Inflammatory cytokines and spontaneous preterm birth in asymptomatic women: a systematic review

Obstet Gynecol. 2010 Aug;116(2 Pt 1):393-401. doi: 10.1097/AOG.0b013e3181e6dbc0.


Objective: To estimate the association between inflammatory cytokines and the risk of spontaneous preterm birth in asymptomatic women.

Data sources: We searched electronic databases of the human literature in PubMed, EMBASE, and the Cochrane Library up to February 2010 using the following key words: "preterm/pre-term + (birth/delivery)" and "cytokine" or "inflammation/inflammatory + marker/biomarker."

Methods of study selection: We included observational studies that reported the association between common inflammatory cytokines and spontaneous preterm birth as an outcome in asymptomatic women. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed and random effects models.

Tabulation, integration, and results: Seventeen primary studies comprising 6,270 participants met the inclusion criteria. Spontaneous preterm birth was strongly associated with increased levels of interleukin-6 (IL-6) in midtrimester cervicovaginal fluid (OR 3.05, 95% CI 2.00-4.67) (number needed to treat=7 for identifying an additional preterm delivery) and amniotic fluid (OR 4.52, 95% CI 2.67-7.65) (number needed to treat=7), but there was no association in plasma specimen (OR 1.5, 95% CI 0.7-3.0). Spontaneous preterm birth was strongly associated with increased C-reactive protein (CRP) levels in midtrimester amniotic fluid (OR 7.85, 95% CI 3.88-15.87) (number needed to treat=3), but the association was weak in plasma specimen (OR 1.53, 95% CI 1.22-1.90). There were insufficient data (fewer than three studies) for meta-analysis in other inflammatory cytokines.

Conclusion: Inflammatory cytokine IL-6 in cervicovaginal fluid and IL-6 and CRP in amniotic fluid but not in plasma are strongly associated with spontaneous preterm birth in asymptomatic women, suggesting that inflammation at the maternal-fetal interface, rather than systemic inflammation, may play a major role in the etiology of such spontaneous preterm births.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Amniotic Fluid / chemistry
  • Biomarkers / analysis
  • Bodily Secretions / chemistry
  • C-Reactive Protein
  • Cervix Uteri
  • Cytokines / analysis*
  • Female
  • Humans
  • Interleukin-6 / analysis*
  • Pregnancy
  • Premature Birth / epidemiology*
  • Premature Birth / immunology
  • Vagina


  • Biomarkers
  • Cytokines
  • Interleukin-6
  • C-Reactive Protein