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.


METHODS
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
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.


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.


CONCLUSIONS
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.
Wei
Shu-Qin
SQ
From the Department of Obstetrics and Gynecology, Sainte-Justine Hospital, University of Montreal, Quebec, Canada.
Fraser
William
W
Luo
Zhong-Cheng
ZC
D000653:Amniotic Fluid / Q000737:chemistry; D015415:Biomarkers / Q000032:analysis; D012634:Bodily Secretions / Q000737:chemistry; D002097:C-Reactive Protein; D002584:Cervix Uteri; D016207:Cytokines / Q000032:analysis*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis*; D011247:Pregnancy; D047928:Premature Birth / Q000453:epidemiology* / Q000276:immunology; D014621:Vagina
D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D002097:C-Reactive Protein