Cervical Length and Uterocervical Angle for Optimal Timing in Predicting Preterm Birth among Twin Pregnancies: A Longitudinal Study

Cervical Length and Uterocervical Angle for Optimal Timing in Predicting Preterm Birth among Twin Pregnancies: A Longitudinal Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cervical Length and Uterocervical Angle for Optimal Timing in Predicting Preterm Birth among Twin Pregnancies: A Longitudinal Study Van Hieu Bui, Thi Hoang Trang Nguyen, Khac Quang Tran, Van Tam Vu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8505360/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background: Twin pregnancies carry a significantly higher risk of preterm birth; however, measuring cervical length with sonography during the mid-trimester provided limited predictive accuracy when used as a standalone test. This study aimed to investigate the relationship between cervical length (CL) and uterocervical angle (UCA) for predicting preterm birth in twins, and to determinethe gestational age at which the combined CL-UCA measurement offers the best predictive ability. Methods: A prospective longitudinal cohort study involving 93 twin pregnancies at 14 weeks of gestation was conducted at Haiphong Medical University Hospital, from 09/2023 to 08/2025. Each patient underwent a transvaginal ultrasound to measure CL and UCA every 2 weeks from 14 to 24 weeks, performed by a certified sonographer. Blood samples for interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) testing were collected at 16 weeks. Patients were followed until delivery to determine pregnancy outcomes, including spontaneous preterm birth (PTB) before 37 weeks and before 34 weeks of gestation. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association between CL-UCA and PTB. A multivariate binary regression model was used to analyze the relationship between CL-UCA and PTB, with p-values <0.05 considered significant. Receiver operating characteristic (ROC) curves assessed the ability of CL-UCA to predict PTB. Results: At 22 weeks of gestation, significant associations were found between both CL and UCA with PTB <34 weeks, with ORs (95% CI) of 0.797 (0.647-0.982) and 1.086 (1.000-1.179), respectively, as well as with PTB <37 weeks, with ORs (95% CI) of 0.906 (0.822-1.000) and 1.038 (1.007-1.070). Combined CL and UCA showed good predictive value for PTB <34 weeks, with an AUC of 0.886 (95% CI: 0.809-0.963) at 22 weeks of gestation, and also demonstrated good predictive value for PTB 0.05). Conclusions: The study's findings show that the 22-week assessment has the highest predictive ability for combined CL and UCA screening for PTB, making it the best timing for mid-trimester screening in twin pregnancies. Preterm birth cervical length uterocervical angle twin pregnancy inflammatory markers Figures Figure 1 Figure 2 Figure 3 BACKGROUND Preterm birth (PTB) is defined as delivery occurring between 20 weeks and 37 weeks of gestation, according to the World Health Organization (WHO). It remains the most significant challenge facing contemporary obstetrics in both high-resource and low-resource settings. Approximately 15 million babies are born each year prematurely worldwide, with more than 60% of PTB occurring in Africa and South Asia [1]. Multiple pregnancies significantly increase the global PTB rate, with reports showing an incidence as high as 61.3% [2]. The risk of very PTB before 32 weeks is ten times higher in twins than in singletons (10% versus 1%), leading to increased neonatal mortality and long-term health problems [3]. Currently, there is no reliable screening test to predict PTB in twins, which presents a challenge for maternal-fetal specialists [4]. The pathophysiological mechanisms behind spontaneous preterm birth (sPTB) in twins seem to differ from those in singletons. Uterine overdistention likely plays a significant role. Excessive stretching of the uterus could prematurely activate an inflammatory cytokine cascade and release labor mediators, leading to early activation of the myometrium and cervical ripening [5, 6]. Furthermore, the effectiveness of interventions aimed at preventing sPTB may vary between twins and singletons [7]. These findings