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

AIMS: The aim of this study was to determine whether cervicovaginal interleukin (IL)-1ß, 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. MATERIAL AND METHODS: Cervicovaginal swab samples for IL-1ß, 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. RESULTS: 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-1ß, 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%. CONCLUSION: 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.

Prediction of the risk of cesarean delivery after labor induction in twin gestations based on clinical and ultrasound parameters.

AIMS: To develop a model based on clinical and ultrasound parameters to predict the risk of cesarean delivery after labor induction in near-term twin gestations. METHODS: This retrospective cohort study included 189 consecutive women with twin gestations at ≥ 36.0 weeks scheduled for labor induction. The Bishop score and transvaginal ultrasonographic measurements of cervical length were obtained immediately before labor induction. Parameters studied included maternal age, height, weight, parity, gestational age, Bishop score, cervical length, epidural analgesia, method of conception, chorionicity and birth weight. Prostaglandin E2 (dinoprostone) and oxytocin were used for labor induction. Logistic regression analysis and receiver operating characteristic curve were used to generate a predictive model for cesarean delivery. RESULTS: Fifty (26.5%) of the 189 women had cesarean deliveries. According to logistic regression analysis, maternal height (P = 0.004), parity (P = 0.005) and cervical length (P = 0.016), but not Bishop score (P = 0.920), were identified as independent predictors of cesarean delivery. A risk score based on a model of these three parameters was calculated for each patient. The model was shown to have an adequate goodness of fit (P = 0.201) and the area under the curve was 0.722, indicating fairly good discrimination. CONCLUSIONS: Maternal height, parity and cervical length were independent parameters for predicting the risk of cesarean delivery after labor induction in twin gestations. A predictive model using these parameters may provide useful information for deciding whether or not to induce labor.

Non-invasive prediction of intra-amniotic infection and/or inflammation in patients with cervical insufficiency or an asymptomatic short cervix (≤15 mm).

PURPOSE: To identify non-invasive parameters to predict intra-amniotic infection and/or inflammation (IAI) in patients with cervical insufficiency or an asymptomatic short cervix (≤15 mm). METHODS: This retrospective cohort study included 72 asymptomatic women with cervical insufficiency (n = 54) or an asymptomatic short cervix (n = 18) at 17-28 weeks. Maternal blood was collected for the determination of the C-reactive protein (CRP) level and white blood cell (WBC) count, and sonography was performed to measure the cervical length shortly after amniocentesis. Amniotic fluid (AF) was cultured and interleukin-6 (IL-6) level and WBC count were determined. RESULTS: The prevalence of intra-amniotic inflammation and a positive AF culture was 22.2 % (16/72) and 8.3 % (6/72), respectively. The best cut-off value for AF IL-6 in predicting the presence of intra-amniotic infection was ≥7.6 ng/mL and was used to diagnose the presence of intra-amniotic inflammation. Women with intra-amniotic inflammation, regardless of culture results, were at increased risk for preterm delivery and adverse outcomes compared to women without intra-amniotic inflammation. In multivariable regression, CRP was the only non-invasive variable statistically significantly associated with IAI. Moreover, the area under the curves for the CRP and AF WBC were not significantly different. CONCLUSIONS: In women with cervical insufficiency or a short cervix, the risk for IAI can be predicted fairly and non-invasively by measurements of serum CRP. Overall, this non-invasive parameter appears to have similar accuracy to the AF WBC counts for predicting IAI.

Clinical and sonographic parameters at mid-trimester and the risk of cesarean delivery in low-risk nulliparas.

BACKGROUND: To examine the potential clinical and sonographic parameters at mid-trimester that predict the risk of intrapartum cesarean delivery at term among low-risk nulliparas. METHODS: This prospective study recruited nulliparas with singleton low-risk pregnancies at 20.0-24.0 weeks. Sonographic measurement of the cervical length and fetal biometry was performed. The data collected at enrollment included maternal age, measured weight at first prenatal visit to the hospital, current weight, height, fetal biometric parameters, and cervical length. A multivariate analysis was conducted, with control for known intra- and postpartum confounding factors associated with cesarean delivery, including sex of the fetus. RESULTS: Based on multivariate analyses of 652 women, of all variables at mid-trimester, only maternal height was significantly associated with increased risk of cesarean delivery (61, 9.4%), whereas for intra- or postpartum variables, induction of labor, epidural analgesia, male gender, and nightshift delivery showed statistically significant association with the risk of cesarean delivery. CONCLUSIONS: Maternal height and fetal gender, as measured at mid-trimester, are potential independent predictors for the risk of intrapartum cesarean delivery at term in low-risk nulliparas; however, sonographic measurements of the cervical length, fetal biometric ratio, maternal age, and current weight at mid-trimester were not predictive of cesarean delivery at term. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:235-242, 2015.

