宫颈分泌物中性粒细胞弹性蛋白酶预测早产临床研究

目的:探讨宫颈分泌物中性粒细胞弹性蛋白酶(NE)预测早产的临床价值。方法:选择2008年1月～2009年4月在我院住院保胎并分娩的孕28～36周单胎妊娠符合条件的78例为研究对象。检测宫颈分泌物NE水平,同时观察宫颈分泌物中性粒细胞百分率,比较不同保胎时间,不同分娩孕周,不同孕周胎膜早破(PPROM)NE水平及中性粒细胞百分率,并分析NE水平与中性粒细胞百分率的相关性。结果:保胎时间<7天宫颈分泌物NE水平及中性粒细胞百分率明显高于保胎时间7～14天和>14天(P<0.01);分娩孕周<32周宫颈分泌物NE水平和中性粒细胞百分率明显高于分娩孕周≥32周(P<0.01,P<0.05);孕周<32周发生PPROM明显高于孕周≥32周(P<0.01);孕周<32周的PPROM宫颈分泌物NE水平和中性粒细胞百分率明显高于孕周≥32周的PPROM(P<0.01);保胎时间<7天、分娩孕周<32周和≥32周及孕周<32周的PPROM宫颈分泌物NE水平与中性粒细胞百分率均呈正相关(P<0.05)。结论:保胎时间<7天、分娩孕周<32周以及孕周<32周的PPROM宫颈分泌物NE水平明显升高,宫颈分泌物NE可能成为早产预测指标,尤其对较早期的早产更有意义。     

Changes in cervical neutrophil elastase levels during the menstrual cycle

Purpose  

Cervical mucus plays an important role in host defense mechanisms and is involved in the ascendance of sperm. To determine the change of neutrophil mediators contained in cervical mucus, we measured total neutrophil elastase (NE) levels throughout the menstrual cycle.     

Cervical alterations in pregnancy

Spontaneous preterm birth (SPTB), defined as delivery before 37 weeks' gestation, remains a significant obstetric dilemma even after decades of research in this field. Although trends from 2007 to 2014 showed the rate of preterm birth slightly decreased, the CDC recently reported the rate of preterm birth has increased for two consecutive years since 2014. Currently, 1 in 10 pregnancies in the US still end prematurely. In this chapter, we focus on the “compartment” of the cervix. The goal is to outline the current knowledge of normal cervical structure and function in pregnancy and the current knowledge of how the cervix malfunctions lead to SPTB. We review the mechanisms by which our current interventions are hypothesized to work. Finally, we outline gaps in knowledge and future research directions that may lead to novel and effective interventions to prevent premature cervical failure and SPTB.     

Cervicovaginal HCG and cervical length for prediction of preterm delivery in asymptomatic women at high risk for preterm delivery

Objective  To predict the risk of preterm birth (<37 weeks) or early preterm birth (<34 weeks) by cervicovaginal HCG and cervical length measured between 24–28 weeks of gestation in asymptomatic women at high risk for preterm birth. Methods  This study was conducted in the departments’ of Obstetrics & Gynaecology and Immunopathology of the Postgraduate Institute of Medical Education and Research, Chandigarh, India. In 75 pregnant women at high risk for preterm birth because of prior one on more preterm births due to spontaneous labour or ruptured membranes, cervicovaginal HCG and cervical length (by TVS) were measured between 24–28 weeks of gestation. These parameters were correlated individually and in combination for prediction of preterm birth. Results  Of the 75 women, 20 (26.7%) delivered <37 weeks and 6 (8%) delivered <34 weeks. To predict delivery <37 weeks, cervical length <2.95 cm had a sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 75%, 80.1%, 71.4% and 90.7% respectively, and cervicovaginal HCG >4.75 mIU/ml had a sensitivity, specificity, PPV, and NPV of 70%, 61.81%, 40% and 85% respectively. To predict delivery <34 weeks, cervical length <2.65 cm had a sensitivity, specificity, PPV, and NPV of 50%, 85.50%, 23.08% and 95.16% respectively; and cervicovaginal HCG >14 mIU/ml had a sensitivity, specificity, PPV and NPV of 83.3%, 85.5%, 33.3% and 98.3% respectively. Cervical length was superior to predict delivery <37 weeks, whereas HCG was superior to predict delivery <34 weeks. Their combination was superior to predict preterm birth both <37 weeks or <34 weeks, than either parameter used alone. Conclusion  In high risk asymptomatic women, increased cervicovaginal HCG and reduced cervical length and between 24 to 28 weeks of gestation increased the risk of preterm delivery.     