highlight the need for well-designed prospective studies to identify the predictors of sPTB specifically in twins. Measuring cervical length (CL) during the mid-trimester ultrasound is the most cost-effective screening method used in clinical practice for both singleton and twin pregnancies [8, 9]. However, its accuracy is limited by low sensitivity when used as a single test [10, 11]. The uterocervical angle (UCA) has recently been suggested as a potential ultrasound parameter for predicting PTB in both singletons and twins [12]. An obtuse UCA causes the cervical canal to be more affected by gravitational forces from the uterus and fetus, resulting in cervical shortening and dilation [13]. Combining the UCA with CL has been shown to improve PTB prediction [14, 15]. In addition, few studies have examined the relationship between cervical morphology and systemic inflammatory activity, even though pro-inflammatory cytokines are believed to contribute to cervical remodeling and the onset of preterm labor. The integration of these sonographic and biochemical markers may therefore yield a more comprehensive understanding of the mechanisms underlying PTB in twin pregnancies. Despite accumulating evidence that CL and UCA are associated with PTB, very few studies have evaluated the combined use of these cervical ultrasound parameters to predict PTB in women with twin pregnancies [16, 17]. Additionally, previous research has typically focused on a single measurement point, leaving the optimal gestational age for assessment in twin pregnancies unclear. Therefore, this study aims to (1) evaluate the relationship between CL and UCA in twin pregnancies with spontaneous PTB, and (2) identify the gestational age at which the combined CL-UCA measurement provides the best predictive ability. METHODS Ethical considerations The study protocol was in accordance with the Declaration of Helsinki, has been approved by the Ethics Committee in Biomedical Research of Hue University (approval No. H2023/461), the Ethics Committee of Hai Phong University of Medicine and Pharmacy (approval No. 206/QD-DHYDHP, dated October 21, 2023), and the Scientific Council of Hai Phong University of Medicine and Pharmacy Hospital. Written informed consent was obtained from all participants before enrollment. Study design This was a prospective longitudinal cohort study at the Hai Phong University of Medicine and Pharmacy Hospital in Vietnam from September 2023 to August 2025. Sample size calculation The required sample size was calculated using the formula for estimating a correlation coefficient: With: α = 0.05, corresponding to Z 1−α/2 =1.96 β = 0.20 (80% power), corresponding to Z 1−β =0.842 r = 0.43, based on the correlation between CL and gestational age reported by Fujita et al. (2002) [18]. This yielded n = 41. To account for design effect and potential attrition, the minimum required sample size was adjusted to 82. Ultimately, 110 women were enrolled. Study populatio n All pregnant women aged 18-40 years with viable twin pregnancies at 14 weeks of gestation were enrolled and invited to participate in this study. They underwent serial transvaginal ultrasound assessments of CL and UCA every two weeks at the 14 th , 16 th , 18 th , 20 th , 22 nd , and 24 th weeks of gestation, performed by a certified sonographer, with close follow-up until delivery. Additionally, maternal blood samples were collected at 16 weeks of gestation to measure pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). Gestational age was determined based on the first day of the last menstrual period, the date of embryo transfer (for assisted reproductive technology), or first-trimester ultrasound when the last menstrual period was unknown or irregular. Women were excluded if they had a history of cervical procedures (such as conisation or loop electrosurgical excision procedure - LEEP), intrauterine fetal demise of one or both fetuses during follow-up, fetal structural or chromosomal anomalies, medically indicated preterm birth, or missing ultrasound data at any scheduled time point. A total of 110 twin pregnant women at 14 th week of gestation voluntarily participated in the study. Demographic information was collected and