Cervical sliding sign and cervical funneling in the third trimester as predictors of spontaneous preterm birth in singleton pregnancy

Introduction

Spontaneous preterm birth (sPTB) is defined as an unplanned birth before 37 complete weeks of gestation due to preterm labor, preterm rupture of membranes, or cervical weakness (1). Preterm birth rates have been reported to range from 5% to 13% per year, and this rate is increasing, with sPTB accounting for half of such cases (2). It is estimated that 13.4 million newborns, or more than 1 in 10, are born prematurely each year (3). Approximately one million newborns die every year from the complications of premature birth (4), with a proportion of these deaths being preventable through timely interventions (5). The prevention of preterm birth involves multiple strategies, such as smoking cessation programs, the use of progestational agents, and cervical cerclage (6) for women with known risk factors, along with pharmacological interventions such as intravenous magnesium sulfate (7), atosiban (8), ritodrine (9), oral nifedipine tablets (10), and indomethacin (11), which are aimed at delaying preterm labor.

Thus, identifying patients at risk of preterm birth should be considered a main goal in prenatal medicine as this can save newborn lives; reduce the burden on society, the economy, and the health sector; and spare families from long-term psychological harm (12,13). The impact of preterm birth on the socio-medical system, especially the consumption of medical resources and the use of neonatal intensive care units (NICUs), is substantial. Studies have shown that preterm births are costly to care for and place a considerable burden on the socio-medical system, and thus reducing the rate of preterm births can help mitigate these costs and lessen parental anxiety and depression (14,15).

Sonographic transvaginal cervical length (CL) and uterocervical angle (UCA; the angle between the lower segment of the uterus and the internal and external os of the cervix) (16) are commonly used as general screening methods for predicting preterm birth. However, these methods are limited by the variability in reference values (17,18). The cervical sliding sign (CSS), defined as the movement of the anterior cervical lip against the posterior cervical lip induced by external pressure, can be defined as positive or negative. As it can be determined without the need for numerical measurements, it involves little variability in reference values. Moreover, a retroverted uterus or the presence of fibroids can generate a suboptimal image that might produce a biased measurement, with the result also being subjective. The CSS has recently been used as a sonographic marker for sPTB (19-21) and can avoid the limitations associated with the CL and UCA in the prediction of preterm delivery. Moreover, the CSS is a noninvasive, inexpensive, reproducible, and easy-to-operate method for predicting preterm delivery, but few studies have examined its application in sPTB. Research has examined twin gestations, singleton pregnant women with preterm premature rupture of membranes, pregnant women with uterine contractions, and pregnant women with induction of labor (22). However, no evidence has been published on the use of the CSS in independently predicting sPTB in asymptomatic singleton pregnancies, and it is uncertain whether funneling contributes to additional risk if CSS and cervical funneling are both present.

Therefore, the aim of this study was examine the relationship between CSS in the third trimester and the risk of sPTB and to determine the possible additional risk of funneling. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-2439/rc).

Methods

Study materials

This study was approved by the Ethics Committee of Shenzhen Baoan Women’s and Children’s Hospital (approval No. LLSCHY-2023-02-08-1) and was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from all participants. This prospective cohort study included 252 singleton pregnant women in the third trimester (at 28^0–7–34^0–6 weeks of gestation) who visited our department for ultrasound examination of the cervix between March 1, 2023 and October 30, 2023. During the groups, 74 cases of full-term cesarean section were excluded. Besides, 10 cases (full-term delivery) with missing data were also excluded. In the remaining cases, there were 32 sPTBs and 136 people full-term births; therefore, the actual preterm birth rate was 12.69% (Figure 1).

Figure 1 Flowchart of study inclusion. sPTB, spontaneous preterm birth.

The exclusion criteria were as follows: smoking habit, a history of cervical conization, fetal congenital or structural abnormalities, iatrogenic preterm birth due to placenta previa, placental abruption, previous cervical surgery, single fetal demise, uterine contractions and/or cervical dilatation, a history of preterm labor at the time of examination, uterine anomalies and multiple pregnancies, polyhydramnios, and oligohydramnios.

All included patients had complete clinical data, including age, delivery weeks, newborn weight, newborn sex, pregnancy weeks, pregnancy and prenatal body mass index (BMI), previous spontaneous or cesarean section history, hypertension, diabetes, anemia, hepatitis B history, induced abortion, spontaneous abortion and premature labor history, test tube status, cervical cerclage, ectopic pregnancy, and allergy history.

