The role of the lower uterine segment thickness in predicting preterm birth in twin pregnancies presenting with threatened preterm labor

Introduction

Preterm birth (PTB) is the most common cause of neonatal morbidity and mortality [1]. According to the World Health Organization, PTB refers to deliveries occurring between 20 and 36 weeks plus 6 days of gestation. Twin pregnancies constitute around 15 % of all PTBs and 25 % of premature births [2], 3]. The mean gestational age at birth in twin pregnancies was previously determined to be 35.3 weeks [4]. Although the mechanisms underlying PTB are not fully understood, inflammation and excessive uterine tension are known contributing factors [5]. Increased uterine tension is the primary reason for the higher risk in twin pregnancies [5]. A history of PTB has also emerged as a significant risk factor for spontaneous PTB in recent years. Identifying the population at a heightened risk of having PTB in the presence of threatened preterm labor (TPL) is crucial for implementing interventions such as tocolysis and corticosteroid administration, which can delay delivery and improve perinatal outcomes [6].

The ultrasonographic evaluation of cervical length (CL) is a useful method for predicting spontaneous PTB [7]. The most objective and effective method for this evaluation is transvaginal ultrasonography [8]. However, CL measurements can yield confusing results in twin pregnancies. A review published in 2010 indicated that CL measurements taken between 20 and 24 weeks of gestation in asymptomatic twin pregnancies were effective for predicting PTB, while those taken after 24 weeks were not [9]. Similarly, a review by Berghella and Saccone showed that the success of transvaginal CL measurement in preventing PTB in asymptomatic twin pregnancies was unclear [10]. However, there is a clearer consensus that in twin pregnancies with TPL, a CL of >25 mm is associated with a low risk of PTB [11], 12].

The thickness of the lower uterine segment (LUS) is a newly explored ultrasonographic marker that has been examined for its association with PTB, particularly in recent years [13], 14]. Research has demonstrated that the thinning of LUS starts sooner in twin pregnancies and is more pronounced throughout the mid-trimester in those presenting with PTB [14].

The primary aim of this study was to evaluate the ability of the LUS thickness to predict spontaneous PTB in twin pregnancies. Our secondary aim was to examine how this predictive capacity changed when considering the combination of other characteristics assessed, including mid-anterior wall thickness, CL, posterior cervical lip thickness (PCLT), cervical sliding sign (CSS), and funneling findings.

Materials and methods

This prospective, observational study was conducted at the Perinatology Clinic of the Ankara Bilkent City Hospital, a tertiary care center, with approval from the local Ethics Committee (approval number: E2-22-2881). A total of 58 patients who met the study criteria between December 2022 and December 2023 were included in the sample. All patients were informed prior to the examination and provided written consent to participate in the study.

Ultrasonographic examination

A single measurement was conducted for each patient between 24 and 32 weeks of gestation. The LUS thickness and mid-anterior wall myometrium thickness were measured using abdominal ultrasonography. CL, PCLT, CSS, and the presence or absence of funneling were assessed through transvaginal ultrasonography.

To ensure standardization, all ultrasonographic measurements were performed by a single operator (E.B.) using the Voluson E8 Expert ultrasound machine (General Electric, Milwaukee, WI) equipped with a 5–9 MHz vaginal probe and a 2–5 MHz convex abdominal probe. The LUS measurement was performed as previously described [13] and is illustrated in Figure 1. With a partially filled bladder, the abdominal probe was placed sagittally immediately above the pubic symphysis to visualize the mid-sagittal plane of the LUS-bladder-cervical canal. The image was then magnified to fill the screen with LUS and the bladder, and the measurement was taken perpendicular to the uterine wall, slightly above the vesico-uterine peritoneal fold. The first caliper was positioned just below the peritoneum, while the second caliper was placed at the amnion-uterine wall interface. The mid-anterior wall thickness was measured in a similar manner, in the midsagittal plane, from the midpoint of the anterior uterine wall perpendicular to the uterine wall. Other measurements and assessments were conducted using transvaginal ultrasonography. CL was measured using the transvaginal probe in the midsagittal plane from the external os to the internal os along the closed endocervical canal (Figure 2). In cases of a straight cervical canal, a single linear measurement was taken, whereas in cases of significant angulation, two linear measurements were used. PCLT was measured in the same sagittal plane as CL, perpendicular to the endocervical canal from the midpoint of the cervical canal to the posterior cervicovaginal junction (Figure 3). CSS, an ultrasonographic finding characterized by anterior cervical lip sliding over the posterior cervical lip upon continuous and gentle pressure with the transvaginal probe, was also evaluated. Lastly, the funneling sign was assessed as an ultrasonographic finding characterized by dilation at the internal cervical os while the external cervical os remains closed, creating a funnel-like appearance. All measurements and findings obtained during the examinations were recorded in a data collection form.

Figure 1:

Measurement of lower uterine segment thickness with transabdominal ultrasonography in the sagittal plane.

Figure 2:

Cervical length measurement with transvaginal ultrasonography in the sagittal plane.

