Cervicovaginal IL-6 Research Articles

Air pollution and inflammation: Findings from concurrent repeated measures of systemic and reproductive tract cytokines during term pregnancy in Mexico City

BackgroundEnvironmental exposures are associated with a number of outcomes including adverse pregnancy outcomes. Although inflammation is hypothesized to play a role, the mechanistic pathways between environmental exposures and adverse health outcomes, including associations between exposures and longitudinal measures of systemic and reproductive tract inflammation, need elucidation. ObjectivesThis study was conducted to evaluate whether exposure to air pollution is associated with immunologic responses in the systemic circulation and lower reproductive tract, and to evaluate whether systemic and reproductive tract immunologic responses are similar. MethodsWe quantified repeated measures of cytokines from cervico-vaginal exudates and serum obtained concurrently among 104 women with term pregnancies and estimated PM10 and CO exposure using the monitor nearest each participant's residence. Serum and cervico-vaginal cytokines were compared using Wilcoxon signed-ranks test and Spearman rank correlations for select gestational months. We used intraclass correlation coefficients (ICCs) to quantify reproducibility of cytokine measurements, and Tobit regression to estimate associations between air pollution and cytokines. ResultsMedian cervico-vaginal levels of IL-6, Eotaxin, IP-10, MCP-1, MIP-1α, MIP-1β, and TNFα were higher than corresponding serum cytokines, significantly so for IL-6 and IP-10. Cervico-vaginal and serum cytokines were not correlated, but cytokines from the same fluid were correlated. ICCs for most serum cytokines were ≤0.40, while ICCs were higher in cervico-vaginal cytokines (range 0.52–0.83). IP-10 and Eotaxin had the highest ICCs for both cytokine sources. In adjusted models, PM10 was positively associated with serum cytokines IL-6, IP-10, MIP-1β and Eotaxin but inversely associated with cervico-vaginal cytokine TNFα, IP-10, MIP-1β, MCP-1 and Eotaxin, controlling for false discovery rate. CO was inversely associated with cervico-vaginal TNFα, IL-6, MIP-1β, MCP-1 and Eotaxin. ConclusionsInflammatory processes are compartment-specific. Systemic inflammatory markers may provide information on immunologic processes and response to environmental exposures, but are not proxies for lower reproductive tract inflammation.

Stress, anxiety, and depression of both partners in infertile couples are associated with cytokine levels and adverse IVF outcome.

Psychiatric disorders and stress in women have been associated with poor IVF outcome. We hypothesized that both partners in the infertile couples are emotionally affected, and cytokines in both may link psychological to reproductive outcome. Forty-five IVF couples completed questionnaires and visual analog scales for stress and psychiatric disorders and had cytokines measured in serum, semen, cervicovaginal, and follicular fluids. Multivariable analyses, t tests, maximum likelihood estimates, Spearman correlation, and data mining were applied. Psychopathology was found in 72% of the couples. Female and male stress were associated with stress, anxiety, and depression in the respective partner, and with a lower likelihood of clinical pregnancy and live birth. Lower serum TGF-β and higher cervicovaginal IL-6 and IL-1β were associated with stress. In data decision trees, cytokines in relation to stress and depression in both partners were found indicative of IVF failure. Infertile couples may benefit from psychiatric evaluation and treatment of both partners.

Prediction of impending preterm delivery based on sonographic cervical length and different cytokine levels in cervicovaginal fluid in preterm labor.

