinarily high recurrence risk. It will also add substantial new evidence for associations of several genetic thrombophilias and abruption risk.