Proinflammatory cytokines and other indications of inflammation in cervico-vaginal secretions and preterm delivery (original) (raw)
Related papers
2007
Background: Absence of fetal fibronectin (fFN) in the cervicovaginal fluid (CVF) of women with symptoms of preterm labor is an excellent predictor of women who will not deliver within 2 weeks of testing. Preliminary studies suggest interleukin (IL)-6 performs similarly to fFN. The positive predictive values of both these assays are poor. Inconsistent specimen collection may explain this poor performance. The objective of this study was to validate the clinical utility of cervicovaginal IL-6 and investigate the utility of the IL-6:albumin ratio to predict delivery within 14 days. Methods: We quantified albumin and IL-6 with the DPC Immulite® in 660 CVF specimens collected for physician-ordered fFN analysis. The clinical utility of IL-6 and IL-6:albumin to predict delivery within 14 days of collection was determined. Results: The sensitivity, specificity, and positive and negative likelihood ratios for delivery within 14 days were 65%, 87%, 4.8, and 0.4, respectively, for fFN and 35%, 91%, 3.8, and 0.7 for IL-6, with a 250 ng/L cutoff. With a preterm delivery prevalence of 4.7%, positive and negative predictive values were 19%, and 98%, respectively for fFN and 16% and 97% for IL-6. The areas under the ROC curves were 0.71 and 0.51 for IL-6 and IL-6:albumin, respectively. Odds ratios for delivery within 14 days of collection were 11.8 (P <0.0001), 5.5 (P ؍ 0.0001), and 2.4 (P ؍ 0.06) for fFN, IL-6, and IL-6:albumin, respectively. Conclusions: Cervicovaginal IL-6 may have utility for predicting preterm labor while offering the potential for substantial cost-savings. Assay performance characteristics are not improved by normalizing IL-6 to albumin.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2001
Objective: To compare the cervicovaginal cytokines IL-1b, IL-6 and IL-8 with fetal ®bronectin (fFN) and cervical dilatation in the prediction of preterm delivery. Study design: Cervicovaginal cytokine concentration and fFN status were measured in 104 women with symptoms of preterm labour and intact membranes between 24 0 and 33 6 weeks and related to delivery within 2 and 7 days. Results: A group of 18% had cervical dilatation ! 1 cm and 18% were positive for fFN. Preterm delivery within 2 and 7 days occurred in 5 and 12%, respectively. Only IL-6 demonstrated any ability to predict delivery within 2 and 7 days (area under the ROC curve 0X63 and 0.75, respectively). Using 35 pg/ml (75th centile) as a cut-off, IL-6 had a sensitivity and speci®city of 60 and 77% for predicting delivery within 2 days, and 62 and 80% for predicting delivery within 7 days. This is similar to the performance of cervical dilatation or fFN status. Conclusions: Measurement of cervicovaginal cytokines has limited ability to predict imminent delivery apart from cervicovaginal IL-6 concentrations, which, in this population, is equivalent to that of fFN status and cervical dilatation ! 1 cm. #
Maternal Serum and Cervicovaginal IL-6 in Patients with Symptoms of Preterm Labor
2020
Background: Preterm birth is a common problem in obstetrics. Objective: To measure maternal serum interleukin-6 in mothers with preterm uterine contractions and compare it with cervicovaginal interleukin-6 in the same women. Methods: In this crosssectional study, we measured interleukin-6 in the sera and cervicovaginal fluids of 86 women with preterm uterine contractions. All participants had an intact membrane. Interleukin-6 was measured by using ELISA method. Statistical analysis was done using U-Mann Whitney, Chi-Square and Kendall's tests. Results: The mean and median (Quartile25, Quartile75) of interleukin-6 in cervicovaginal fluid were higher than maternal serum interleukin-6. There was a statistically significant difference in the median of interleukin-6 in sera and cervicovaginal fluid (P<0.0001). There was no significant correlation between serum and cervicovaginal interleukin-6 (r=0.048, p=0.548). There was no significant correlation between serum and cervicovagina...