The aim of this study was to determine whether cervicovaginal interleukin (IL)-1β, IL-6 and IL-8 levels, and cervical length, alone or in combination, could predict impending preterm delivery in women with preterm labor and intact membranes. Cervicovaginal swab samples for IL-1β, IL-6, and IL-8 assays were taken from 136 consecutive women with preterm labor (23-34 weeks) before the transvaginal ultrasonography examination to measure cervical length. The primary outcome measurement was spontaneous preterm delivery within 7 days of sampling. Spontaneous preterm delivery within 7 days occurred in 28.6% (39/136) of patients. Receiver-operator characteristic (ROC) curves indicated that cervical length (P < 0.001), cervicovaginal IL-6 (P < 0.001) and IL-8 (P = 0.014), but not IL-1β, could predict delivery within 7 days. According to the logistic regression analysis, high cervicovaginal IL-8 (P = 0.008) and IL-6 (P = 0.038) levels and short cervical length (P < 0.001) were significantly associated with delivery within 7 days, even after controlling for baseline variables. A combination of cervix length and cervicovaginal IL-8 increased the specificity of detecting delivery within 7 days to 92.8%, which was superior to either test alone (P < 0.001), but the sensitivity was only 56.4%. In women with preterm labor, among the parameters assessed, cervicovaginal IL-6 and IL-8 and cervical length are the most important parameters in predicting impending preterm delivery. A combination of cervix length and cervicovaginal IL-8 appeared to be the best for predicting impending preterm delivery, but the relatively low sensitivity of this test may limit its clinical usefulness.

Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in women with preterm labor and intact membranes

Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2). This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N= 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N= 306). MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%,specificity 78%, positive predictive value 38%, and negative predictive value 97%. High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.

Interleukin 6 and fetal fibronectin as a predictors of preterm delivery in symptomatic patients

Preterm delivery is the leading cause of neonatal mortality and morbidity. The rate of preterm births has been estimated to be about 15 million, which accounts for 11.1% of all live births worldwide. The purpose of this study was to evaluate the cervico-vaginal (CVF) cytokine IL-6 and fetal fibronectin (fFN) status as predictors of preterm delivery in patients with symptoms of preterm labor. Patients with symptoms suggestive of preterm labor were recruited from September 2013 to March 2014. Vaginal swabs were taken for fetal fibronectin test (fFN) and CVF IL-6. Antibiotics, steroids and tocolytics were administered, where appropriate. The outcome was measured by the occurrence of preterm delivery within 14 days from the day of hospital admission. Cut-off value of 1305 pg/mL for the concentration of IL-6 in the CVF was the best predictor of preterm delivery, with the sensitivity of 69.4% and specificity of 68.2%. Patients with positive fFN test had the OR of 6.429 (95%CI 1.991-20.758) to deliver prematurely. The multivariate analysis of combined fFN and CVF IL-6 tests resulted in risk of 86.7% to deliver prematurely, if both tests were positive. The combination of both tests performed better than the individual tests and decreased the false positive rate, which in turn reduced the chances for inappropriate patient treatment, bringing down the costs.

82: Detection of microbial invasion of the amniotic cavity by analysis of cervicovaginal proteins in preterm labor with intact membranes

Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor (PTL) and is associated with maternal and neonatal infectious morbidity. MIAC is often occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort with PTL and to validate the test in an independent cohort. Prospective study of women with PTL who had amniocentesis to screen for MIAC. MIAC was defined as a positive culture and/or 16S-rDNA by PCR. Nine candidate CVF proteins were analyzed by ELISA. Logistic regression was used to identify combinations of up to 3 CVF proteins that could accurately classify the Phase 1 cohort (N=108) into those with or without MIAC. The best models were selected based on ROC area-under-curve (AUC) in Phase 1. Model performance was then tested in a second cohort (Phase 2, N=306). MIAC was present in 15% of cases in Phase 1, 9% in Phase 2. A 3-marker CVF model using IL6, Gro-α, and IGF-BP1 had AUC 0.87 in Phase 1 and AUC 0.78 in Phase 2. Two-marker CVF models using IL6+Gro-α or AFP+Gro-α performed similarly in Phase 2 (AUC 0.78, 0.75 respectively), but were not superior to CVF-IL6 alone (AUC 0.80, Figure). A cut-off value of CVF-IL6 >463 pg/ml (which had 81% sensitivity in Phase 1) predicted MIAC in Phase 2 with sensitivity 79%, specificity 78%, PPV 38%, NPV 97%, +LR 3.6, -LR 0.27. CVF-IL6 was also a strong predictor of severely elevated amniotic fluid IL6 (≥11.3 ng/mL) in phase 2 (AUC 0.83). Cervicovaginal fluid IL-6, alone or in combination with Gro-α, is strongly associated with MIAC. If developed into a bedside test or rapid lab assay, a test based on cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.

