Preterm delivery (PTD) is the leading cause of infant morbidity and mortality in the United States, and prevention of PTD is a primary goal in perinatal health care. Recent data indicates a strong association a strong association between maternal genital tract infection, including bacterial vaginosis, and PTD, with compelling evidence that micro- organisms are a cause of PTD. However, the relationship between concentrations of vaginal microorganisms and PTD, the identification of key microbial populations that are significant risk factors for PTD, and the pathophysiologic mechanisms by which bacteria contribute to PTD remain to be determined. In addition, the interactions between microbial populations of significance to PTD are unknown. Preterm labor may be initiated by bacterial phospholipases A2 and which release arachidonic acid-the primary substance for prostaglandins which are considered fundamental to the initiation of labor. It has been hypothesized that the combined activities of lipase and phospholipases also account for a variety of effects associated with membrane damage. However, the relationship between these combined enzyme activities in the vagina and pregnancy outcome has not been determined. The objective of the proposed project is to prospectively collect quantitative data on microbiologic populations and enzyme activities and to receptor the presence or absence of bacterial vaginosis in two cohorts at high risk for PTD and one to record the presence or absence of bacterial vaginosis in two cohorts at high risk for PTD and one cohort at low risk. Generalized estimating equation regression will be used to analyze repeat measurement data and to formulate quantitative models to predict PTD. The following Specific Aims will be addressed: (1) quantitatively identify key microbial population as risk factors for PTD, (2) identify interactions between microbial populations that contribute to PTD, (3) determine whether there is an association between vaginal enzyme (lipase, phospholipase) activities and PTD, and (4) document any relationship between the presence or absence of bacterial vaginosis and PTD, and (4) document any relationship between the presence of absence of bacterial vaginosis and PTD. Recognition of predictive pathway(s) for PTD may permit the identification of individuals at risk for PTD may permit the identification of individuals at risk for PTD and, ultimately, the implementation of noel strategies for its prevention.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD035667-01A2
Application #
2760359
Study Section
Special Emphasis Panel (ZRG5-BM-2 (07))
Program Officer
Spong, Catherine
Project Start
1999-01-01
Project End
2001-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115
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Genc, Mehmet R; Delaney, Mary L; Onderdonk, Andrew B et al. (2006) Vaginal nitric oxide in pregnant women with bacterial vaginosis. Am J Reprod Immunol 56:86-90
Genc, Mehmet R; Karasahin, Emre; Onderdonk, Andrew B et al. (2005) Association between vaginal 70-kd heat shock protein, interleukin-1 receptor antagonist, and microbial flora in mid trimester pregnant women. Am J Obstet Gynecol 192:916-21
Genc, Mehmet R; Witkin, Steven S; Delaney, Mary L et al. (2004) A disproportionate increase in IL-1beta over IL-1ra in the cervicovaginal secretions of pregnant women with altered vaginal microflora correlates with preterm birth. Am J Obstet Gynecol 190:1191-7
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Nguyen, Daniel P; Genc, Mehmet; Vardhana, Santosh et al. (2004) Ethnic differences of polymorphisms in cytokine and innate immune system genes in pregnant women. Obstet Gynecol 104:293-300
Genc, Mehmet R; Onderdonk, Andrew B; Vardhana, Santosh et al. (2004) Polymorphism in intron 2 of the interleukin-1 receptor antagonist gene, local midtrimester cytokine response to vaginal flora, and subsequent preterm birth. Am J Obstet Gynecol 191:1324-30
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Delaney, M L; Onderdonk, A B (2001) Nugent score related to vaginal culture in pregnant women. Obstet Gynecol 98:79-84