Increased interleukin-6 concentrations in cervical secretions are associated with preterm delivery
American Journal of Obstetrics and Gynecology, 1994
OBJECTIVE: This study sought to determin~ whether elevated concentrations of interteukin"6 in the cervical and vaginal secretions of patients between 24 and 36 weeks' gestation predicted subsequent preterm delivery and/or identified those preterm deliveries associated with maternal infec:tious morbidity. STUDY DESIGN: A cohort study was undertaken with cervical and vaginal samples collected from 161 consenting patients seen at 3-to 4-week intervals between 24 and 36 weeks. Levels of interleukin-6 were measured by immunoassay. Demographic, obstetric, neonatal, and laboratory data were analyzed by Fisher's exact test, Student t test, or Wilcoxon rank sum test, linear and multiple logistic regression, and receiver-operator characteristic curve analysis. RESULTS: There wete 4.2-fold and 3.4-fold increases in maximal cervical and vaginal interleukin-6 concentrations, respectively, among patients with preterm deliveries versus term deliveries. The receiver-operator characteristics curve analysis indicated that a single cervical interleukin-6value >250 pg!ml of sample buffer, present between 24 and 36 weeks' gestation, optimally identified patients with subsequent preterm deliveries versus term deliveries .(sensitivity 50.0%, 95% confidence interval 33.2% to 66.8%; specificity 85.0%, 95% confidence interval 78.8% to 91.2%; positive predictive value 47.2%, 95% confidence interval 30.9% to 63.5%; negative predictive value 86.4%, 95% confidence interval 80.4% to 92.4%). The optimal vaginal interleukin-6 cutoff value (> 125 pg/ml) proved less sensitive (45.5%, 95% confidence interval 28.5% to 62.4%) but equally specific (86.6%, 95% confidence interval 80.7% to 92.5%). Multiple logistic regression indicated that a cervical interleukin-6 level >250 pg/mi was an independent predictor of preterm delivery (adjusted odds ratio 4.8, 95% confidence interval 1.7 to 14.3). Cervical interleukin-6 levels did not correlate with cervical change or gestational age at sampling. Among patients delivered preterm there were no differences in the mean white blood cell count on admission or the prevalence of vaginal pathogens, alkaline vaginal pH, chorioamnionitis, or endometritis among patients with cervical interleukin-6 values > 150 or s 250. pg/ml. CONCLUSIONS: Cervical interleukin-6 is a relatively insensitive, although fairly specific discriminator of patients with subsequent preterm deliveries. Among patients delivered preterm, elevated cervical interleukin-6 values are not apparently associated with maternal infectious morbidity. (AM J OBSTET GYNECOL 1994;171 :1097-102.) Key words: Interleukin-6, premature labor, rupture of membranes Clinical methods of detecting women at risk for preterm delivery are insensitive and nonspecific. The presence of fetal fibronectin in cervical and vaginal secretions between 24 and 36 weeks has been shown to be predictive of subsequent preterm delivery in symptomatic'· 2 and initially asymptomatic" women. These studies suggest that other biochemical indicators of pre term delivery may be identifiable in cervical and vaginal secretions.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2011
The outcome for babies delivered after 34 weeks' gestation is generally good, but deliveries at extreme prematurity between 24 and 32 weeks are at high risk of complications. Previous studies investigating risk factors predictive for premature delivery have demonstrated a clear association between ultrasonographic cervical length and preterm delivery. Another possible preterm delivery predictive risk factor is the concentration of cervical interleukin-6 (IL-6). Through increased production of prostaglandins, this cytokine seems to be involved in events leading to cervical ripening and uterine contractions. This observational prospective study was designed to investigate cervical IL-6 presence and concentrations for preterm delivery, alone and in association with cervical length as a predictive diagnostic test for preterm delivery in high-risk symptomatic women. The study subjects were 100 women between 24 and 34 weeks of gestation with intact membranes but threatened preterm labor who had been admitted to a hospital in Spain from 2006 to 2008. Cervical fluid was analyzed with transvaginal scan to determine cervical length, and a cervical swab was taken for detection of IL-6. Statistical tests performed included 2 test, Cox and logistic regression, receiver operating characteristic curve analysis, and Kaplan-Meier survival analysis. Preterm delivery occurred in 35% of the babies born before 37 weeks and in 5% before 32 weeks. Cervical length was Ͻ15 mm in 12% and Ͻ30 mm in 62% of the subjects. Receiver operating characteristic curve analysis showed that an IL-6 value Ͼ210 pg/mL and a cervical length Ͻ30 mm were useful predictors of preterm delivery within 48 hours, within 7 days, and at Ͻ32, Ͻ34, and Ͻ37 weeks; there was no difference between the predictive accuracy of IL-6 and cervical length. Their additive predictive value was greater than either alone. These findings suggest that cervical IL-6 and cervical length are predictive risk factors for preterm delivery in symptomatic women at high risk and that when combined, the predictive accuracy of both is better than each test alone.