documented at the time of recruitment through interviews, using self-designed records. Pregnancy and neonatal outcomes were recorded in electronic medical records. Women who delivered at hospitals other than the study site were contacted by phone. After excluding 17 pregnant women who had a history of LEEP, missing ultrasound data, or medically indicated preterm birth, the final study population consisted of 93 twin pregnant women (Figure 1). Assessment of CL and UCA CL and UCA were assessed transvaginally by a single physician certified and supervised by the Fetal Medicine Foundation, using a GE HealthCare Voluson S8 ultrasound system with a 7.5-10 MHz vaginal probe. Participants were examined in the lithotomy position with an empty bladder. The probe was placed in the anterior vaginal fornix and adjusted to obtain a sagittal view of the cervix without excessive pressure, ensuring that the cervical canal occupied approximately 50–75% of the image. For CL measurement, a straight line was drawn from the internal os to the external os along the cervical canal. Three measurements were obtained, and the shortest value was recorded (Figure 2a). The UCA was measured following the method described by Dziadosz et al. [19]. The first line was drawn along the cervical canal from the external os to the internal os, and the second line was drawn tangent to the anterior wall of the lower uterine segment, intersecting the internal os. Three measurements were performed, and the widest angle was used for analysis (Figure 2b). Assessment of biochemical markers At 16 weeks of gestation, blood samples were collected from all participants. Serum levels of IL-1β, IL-6, and TNF-α were measured using the sandwich enzyme-linked immunosorbent assay (ELISA), following the manufacturer’s instructions. Concentrations were determined from optical absorbance values using a standardized calibration curve. Each assay was performed alongside negative, positive, and internal standards to account for potential technical variability. Statistical analysis SPSS version 26.0 (SPSS, Armonk, NY, USA) was used for the statistical analysis. Categorical variables are presented as numbers and percentages, while continuous variables are expressed as means and standard deviations. The Chi-square test was used to compare the differences in rates. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association between outcomes and independent variables. A multivariate binary regression analysis was performed to examine the relationships among CL, UCA, and preterm birth. Receiver operating characteristic (ROC) curves were utilized to assess the predictive ability of CL and UCA for PTB. A p-value <0.05 was considered statistically significant. RESULTS Among the 93 women with twin pregnancies included in our study, preterm birth before 37 weeks occurred in 44.1% of cases, and before 34 weeks in 12.9%. The mean CL was significantly shorter in participants who delivered preterm compared to those who delivered at term, and the mean UCA was significantly larger in those who delivered preterm. Inflammatory biomarkers (IL-1β, IL-6, TNF-α) showed no significant associations with PTB (Table 1). Table 1 . Baseline characteristics of the study population (n=93). Characteristics n (%) or median PTB <34 weeks PTB <37 weeks No Yes p No Yes p Conception method Natural 22 (84.6) 4 (15.4) 0.733 a 8 (30.8) 18 (69.2) 0.002 a IVF 59 (88.1) 8 (11.9) 44 (65.7) 23 (34.3) Chorionicity dichorionic 70 (88.6) 9 (11.4) 0.382 b 48 (60.8) 31 (39.2) 0.039 b Others 11 (78.6) 3 (21.4) 4 (28.6) 10 (71.4) PTB Prevention No 46 (93.9) 3 (6.1) 0.061 b 33 (67.3) 16 (32.7) 0.019 a Yes 35 (79.5) 9 (20.5) 19 (43.2) 25 (56.8) Yes 7 (87.5) 1 (12.5) 4 (50.0) 5 (50.0) Obstetric history Nulliparous 48 (84.2) 9 (15.8) 0.357 b 32 (56.1) 25 (43.9) 1.000 a Multiparous 33 (91.7) 3 (8.3) 20 (55.6) 16 (44.4) Mother with a chronic illness No 57 (85.1) 10 (14.9) 0.499 b 39 (58.2) 28 (41.8) 0.474 a Yes 24 (92.3) 2 (7.1) 13 (50.0) 13 (50.0) Maternal age (years) 32.6±4.3 28.8±5.4 0.008 c 32.9±4.3 31.1±4.9 0.056 c BMI (kg/ m 2 ) 21.2±2.3 20.3±2.0 0.195 c 21.1±1.9 21.1±2.7 0.961 c CL (mm) 37.2 ± 5.6 32.1 ± 6.7 <0.001 c 38.0 ± 5.4 34.7 ± 6.2 <0.001 c UCA (degree) 99.2 ± 