Evidence of placental abruption as a chronic process: Associations with vaginal bleeding early in pregnancy and placental lesions Cande V. Ananth a, * , Yinka Oyelese b , Vinay Prasad c , Darios Getahun a , John C. Smulian b a Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School/Robert Wood Johnson University Hospital, NJ, United States b Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School/Robert Wood Johnson University Hospital, NJ, United States c Department of Pathology and Laboratory Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School/Robert Wood Johnson University Hospital, NJ, United States Received 11 October 2005; received in revised form 11 January 2006; accepted 12 January 2006 Abstract Background: Clinicians widely regard placental abruption as an acute event, though accumulating data point towards abruption being the end-result of chronic processes early in pregnancy, and perhaps even extending to conception. The Collaborative Perinatal Project was a prospective cohort study performed from 1959 to 1966 in the United States. Since enrolled pregnancies were managed without the biases created by modern perinatal surveillance and interventions, the natural history of disease in these data is ideal to study obstetrical complications such as placental abruption. Objective: We assessed the associations versus contributions of the clinical feature of early gestational vaginal bleeding and histologic lesions (chronic and acute) with placental abruption. Study design: Women enrolled in the Collaborative Perinatal Project (1959–1966) were used, restricting the analysis to those that delivered singleton births (n = 46,364). Risks of placental abruption were compared between women with and without vaginal bleeding at <20 weeks gestation. We also examined the relationships between placental abruption and chronic and acute histologic lesions, including infarcts, decidual necrosis, presence of macrophages in the decidua, amnion or chorion, and neutrophil infiltration in the amnion, chorion, placental surface, and umbilical vein. Results: Any episode of vaginal bleeding at <20 weeks in pregnancy conferred an increased risk of placental abruption (adjusted relative risk (RR) 1.6, 95% confidence interval (CI) 1.3, 1.8). The greatest risk occurred with bleeding in both the first two trimesters (RR 3.1, 95% CI 2.3, 4.1). The presence of histologic lesions in the placenta, cord and membranes similarly carried an increased risk of placental abruption, even in the absence of vaginal bleeding. The risk of abruption was, however, highest in the presence of both histologic lesions and vaginal bleeding early in pregnancy. Conclusion: Vaginal bleeding early in pregnancy and histologic lesions of the placenta, umbilical cord, and membranes are associated with increased risk of placental abruption in later pregnancy. However, the increased risk associated with placental lesions, especially chronic inflammatory lesions, even in the absence of early vaginal bleeding, suggests that prolonged inflammation may be implicated in placental abruption. # 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Placental abruption; Histology; Chronic lesions; Acute lesions; Etiology; Vaginal bleeding 1. Introduction Placental abruption, defined as the premature separation of the placenta prior to the delivery of the fetus, occurs in approximately 1% of pregnancies [1,2]. The classic clinical hallmarks of placental abruption include vaginal bleeding www.elsevier.com/locate/ejogrb European Journal of Obstetrics & Gynecology and Reproductive Biology 128 (2006) 15–21 * Corresponding author at: Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology, and Reproductive Sciences, UMDNJ-Robert Wood Johnson Medical School, 125 Paterson Street, New Brunswick, NJ 08901-1977, United States. Tel.: +1 732 235 7940; fax: +1 732 235 6627. E-mail address: cande.ananth@umdnj.edu (C.V. Ananth). 0301-2115/$ – see front matter # 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejogrb.2006.01.016