Cervicovaginal Levels of Proinflammatory Cytokines Are Increased During Chlamydial Infection in Bacterial Vaginosis But Not in Lactobacilli-Dominated Flora

The purpose of this study was to assess the cervicovaginal levels of proinflammatory cytokines in women with Chlamydia trachomatis (CT) infection in the presence of bacterial vaginosis (BV) and normal flora and to compare with those negative for CT. In this cross-sectional study, nonpregnant women were enrolled at 2 outpatient clinics and at 1 primary medical care unit in São Paulo State, Brazil. Cervicovaginal samples from 256 women with BV, of which 68 (26.6%) had concomitant CT infection and 188 (73.4%) were CT-negative, were measured for interleukin-1β (IL-1β), IL-6, and IL-8 by enzyme-linked immunosorbent assay. A matching number of samples from women with normal flora, CT-positive (n = 68) and negative (n = 188), were evaluated as control. Cytokine levels were compared by Mann-Whitney test and differences were considered significant at p < .05. In CT-negative women, IL-1β was increased in BV (p < .001) when compared to normal flora, while the levels of IL-6 and IL8 were unchanged. The presence of CT infection was not associated with differences on cytokine levels in women with normal flora. However, women with BV had higher levels of IL-1β (p = .02), IL-6 (p = .02), and IL-8 (p = .03) in the presence of CT when compared to those who tested negative for CT. Detection of endocervical CT is associated with increased cervicovaginal IL-1β, IL-6, and IL-8 levels in women with concomitant BV but not in those with normal flora.

Noninvasive Prediction of Intra-amniotic Infection and/or Inflammation in Women With Preterm Labor: Various Cytokines in Cervicovaginal Fluid

To determine the value of cervicovaginal interleukin (IL)-1β, IL-6, and IL-8 in predicting intra-amniotic infection and/or inflammation (IAI) in women with preterm labor. Cervicovaginal fluid samples were collected for IL-1β, IL-6, and IL-8 measurements immediately before amniocentesis in 85 consecutive women with preterm labor. The IAI was defined as a positive amniotic fluid (AF) culture and/or an elevated AF IL-6 level (>2.6 ng/mL). Receiver-operating characteristic curves demonstrated that cervicovaginal IL-6 and IL-8, but not IL-1β, predicted IAI. Cervicovaginal IL-6 had a significantly higher area under the curve (AUC) than cervicovaginal IL-8 (P = .009). However, the AUCs for the cervicovaginal IL-6 and AF white blood cell (WBC) were not significantly different. Among measured cytokines, cervicovaginal IL-6 is the best marker to noninvasively identify IAI in women with preterm labor. Overall, this noninvasive parameter performed as well as AF WBC count for predicting IAI.

Predictive value of combined cervicovaginal cytokines and gestational age at sampling for intra‐amniotic infection in preterm premature rupture of membranes

To determine whether interleukin (IL)-1β, IL-6, and IL-8 in cervicovaginal fluid, alone or in combination with clinical risk factors, could predict intra-amniotic infection in women with preterm premature rupture of membranes (PPROM). A prospective cohort study. University teaching hospital. Women with singleton pregnancies presenting PPROM between 20 and 35weeks of gestation (n=76). Cervicovaginal fluid samples were collected for IL-1β, IL-6, and IL-8 measurements immediately before amniocentesis. Amniotic fluid obtained by amniocentesis was cultured and the white blood cell count was determined. Clinical risk factors analyzed included demographics and gestational age. Cervicovaginal concentrations of cytokines were measured using a multiplex bead array assay. A positive amniotic fluid culture. The prevalence of a positive amniotic fluid culture was 46.1% (35/76). Stepwise multivariate regression analysis yielded a model using cervicovaginal IL-6 and gestational age at sampling with the area under the curve (AUC) of 0.807 for predicting intra-amniotic infection. The AUC for this model was significantly higher than either parameter retained in this model but no differences were observed between the AUC of this model based on non-invasive variables, and amniotic fluid white blood cell count using invasive amniocentesis for the prediction of intra-amniotic infection. Among measured cytokines, the combination of cervicovaginal IL-6 and gestational age appears to be best in predicting intra-amniotic infection and allows for a considerably better accuracy than the use of either factor alone. Overall, this combination performed as well as amniotic fluid WBC count for predicting intra-amniotic infection.

