Inflammatory Cytokines and Spontaneous Preterm Birth in Asymptomatic Women A Systematic Review

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.