21.9 102.7 ± 22.1 0.210 c 97.0 ± 21.8 103.0 ± 21.8 0.001 c IL1 (median, IQR) 197.0(50.9) 190.4(115.2) 0.814 d 197.2(47.1) 195.3(78.7) 0.736 d IL6 (median, IQR) 19.6(20.0) 29.4(29.5) 0.590 d 19.4(19.1) 23.6(19.1) 0.612 d TNF (median, IQR) 15.5(8.5) 14.1(11.4) 0.393 d 15.3(7.9) 14.4(7.9) 0.160 d a Chi-square test, b Fisher’s exact test, c T-test, d Mann-Whitney U test. Abbreviations: IVF, in vitro fertilization; BMI, body mass index; IL-1β, interleukin-1β; IL-6, interleukin-6; TNF-α, tumor necrosis factor-α Beginning from the 16 th week, a difference in CL was observed between the PTB and non-PTB groups, with the PTB group showing a shorter CL. Starting from the 22 nd week, a difference in UCA was noted, with the PTB group having a larger UCA (Table 2). Table 2. Characteristics of longitudinal CL and UCA in the study population. Times (Weeks) Variable (mean±SD) Overall (mm/ degree) PTB <34 weeks PTB <37 weeks No Yes pd No Yes pd 14 weeks CL 36.8±5.8 36.9±5.8 36.1±6.1 0.517 37.2±5.6 36.4±6.1 0.479 UCA 96.4±24.8 97.5±23.8 88.6±30.3 0.154 98.6±24.2 93.6±25.5 0.479 16 weeks CL 26.1±5.6 36.4±5.6 34.0±4.9 0.094 37.2±5.7 34.7±5.0 0.046 UCA 100.2±22.5 101.4±22.4 92.3±22.6 0.142 101.3±22.9 98.9±22.3 0.580 18 weeks CL 37.2±4.7 37.7±4.6 33.5±3.8 0.004 38.1±4.7 35.9±4.4 0.038 UCA 102.6±18.5 103.0±18.8 99.5±16.8 0.406 101.8±18.1 103.5±19.1 0.716 20 weeks CL 36.4±5.4 37.2±4.8 31.0±6.3 0.001 37.8±4.8 34.6±5.7 0.004 UCA 102.1±20.8 101.5±21.1 105.8±18.8 0.663 98.4±20.7 106.7±20.2 0.090 22 weeks CL 36.5±6.5 37.7±5.5 28.9±7.6 <0.001 38.6±5.3 33.9±6.8 0.001 UCA 99.6±19.9 97.6±20.2 112.9±10.7 0.007 94.6±19.2 105.9±19.2 0.002 24 weeks CL 36.4±7.6 37.5±7.0 29.2±7.9 0.001 39.2±6.1 32.9±8.0 <0.001 UCA 97.1±24.4 94.1±24.1 117.0±16.6 0.001 87.4±22.6 109.4±21.1 <0.001 d Mann-Whitney U test. For PTB <34 weeks, at 20 weeks, CL was associated with PTB with an OR (95% CI) of 0.783 (0.633-0.970). At 22 weeks, both CL and UCA were associated with PTB, with ORs of 0.797 (0.647-0.982) and 1.086 (1.000-1.179), respectively. In contrast, for PTB <37 weeks, the UCA was associated with PTB starting from 20 weeks, with ORs (95% CI) at 20, 22, and 24 weeks being 1.027 (1.000-1.055), 1.038 (1.007-1.070), and 1.044 (1.015-1.073), respectively. Additionally, at 22 weeks of gestation, there was also an association between CL and PTB with an OR (95% CI) of 0.906 (0.822-1.000) (Table 3). Table 3. Association between CL, UCA, and preterm birth e . Preterm birth Variables Preterm birth <34 weeks Preterm birth <37 weeks OR (95% CI) p OR (95% CI) p 14 weeks CL 1.089 (0.934-1.270) 0.274 1.009 (0.925-1.101) 0.837 UCA 0.982 (0.948-1.016) 0.291 0.997 (0.978-1.017) 0.796 16 weeks CL 0.968 (0.795-1.178) 0.742 0.932 (0.842-1.032) 0.176 UCA 0.996 (0.959-1.035) 0.850 1.001 (0.980-1.023) 0.911 18 weeks CL 0.755 (0.552-1.034) 0.079 0.919 (0.819-1.031) 0.150 UCA 0.965 (0.916-1.016) 0.175 1.005 (0.979-1.032) 0.709 20 weeks CL 0.783 (0.633-0.970) 0.025 0.897 (0.803-1.001) 0.052 UCA 0.998 (0.953-1.045) 0.940 1.027 (1.000-1.055) 0.050 22 weeks CL 0.797 (0.647-0.982) 0.033 0.906 (0.822-1.000) 0.049 UCA 1.086 (1.000-1.179) 0.049 1.038 (1.007-1.070) 0.016 24 weeks CL 0.968 (0.841-1.113) 0.646 0.912 (0.830-1.003) 0.058 UCA 1.050 (0.986-1.117) 0.128 1.044 (1.015-1.073) 0.002 e Adjusted for: Maternal age, BMI, Conception method, Chorionicity, PTB prevention , Obstetric history , Mother with a chronic illness, and Interleukin s. At 22 weeks, the combination of CL and UCA showed good predictive value for PTB <34 weeks for PTB <34 weeks, with an AUC of 0.886 (95% CI: 0.809-0.963) (Figure 3a). At 24 weeks, the combination of CL and UCA demonstrated good predictive value for PTB <37 weeks, with an AUC of 0.825 (95% CI: 0.743-0.907) (Figure 3b). ] DISCUSSION This study on 93 women with twin pregnancies found a significant and independent association between CL, UCA, and PTB <37 weeks, as well as PTB <34 weeks, at 22 weeks of gestation. Furthermore, at the aforementioned gestational age, the combination of CL and UCA yielded the highest predictive ability for PTB. As shown in Table 1, women who delivered preterm had a significantly higher mean UCA than those who delivered at term, suggesting that UCA may be a predictor of PTB in twin