Figure 3:

Posterior cervical lip thickness measurement with transvaginal ultrasonography in the sagittal plane.

Results

No significant differences were observed between the group with an onset of labor at <34^0/7 weeks (n=17) and the group with an onset of labor at ≥34^0/7 weeks (n=41) in terms of age, gravidity, parity, gestational week at examination, mid-anterior wall thickness, CL, PCLT, CSS, or funneling findings (p>0.05 for all). However, the LUS thickness was 3.8 ± 0.9 mm in the <34^0/7 group and 4.6 ± 1.1 mm in the ≥34^0/7 group, and the difference was statistically significant (p=0.012). The latency period between ultrasonographic measurements and time of delivery was 3.7 ± 2.9 weeks in those who gave birth before 34th week, while this period was 6.1 ± 3.2 weeks in those who gave birth after 34th week (Table 1). Similarly, when comparing the groups with an onset of labor at <35^0/7 (n=25) and ≥35^0/7 weeks (n=33), no significant differences were detected in terms of age, gravidity, parity, gestational week at examination, mid-anterior wall thickness, CL, PCLT, CSS, or funneling findings (p>0.05 for all). However, the LUS thickness measured 4.0 ± 1.0 mm in the <35^0/7 group vs. 4.7 ± 1.0 mm in the ≥35^0/7 group, indicating a statistically significant difference (p=0.022). The latency period was 3.9 ± 2.9 weeks in those who delivered before 35th weeks, and 6.5 ± 3.1 weeks in those who delivered later (Table 2).

According to both univariate and multivariate analyses, LUS thickness alone was more effective in predicting PTB. Among those with an onset of labor before the 34th gestational week, the p-value for the LUS thickness was 0.017 in univariate analysis and 0.04 in multivariate analysis. Among those with an onset of labor before the 35th gestational week, the p-value for the LUS thickness was 0.028 in univariate analysis, showing statistical significance. However, in multivariate analysis, the p-value was 0.06, indicating no statistical difference. There were no significant statistical differences in predicting births before the 34th and 35th weeks in terms of the remaining parameters in univariate or multivariate analyses (p>0.05 for all) (Table 3).

ROC curve analysis was used to determine the optimal LUS thickness for the prediction of spontaneous PTB at <34 and <35 weeks of gestation. The optimal cut-off value of the LUS thickness was found to be 4.3 mm for predicting PTB before 34 weeks (sensitivity: 71 %, specificity: 59 %, area under the curve: 0.707, confidence interval: 0.56–0.85) and before 35 weeks (sensitivity: 64 %, specificity: 61 %, area under the curve: 0.678, confidence interval: 0.54–0.82) (Table 4). Figures 4 and 5 present the ROC curve graphs for the prediction of PTB before 34 weeks and before 35 weeks, respectively.

Figure 4:

ROC curve of the LUS thickness for the prediction of spontaneous preterm birth at <34 weeks of gestation.

Figure 5:

ROC curve of the LUS thickness for the prediction of spontaneous preterm birth at <35 weeks of gestation.

Discussion

In this study, our primary aim was to evaluate the ability of the LUS thickness to predict spontaneous PTB in twin pregnancies presenting with TPL. According to our findings, the LUS thickness measured between 24 and 32 weeks was significantly thinner in those with an onset of labor before 34 and 35 weeks compared to those who delivered at or beyond these gestational ages. Furthermore, this difference was not observed in CL, a parameter traditionally used for predicting PTB for many years. Other parameters we assessed, namely the mid-anterior wall thickness, PCLT, CSS, and funneling findings, did not independently predict PTB. In univariate analysis, the LUS thickness was more effective in predicting spontaneous PTB, but its predictive power decreased when combined with other measurements.

Approximately 60 % of twin pregnancies result in delivery before 37 weeks of gestation, and 10 % before 32 weeks [16]. Consequently, despite constituting a small portion of all pregnancies, twin pregnancies are responsible for the majority of PTBs. Hence, there is an ongoing search for a reliable method to predict spontaneous PTB in these pregnancies. In cases where the risk of PTB is high or where twin pregnancies have experienced TPL, interventions such as corticosteroids and tocolysis administration can be employed to improve outcomes. Additionally, cervical pessary and vaginal progesterone are options that can be considered for intervention. In a study by Merced et al., among twin pregnancies with TPL and identified short cervix, the rate of delivery before 34 weeks was 32 % in the group without pessary application compared to 16 % in the group with pessary application [17]. Another study undertaken by Romero et al. demonstrated that vaginal progesterone significantly reduced the risk of PTB in twin pregnancies presenting with a short cervix [18]. The existence of such preventive and risk-reducing interventions underscores the importance of identifying the at-risk group. Furthermore, determining the group with a low probability of PTB is crucial for reducing unnecessary interventions.