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

OBJECTIVE: To determine whether interleukin (IL)-1ß, 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). DESIGN: A prospective cohort study. SETTING: University teaching hospital. POPULATION: Women with singleton pregnancies presenting PPROM between 20 and 35 weeks of gestation (n = 76). METHODS: Cervicovaginal fluid samples were collected for IL-1ß, 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. MAIN OUTCOME MEASURE: A positive amniotic fluid culture. RESULTS: 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. CONCLUSIONS: 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.

Intra-amniotic infection/inflammation as a risk factor for subsequent ruptured membranes after clinically indicated amniocentesis in preterm labor.

The aim of this study was to determine whether intra-amniotic infection/inflammation (IAI) was associated with subsequent ruptured membranes in women with preterm labor and intact membranes who had a clinically indicated amniocentesis. This retrospective cohort study included 237 consecutive women with preterm labor (20-34.6 weeks) who underwent amniocentesis. The clinical and laboratory parameters evaluated included demographic variables, gestational age, C-reactive protein (CRP) and amniotic fluid (AF) white blood cell, interleukin-6 (IL-6) and culture results. IAI was defined as a positive AF culture and/or an elevated AF IL-6 level (>2.6 ng/mL). The primary outcome was ruptured membranes in the absence of active labor occurring within 48 hours of amniocentesis. Preterm premature rupture of membranes subsequently developed in 10 (4.2%) women within 48 hr of amniocentesis. Multivariate analysis demonstrated that only IAI was independently associated with the ruptured membranes occurring within 48 hr of amniocentesis. In the predictive model based on variables assessed before amniocentesis, only CRP level was retained. IAI is an independent risk factor for subsequent ruptured membranes after clinically indicated amniocentesis in preterm labor. Prior to amniocentesis, measurement of serum CRP level can provide a risk assessment for the subsequent development of ruptured membranes after the procedure.

The change in cervical length over time as a predictor of preterm delivery in asymptomatic women with twin pregnancies who have a normal mid-trimester cervical length.

AIM: To determine whether or not the change in cervical length (CL) over time is valuable in predicting spontaneous preterm delivery (SPTD) in asymptomatic twin pregnancies with a normal mid-trimester CL (>25 mm). METHODS: This was a prospective study including 190 consecutive asymptomatic twin gestations with a CL>25 mm at 20-24 weeks. The women underwent an initial CL measurement at the time of routine ultrasound examination between 20 and 24 weeks' gestation, followed 4-5 weeks later by a repeat CL measurement. The primary outcome measure was SPTD at <32 completed weeks' gestation. Multicollinearity was a concern in the multivariable model since change in CL and follow-up CL were highly correlated. RESULTS: The rate of SPTD at <32 weeks was 4.2%. Multiple logistic regression analyses demonstrated that the change in CL and the follow-up CL were significantly associated with SPTD before 32 weeks after adjusting for baseline covariate such as in vitro fertilization. The best cut-off values for the prediction of SPTD at <32 weeks' gestation were 13% for the change in CL with a sensitivity of 87.5% and a specificity of 63.2%. There was no significant difference in the area under the receiver operating characteristic curves between the change in CL and the follow-up CL. CONCLUSIONS: A greater change in CL is a good predictor of SPTD in asymptomatic twin pregnancies with a normal mid-trimester CL. However, the change in CL cannot provide data beyond the follow-up CL. In the setting of a normal mid-trimester CL, a follow-up CL measurement should be considered in asymptomatic twin pregnancies.

Bishop score and cervical length at 33-35 weeks of gestation and the risk of intrapartum cesarean delivery of twins.