pregnancies. This finding supports previous studies in twins: Benito Vielba et al. (2021) demonstrated that at 20 weeks, a UCA >120° was a strong predictor of PTB, with an OR of 2.66 (p <0.01) [20]. Similarly, Ponce et al. (2025) found that the preterm group had a significantly wider UCA compared with the term group (137° vs. 120°, p = 0.004) [14]. Additionally, the mean CL was shorter in participants who delivered preterm. These results are consistent with prior studies showing that a shorter CL is strongly associated with PTB [21]. PTB poses significant risks in twin pregnancies, especially with a short CL or dilated cervix, although CL alone has low sensitivity as a screening test. Current guidelines recommend transvaginal ultrasound CL measurement as the routine method for screening for PTB in twins, with a cutoff of 25 mm between 18 and 24 weeks of gestation; however, these parameters (CL and UCA) have been measured only at specific gestational ages [8]. In contrast, in our study, CL and UCA were assessed every two weeks from 14 to 24 weeks of gestation to monitor their changes over time in women with twin pregnancies, beginning at 14 weeks, in accordance with guidelines that recommend starting cervical length screening to evaluate the risk of preterm birth in twin pregnancies. Still, from 16 weeks onward, CL was significantly shorter in the preterm group, indicating that cervical shortening begins early in the second trimester. Fujita et al. previously reported that CL decreases from 47 mm at 13 weeks to 32 mm at 32 weeks [18]. Bergelin et al. observed a weekly decline of 1.8 mm in term twin pregnancies compared with 2.9 mm in preterm cases [22]. Other meta-analyses also confirmed that CL measured at 20–24 weeks is a reliable predictor of PTB [23]. In a large individual patient data meta-analysis, Hughes et al. found that each 1 mm increase in CL reduced the risk of PTB <37 weeks by approximately 4% (HR = 0.96; 95% CI 0.95–0.97) and PTB <34 weeks by 6.8% (HR = 0.93; 95% CI 0.92–0.95) [24]. These findings emphasize that early CL reduction is a sensitive indicator of PTB risk in twin gestations in the early second trimester. In contrast, UCA widened later, with significant divergence only from 22 weeks (p < 0.05), suggesting that UCA reflects PTB risk primarily during the mid-to-late second trimester. Lynch et al. (2020) similarly reported that women with PTB had a mean UCA of 133° compared with 118° in those delivering at term (p = 0.002), and a UCA >110° could be a significant predictor of PTB <37 weeks [25]. However, its predictive strength for earlier PTB (<34 weeks) was limited, underscoring that UCA may be most informative in the second half of the second trimester. Physiological mechanisms may explain these differing trajectories of CL and UCA. CL shortening reflects early biochemical remodeling and softening of cervical connective tissue. At the same time, UCA widening occurs later as a mechanical consequence of increasing uterine mass and intrauterine pressure on a progressively weakened cervix. An obtuse UCA may exert a direct force on the cervical canal, increasing the risk of cervical shortening and dilation, while an acute UCA may help preserve cervical strength. Zhang et al. also observed that CL decreases while UCA increases throughout mid-gestation, with both parameters diverging significantly between preterm and term groups only after 20 weeks [21]. This aligns with our observation that CL changes become evident earlier, whereas UCA becomes a significant marker from approximately 22 weeks onward. Together, these findings highlight the dynamic and sequential nature of cervical remodeling in twin pregnancies, supporting the use of longitudinal sonographic assessment to capture these time-dependent changes. Our results showed that 22 weeks of gestation is the best time to assess CL and UCA for predicting PTB. At this point, both parameters remain significant independent predictors for PTB <34 weeks and <37 weeks in multivariate models (Table 3), with the highest predictive accuracy (Figure 3). Previous studies have generally suggested that mid-trimester cervical assessment improves the prediction of PTB in twins. Still, most reported a relatively