The use of cervical length and change in cervical length for prediction of spontaneous preterm birth in asymptomatic twin pregnancies

Objective

To assess the association between cervical length (CL) and change of CL over two measurements and preterm birth (PTB) at <32 weeks in asymptomatic twin pregnancies.

Study design

This study was undertaken in the multiple pregnancy antenatal clinic at the Security Forces Hospital (SFH), a tertiary care hospital in Riyadh, Saudi Arabia, between November 2005 and October 2010. This study involved 420 women with asymptomatic twin gestations, but only 209 unselected patients completed the study and met the inclusion criteria. All patients had a CL measurement by transvaginal ultrasound at 20–23 weeks, and a second CL measurement was done within 3–5 weeks of the initial measurement. Patients were classified into two groups, group A with significant shortening of CL, and group B without significant shortening of CL. Comparisons between the groups were performed using a chi-square test or a Fisher exact test for categorical variables, whereas Student's t-test or Wilcoxon's rank-sum test was used for continuous variables. We employed ROC curves to compare the diagnostic accuracy of actual cervical length and percent change in cervical length in predicting preterm birth events. All analyses were performed using the SAS/STAT software.

Results

There were 35 (16.7%) patients whose CL shortened by ≥25% (group A), and 174 (83.3%) whose CLs either did not shorten or shortened by <25% (group B). Preterm birth at <28, <30, <32, and <34 weeks gestation was higher in group A than in group B even if the CL was >25 mm. The use of CL shortening was superior, but not statistically significantly, to the use of CL for the prediction of PTB at <32 (P = 0.0524) and <34 weeks (P = 0.281), but CL was preferred for the prediction of PTB at <28 (P = 0.037) and <30 weeks (P = 0.0457).

Conclusion

The test of two CL measurements, the first between 20 and 23 weeks gestation and another CL measurement 3–5 weeks later, with a difference of ≥25%, is a good predictor for preterm birth in asymptomatic twin pregnancies, even if the CL is >25 mm.     

Neutrophil elastase and interleukin-6 in amniotic fluid as indicators of chorioamnionitis and funisitis

Objective

We wished to assess the diagnostic value of amniotic fluid concentrations of neutrophil elastase and interleukin-6 concentrations for the rapid detection of chorioamnionitis and funisitis.

Study design

A retrospective study of 56 women who underwent transabdominal amniocentesis within 48 h before preterm delivery or spontaneous abortion. Statistical analyses included Student's t-test and Tukey–Kamer's HSD test. Receiver operating characteristics (ROC) curves were drawn to assess the predictive performance of the two markers.

Results

Neutrophil elastase concentrations differed significantly between patients with chorioamnionitis and other stages of chorioamnionitis, while interleukin-6 concentrations did not. To predict chorioamnionitis, concentrations of 3563 ng/ml for neutrophil elastase and 11,279 pg/ml for interleukin-6 were optimal. Comparison of ROC curves showed that neutrophil elastase was a significantly more sensitive predictor of funisitis than interleukin-6.

Conclusion

Amniotic fluid concentrations of neutrophil elastase are more sensitive than interleukin-6 for the rapid detection of chorioamnionitis and funisitis.     

The combination of short cervical length and phIGFBP-1 in the prediction of preterm delivery in symptomatic women

Objective.?To assess the combined use of cervical length and cervical phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) in the prediction of preterm delivery in symptomatic women.

Methods.?Cervical length was prospectively measured in 102 consecutive singleton pregnancies with intact membranes and regular contractions at 24–32 weeks, and phIGFBP-1 was assessed in those with a cervix?≤30 mm.