AIM: The aim of this study is to determine the association between Bishop score and cervical length measured at 33-35 weeks of gestation and the intrapartum risk of cesarean delivery of twins. METHODS: This prospective observational study recruited women with vertex/vertex twin gestations at 33-35 weeks of gestation. Determination of the Bishop score and ultrasound measurement of the cervical length were performed. A regression model was constructed with control for known intrapartum and postpartum confounders. RESULTS: One hundred and forty-six women were analyzed; 18 women (12.3%) had cesarean deliveries during labor. Based on univariate analysis, the Bishop score at 33-35 weeks was significantly associated with the risk of intrapartum cesarean delivery of twins, whereas cervical length, maternal age, height, and weight at 33-35 weeks were not associated. Multivariate logistic regression analysis identified induction of labor and birth weight of the first-born twin, but not Bishop score, as independent predictors of intrapartum cesarean delivery of twins. CONCLUSIONS: A low Bishop score at 33-35 weeks of gestation was associated with an increased risk of intrapartum cesarean delivery of twin gestations. However, this relationship disappeared after adjusting for relevant intrapartum or postpartum confounders. Only labor induction and high birth weight of the first-born twin were independently associated with an increased risk of cesarean delivery in labor.

Relationship between maternal serum C-reactive protein, funisitis and early-onset neonatal sepsis.

The aim of this study was to determine whether maternal serum C-reactive protein (CRP) is of value in predicting funisitis and early-onset neonatal sepsis (EONS) in women with preterm labor or preterm premature rupture of membranes (PROM). This retrospective cohort study included 306 consecutive women with preterm labor or preterm PROM who delivered preterm singleton neonates (23-35 weeks gestation) within 72 hr of CRP measurement. The CRP level was measured with a highly sensitive immunoassay. The sensitivity, specificity, positive predictive value, and negative predictive value of an elevated serum CRP level (≥ 8 mg/L) were 74.1%, 67.5%, 32.8%, and 92.4% for funisitis, and 67.7%, 63.3%, 17.2%, and 94.6% for EONS, respectively. Logistic regression analysis demonstrated that elevated levels of serum CRP were significantly associated with funisitis and EONS, even after adjusting gestational age. The maternal serum CRP level obtained up to 72 hr before delivery is an independent predictor of funisitis and EONS in women with preterm labor or preterm PROM. A low serum CRP level (< 8 mg/L) has good negative predictive value in excluding funisitis and EONS, and may therefore be used as a non-invasive adjunct to clinical judgment to identify low-risk patients.

Prediction of imminent preterm delivery in women with preterm premature rupture of membranes.

AIMS: To develop a model based on non-invasive clinical parameters to predict the probability of imminent preterm delivery (delivery within 48 h) in women with preterm premature rupture of membranes (PPROM), and to determine if additional invasive test results improve the prediction of imminent delivery based on the non-invasive model. METHODS: Transvaginal ultrasonographic assessment of cervical length was performed and maternal serum C-reactive protein (CRP) and white blood cell (WBC) count were determined immediately after amniocentesis in 102 consecutive women with PPROM at 23-33+6 weeks. Amniotic fluid (AF) obtained by amniocentesis was cultured and interleukin-6 (IL-6) levels and WBC counts were determined. RESULTS: Serum CRP, cervical length, and gestational age were chosen for the non-invasive model (model 1), which has an area under the curve (AUC) of 0.804. When adding AF IL-6 as an invasive marker to the non-invasive model, serum CRP was excluded from the final model (model 2) as not significant, whereas AF IL-6, cervical length, and gestational age remained in model 2. No significant difference in AUC was found between models 1 and 2. CONCLUSIONS: The non-invasive model based on cervical length, gestational age, and serum CRP is highly predictive of imminent delivery in women with PPROM. However, invasive test results did not add predictive information to the non-invasive model in this setting.

Predicting outcomes of emergency cerclage in women with cervical insufficiency using inflammatory markers in maternal blood and amniotic fluid.

