ASSOCIATIONS BETWEEN HERPES SIMPLEX VIRUS TYPES 1 AND 2 (HSV-1 AND HSV-2), CYTOMEGALOVIRUS (CMV), EPSTEIN BARR VIRUS (EBV), HUMAN PAPILLOMA VIRUS (HPV), CHLAMYDIA TRACHOMATIS, NEISSERIA GONORRHOEAE INFECTIONS AND PREECLAMPSIA

摘要

BACKGROUND Atherosclerosis, endothelial dysfunction and inflammation are thought to be key pathophysiologic processes in preeclampsia. The basic thesis of this dissertation is that maternal infections may trigger upregulation of proinflammatory cytokines in women with preeclampsia resulting in vascular injury.OBJECTIVES We evaluated the evidence for a potential infectious disease etiology for preeclampsia in three papers. METHODS For the first paper, we conducted a 1:3 matched case control study. In this study we measured immunoglobulin G (IgG) antibodies to HSV-1, HSV-2, CMV, and EBV in serum samples obtained from 50 cases with preeclampsia and 150 normotensive controls, matched on age, parity and race. For the second paper, we conducted a comprehensive review of published studies that explored the association between both bacterial and viral infections, and examined the strength of this association. For the third paper, we investigated the association between self-reported Genital Warts (HPV), Genital Herpes (HSV-2), Chlamydia (C. trachomatis), Gonorrhea (N. gonorrhoeae) infections, sociodemographic, and behavioral risk factors and the risk of preeclampsia in a representative national sample of 10,847 reproductive age women.RESULTS We found that seroconversion for HSV 1 /2 or CMV was associated with a five-fold increased risk for developing preeclampsia (OR 5.4, 95% CI 1.0-29.0) after adjusting for education, income, smoking, years of cohabitation, medical insurance, and type of birth control. Pooling of relevant epidemiologic data, also revealed a two-fold increased risk of preeclampsia associated with bacterial and viral infections (OR 2.1, 95% CI 1.8-2.6). Additionally, population-based results suggest that Genital Warts, Genital Herpes, and C. trachomatis significantly increased the risk of preeclampsia (OR 3.0, 95% CI 1.0-8.8; OR 7.4, 95% CI 1.4-47.4; OR 5.2, 95% CI 1.3-20.2, respectively), after adjusting for socio-demographic, behavioral, and infection-related risk factors. PUBLIC HEALTH RELEVANCE Given the widespread prevalence of these infections, and the potential to prevent infection, our findings have important public health implications in the context of potential preventive strategies and identification of high-risk individuals.