Results.?Among women with a cervix?>30 mm (n?=?42), none delivered?<34 weeks or within 7 days. Among women with a cervical length?≤30 mm (n?=?60), eight delivered?<34 weeks, four of which within 7 days. A positive phIGFBP-1 conferred a significantly increased risk of delivery before 34 weeks in women with a cervix ≤30 mm (likelihood ratio 2.32, 95% confidence interval 1.15–4.67), and a significantly increased risk of delivering within 7 days in the subgroup of women with a cervical length of 20–30 mm (likelihood ratio 3.64, 95% confidence interval 2.20–6.01).

Conclusions.?In symptomatic women with a cervical length?>30 mm the risk of preterm delivery is very low. In women with a cervix ≤30 mm, adding phIGFBP-1 assessment may improve the risk assessment for preterm delivery, and help to plan subsequent pregnancy management.     

Prediction of spontaneous preterm delivery in asymptomatic twin pregnancies using cervical length and granulocyte elastase

Objective

The purpose of this study was to evaluate sonographic cervical length (CL) and granulocyte elastase (GE) in cervical secretion as predictors of preterm delivery in asymptomatic twin pregnancies.

A short cervix in women with preterm labor and intact membranes: a risk factor for microbial invasion of the amniotic cavity

OBJECTIVE: The purpose of this study was to determine whether there was a relationship between sonographic cervical length and the presence of culture-proven microbial invasion of the amniotic cavity in women with preterm labor and intact membranes. STUDY DESIGN: Ultrasonography and amniocentesis were performed in 401 patients admitted with preterm labor (22-35 weeks) and cervical dilatation of < or = 3 cm, as assessed by digital examination. Cervical length was determined by transvaginal ultrasound at admission. Outcome variables were the presence of microbial invasion of the amniotic cavity (defined as a positive amniotic fluid culture) and the occurrence of preterm delivery before 35 weeks. Contingency tables, chi2 test, receiver-operator characteristic (ROC) curves, and logistic regression were used for statistical analysis. RESULTS: The prevalence of microbial invasion of the amniotic cavity was 7% (28/401). Spontaneous preterm delivery (< or = 35 weeks) occurred in 21.4% (82/384) of patients. ROC curve analysis showed a significant relationship between the frequency of microbial invasion of the amniotic cavity and the length of the uterine cervix (area under the curve: 0.77; P < .005). Patients with a cervical length < 15 mm had a higher rate of a positive amniotic fluid culture than patients with a cervical length > or = 15 mm (26.3% [15/57] vs. 3.8% [13/344], respectively; P < .05). Moreover, patients with a short cervix (defined as < 15 mm) were more likely to deliver spontaneously before 35 weeks, 32 weeks, within 7 days, and within 48 hours of admission ( P < .05 for all comparisons). Forty percent of patients (161/401) had a cervical length > or = 30 mm. These patients had a very low risk of microbial invasion of the amniotic cavity (1.9% [3/161]), spontaneous delivery < or = 35 weeks (4.5% [7/154]), < or = 32 weeks (2.6% [2/76]), within 7 days (1.9% [3/154]), and within 48 hours (0% [0/154]) of admission. CONCLUSION: Endovaginal ultrasonographic examination of the uterine cervix in women with preterm labor identifies patients at increased risk for intrauterine infection.     

Cervicovaginal fibronectin improves the prediction of preterm delivery based on sonographic cervical length in patients with preterm uterine contractions and intact membranes

OBJECTIVE: The purpose of this study was to examine the diagnostic performance of ultrasonographic measurement of the cervical length and vaginal fetal fibronectin determination in the prediction of preterm delivery in patients with preterm uterine contractions and intact membranes. STUDY DESIGN: Ultrasound examination of the cervical length and fetal fibronectin determination in vaginal secretions were performed in 215 patients admitted with preterm uterine contractions (22-35 weeks) and cervical dilatation of 相似文献   

Concentrative relationship between polymorphonuclear elastase and urinary trypsin inhibitor in amniotic fluid

