Predictive value of vaginal IL-6 and TNFα bedside tests repeated until delivery for the prediction of maternal-fetal infection in cases of premature rupture of membranes

Eur J Obstet Gynecol Reprod Biol. 2017 Apr;211:8-14. doi: 10.1016/j.ejogrb.2017.01.013. Epub 2017 Jan 12.


Objective: Examine the predictive value for maternal-fetal infection of routine bedside tests detecting the proinflammatory cytokines, TNFα and IL-6, in the vaginal secretions of women with premature rupture of the membranes (PROM).

Study design: This prospective two-center cohort study included all women hospitalized for PROM over a 2-year period. A bedside test assessed IL-6 and TNFα in vaginal secretions. Both centers routinely tested CRP and leukocytes, assaying both in maternal serum, and analyzed vaginal bacterial flora; all samples were repeated twice weekly until delivery.

Results: The study included 689 women. In cases of preterm PROM (PPROM) before 37 weeks (n=184), a vaginal sample positive for one or more bacteria was the only marker associated with early neonatal infection (OR 5.6, 95%CI; 2.0-15.7). Its sensitivity was 82% (95%CI; 62-94) and its specificity 56% (95%CI; 47-65). All positive markers of infection were associated with the occurrence of chorioamnionitis. In cases of PROM from 37 weeks onward (n=505), only CRP >5mg/dL was associated with early neonatal infection (OR=8.3, 95%CI; 1.1-65.4) or clinical chorioamnionitis (OR=6.8, 95%CI; 1.5-30.0). The sensitivity of CRP >5mg/dL was 91% (95%CI; 59-100) and its specificity 45% (95%CI; 40-51) for predicting early neonatal infection, and 89% (95%CI; 65-99) and 46% (95%CI; 41-51), respectively, for predicting clinical chorioamnionitis.

Conclusion: The association of vaginal cytokines with maternal-fetal infection is weak and thus prevents their use as a good predictor of maternal-fetal infection. CRP and vaginal samples may be useful for identifying a group of women at low risk of infection.

Keywords: IL-6; Maternal-fetal infection; Rupture of membranes; TNFα.

MeSH terms

  • Adult
  • Bacterial Infections / diagnosis*
  • Biomarkers
  • Body Fluids / chemistry*
  • Female
  • Fetal Membranes, Premature Rupture / metabolism
  • Fetal Membranes, Premature Rupture / microbiology*
  • Humans
  • Infant, Newborn
  • Interleukin-6 / analysis*
  • Predictive Value of Tests
  • Pregnancy
  • Prospective Studies
  • Sensitivity and Specificity
  • Tumor Necrosis Factor-alpha / analysis*
  • Vagina / metabolism*


  • Biomarkers
  • Interleukin-6
  • Tumor Necrosis Factor-alpha