Maternal stress, low cervicovaginal β-defensin, and spontaneous preterm birth

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 spontaneous preterm birth, but mechanisms are poorly delineated. Antimicrobial proteins in the cervicovaginal space, such as β-defensins, modulate immune responses to bacteria and have been shown to modulate the risk of spontaneous preterm birth from nonoptimal microbiota. Although stress is known to induce immunological changes, no study has examined the interplay between maternal stress and the immune response in association with spontaneous preterm birth. Objectives: Our objectives were to determine whether psychosocial stress was associated with a mediator of the immune system in the cervicovaginal space, β-defensin–2, and to examine the combined impact of high stress and low cervicovaginal β-defensin–2 levels on the odds of sPTB. Materials and Methods: 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 who went on to have a spontaneous preterm birth and 409 a term birth). Stress and cervicovaginal β-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 β-defensin–2 levels with enzyme-linked immunosorbent assay and dichotomized at the median. We modeled associations of high stress and low cervicovaginal β-defensin–2 levels using multivariable logistic regression. We also compared the proportion of women with high stress and low cervicovaginal β-defensin–2 levels among women with spontaneous preterm and term births using χ² tests. We modeled adjusted associations of stress and cervicovaginal β-defensin–2 levels with odds of spontaneous preterm birth using logistic regression. Results: The majority of the study population was non-Hispanic black (72.8%), insured by Medicaid (51.1%), and had a Perceived Stress Scale−14 score <30 (80.2%). High stress was associated with reduced adjusted odds of low β-defensin–2 levels (adjusted odds ratio, 0.63; 95% confidence interval, 0.38−0.99). In a model adjusted for race and smoking, both high stress (adjusted odds ratio, 1.72, 95% confidence interval, 1.03−2.90) and low β-defensin–2 (adjusted odds ratio, 1.58, 95% confidence interval, 1.004−2.49) were associated with increased odds of spontaneous preterm birth. We then built a model of the 4 possible combinations of low and high stress and low and high β-defensin–2 levels with the odds of spontaneous preterm birth. Women with either high stress (adjusted odds ratio, 1.37, 95% confidence interval, 0.68−2.78) or low β-defensin–2 (adjusted odds ratio, 1.40, 95% confidence interval, 0.83-2.34) had slightly elevated but not significantly increased odds of sPTB compared to women without either exposure. However, women with both high stress and low β-defensin–2 had significantly elevated odds of sPTB compared to women without either exposure (adjusted odds ratio, 3.16, 95% confidence interval, 1.46−6.84). Conclusion: High perceived stress and low cervicovaginal β-defensin–2 levels are associated with higher odds of spontaneous preterm birth, and, when present concurrently, they resulted in the highest odds of spontaneous preterm birth 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 spontaneous preterm birth.