broad screening interval or relied on cross-sectional or meta-analytic data rather than serial measurements in the same cohort. Lim et al. reported that CL measured within 4 weeks (20–24 weeks) provides better predictive value for PTB than earlier or later assessments [26], while Benito Vielba et al. found that both CL and UCA measured at 19–22 weeks predicted PTB, with UCA showing more substantial predictive value [27]. Our longitudinal observations show that 22–24 weeks provide the optimal balance between structural cervical change and mechanical load, which likely explains the peak predictive accuracy we observed. Moreover, this timing aligns with recommendations for routine CL screening between 16 and 24 weeks to identify women at risk and start preventive measures such as vaginal progesterone or cerclage [28]. Detecting high-risk patients at 22–24 weeks allows intervention before the threshold of viability, especially for those at risk of early PTB before 34 weeks. Biologically, this period corresponds to the onset of cervical remodeling, during which UCA widening and CL shortening accelerate in women predisposed to preterm labor [21]. The optimal timing of 22 weeks may therefore reflect the point at which these structural and mechanical differences between preterm and term groups are maximal. Earlier assessments capture insufficient change, while later evaluations may be confounded by interventions or early deliveries [29]. Based on current knowledge, this is the first longitudinal serial assessment of combined CL-UCA in twin pregnancies, providing valuable data from a Vietnamese cohort. However, the modest sample size may limit generalizability, and inflammatory biomarkers were measured only once at 16 weeks, potentially underestimating their predictive value. Future research should validate these findings in larger multicenter cohorts and explore integrated predictive models combining CL, UCA, maternal factors, and biomarkers, as well as the impact of targeted preventive interventions. CONCLUSION The results of this study indicated that the 22-week assessment had the highest predictive ability for combined CL and UCA screening, suggesting it is the best timing for mid-trimester screening for PTB in twin pregnancies. Declarations Ethics approval and consent to participate The study protocol was in accordance with the Declaration of Helsinki, has been approved by the Ethics Committee in Biomedical Research of Hue University (approval No. H2023/461), the Ethics Committee of Hai Phong University of Medicine and Pharmacy (approval No. 206/QD-DHYDHP, dated October 21, 2023), and the Scientific Council of Hai Phong University of Medicine and Pharmacy Hospital. Written informed consent was obtained from all participants before enrollment. Consent for publication Not applicable. Availability of data and materials The dataset used and/or analyzed in the current study is available in the supplementary file. Competing interests The authors declare that they have no competing interests. Funding This research did not receive specific grants from funding agencies in the public, commercial, or nonprofit sectors. A uthors contributions B.V.H., N.V.Q.H., L.M.T., and N.T.H.T. designed the study. B.V.H., T.K.Q., and N.T.H.T. collected the data. B.V.H., N.V.Q.H., N.T.H.T., and T.K.Q. performed statistical analyses and wrote the first manuscript. B.V.H., N.V.Q.H., N.T.H.T, T.K.Q., V.V.T., N.T.H.T., and N.T.T.N. critically revised successive drafts of the paper. All the authors have read and approved the final version of the manuscript. Acknowledgments The authors would like to thank all the pregnant women who participated in this study. 