We propose a five year population-based prospective cohort study to evaluate the relative contributions to pre term birth of 10 genital tract infection, maternal stress and a genetic predisposition to an enhanced immune response among African American and white women resident in King County, Washington. Potential subjects will be identified through birth certificate data, with appropriate measures to protect confidentiality. We will enroll 100 African American and 100 white women with a prior early preterm birth at 20-34 weeks gestation and a comparison group of 100 African American and 100 white women with prior term birth at >36 weeks. The initial assessment will be performed at least 6 months after the index delivery and will include evaluation of vaginal flora and endometritis, maternal stress by qualitative and quantitative measures, periodontitis, and genetic variability in cytokine production. We will offer participants treatment or referral for any modifiable risk factors for preterm birth that are identified in the initial evaluation. We will then follow subjects prospectively and anticipate that 30-40% of the cohort will have a subsequent pregnancy during follow-up. Women with a subsequent pregnancy will be offered evaluation of vaginal flora, cervical length, and maternal stress with treatment or referral offered for modifiable risk factors. Outcomes for second pregnancies will be ascertained. This study design will allow us to examine the following specific aims: 1. Study the role of increased antigenic stimulation from lower genital tract infection as a determinant of endometritis, chorioamnionitis and preterm birth among African American and white women. 2. Examine the correlation of maternal stress with inflammatory arousal, stratified by race and prior pregnancy history. 3. Assess maternal and fetal genetic contributions to the pro-inflammatory response and correlate these with preterm birth and neonatal outcome. In combination, these inter-related aims will address the most plausible mechanisms by which African American women continue to be at least twice as likely as white women to deliver prematurely. We also plan to explore the synergy between genetic predisposition, maternal stress, inflammatory arousal, lower genital tract infection, and preterm birth. We hypothesize that women with more than one predisposing factor are at a markedly increased risk for preterm birth, and that African American women are more likely than white women to have multiple predisposing factors. We hope that these studies may eventually lead to the development of more effective strategies to prevent preterm birth and to reduce the disparity in preterm birth, low birthweight and infant mortality between African American and white women.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHD1-DSR-H (05))
Program Officer
Spong, Catherine
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Washington
Obstetrics & Gynecology
Schools of Medicine
United States
Zip Code
Mitchell, Caroline; Fredricks, David; Agnew, Kathy et al. (2015) Hydrogen Peroxide-Producing Lactobacilli Are Associated With Lower Levels of Vaginal Interleukin-1?, Independent of Bacterial Vaginosis. Sex Transm Dis 42:358-63
Balkus, Jennifer; Agnew, Kathy; Lawler, Richard et al. (2010) Effects of pregnancy and bacterial vaginosis on proinflammatory cytokine and secretory leukocyte protease inhibitor concentrations in vaginal secretions. J Pregnancy 2010:385981
Boutain, Doris M (2009) Collective knowledge sharing as a social justice strategy: the difference it made in a service project about preterm birth disparity. ANS Adv Nurs Sci 32:E68-80
Persson, Rutger; Hitti, Jane; Verhelst, Rita et al. (2009) The vaginal microflora in relation to gingivitis. BMC Infect Dis 9:6
Paul, Kathleen; Boutain, Doris; Agnew, Kathy et al. (2008) The relationship between racial identity, income, stress and C-reactive protein among parous women: implications for preterm birth disparity research. J Natl Med Assoc 100:540-6
Mitchell, Caroline M; Balkus, Jennifer; Agnew, Kathy J et al. (2008) Bacterial vaginosis, not HIV, is primarily responsible for increased vaginal concentrations of proinflammatory cytokines. AIDS Res Hum Retroviruses 24:667-71
Paul, Kathleen; Boutain, Doris; Manhart, Lisa et al. (2008) Racial disparity in bacterial vaginosis: the role of socioeconomic status, psychosocial stress, and neighborhood characteristics, and possible implications for preterm birth. Soc Sci Med 67:824-33
Persson, G Rutger; Hitti, Jane; Paul, Katie et al. (2008) Tannerella forsythia and Pseudomonas aeruginosa in subgingival bacterial samples from parous women. J Periodontol 79:508-16
Hitti, Jane; Nugent, Robert; Boutain, Doris et al. (2007) Racial disparity in risk of preterm birth associated with lower genital tract infection. Paediatr Perinat Epidemiol 21:330-7
Boutain, Doris M; Hitti, Jane (2006) Orienting multiple interviewers: the use of an interview orientation and standardized interview. Qual Health Res 16:1302-9

Showing the most recent 10 out of 11 publications