Evaluation of the lymphocyte trafficking drug FTY720 in vaginal tissues

FTY720 is an immunomodulatory agent that reduces lymphocytes in peripheral tissues and circulation. Such agents may be effective as vaginal microbicides for HIV prevention. Systemic or vaginal application of FTY720 may reduce lymphocyte concentrations in genital tissues, reducing HIV target cell numbers. Five female pigtail macaques received topical vaginal gel FTY720 (n = 2), intravenous (i.v.) FTY720 (n = 2), or placebo gel (n = 1) in this pilot study. Circulating and mucosal lymphocytes and genital mucosa, cytokines, and tissue histology were analyzed to document topical and i.v. FTY720 effects. Topical and i.v. FTY720 appeared to decrease the levels of cervicovaginal IL-8, IL-1ra, and genital inflammatory cells. Small sample size precluded statistical analysis. Topical administration had no overt adverse effects. This study introduces FTY720 as an immunomodulatory agent for the vaginal mucosa, compares topical effects to those of i.v. administration, and provides the basis for future studies involving FTY720 for HIV prevention.

485: Early prediction of spontaneous preterm birth

Jelle M. Schaaf, Anita Ravelli, Ben Mol, Ameen Abu Hanna Academic Medical Center, Medical Informatics, Amsterdam, Netherlands, Academic Medical Center, Medical Informatics, Amsterdam, Netherlands, Academic Medical Center, Department of Obstetrics and Gynaecology, Amsterdam, Netherlands OBJECTIVE: Many separate risk factors for preterm birth have been identified but the pathogenesis of preterm birth and the prognostic value of their combination is not well understood. A prognostic model for assigning risk of preterm birth to individual women is lacking. Assessment of womens risk is essential in reducing the impact of preterm birth as it is the leading cause of perinatal morbidity and mortality. This study aims to develop a prognostic model for predicting preterm birth after a spontaneous onset of labour. STUDY DESIGN: Data were obtained from the Netherlands Perinatal Registry (PRN). We included all singleton pregnancies 22 weeks of gestation that resulted in a spontaneous onset of birth. Preterm birth was defined as birth before 37 completed weeks of gestation. We used logistic regression methods to develop the prognostic model for predicting preterm birth. We used the Hosmer-Lemeshow C-statistic to assess the models goodness of fit, and the AUC to assess models discriminative abilities. RESULTS: We analyzed data of 1,011,047 women who gave birth between January 1999 and December 2007 in The Netherlands. The incidence of spontaneous preterm birth was 5.6% (n 56,698). Independent risk factors of preterm birth were history of preterm birth, maternal age 35 years, Black or South-Asian ethnicity, low socioeconomic status, living in a deprived area, being nulliparous, getting late into obstetric care and being pregnant of a male infant (table 1). The models Hosmer Lemeshow C-test had p-value 0.0001, and the AUC was 0.64. CONCLUSION: The developed prognostic model predicting preterm birth, applicable around 20 weeks of gestation, had fair discrimination ability and poor goodness of fit. It confirms the known risk factors of preterm birth and identifies new ones particularly being late into obstetric care and living in a deprived area. Some risk factors can potentially be influenced by interventions before and during pregnancy in order to reduce the incidence of preterm birth. Our prediction model will be improved with the addition of data on laboratory and ultrasound results. 486 Non-invasive prediction of intra-amniotic infection and/or inflammation in women with preterm labor: various cytokines in cervicovaginal fluid Jeong Woo Park, Kyo Hoon Park, Sung Youn Lee Seoul National University College of Medicine, Deptartment of Obstetrics and Gynecology, Seoul, Korea, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Department of Obstetrics and Gynecology, Seongnam-si, South Korea OBJECTIVE: To determine the value of cervicovaginal interleukin (IL)1 , IL-6, and IL-8 in predicting intra-amniotic infection and/or inflammation (IAI) in women with preterm labor and intact membranes, and to compare the predictability with the amniotic fluid (AF) white blood cell (WBC) count. STUDY DESIGN: Cervicovaginal secretions were collected immediately before amniocentesis in 86 consecutive women admitted for preterm labor (20 0-34 6 weeks) with singleton pregnancies. AF obtained by amniocentesis was cultured and the WBC count was determined, and the following cytokines were measured in cervicovaginal fluid: IL-1 , IL-6, and IL-8. IAI was defined as a positive AF culture for microorganisms and/or the presence of high levels ( 2.6 ng/mL) of IL-6 in AF. RESULTS: The prevalence of a positive AF culture was 9% (8/86) and the prevalence of intra-amniotic inflammation was 23% (20/86). Receiver operating characteristic (ROC) curves demonstrated that cervicovaginal IL-6 and IL-8, but not IL-1 , had abilities to predict IAI. Cervicivaginal IL-6 had a significantly higher area under the curve (AUC) than cervicovaginal IL-8 (0.85 [95% CI, 0.76-0.92]) vs. 0.70 [95% CI, 0.59-0.79], respectively; P 0.01). However, the AUCs for the cervicovaginal IL-6 and AF WBC were not significantly different. Using ROC curve, the best cut-off value for cervicovaginal IL-6 in predicting IAI was 0.216 ng/mL, with a sensitivity of 75% and a specificity of 86%. CONCLUSION: Cervicovaginal IL-6 is the most important non-invasive marker for predicting IAI in women with preterm labor. Overall, the measurement of the cervicovaginal IL-6 level performed as well as the AF WBC counts for predicting IAI. www.AJOG.org Doppler Assessment, Fetus, Prematurity Poster Session III