In the amniotic fluid, urinary trypsin inhibitor (UTI) seems to inhibit polymorphonuclear elastase (PMNE) activity. The PMNE and UTI concentrations in normal amniotic fluid at 16–20 and 38–40 gestational weeks were measured. The PMNE concentration increased significantly at 38–40 weeks, whereas UTI concentration decreased significantly. According to concentrative relationships between both substances, PMNE may be activated more at the full term pregnancy. Since PMNE-induced tissue injury potentially causes degradation of amniotic collagen, the present result suggests that the quotient of PMNE and UTI concentrations is a reliable index to estimate the occurrence of rupture of the membranes. Received: May 1999 / Accepted: 11 January 2000     

Frequency of uterine contractions in asymptomatic pregnant women with or without a short cervix on transvaginal ultrasound scan

OBJECTIVE: The purpose of this study was to compare the frequency of uterine contractions in asymptomatic pregnant women with and without a short cervix (< 25 mm) on transvaginal ultrasound (TVU) and to determine the additive risk of contractions on the risk of preterm birth. STUDY DESIGN: The study involved secondary analysis of a blinded observational study of asymptomatic singleton pregnancies who were at high risk for preterm birth and who received both home uterine activity monitoring daily and transvaginal ultrasound of the cervix at 22 to 24 and 27 to 28 weeks of gestation. Thresholds for the maximum frequency of uterine contractions of 4 per hour and transvaginal ultrasound cervical length of 25 mm were used for analysis. Contraction frequency was compared in women with cervical length < 25 mm and > or =25 mm and was correlated with the risk of spontaneous preterm birth at < 35 weeks of gestation. RESULTS: Of the 303 women whose pregnancy was evaluated at 22 to 24 weeks of gestation, the 39 women (13%) with a cervical length of < 25 mm had 1.6 +/- 2.7 versus 1.2 +/- 2.0 contractions per hour in the 264 women (87%) with a cervical length of > or =25 mm (P=.37). At 27 to 28 weeks of gestation (n=295 women), contraction frequency was 3.2 +/- 3.7 versus 2.8 +/- 3.1 contractions per hour in women with a cervical length of < 25 mm (n=59 women; 20%) versus those with a cervical length of > or =25 mm (n=236 women; 80%; P=.34). Among women with a short cervix, the relative risks for spontaneous preterm birth were 2.0 (95% CI, 0.95-4.2) and 2.1 (95% CI, 1.06-4.3) for women with > or =4 contractions per hour compared with women with < 4 contractions per hour at 22 to 24 and 27 to 28 weeks of gestation, respectively. Results were confirmed by logistic regression analysis. CONCLUSION: The frequency of uterine contractions in asymptomatic women was not related significantly to cervical length of < 25 mm versus > or =25 mm. Among women with a cervical length of < 25 mm at 22 to 24 or 27 to 28 weeks of gestation, there was a trend toward a 2-fold increased risk of spontaneous preterm birth when the maximum contraction frequency was > or =4 per hour, compared to < 4 per hour.     

Decrease in the incidence of threatened preterm labor after implementation of transvaginal ultrasound cervical length universal screening

Background: It is unknown if universal second-trimester transvaginal ultrasound (TVU) cervical length (CL) screening in asymptomatic women with singleton gestations and no prior spontaneous preterm birth (SPTB) affects the incidence of symptoms of preterm labor (PTL) later in pregnancy.

Objective: To evaluate the incidence of threatened PTL before and after the implementation of universal second trimester TVU CL screening.

Study design: This was a retrospective cohort study of all consecutive singleton gestations without prior SPTB presenting to obstetric triage for threatened PTL between 23 0/7 and 33 6/7 week in 2011 (1 January–31 December), and in 2014 (1 January–31 December) at Thomas Jefferson University Hospital (TJU) (Philadelphia, PA). These 2 years were chosen as a new protocol for universal TVU CL screening was started on 1 January 2012. This protocol involved one measurement of TVU CL in all singleton gestations without a prior SPTB at 18 0/7???23 6/7 week, the time of the “anatomy” scan. Women with prior SPTB were excluded from this study. The primary outcome included the incidence of threatened PTL, defined as the number of women with singleton gestations without prior SPTB who presented with threatened PTL to our labor and delivery (L&;D) triage unit annually, divided by the total number of annual deliveries of women with singleton gestation without prior SPTB. Secondary outcomes were the incidence of PTL, defined as the number of women with singleton gestations without prior SPTB admitted for PTL annually divided by the total number of annual deliveries of women with singleton gestation and without prior SPTB; and length of stay in the hospital. We aimed to compare primary and secondary outcome in the “2011” versus the “2014” group.

