Epidemiologic Study of Placental Abruption

在正常妊娠中，胎盘分离在出生后立即发生，而在妊娠并发症中，胎盘更早开始分离。 早产是早产和围产期死亡的一个重要和潜在的可预防的原因。 胎盘早剥使大约1%的怀孕复杂化，但高达50%的早产可归因于这种情况。 值得注意的是，在一次怀孕中发生流产会使随后怀孕的风险增加20 - 30倍。 我们假设这种非常高的复发风险反映了可能具有遗传倾向的生理异常，并与遗传性血栓形成相关。 为了验证这些假设，我们提出了一个病例对照研究的预防。 我们将在分娩/分娩时出现便秘的女性作为病例入组。 对照组将包括未发生流产的女性，并将根据产次（0、1、2+）和人种/种族（高加索人、非洲裔美国人、西班牙裔、其他）与病例（1：1）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例病例和235例对照，为期4.5年，将提供足够的数据来检验假设。 分娩后将对分娩患者进行访谈，以获得详细的社会、行为、生殖和产科史。 病例组和对照组妇女的所有分娩均需获得医疗记录。 将检查病例和对照胎盘的组织学病变。采访后将立即从病例和对照组中获取血液（出院前）从中提取DNA并分析基因突变和多态性，包括因子V Leiden（1691 G产生A），凝血酶原基因（20210 G产生A），677 C产生T和1298 A产生C多态性，5，10-亚甲基四氢叶酸还原酶（MTHFR），甲硫氨酸合成酶还原酶（MTRR）66 A产生G多态性，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。 我们还将检测获得性（可能是暂时性）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倾向，包括蛋白C缺乏症、活化蛋白C抵抗、因子VIII和Xi凝血异常。 此外，我们还将评估是否存在两个MTHFR，MTRR和BHMT基因异常和叶酸代谢和维生素B12缺乏之间的基因-环境相互作用，导致高同型半胱氨酸血症，从而导致胎盘血管病变。这项研究将提供可靠的数据，这对建立一个非常高的复发风险的遗传假说至关重要。 它也将为几种遗传性血栓形成倾向和预防风险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.