Bacterial vaginosis (BV), the most common reproductive tract infection in pregnancy, is associated with an increased risk for preterm birth. The determinants of susceptibility for developing BV and infection-related preterm birth are not well understood. Moreover, the causes of racial/ethnic differences in the prevalence and sequella of BV are largely unexplained. We propose a biobehavioral framework to study these issues, with the central hypothesis that prenatal stress, operationalized as a biological construct, heightens susceptibility for acquiring BV and potentiates its pathophysiological consequences. We focus on the maternal-placental-fetal endocrine and immune-inflammatory processes as the primary mechanisms of interest because both systems play a critical role in regulating susceptibility to infection, participate in the physiology and pathophysiology of term and preterm parturition, and are highly responsive to stress. We propose a longitudinal, cohort study of 900 African-American, Hispanic and nonHispanic White pregnant women to assess the prevalence of BV at two time points during early and mid gestation, quantify the endocrine and immune-inflammatory milieu at each of these times, measure behaviors known to be associated with the acquisition of BV, and follow subjects through delivery. BV status will be assessed by Gram stained vaginal smears. Endocrine stress parameters will be assessed by measures of cortisol, corticotropin-releasing hormone (CRH), and estriol (E3). Immune-inflammatory process will be quantified from responses of the cytokines interleukin (IL)-1, IL-6, TNFalpha, IL-10 and IL-12 to bacterial endotoxin (LPS) challenge using ex-vivo whole blood tissue culture system.
Our specific aims are to examine: (1) the role of endocrine stress physiology in increasing susceptibility to developing bacterial vaginosis (BV) in pregnancy, and the role of immunosuppression as a mediator of this effect; (2) the role of endocrine stress physiology in increasing the susceptibility of BV+ women for spontaneous preterm birth, and the role of pro-inflammatory immune responses as a mediator of this effect; and (3) the extent to which stress-related endocrine and immune processes account for racial/ethnic disparities in prevalence of infection and infection-related preterm birth The scientific significance of this proposal pertains to elucidating biological mechanisms that determine susceptibility or vulnerability for developing reproductive tract infection in pregnancy and its adverse consequences (preterm birth), and clarifying the physiological basis for the observed effects of race/ethnicity on these outcomes. The practical significance of this proposal is the development and assessment of new ways (e.g., the ex-vivo immune challenge methodology) to identify women who are at heightened risk for infection and infection-related preterm birth, thereby improving obstetric risk assessment.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD041696-03
Application #
6782482
Study Section
Biobehavioral and Behavioral Processes 3 (BBBP)
Program Officer
Reddy, Uma M
Project Start
2002-08-05
Project End
2007-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
3
Fiscal Year
2004
Total Cost
$403,058
Indirect Cost
Name
University of California Irvine
Department
Psychiatry
Type
Schools of Medicine
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Moog, Nora K; Buss, Claudia; Entringer, Sonja et al. (2016) Maternal Exposure to Childhood Trauma Is Associated During Pregnancy With Placental-Fetal Stress Physiology. Biol Psychiatry 79:831-839
Voellmin, Annette; Entringer, Sonja; Moog, Nora et al. (2013) Maternal positive affect over the course of pregnancy is associated with the length of gestation and reduced risk of preterm delivery. J Psychosom Res 75:336-40
Cammack, Alison L; Buss, Claudia; Entringer, Sonja et al. (2011) The association between early life adversity and bacterial vaginosis during pregnancy. Am J Obstet Gynecol 204:431.e1-8
Denney, Jeffrey M; Nelson, Edward L; Wadhwa, Pathik D et al. (2011) Longitudinal modulation of immune system cytokine profile during pregnancy. Cytokine 53:170-7
Entringer, Sonja; Buss, Claudia; Shirtcliff, Elizabeth A et al. (2010) Attenuation of maternal psychophysiological stress responses and the maternal cortisol awakening response over the course of human pregnancy. Stress 13:258-68
Buss, Claudia; Entringer, Sonja; Reyes, Jonazary F et al. (2009) The maternal cortisol awakening response in human pregnancy is associated with the length of gestation. Am J Obstet Gynecol 201:398.e1-8
Entringer, Sonja; Kumsta, Robert; Hellhammer, Dirk H et al. (2009) Prenatal exposure to maternal psychosocial stress and HPA axis regulation in young adults. Horm Behav 55:292-8
Entringer, Sonja; Buss, Claudia; Kumsta, Robert et al. (2009) Prenatal psychosocial stress exposure is associated with subsequent working memory performance in young women. Behav Neurosci 123:886-93
Entringer, Sonja; Kumsta, Robert; Nelson, Edward L et al. (2008) Influence of prenatal psychosocial stress on cytokine production in adult women. Dev Psychobiol 50:579-87
Entringer, Sonja; Wust, Stefan; Kumsta, Robert et al. (2008) Prenatal psychosocial stress exposure is associated with insulin resistance in young adults. Am J Obstet Gynecol 199:498.e1-7

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