Cervicovaginal Biomarkers and C-reactive Protein Levels in Preterm and Term Labor
Objective: To assess the levels of cervicovaginal biomarkers (HCG and FFN) and serum CRP in primigravida women who terminated their gestation with term labor versus those who delivered prematurely. Design and setting: In this nested cohort study, 89 patients with symptoms of labor were enrolled in Beasat Hospital in Sanandaj, Capital in Kurdistan province, in Iran. Methods: Data regarding the patients' age, education, BMI, and hemoglobin level were recorded. Laboratory test results including the levels of CRP, FFN, and HCG were also recorded and patients were monitored until the end of gestation to obtain the ultimate pregnancy result (preterm/term). The mean difference between groups was determined using the t test. Results: 43 patients were 21-24 years old, 53.93% patients had a BMI of 20-24, and 63.87% patients had term labor. 49.43% were CRP negative . 26 and 80 patients were HCG negative and FFN positive respectively. FFN and CRP were the only markers that were significantl...
BMC Pregnancy and Childbirth, 2018
Background: A hypothesis of preterm parturition is that the pathogenesis of spontaneous preterm birth (sPTB) may be associated with an inflammatory process. Based on this theory, we have hypothesized that an inflammatory biomarker, procalcitonin (PCT), may be a good predictive marker of sPTB at the admission for threatened preterm labour (TPL). The present study was aimed to investigate the association between serum PCT and sPTB in women with TPL and to evaluate whether PCT levels may predict sPTB in women with TPL within 7 or 14 days. Methods: In a prospective observational laboratory-based study, women with singleton pregnancies, TPL between 24 and 36 weeks and intact membranes, were enrolled between January 2014 and June 2016. Participants received routine medical management of TPL (tocolysis with atosiban, antenatal corticosteroids, and biological tests at admission (C-reactive protein, white blood cell count, and PCT measured on electrochemiluminescence immunoassay)). The primary endpoint was sPTB before 37 weeks of gestation. The value of serum PCT levels to predict sPTB within 7 or 14 days were evaluated using receiver-operating curves (ROC) analysis. Results: A total of 124 women were included in our study. PCT levels did not statistically differ between women with sPTB (n = 30, 24.2%) and controls (n = 94) (median in ng/mL [interquartile range]: 0.043 [0.02-0.07] compared to 0.042 [0.02-0.13], respectively; P = 0.56). PCT levels did not also statistically differ between women with sPTB within 7 days (n = 7, 5.6%) or 14 days (n = 12, 9.7%) after testing and controls. Moreover, subgroup analysis revealed no difference among PCT levels at admission between 24 and 28 weeks, between 28 and 32 weeks and over 32 weeks, and controls. On the basis of the receiver-operating characteristic curve, the highest sensitivity and specificity corresponded to a PCT concentration of 0.038 ng/mL, with poor predictive values for sPTB within 7 or 14 days. Conclusion: Serum PCT was not relevant to predict sPTB within 7 or 14 days in women admitted with TPL between 24 and 36 weeks, and thus it is not a suitable biological marker to confirm the hypothesis of an inflammatory process associated with preterm parturition. Trial registration: Clinicaltrials.gov (NCT01977079), Registered