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Dziadosz M, Bennett TA, Dolin C, West Honart A, Pham A, Lee SS, Pivo S, Roman AS: Uterocervical angle: a novel ultrasound screening tool to predict spontaneous preterm birth . Am J Obstet Gynecol 2016, 215 (3):376.e371-377. Benito Vielba M, De Bonrostro Torralba C, Álvarez Sarrado L, Tajada Duaso M, Campillos Maza JM, Castán Mateo S: Uterocervical angle at 20 weeks: A promising predictor of spontaneous preterm birth in twin pregnancies . European journal of obstetrics, gynecology, and reproductive biology 2021, 260 :131-136. Zhang M, Li S, Tian C, Li M, Zhang B, Yu H: Changes of uterocervical angle and cervical length in early and mid-pregnancy and their value in predicting spontaneous preterm birth . Front Physiol 2024, 15 :1304513. Bergelin I, Valentin L: Patterns of normal change in cervical length and width during pregnancy in nulliparous women: a prospective, longitudinal ultrasound study . Ultrasound Obstet Gynecol 2001, 18 (3):217-222. Conde-Agudelo A, Romero R, Hassan SS, Yeo L: Transvaginal sonographic cervical length for the prediction of spontaneous preterm birth in twin pregnancies: a systematic review and metaanalysis . Am J Obstet Gynecol 2010, 203 (2):128.e121-112. Hughes KM, Aberoumand M, Seidler AL, Swan P, Aboulghar M, de Lourdes Brizot M, Brock C, Benito Vielba M, Fox N, Gyamfi-Bannerman C et al : Prognostic value of cervical length for spontaneous preterm birth in asymptomatic women with twin pregnancy: meta-analysis of individual participant data . BMJ Med 2025, 4 (1):e000877. Lynch TA, Szlachetka K, Seligman NS: Second trimester uterocervical angle and spontaneous preterm birth in twins . J Matern Fetal Neonatal Med 2020, 33 (18):3125-3131. Lim AC, Hegeman MA, Huis In TVMA, Opmeer BC, Bruinse HW, Mol BW: Cervical length measurement for the prediction of preterm birth in multiple pregnancies: a systematic review and bivariate meta-analysis . Ultrasound Obstet Gynecol 2011, 38 (1):10-17. 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Supplementary Files DataCLUCAintwins93.xlsx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 29 Apr, 2026 Reviewers invited by journal 12 Jan, 2026 Editor invited by journal 07 Jan, 2026 Editor assigned by journal 06 Jan, 2026 Submission checks completed at journal 06 Jan, 2026 First submitted to journal 03 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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2","display":"","copyAsset":false,"role":"figure","size":765906,"visible":true,"origin":"","legend":"\u003cp\u003e(2a). Measurement of CL: straight line drawn from the external os (E) to the internal os (I). (2b). Measurement of UCA: angle between the cervical canal and the anterior uterine wall, with the external os indicated by a thick arrow and the internal os by a thin arrow.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8505360/v1/70b7e529b5e2207278a715a2.png"},{"id":100402003,"identity":"ebdce5aa-5d61-4e43-98cf-711f3ea8d9c8","added_by":"auto","created_at":"2026-01-16 11:59:33","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":292943,"visible":true,"origin":"","legend":"\u003cp\u003e(3a). The receiver operating characteristic curves for CL combined with the UCA and PTB \u0026lt;34 weeks. (3b). The receiver operating characteristic curves for CL combined with the UCA and PTB \u0026lt;37 weeks.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8505360/v1/6702b7c01b0c655b4777c1aa.png"},{"id":100422898,"identity":"785bd297-a559-4026-b3f2-4164f0dfb462","added_by":"auto","created_at":"2026-01-16 14:12:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3407245,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8505360/v1/8a9799ac-49aa-47f6-ae6e-463062bb6672.pdf"},{"id":100401839,"identity":"0082a07b-c2eb-4c31-b747-dc401af4b08c","added_by":"auto","created_at":"2026-01-16 11:59:21","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":44820,"visible":true,"origin":"","legend":"","description":"","filename":"DataCLUCAintwins93.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-8505360/v1/5534a90d62e24df70c2195ec.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cervical Length and Uterocervical Angle for Optimal Timing in Predicting Preterm Birth among Twin Pregnancies: A Longitudinal Study","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003ePreterm birth (PTB) is defined as delivery occurring between 20 weeks and 37 weeks of gestation, according to the World Health Organization (WHO). It remains the most significant challenge facing contemporary obstetrics in both high-resource and low-resource settings. Approximately 15 million babies are born each year prematurely worldwide, with more than 60% of PTB occurring in Africa and South Asia [1]. Multiple