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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21HD067670-02
Application #
8294406
Study Section
Special Emphasis Panel (ZRG1-BBBP-R (06))
Program Officer
Raju, Tonse N
Project Start
2011-07-04
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2012
Total Cost
$228,750
Indirect Cost
$78,750
Name
Ohio State University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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 (2014) Effects of stress and depression on inflammatory immune parameters in pregnancy. Am J Obstet Gynecol 211:275-7
Christian, Lisa M; Porter, Kyle (2014) Longitudinal changes in serum proinflammatory markers across pregnancy and postpartum: effects of maternal body mass index. Cytokine 70:134-40
Christian, Lisa M (2014) Optimizing benefits of influenza virus vaccination during pregnancy: potential behavioral risk factors and interventions. Vaccine 32:2958-64
Christian, Lisa M; Glaser, Ronald; Porter, Kyle et al. (2013) Stress-induced inflammatory responses in women: effects of race and pregnancy. Psychosom Med 75:658-69
Christian, Lisa M; Iams, Jay; Porter, Kyle et al. (2013) Self-rated health among pregnant women: associations with objective health indicators, psychological functioning, and serum inflammatory markers. Ann Behav Med 46:295-309
Christian, Lisa M; Porter, Kyle; Karlsson, Erik et al. (2013) Serum proinflammatory cytokine responses to influenza virus vaccine among women during pregnancy versus non-pregnancy. Am J Reprod Immunol 70:45-53
Christian, Lisa M (2012) Psychoneuroimmunology in pregnancy: immune pathways linking stress with maternal health, adverse birth outcomes, and fetal development. Neurosci Biobehav Rev 36:350-61
Christian, Lisa M; Iams, Jay D; Porter, Kyle et al. (2011) Inflammatory responses to trivalent influenza virus vaccine among pregnant women. Vaccine 29:8982-7