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The role of host immunity and maternal psychosocial stress in the pathogenesis of spontaneous preterm birth (sPTB) remains unclear. Antimicrobial proteins in the cervicovaginal CV) space, such as beta-defensins (βD), modulate immune responses to bacteria. While stress is known to induce immunological changes, no study has examined the interplay between stress and the CV immune response in association with sPTB.
From the Motherhood & Microbiome cohort (n=2000), we performed a nested case-control study of 519 pregnant women (110 sPTB and 409 term). Stress and CV-βD were measured at 16-20 weeks’ gestation. Stress was dichotomized at 30 on Cohen’s Perceived Stress Scale (PSS-14). We measured CV-βD with ELISA and dichotomized at the median. We compared sPTB rates with Chi-Square tests and modeled adjusted associations of stress and CV-βD with odds of sPTB with logistic regression.
In the dataset, 73% were African American, 64% were overweight or obese, 31% were married, 51% had Medicaid insurance, and 20% had a PSS-14 score >30. Median CV-βD levels were 17,098 pg/mL, IQR: 64,559. The cohort sPTB rate was 6%, but 21% in the analytic dataset. sPTB rates were 28% and 19% with high and low stress, respectively, and 24% and 18% with low and high CV-βD levels, respectively. Women with both low stress and high βD had the lowest sPTB rate (17%) and women with both high stress and low βD had the highest rate of sPTB (38%) (Fig 1). In adjusted models, high stress and low βD were each associated with increased odds of sPTB (aOR 1.8 (1.1- 3.0) and 1.6 (1.001-2.5), respectively), (interaction P=0.4). Women with both high stress and low CV-βD had much higher odds of sPTB compared with all other women (aOR 2.7 (1.3-5.5)). Restricting to African American women, the results were stronger (aOR 3.2 (1.4-7.0)).
High stress and low CV-βD levels are associated with increased odds of sPTB. The presence of both result in high odds of sPTB in a majority African American cohort. Understanding whether stress induces changes in the CV immune response or whether these are independent risk factors for sPTB in African American women will help guide therapeutic strategies to reduce sPTB. (R01NR014784; ME)