Maternal stress, low cervicovaginal beta defensin, and spontaneous preterm birth

Abstract Background Spontaneous preterm birth (sPTB) is a major contributor to infant mortality and its etiology remains poorly understood. Host immunity and maternal stress may play a role in the pathogenesis of sPTB but mechanisms are poorly delineated. Antimicrobial proteins in the cervicovaginal space, such as beta defensins, modulate immune responses to bacteria and have been shown to modulate the risk of sPTB from non-optimal microbiota. While stress is known to induce immunological changes, no study has examined the interplay between maternal stress and the immune response in association with sPTB. Objectives Our objectives were to determine whether psychosocial stress was associated with a mediator of the immune system in the cervicovaginal space, beta defensin-2, and to examine the combined impact of high stress and low cervicovaginal beta defensin-2 levels on the odds of sPTB. Study Design From the Motherhood & Microbiome cohort study (n=2000), we performed a secondary, nested case-control study, frequency matched by race/ethnicity, of 519 pregnant women (110 sPTB and 409 term). Stress and cervicovaginal beta defensin-2 levels were measured at 16-20 weeks of gestation. Stress was dichotomized at a score of 30 on Cohen’s Perceived Stress Scale (PSS-14). We measured cervicovaginal beta defensin-2 levels with ELISA and dichotomized at the median. We modeled associations of high stress and low cervicovaginal beta defensin-2 levels using multivariable logistic regression. We also compared the proportion of women with high stress and low cervicovaginal beta defensin-2 levels among women with spontaneous preterm and term births using Chi-Square tests. We modeled adjusted associations of stress and cervicovaginal beta defensin-2 levels with odds of sPTB using logistic regression. Results The majority of the study population was non-Hispanic black (72.8%), insured by Medicaid (51.1%), and had a PSS-14 score Conclusion High perceived stress and low cervicovaginal beta defensin-2 levels are associated with higher odds of sPTB, and when present concurrently, they result in the highest odds of sPTB in a largely non-Hispanic black cohort. Our findings warrant further work to examine social determinants of health and the host cervicovaginal immune responses that may modulate the pathogenesis of sPTB.