The Preterm Prediction Study: association between cervical interleukin 6 concentration and spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.

Academic Article

Abstract

  • OBJECTIVE: The aim of this study was to determine the interrelationship between cervical concentration of interleukin 6 and detection of fetal fibronectin and other risk factors for spontaneous preterm birth. STUDY DESIGN: All patients with spontaneous preterm birth at <35 weeks' gestation (case patients; n = 125) and subjects matched for race, parity, and center delivered at > or = 37 weeks' gestation (n = 125; control subjects) were selected from women enrolled in the National Institute of Child Health and Human Development's Preterm Prediction Study. Interleukin 6 concentrations were determined by enzyme-linked immunosorbent assay in cervical swabs obtained at 22 weeks' to 24 weeks 6 days' gestation. Cutoffs to define an elevated interleukin 6 concentration included the 90th and 95th percentiles for control subjects (>305 and >538 pg/mL, respectively). RESULTS: The mean (+/-SD) interleukin 6 concentration was significantly higher in case patients than in control subjects (212 +/- 339 vs 111 +/- 186 pg/mL; P = .008). With either cutoff value elevated interleukin 6 concentration was significantly associated with spontaneous preterm birth (90th percentile, 20% vs 9.6%; P = .02; 95th percentile, 12% vs 4.8%; P = .04). Cervical interleukin 6 levels were highest within 4 weeks of delivery, and the trend continued until term. Elevated interleukin 6 concentration was not significantly associated with bacterial vaginosis, maternal body mass index <19.8 kg/m2, or a short cervix (< or = 25 mm), but it was significantly associated with a positive cervicovaginal fetal fibronectin test result (90th percentile, odds ratio, 5.5; 95% confidence interval, 2.6-11.9; 95th percentile, odds ratio, 5.3, 95% confidence interval, 2.1-12.9). The mean interleukin 6 concentration among women with a positive fibronectin test result was 373 +/- 406 pg/mL; that among women with a negative fetal fibronectin test result was 130 +/- 239 pg/mL (P = .001). In a regression analysis that adjusted for risk factors significantly associated with spontaneous preterm birth in this population (positive fetal fibronectin test result, body mass index <19.8 kg/m2, vaginal bleeding in the first or second trimester, previous spontaneous preterm birth, and short cervix) elevated cervical interleukin 6 concentration was not independently associated with spontaneous 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' gestation was significantly elevated relative to those who were delivered at term. The association was particularly strong within 4 weeks of testing. A positive fetal fibronectin test result was strongly associated with elevated cervical interleukin 6 concentration, but bacterial vaginosis was not.
  • Keywords

  • Case-Control Studies, Cervix Uteri, Enzyme-Linked Immunosorbent Assay, Female, Fetus, Fibronectins, Humans, Interleukin-6, Logistic Models, Obstetric Labor, Premature, Pregnancy, Prospective Studies, Regression Analysis, Risk Factors, Statistics, Nonparametric, Vaginosis, Bacterial
  • Digital Object Identifier (doi)

    Author List

  • Goepfert AR; Goldenberg RL; Andrews WW; Hauth JC; Mercer B; Iams J; Meis P; Moawad A; Thom E; VanDorsten JP
  • Start Page

  • 483
  • End Page

  • 488
  • Volume

  • 184
  • Issue

  • 3