OBJECTIVE: To identify inflammatory markers in maternal blood and amniotic fluid that can predict outcomes of emergency cerclage in women with cervical insufficiency. METHODS: This retrospective cohort study included patients at 18-24 weeks of pregnancy who underwent amniocentesis before receiving emergency cerclage for cervical insufficiency between August 2004 and August 2013 at a university teaching hospital in South Korea. Total and differential white blood cell counts were measured during amniocentesis. Amniotic fluid was cultured and analyzed for the presence of interleukin (IL)-6 and IL-8. The primary outcome measure was spontaneous preterm delivery (SPTD) at less than 32weeks of pregnancy following cerclage placement. RESULTS: Of 37 patients, 18 (49%) experienced SPTD at less than 32weeks of pregnancy. These patients were found to have significantly more advanced cervical dilatation at presentation, as well as higher mean neutrophil-lymphocyte ratios (NLRs) and higher IL-6 and IL-8 levels in amniotic fluid in comparison with those who did not experience SPTD at less than 32weeks of pregnancy. In a multivariable analysis, a high NLR and high amniotic fluid IL-8 levels showed a significant correlation with the occurrence of SPTD at less than 32weeks of pregnancy (P=0.032). CONCLUSION: Pre-operative NLR and amniotic fluid IL-8 levels may be important markers for predicting emergency cerclage outcomes in women with cervical insufficiency.

Noninvasive prediction of intra-amniotic infection and/or inflammation in women with preterm labor: various cytokines in cervicovaginal fluid.

OBJECTIVE: To determine the value of cervicovaginal interleukin (IL)-1ß, IL-6, and IL-8 in predicting intra-amniotic infection and/or inflammation (IAI) in women with preterm labor. METHODS: Cervicovaginal fluid samples were collected for IL-1ß, 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). RESULTS: Receiver-operating characteristic curves demonstrated that cervicovaginal IL-6 and IL-8, but not IL-1ß, 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. CONCLUSIONS: 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.

The relationship between cord blood cytokine levels and perinatal factors and retinopathy of prematurity: a gestational age-matched case-control study.

PURPOSE: To investigate the relationship between cytokine levels in cord blood and perinatal factors and retinopathy of prematurity (ROP) in gestational age-matched, preterm, newborn infants. METHODS: Each of 20 premature singleton infants with ROP (gestational age < 32 weeks) was matched for gestational age, birth weight, and sex with two control infants without ROP. The concentration of 10 cytokines in cord blood extracted at birth was measured using a multiplex bead array assay. Data on maternal factors, labor and delivery characteristics, and neonatal parameters were also collected from both groups. The variables obtained were compared using the conditional logistic regression model. RESULTS: No differences in the levels of inflammatory cytokines (IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-12, interferon-γ, and TNF-α) and growth factors (insulin-like growth factor-1 and VEGF) were detected between the two groups. Multivariate conditional logistic regression analysis indicated that elevated maternal leukocyte count on admission and low Apgar scores at 5 minutes were significantly associated with an increased risk of ROP. CONCLUSIONS: Cytokine levels in cord blood are not associated with the risk of ROP, whereas elevated maternal blood leukocyte count and low Apgar score are associated with ROP. These data suggest that the determination of cytokine levels in cord blood samples in premature infants may be of little value for predicting ROP.

Noninvasive prediction of intra-amniotic infection and/or inflammation in preterm premature rupture of membranes.

OBJECTIVE: To develop a model based on noninvasive parameters to predict the probability of intra-amniotic infection and/or inflammation (IAI) in women with preterm premature rupture of membranes (PPROMs). METHODS: Maternal blood was collected for determination of the C-reactive protein (CRP) level and white blood cell (WBC) count immediately after amniocentesis in 171 consecutive women with PPROMs. Intra-amniotic infection and/or inflammation was defined as a positive amniotic fluid (AF) culture and/or an elevated AF interleukin 6 level (≥2.6 ng/mL). RESULTS: A risk score based on a model including maternal blood CRP, WBC, parity, and gestational age was calculated for each patient. The model was shown to have an adequate goodness of fit (P = .516), and the area under the receiver-operating characteristic curve was 0.848, indicating very good discrimination. CONCLUSION: The noninvasive model based on maternal blood CRP, WBC, parity, and gestational age is highly predictive of IAI in women with PPROMs.