450: Permeability properties of cervical mucus in women at high risk for preterm birth

Receiver-operating characteristics (ROC) curve and logistic regression analysis were used for statistical analysis. RESULTS: The prevalence of a positive AF culture was 45.9% (34/74). Univariate analyses showed that both all the cytokines tested in cervicovaginal fluids and gestational age had a significant relationship with intra-amniotic infection. Stepwise multivariate regression analysis yielded a model using cervicovaginal IL-6 and gestational age with the area under the ROC curve (AUC) of 0.829 for predicting intra-amniotic infection. The AUC for this model was significantly higher than either parameter retained in this model, but no differences were observed between the AUC of this model and AF WBC for the prediction of intra-amniotic infection. CONCLUSION: In women with PPROM, a model combining cervicovaginal IL-6 and gestational age provides a better prediction of intraamniotic infection than either variable alone. Overall, this non-invasive model performed as well as AF WBC count for predicting intraamniotic infection.

501: Ethnic variations in cervicovaginal MMP8 and IL-6 levels in preterm birth

501: Ethnic variations in cervicovaginal MMP8 and IL-6 levels in preterm birth

Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling

Screening to prevent spontaneous preterm birth: systematic reviews of accuracy and effectiveness literature with economic modelling

Diagnostic Accuracy of Cervicovaginal Interleukin-6 and Interleukin-6:Albumin Ratio as Markers of Preterm Delivery

Abstract 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 &amp;lt;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.

Diagnostic Accuracy of Cervicovaginal Interleukin-6 and Interleukin-6:Albumin Ratio as Markers of Preterm Delivery

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. 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. 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. 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.

Assessing the Pregnant Patient: A Review of New Potential Screening Tests

Nearly 28,000 infants die each year. Some causes of infant death cannot be prevented. Others could perhaps be prevented if physicians were able to predict and/or diagnose disease early enough to allow treatment. This review focuses on new laboratory tests that could impact the leading causes of infant mortality. It is unclear if any of these tests will become incorporated into clinical practice, but all demonstrate potential advantages over currently available laboratory testing. Urine invasive trophoblast antigen may improve the sensitivity of screening for Down syndrome. Cervicovaginal IL-6 has a negative predictive value identical to fetal fibronectin but is far less expensive. Serum soluble fms-like tyrosine 1 and placental growth factor may have the ability to predict preeclampsia at 5 to 6 days prior to the onset of symptoms. Finally, a new FDA-approved, rapid PCR for Group B streptococcus offers a faster turnaround time.