Ultrasonography

The ultrasound examinations were performed by an experienced attending physician who had received a Fetal Medicine Foundation Certificate of Competence in Cervical Assessment (http://www.fetalmedicine.com) via the Voluson E8 ultrasound system with a 5 to 9-MHz frequency vaginal probe (GE HealthCare, Chicago, IL, USA). The analysis of the results was performed by two attending physicians who evaluated the recorded videoclips together. A positive result was considered only if both parties reached an agreement. The pregnant women were asked to empty their bladder and were placed in the dorsal lithotomy position. The vaginal ultrasound probe was set with a disposable condom, its inside and outside were coated with sterile medical coupling agent, and the probe was slowly moved to the vaginal fornix. The captured image occupied two-thirds of the whole picture, the lower portion of the uterus and the inner and outer openings of the cervix were clearly identified, and care was taken so the probe do not exert pressurization, which could artificially elongate the cervix. CSS was defined as the sliding of the anterior lip of the cervix over the posterior lip via the application of gentle and continuous pressure on the cervix from the anterior fornix via a transvaginal ultrasound probe (18,19). The anterior lip of the cervix flattening (Figure 2) and moving more than one-third of the length of the cervix relative to the posterior lip was considered a positive result (Video 1).

Figure 2 With the mid-cervical gas line as a reference point, the anterior and posterior lips of the cervix will flatten out significantly when the probe is placed in the vaginal fornix under light pressure, and the anterior lip will move downward significantly.

Meanwhile, no softening (Figure 3) or the anterior and posterior lips move less than one-third of their own lengths in the cervix when pressure was applied with the vaginal probe was considered to be a negative CSS result (Video 2).

Figure 3 With the mid-cervical gas line as a reference object, the anterior and posterior lips of the cervix will have no obvious deformation of the cervix under light pressure when the probe is placed in the vaginal fornix, and the posterior lip of the cervix will be stiffer.

Cervical funneling was considered present when sonography showed ballooning of the membranes into a dilated internal os with a closed external os and protrusions of at least 15% of the entire CL (23,24) (Figure 4).

Figure 4 Transvaginal ultrasound of the cervix with funneling, showing (A) funnel length, (B) functional length, (C) and funnel width. Cervical funneling was defined by sonography indicating ballooning of the membranes into a dilated internal os with a closed external os and protrusions of at least 15% of the entire cervical length. Here the percentage of funneling is 23%. Yellow dotted lines show the funneling and the length of the residual cervix.

Statistical analysis

R software version 4.2.2 (R Core Team 2022) was used to conduct statistical analyses. Econometric data were subjected to normality and homogeneity of variance tests. If normality and homogeneity of variance were met, the data were expressed as the mean ± standard deviation. Independent sample t-tests were used for intergroup comparisons, with results expressed as the median and interquartile range. Meanwhile, independent sample Wilcoxon rank-sum and chi-square tests were used for intergroup comparisons, with count data being expressed as frequencies (percentages). If the theoretical frequency was relatively small, the Fisher exact test was used. Receiver operating characteristic (ROC) curves and logistic multiple regression models were used to evaluate the efficacy of cervical funneling and CSS, used alone and in combination, in predicting premature birth. Odds ratio (OR), area under the curve (AUC), sensitivity, specificity, and negative predictive values, and 95% confidence intervals (CIs), were calculated to evaluate the diagnostic efficacy of each model. The comparison between AUCs was performed with the DeLong test. Differences were considered statistically significant at P<0.05.

Results

The descriptive data of 168 singleton pregnancies are provided in Table 1. The pregnant women were placed into term birth and sPTB groups. There was no significant difference in age, infant sex, gestational week at the time of the examination, use of in conception; history of induced abortion, medication abortion, spontaneous abortion, previous history of preterm labor (induction of labor), hepatitis B, diabetes mellitus, hypertension, or anemia, pregnant BMI, prenatal BMI, history of normal delivery, cesarean section, ectopic pregnancy, or allergies between the two groups. However, there were statistically significant differences with respect to gestational week at delivery, neonatal birth weight, cervical funneling, and CSS (P<0.05). The kappa coefficient was 0.894 for interobserver variability and 0.870 for intraobserver variability, both evident of strong agreement between measured CSS.