Results: In 2011, there were a total of 1745 deliveries at TJU, of which 1550 (88.8%) were singletons without prior SPTB. In 2014, there were a total of 1924 deliveries at TJU, 1751 (91.0%) were singletons without prior SPTB who were offered universal TVU CL screening. One hundred and seventy-two women with singletons without prior SPTB presented in L&;D triage unit in 2011; and 118 women with singletons without prior SPTB presented in L&;D triage unit in 2014. There were significant decreases in the incidence of threatened PTL from 11.1% (172/1550) in 2011 to 6.7% (118/1751) in 2014 (p?p?=?.04). Length of stay was not significantly different between the two groups.

Conclusion: The introduction of a universal TVU CL screening program in women with singleton gestations without a history of SPTB is associated with a reduction in the frequency of threatened PTL and admission for PTL.

• Key Message

• The introduction of a second trimester universal transvaginal ultrasound (TVU) cervical length (CL) screening program in women without a history of spontaneous preterm birth (SPTB) is associated with a reduction in the incidence of threatened preterm labor (PTL) and admission for PTL.

     

Cervical pessary for preventing preterm birth in twin pregnancies with short cervical length: a systematic review and meta-analysis

Objective: To evaluate the effectiveness of cervical pessary for preventing spontaneous preterm birth (SPTB) in twin pregnancies with an asymptomatic transvaginal ultrasound cervical length (TVU CL) in the second trimester.

Methods: We performed a meta-analysis including all randomized clinical trials (RCTs) comparing the use of cervical pessary (i.e. intervention group) with expectant management (i.e. control group). The primary outcome was incidence of SPTB?<34 weeks.

Results: Three trials, including 481 twin pregnancies with short cervix, were analyzed. Two RCTs defined short cervix as TVU CL?≤25?mm and one as TVU CL?≤38?mm. Pessary was not associated with prevention of SPTB, and the mean gestational age at delivery and the mean latency were similar in the pessary group compared to the control group. Moreover, no benefits were noticed in neonatal outcomes.

Conclusions: Use of the Arabin pessary in twin pregnancies with short TVU CL at 16–24 weeks does not prevent SPTB or improve perinatal outcome.     

Effectiveness of dydrogesterone, 17-OH progesterone and micronized progesterone in prevention of preterm birth in women with a short cervix

Objective: To compare the efficacy of dydrogesterone, 17-OH progesterone (17OHP) and oral or vaginal micronized progesterone with cerclage for the prevention of preterm birth in women with a short cervix.

Methods: The study included 95 women with singleton gestation and cervical length (CL) ≤?25?mm. Among these, 35 women were asymptomatic at 15–24?weeks and 60 had symptoms of threatened late miscarriage (LM) or preterm delivery (PD) at 15–32 weeks. Patients were randomized to receive dydrogesterone, 17OHP or oral/vaginal micronized progesterone; after one week of therapy 15 women underwent cerclage.

Results: Efficacy of vaginal progesterone (VP) for the prevention of preterm birth reached 94.1%. In asymptomatic women pregnancy outcomes were comparable to cerclage. In women with threatened LM/PD, combination therapy with VP, indomethacin and treatment of bacterial vaginosis (BV) with the subsequent use VP until 36?weeks together with CL monitoring significantly decreased the rate of preterm birth (RR 0.01; 0.0001–0.24) and low birth weight (LBW) (RR 0.04; 0.01–0.96). CL increase during the first week of treatment with a subsequent plateau phase indicated treatment efficacy. Dydrogesterone, 17OHP, and micronized oral progesterone (OP) were associated with PD in 91.7% of women.

Conclusions: Combination management strategy including VP significantly benefits pregnancy outcomes in women with a short cervix compared with cerclage. Dydrogesterone, 17OHP, and OP were not found to be efficacious.