Atosiban et nifédipine pour le traitement de la menace d’accouchement prématuré

Microbial invasion of the amniotic cavity (MIAC) is common in early preterm labor and is associated with maternal and neonatal infectious morbidity. MIAC is usually occult and is reliably detected only with amniocentesis. We sought to develop a noninvasive test to predict MIAC based on protein biomarkers in cervicovaginal fluid (CVF) in a cohort of women with preterm labor (phase 1) and to validate the test in an independent cohort (phase 2).This was a prospective study of women with preterm labor who had amniocentesis to screen for MIAC. MIAC was defined by positive culture and/or 16S ribosomal DNA results. Nine candidate CVF proteins were analyzed by enzyme-linked immunosorbent assay. Logistic regression was used to identify combinations of up to 3 proteins that could accurately classify the phase 1 cohort (N = 108) into those with or without MIAC. The best models, selected by area under the curve (AUC) of the receiver operating characteristic curve in phase 1, included various combinations of interleukin (IL)-6, chemokine (C-X-C motif) ligand 1 (CXCL1), alpha fetoprotein, and insulin-like growth factor binding protein-1. Model performance was then tested in the phase 2 cohort (N = 306).MIAC was present in 15% of cases in phase 1 and 9% in phase 2. A 3-marker CVF model using IL-6 plus CXCL1 plus insulin-like growth factor binding protein-1 had AUC 0.87 in phase 1 and 0.78 in phase 2. Two-marker models using IL-6 plus CXCL1 or alpha fetoprotein plus CXCL1 performed similarly in phase 2 (AUC 0.78 and 0.75, respectively), but were not superior to CVF IL-6 alone (AUC 0.80). A cutoff value of CVF IL-6 ≥463 pg/mL (which had 81% sensitivity in phase 1) predicted MIAC in phase 2 with sensitivity 79%, specificity 78%, positive predictive value 38%, and negative predictive value 97%.High levels of IL-6 in CVF are strongly associated with MIAC. If developed into a bedside test or rapid laboratory assay, cervicovaginal IL-6 might be useful in selecting patients in whom the probability of MIAC is high enough to warrant amniocentesis or transfer to a higher level of care. Such a test might also guide selection of potential subjects for treatment trials.

Proinflammatory cytokines and other indications of inflammation in cervico-vaginal secretions and preterm delivery

To compare the usefulness of evaluating cervico-vaginal concentrations of proinflammatory cytokines (interleukin [IL]-1alpha, IL-1beta, IL-6 and IL-8) and procalcitonin (PCT), as well as serum levels of C-reactive protein (CRP), leucocytosis and band form granulocytes in the prediction of preterm delivery (PTD). A total of 65 pregnant women experiencing preterm labor (PTL) were enrolled in the study. Concentrations of the studied markers in women who delivered prematurely and in women who, after treatment, delivered at term were compared. Receiver operator characteristic (ROC) curve analysis was used for all study parameters. Cervico-vaginal IL-6 and procalcitonin as well as serum CRP concentrations were higher in women who delivered prematurely than in those who delivered near term. A cervico-vaginal IL-6 level greater than 660 pg/ml was the best predictive value of preterm delivery (sensitivity, 50%; specificity 90%; positive predictive value [PPV], 85%; NPV, 62%; likelihood ratio, 5.17). Moreover, the area under the ROC curve of 0.75 for cervico-vaginal IL-6 was greater than for other markers. Although cervico-vaginal concentrations of procalcitonin and serum concentration of CRP are higher in women who deliver prematurely, only cervico-vaginal concentration of IL-6 is a good predictor of preterm delivery.

Predicting preterm delivery: comparison of cervicovaginal interleukin (IL)-1β, IL-6 and IL-8 with fetal fibronectin and cervical dilatation

Objective: To compare the cervicovaginal cytokines IL-1β, IL-6 and IL-8 with fetal fibronectin (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=0.63 and 0.75, respectively). Using 35 pg/ml (75th centile) as a cut-off, IL-6 had a sensitivity and specificity 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.