Lower genital tract inflammatory milieu and the risk of subsequent preterm birth: an exploratory factor analysis

The inflammatory milieu of the cervix may play a role in preventing intrauterine infection and subsequent preterm birth. The objectives of this study were to use exploratory factor analysis to discover the underlying structure of cytokines in the lower genital tract immunological milieu, and evaluate the association between the cytokine factors and risk of preterm birth. Women (n=613) enrolled in a prospective pregnancy cohort study in Pittsburgh, Pennsylvania had cervical cytokine concentrations assayed at <16 weeks and were followed for data on pregnancy outcomes. Principal factor analysis identified two primary cytokine patterns at <16 weeks gestation: Factor 1 (pro-inflammatory/immunomodulatory factor), which loaded highly on interleukin (IL)-1β, IL-6, IL-8, monocyte chemotactic protein-1, and IL-10, and Factor 2 (anti-inflammatory factor), which loaded heavily on IL-4, IL-10, and IL-13. Women in the highest tertile of anti-inflammatory cytokine factor scores at <16 weeks had an increased risk of spontaneous preterm birth (confounder-adjusted odds ratio [95% confidence interval]: 2.4 [1.1, 5.7]). There was no association between pro-inflammatory cytokine factor scores and preterm birth risk. These data support the hypothesis that increased concentrations of anti-inflammatory cytokines may represent a cervical immune milieu that permits subsequent microbial invasion of the uterus during pregnancy, leading to subsequent spontaneous preterm birth.