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.
| Ananth, Cande V; Nath, Carl A; Philipp, Claire et al. (2010) The Normal anticoagulant system and risk of placental abruption: protein C, protein S and resistance to activated protein C. J Matern Fetal Neonatal Med 23:1377-83 |
| Elsasser, Denise A; Ananth, Cande V; Prasad, Vinay et al. (2010) Diagnosis of placental abruption: relationship between clinical and histopathological findings. Eur J Obstet Gynecol Reprod Biol 148:125-30 |
| Peltier, Morgan R; Ananth, Cande V; Oyelese, Yinka et al. (2009) Thromboembolic diseases in families of women with placental abruption. Epidemiology 20:733-7 |
| Kinzler, Wendy L; Prasad, Vinay; Ananth, Cande V et al. (2009) The effect of maternal thrombophilia on placental abruption: Histologic correlates. J Matern Fetal Neonatal Med 22:243-8 |
| Nath, Carl A; Ananth, Cande V; DeMarco, Celeste et al. (2008) Low birthweight in relation to placental abruption and maternal thrombophilia status. Am J Obstet Gynecol 198:293.e1-5 |
| Ananth, Cande V; Peltier, Morgan R; Moore, Dirk F et al. (2008) Reduced folate carrier 80A-->G polymorphism, plasma folate, and risk of placental abruption. Hum Genet 124:137-45 |
| Getahun, Darios; Nath, Carl; Ananth, Cande V et al. (2008) Gestational diabetes in the United States: temporal trends 1989 through 2004. Am J Obstet Gynecol 198:525.e1-5 |
| Ananth, Cande V; Peltier, Morgan R; Chavez, Martin R et al. (2007) Recurrence of ischemic placental disease. Obstet Gynecol 110:128-33 |
| Joseph, K S; Huang, Ling; Liu, Shiliang et al. (2007) Reconciling the high rates of preterm and postterm birth in the United States. Obstet Gynecol 109:813-22 |
| Chavez, Martin R; Ananth, Cande V; Smulian, John C et al. (2007) Fetal transcerebellar diameter measurement for prediction of gestational age at the extremes of fetal growth. J Ultrasound Med 26:1167-71;quiz 1173-4 |
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