Stress, Race, and Immune Adaptation Across Pregnancy: Predictors of Preterm Birth

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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.