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.
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