High cervical IL-6 levels predict spontaneous preterm birth among women in western Kenya

BACKGROUND

Spontaneous preterm birth (sPTB) increases neonatal morbidity and mortality. Infection and subsequent inflammation of the genital tract have been identified as risk factors for sPTB, however the role of cytokines in this relationship remains unclear.

OBJECTIVES

This study determined the association between genital cytokines and sPTB, identified cofactors for high genital cytokine levels, and evaluated the correlation between cervical and vaginal cytokine levels.

METHODS

We conducted a case control analysis nested in a cohort study in western Kenya. Cases were women who delivered preterm and were matched 1:1 by gestational age at time of genital swab collection to controls who delivered at or post-term. Genital cytokine levels and diagnoses of genital infections were ascertained in pregnancy in cervical and vaginal swab swabs. Conditional logistic regression was used to determine the association between levels of genital interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α) and sPTB. Linear regression was used to determine the association between genital infections and cytokine concentrations during pregnancy, and the relationship between vaginal and cervical cytokines.

RESULTS

Among 86 cases and 86 matched controls, IL-1, IL-6, and TNF-α levels were significantly higher in the cervix than the vagina (p<0.001 for each); levels for all assessed cytokines were correlated between compartments (p<0.005 for each). Odds of sPTB were increased by 54% for each 1 log10- increase in cervical IL-6 level (OR 1.54, 95% CI: 1.00 – 2.38, but not other cervical or vaginal cytokines. High cervical IL-6 concentrations during pregnancy were associated with a concurrent diagnosis of trichomonas (β=0.67, 95% CI: 0.37-0.97) and abnormal vaginal discharge (β=0.84, 95% CI: 0.55-1.14). Trichomonas, bacterial vaginosis, and abnormal vaginal discharge were each associated with an inflammatory vaginal milieu with elevated IL-1, IL-6, and TNF-α (p<0.005 for all).

CONCLUSION

Our findings suggest that trichomonas infection may mediate risk of sPTB through IL-6 release, and warrants further studies to explore this mechanistic link and potential interventions.