Preterm delivery, an increasingly frequent occurrence in the United States, is associated with significant family burden and an estimated societal cost of at least $26 billion per year. Psychosocial stress and related physiological sequelae may contribute to preterm birth in general, as well as racial disparities in preterm birth. It is well-established that among nonpregnant adults, chronic stress promotes immune dysregulation. Importantly, immune function changes substantially to support healthy pregnancy, with mild elevations in circulating inflammatory cytokines, attenuation of inflammatory responses, and impairment of cell-mediated immunity. However very limited research has examined the extent to which measures of psychosocial stress or race predict differential immune adaptation longitudinally across pregnancy. Chronic stress can directly stimulate the production of proinflammatory cytokines and prime the immune system to respond in an exaggerated manner upon exposure to biological challenges. Excessive elevations in maternal circulating inflammatory markers and a tendency toward inflammatory responding have been associated with adverse perinatal health outcomes, including preterm birth. In addition, stress can suppress cellular immune function. Typically kept in a latent state by cell-mediated immunity, Epstein-Barr Virus (EBV) may reactivate under conditions of immunosuppression, including stress. Thus, EBV latency provides a measure of cellular immune function. Due to suppression of cell-mediated immunity, EBV is more likely to be reactivated during pregnancy than nonpregnancy. Further, EBV reactivation has been associated with shorter gestation and lower birth weight, although it is not known if this plays a causal role or serves as a marker of a pathological process. Despite unique implications for health, limited data are available regarding effect of race or stress on immune parameters during pregnancy. The current study will build upon and address important gaps in the literature by examining immune parameters among 80 pregnant women (40 African-American and 40 European-American) longitudinally across pregnancy. This research will a) provide more comprehensive information about immune adaptation during pregnancy by examining circulating cytokine levels, in vitro stimulated cytokine production, and cellular immune function (i.e., EBV reactivation) longitudinally during each trimester of pregnancy, b) examine effects of stress and race on such adaptation and, c) provide preliminary data regarding whether differential immune profiles predict increased risk of preterm birth. Thus, this research is designed to ultimately lead to the identification of women at greater risk for negative perinatal outcomes and elucidation of mechanisms underlying increased risk, providing a basis for individualized health care services.

Public Health Relevance

This study will fill important gaps in our knowledge regarding immune changes during pregnancy and effects of psychological stress and racial minority on such adaptation. Information gained from this study will provide the groundwork for the following: 1) identification of women at greater risk of adverse perinatal health outcomes, particularly preterm birth;2) describing physiological mechanisms underlying the link between stress and risk of preterm delivery;and 3) providing interventions designed to reduce the effects of stress and promote healthy pregnancy and fetal development.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-BBBP-R (06))
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Signore, Caroline
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Ohio State University
Schools of Medicine
United States
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Mitchell, Amanda M; Palettas, Marilly; Christian, Lisa M (2017) Fetal sex is associated with maternal stimulated cytokine production, but not serum cytokine levels, in human pregnancy. Brain Behav Immun 60:32-37
Mitchell, Amanda M; Porter, Kyle; Christian, Lisa M (2017) Examination of the Role of Obesity in the Association Between Childhood Trauma and Inflammation During Pregnancy. Health Psychol :
Gillespie, Shannon L; Christian, Lisa M (2016) Body Mass Index as a Measure of Obesity: Racial Differences in Predictive Value for Health Parameters During Pregnancy. J Womens Health (Larchmt) 25:1210-1218
Gillespie, Shannon L; Porter, Kyle; Christian, Lisa M (2016) Adaptation of the inflammatory immune response across pregnancy and postpartum in Black and White women. J Reprod Immunol 114:27-31
Christian, Lisa M; Blair, Lisa M; Porter, Kyle et al. (2016) Polyunsaturated Fatty Acid (PUFA) Status in Pregnant Women: Associations with Sleep Quality, Inflammation, and Length of Gestation. PLoS One 11:e0148752
Blair, Lisa M; Porter, Kyle; Leblebicioglu, Binnaz et al. (2015) Poor Sleep Quality and Associated Inflammation Predict Preterm Birth: Heightened Risk among African Americans. Sleep 38:1259-67
Christian, Lisa M; Galley, Jeffrey D; Hade, Erinn M et al. (2015) Gut microbiome composition is associated with temperament during early childhood. Brain Behav Immun 45:118-27
Christian, Lisa M; Porter, Kyle; Karlsson, Erik et al. (2015) Proinflammatory cytokine responses correspond with subjective side effects after influenza virus vaccination. Vaccine 33:3360-6
Christian, Lisa M (2015) Stress and Immune Function during Pregnancy: An Emerging Focus in Mind-Body Medicine. Curr Dir Psychol Sci 24:3-9
Galley, Jeffrey D; Bailey, Michael; Kamp Dush, Claire et al. (2014) Maternal obesity is associated with alterations in the gut microbiome in toddlers. PLoS One 9:e113026

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