In singleton pregnancies with a history of spontaneous PTB, it has been shown that a CL measurement of <25 mm between 16 and 18 weeks and 6 days has a 75 % positive predictive value in predicting birth before 35 weeks [19]. In a review by Berghella et al., it was shown that the transvaginal CL measurement reduced the rate of PTB in singleton pregnancies that experienced TPL [7]. Despite the established benefit of the CL measurement in predicting PTB in singleton pregnancies, this relationship is more uncertain in twin pregnancies. A previous study demonstrated that measuring CL twice during asymptomatic twin pregnancies, once between 14 and 16 weeks and again between 21 and 24 weeks, and examining the difference between these measurements, was not a dependable approach for predicting spontaneous PTB [20]. Consistently, in our sample consisting of twin pregnancies experiencing TPL, we did not detect any statistical difference in CL measurements between the groups. If we consider that the shortening of the cervical length is a result of uterine activity and that time is required for the change, we can comment that the thinning of the LUS in twin pregnancies starts earlier than the change in CL.

The quest for more effective and alternative methods for predicting spontaneous PTB continues, albeit with a predominant focus on singleton pregnancies. One such method is the measurement of the uterocervical angle. Research has demonstrated that an increased uterocervical angle is associated with an increased frequency of PTB in singleton pregnancies [21]. Another useful parameter can be considered the combined utero-cervical index, which has been recently described in a study, concluding that an increased value of this index was successful in predicting the onset of labor at <37 weeks of gestation in singleton pregnancies [22]. Such alternative methods may also be beneficial, especially in twin pregnancies where there are conflicting findings regarding CL. A recent review of the quality of clinical practice guidelines on CL measurement in twins found that most of the guidelines included in the review were of good quality. However, although the quality of these guidelines was adequate, there were no clear recommendations on CL measurement in twins and no cut-offs for interventions were specified [23].

In the last 10–15 years, LUS thickness has emerged as a parameter of interest in investigating both PTB and other clinical conditions and adverse outcomes. There are numerous studies in the literature evaluating the LUS thickness in singleton pregnancies and various clinical conditions. These studies have assessed the risk of PTB in singleton pregnancies [13], 24], uterine scar defects [25], risk of uterine rupture [26], 27], prediction of the latent period in premature rupture of the membranes [28], LUS thickness in pregnancies with a history of cesarean section [29], LUS thickness during active labor [30], and prediction of the success of labor induction [31]. To our knowledge, there is only one study in the literature that examined the relationship between LUS thickness and spontaneous PTB in twin pregnancies [14].

During the early stages of pregnancy, the uterine wall thickens, but as pregnancy progresses, it gradually thins, with the most significant thinning occurring in LUS [32]. The LUS thickness shows an inverse correlation with gestational age [33]. In a prospective cohort study involving 524 singleton pregnancies, the mean lower uterine wall thickness measured between 18 and 22 weeks was found to be 6.2 mm, and it was demonstrated that having measurements below 4.5 mm increased the risk of PTB by 2.3 times [13]. However, the same study was unable to demonstrate the superiority of the LUS thickness over CL in predicting PTB in singleton pregnancies [13]. In another study by Woraboot et al., a high correlation was observed between the transabdominal LUS measurement and the transvaginal CL measurement in singleton pregnancies [34]. In the third trimester, there is a significant thinning in LUS in all twin pregnancies without marked changes in anterior and fundal myometrial thickness, with this thinning beginning in earlier gestational weeks in twin pregnancies that result in PTB [14]. Another finding from the same study is that while thinning in LUS correlated with CL in term twins, there was no correlation between thinning in LUS and shortening of CL in preterm twins [14]. Consistent with these findings, in our study, there were no statistical differences between the groups in relation to the CL and anterior wall thickness measurements, whereas the LUS measurements were lower in the early onset of labor group at a statistically significant level.

The presence of funneling in cases with a CL of 25 mm or greater has previously been shown not to predict PTB in singleton pregnancies [19]. In the current study, similar to singleton pregnancies, we found that the presence of funneling alone was not an effective predictor of PTB in twin pregnancies.

The prospective design of our study is one of its strengths. In addition, having all measurements conducted by a single operator eliminates interobserver variability, which is important. While transvaginal ultrasound is a harmless examination, it can be uncomfortable for many patients and is often avoided if possible. In addition, the transvaginal ultrasound probe may not always be readily available. Therefore, conducting LUS thickness measurements via the transabdominal route provides an advantage over CL measurements that require the transvaginal approach. On the other hand, one of the disadvantages of this method is that it can be challenging to ensure accurate measurements when the bladder is completely empty. Another disadvantage is that it may be more affected by factors such as maternal body mass index and device quality compared to transvaginal sonography. Nevertheless, it is possible to obtain appropriate images and accurate measurements in all patients, even in the presence of some residual urine.

In conclusion, we found that measuring the LUS thickness in twin pregnancies presenting with TPL is particularly effective in predicting deliveries before 34 and 35 weeks of gestation. As a non-invasive, repeatable, and easy-to-implement method in clinical practice, we believe that the measurement of the LUS thickness can be used in predicting spontaneous PTB in twin pregnancies. Further studies with larger sample sizes can help better understand the clinical usability of this method and its impact on outcomes.