The proportion of CSS positivity was higher in the sPTB group, while that of funnel sign was higher in the term birth group (65.62% and 11.36%, respectively) (Figure 5).

Figure 5 With the mid-cervical gas line as a reference point, the anterior and posterior lips of the cervix will flatten out significantly when the probe is placed in the vaginal fornix under light pressure, and the anterior lip will move downward significantly. CSS, cervical sliding sign; sPTB, spontaneous preterm birth.

The number of CSS-positive and CSS-negative pregnancies by gestational age are presented in Table 2.

The mean delivery time of patients with CSS was significantly lower than that of those without CSS (35.62 vs. 39.02; P=0.009) (Table 3).

The AUC for CSS in predicting preterm birth (<37 weeks) was 0.799 (95% CI: 0.713–0.885). The corresponding sensitivity, specificity, positive predictive value, and negative predictive value were 65.6%, 94.1%, 72.4%, and 92.1%, respectively.

The AUC of CSS combined with cervical funneling for predicting preterm birth (<37 weeks) was 0.801 (95% CI: 0.710–0.892). The corresponding sensitivity, specificity, positive predictive value, and negative predictive value were 65.6%, 94.1%, 72.4%, and 92.1%, respectively.

The AUC of cervical funneling for predicting sPTB was 0.648 (95% CI: 0.558–0.738). The corresponding sensitivity, specificity, positive predictive value, and negative predictive value were 40.6%, 89%, 46.4%, and 86.4%, respectively (Figure 6 and Table 4).

Figure 6 The AUC for predicting preterm birth (<37 weeks) of cervical funneling, CSS, and CSS combined with cervical funneling, respectively. AUC, area under the curve; CI, confidence interval; CSS, cervical sliding sign.

In predicting preterm labor, the AUC for CSS was greater than that for funneling (0.799 vs. 0.648; P=0.001), and the AUC for CSS combined with cervical funneling was significantly greater than that for funneling (0.801 vs. 0.648; P<0.001). However, there was no statistically significant difference between AUCs of CSS alone and CSS combined with funneling (0.799 vs. 0.801; P=0.89) (Table 5).

To determine the independent risk factors for predicting delivery, multiple logistic regression analyses were performed, as shown in Table 6.

Logistic regression analysis demonstrated that funneling did not significantly contribute to the prediction of spontaneous delivery before 37 weeks as compared to CSS (funneling: OR =1.224, z =0.311, P=0.76; CSS: OR =27.903, z =5.628, P<0.001). CSS increased the accuracy in predicting sPTB by 30.545-fold (z =6.564, P<0.001), and funneling increased the accuracy by 5.519-fold (z =3.778, P<0.001).

Discussion

This study is the first to examine the combination of CSS and cervical funneling in predicting sPTB in singleton pregnancies. The results show that both CSS sign and funneling could independently predict preterm birth. However, ROC analysis revealed that the AUC for CSS sign was significantly greater than that of funneling. Therefore, the CSS is a more promising indicator for sPTB in singleton pregnancies.

We found CSS to be a significant independent risk factor for sPTB birth in singleton pregnancies via ROC curve and logistic regression analyses. Volpe et al.’s study (21) reported CSS to be sonographic marker of imminent delivery in women with preterm uterine contractions. In another study (22), these authors found CSS to be associated with a greater frequency of vaginal delivery within 24 hours and a shorter induction-to-active-labor time in women who underwent induction of labor with an unfavorable cervix (a Bishop score ≤6). Uyan Hendem et al. (20) concluded that compared with CL, CSS is a superior marker for predicting preterm delivery in patients with preterm premature rupture of membranes. Tugrul Ersak et al. (19) reported that CSS was shown to be superior to CL in providing a better insight to predict early preterm birth in twin pregnancies. We further supplemented the research on CSS through our study, which revealed that CSS is also related to sPTB in singleton pregnancy, addressing a critical gap in this field.

