The Preterm Prediction Study: Association between cervical interleukin 6 concentration and spontaneous preterm birth

OBJECTIVE: The aim of this study was to determine the interrelationship bet ween cervical concentration of interleukin 6 and detection of fetal fibrone ctin and other risk factors for spontaneous preterm birth. STUDY DESIGN: All patients with spontaneous preterm birth at <35 weeks' ges tation (case patients; n = 125) and subjects matched for race, parity, and center delivered at <greater than or equal to>37 weeks' gestation (n = 125; control subjects) were selected from women enrolled in the National Instit ute of Child Health and Human Development's Preterm Prediction Study. Inter leukin 6 concentrations were determined by enzyme-linked immunosorbent assa y in cervical swabs obtained at 22 weeks' to 24 weeks 6 days' gestation. Cu toffs to define an elevated interleukin 6 concentration included the 90th a nd 95th percentiles for control subjects (>305 and >538 pg/mL, respectively ). RESULTS: The mean (+/-SD) interleukin 6 concentration was significantly hig her in case patients than in control subjects (212 +/- 339 vs 111 +/- 186 p g/mL; P=.008). With either cutoff value elevated interleukin 6 concentratio n was significantly associated with spontaneous preterm birth (90th percent ile, 20% vs 9.6%; P=.02; 95th percentile, 12% vs 4.8%; P=.04). Cervical int erleukin 6 levels were highest within 4 weeks of delivery, and the trend co ntinued until term. Elevated interleukin 6 concentration was not significan tly associated with bacterial vaginosis, maternal body mass index <19.8 kg/ m(2), or a short cervix (<less than or equal to>25 mm), but it was signific antly associated with a positive cervicovaginal fetal fibronectin test resu lt (90th percentile, odds ratio, 5.5; 95% confidence interval, 2.6-11.9; 95 th percentile, odds ratio, 5.3, 95% confidence interval, 2.1-12.9). The mea n interleukin 6 concentration among women with a positive fibronectin test result was 373 +/- 406 pg/mL; that among women with a negative fetal fibron ectin test result was 130 +/- 239 pg/mL (P=.001). In a regression analysis that adjusted for risk factors significantly associated with spontaneous pr eterm birth in this population (positive fetal fibronectin test result, bod y mass index <19.8 kg/m(2), vaginal bleeding in the first or second trimest er, previous spontaneous preterm birth, and short cervix) elevated cervical interleukin 6 concentration was not independently associated with spontane ous preterm birth (odds ratio, 1.8; 95% confidence interval. 0.8-4.3). CONCLUSIONS: At 24 weeks' gestation cervical interleukin 6 concentration in women who subsequently had a spontaneous preterm birth at <35 weeks' gesta tion was significantly elevated relative to those who were delivered at ter m. The association was particularly strong within 4 weeks of testing. A pos itive fetal fibronectin test result was strongly associated with elevated c ervical interleukin 6 concentration, but bacterial vaginosis was not.