Association of vaginal microbiome, cytokines, and spontaneous preterm birth among Chinese women: a nested case-control study

An imbalance of the vaginal microbiome and dysregulation of cytokines are associated with spontaneous preterm birth (sPTB). To date, the relationship between the vaginal microbiome, cytokines, and sPTB remains unclear in the Chinese population. Herein, we conducted a nested case-control study using data from a prospective cohort of 749 Chinese women with a singleton pregnancy who were enrolled between 16 and 28 weeks of pregnancy. Cases consisted of individuals experiencing sPTB (<i>n</i> = 38), while controls were selected randomly at a 4:1 ratio to cases (<i>n</i> = 152). Compared to the term group, the sPTB group exhibited significantly increased abundance of vaginal <i>Aerococcus christensenii</i>, <i>Gardnerella swidsinskii</i>, and <i>Lactobacillus iners</i>, along with elevated levels of interleukin (IL)-1β, IL-6, and IL-12p70 in vaginal fluid (<i>P</i> < 0.05). Least absolute shrinkage and selection operator (LASSO) regression identified <i>L. iners</i>, <i>G. swidsinskii</i>, and IL-6 as significant risk factors for sPTB, with adjusted odds ratios (ORs) (95% CI) of 1.57 (1.06-2.34), 1.45 (1.03-2.05), and 2.05 (1.43-2.93), respectively. Finally, a logistic regression model for sPTB was established incorporating <i>L. iners</i>, <i>G. swidsinskii</i>, and IL-6, which yielded an area under the receiver operating characteristic curve (AUC) of 0.73. These findings suggest that alterations in the vaginal microbiome and cytokine levels may contribute to sPTB in the Chinese population.IMPORTANCEPreterm birth (PTB) is the leading cause of death in children under 5 years of age, of which about 70% were spontaneous ones (sPTB); while genitourinary infections are implicated in 25-40% of sPTB cases. Previous studies have revealed some features of vaginal microbiome and cytokines related to sPTB: increased richness and diversity, increased levels of <i>Lactobacillus iners</i>, BV-associated bacteria, low abundance of <i>L. crispatus</i>, and high levels of pro-inflammatory cytokines. However, there were also some inconsistent findings, and little is known in the Chinese population. This study confirmed the correlations between vaginal microbiome, cytokines, and sPTB in Chinese pregnant women. Specifically, elevated vaginal <i>L. iners, G. swidsinskii</i>, and IL-6 levels were significantly associated factors, which may help to identify women at high risk of sPTB.