The high preterm birth rate in patients with CSS may be related to cervical remodeling (25). The cervix is a fibrous tissue composed of a large amount of collagen fibers, matrix, and water, with a small number of elastic fibers and smooth muscles. Among collagen fibers, 70% are type I and 30% are type II. Collagen disorganization, glycosaminoglycans, and other factors determine the hardness of the cervix, whose primary main function is to maintain the cervix in a closed state (26,27). The breakdown of collagen fibers mediated by collagenase plays a decisive role in the maturation and expansion of the cervix (28,29). The content of collagenase increases in late pregnancy, and collagen fibers decompose. This leads to the degradation of the cervical fiber network structure, a decrease in cervical collagen content, an increase in water content, and a significant softening of the cervix, facilitating dilation (30). Rechberger et al. observed an increase in cervical collagenase and a decrease in collagen inhibitors in pregnant women approaching delivery (31). Vink et al. (32) reported an increase in the ratio of decorin (dermatan sulfate proteoglycan) to collagen/water content in sPTB processes. This may partly account for the cervical remodeling present in patients with CSS, which may lead to premature birth in pregnant women.

Cervical funneling alone can also predict premature birth. Several authors have suggested that funneling is an early sign of cervical incompetence (22-24,33), and this was corroborated by our findings. We believe cervical funneling is also related to cervical remodeling and ripening. However, the AUC and OR were significantly greater for women with CSS than for those with funneling in the prediction of sPTB, indicating CSS to be the superior indicator. According to the ROC curve analysis, there was no significant difference in the AUC between CSS and CSS combined with cervical funneling for the prediction of sPTB. Logistic regression analysis demonstrated that funneling did not significantly contribute to the prediction of spontaneous delivery before 37 weeks (CSS: OR =27.903, z =5.628, P<0.001; funneling: OR =1.224, z =0.311, P=0.76). This finding indicates that in pregnant women with both funneling and CSS, the former does not increase the risk of premature birth. In the study of To et al. (34), for patients with both funneling and short cervical canals, funneling did not contribute to the prediction of preterm birth. This may be attributed to the presence of false positives: patients may become nervous during the testing process, which may lead to transient uterine contractions, with the contractions in the lower segment of the uterus and cervix producing a false funnel sign. Moreover, in Berghella et al.’s study (33), 60 women with funneling present for at least one evaluation reported that the progression of internal os cervical anatomy from a “T” to a “V” to a “U” shape over time was associated with earlier gestational age at delivery, whereas the resolution of “V” shape funnels was associated with term delivery. These findings suggest that the value of the funnel test in predicting preterm birth is limited. We speculate that the reason for this is that some pregnant women have a V-shaped funnel in their cervix. According to Berghella et al.’s study, only funnel signs other than the V-shaped funnel are related to preterm birth, and some patients may have temporary funneling due to nervousness leading to contraction of uterus during examination, leading to false contractions. The detection of CSS should involve continuous observation of the relative movement of the anterior and posterior lips of the cervix for 30 seconds, as this provides more reliable results. Therefore, the use of CSS for the prediction of premature birth is effective and has high specificity.

Limitations

This study involved several limitations which should be mentioned. First, the participants were singleton pregnant women in the third trimester of pregnancy, which might have introduced selection bias. Second, due to the small sample of patients and the single-center nature of the design, the results may not be highly representative. In the future, we plan to conduct multicenter studies, increase the sample size of patients, and expand the study of period to 16 to 24 weeks in the midtrimester.

Interpretation

Although our findings suggest the potential clinical value of these factors, there is still a need to further validate their applicability and generalizability on a larger scale and in a wider diversity of ethnicities and geographic regions, as the study data were derived from a single center and the patients were exclusively Chinese. In addition, changes in cervical parameters may be influenced by a variety of factors, including the lifestyle of pregnant women, nutritional status, and geographic differences, and these variables may affect the stability and reproducibility of the results.

Generalizability

The results of this study are mainly based on a sample of pregnant Chinese women from a single region. Therefore, although we observed significant associations among cervical angle CL and CSS and preterm labor, the generalizability of these findings still needs to be interpreted with caution. Future multicenter studies should include different regions and populations, including pregnant women of different ethnic and cultural backgrounds, to validate the generalizability and validity of these cervical parameters as predictive tools for preterm labor.

Conclusions

Although cervical funneling can offer some predictive value for sPTB, CSS is generally more effective as a diagnostic indicator. However, it is important to note that the presence of CSS and cervical funneling does not necessarily imply a higher likelihood of preterm birth as compared to the presence of CSS alone.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-2439/rc

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-2439/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and was approved by the Ethics Committee of Shenzhen Baoan Women’s and Children’s Hospital (approval No. LLSCHY-2023-02-08-1). Written informed consent was obtained from all participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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