pregnancies significantly increase the global PTB rate, with reports showing an incidence as high as 61.3% [2]. The risk of very PTB before 32 weeks is ten times higher in twins than in singletons (10% versus 1%), leading to increased neonatal mortality and long-term health problems [3]. Currently, there is no reliable screening test to predict PTB in twins, which presents a challenge for maternal-fetal specialists [4]. The pathophysiological mechanisms behind spontaneous preterm birth (sPTB) in twins seem to differ from those in singletons. Uterine overdistention likely plays a significant role. Excessive stretching of the uterus could prematurely activate an inflammatory cytokine cascade and release labor mediators, leading to early activation of the myometrium and cervical ripening [5, 6]. Furthermore, the effectiveness of interventions aimed at preventing sPTB may vary between twins and singletons [7]. These findings highlight the need for well-designed prospective studies to identify the predictors of sPTB specifically in twins. Measuring cervical length (CL) during the mid-trimester ultrasound is the most cost-effective screening method used in clinical practice for both singleton and twin pregnancies [8, 9]. However, its accuracy is limited by low sensitivity when used as a single test\u0026nbsp;[10, 11]. The uterocervical angle (UCA) has recently been suggested as a potential ultrasound parameter for predicting PTB in both singletons and twins\u0026nbsp;[12]. An obtuse UCA causes the cervical canal to be more affected by gravitational forces from the uterus and fetus, resulting in cervical shortening and dilation\u0026nbsp;[13]. Combining the UCA with CL has been shown to improve PTB prediction\u0026nbsp;[14, 15]. In addition, few studies have examined the relationship between cervical morphology and systemic inflammatory activity, even though pro-inflammatory cytokines are believed to contribute to cervical remodeling and the onset of preterm labor. The integration of these sonographic and biochemical markers may therefore yield a more comprehensive understanding of the mechanisms underlying PTB in twin pregnancies.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDespite accumulating evidence that CL and UCA are associated with PTB, very few studies have evaluated the combined use of these cervical ultrasound parameters to predict PTB in women with twin pregnancies [16, 17]. Additionally, previous research has typically focused on a single measurement point, leaving the optimal gestational age for assessment in twin pregnancies unclear. Therefore, this study aims to (1) evaluate the relationship between CL and UCA in twin pregnancies with spontaneous PTB, and (2) identify the gestational age at which the combined CL-UCA measurement provides the best predictive ability.\u0026nbsp;\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthical considerations\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was in accordance with the Declaration of Helsinki, has been approved by the Ethics Committee in Biomedical Research of Hue University (approval No. H2023/461), the Ethics Committee of Hai Phong University of Medicine and Pharmacy (approval No. 206/QD-DHYDHP, dated October 21, 2023), and the Scientific Council of Hai Phong University of Medicine and Pharmacy Hospital. Written informed consent was obtained from all participants before enrollment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy design\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a prospective longitudinal cohort study at the Hai Phong University of Medicine and Pharmacy Hospital in Vietnam from September 2023 to August 2025.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSample size calculation\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe required sample size was calculated using the formula for estimating a correlation coefficient:\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"https://myfiles.space/user_files/58895_8739fc6c57c1c19a/58895_custom_files/img1768395581.png\" width=\"337\" height=\"166\"\u003e\u003c/p\u003e\n\u003cp\u003eWith:\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u0026alpha; = 0.05, corresponding to\u0026nbsp;Z\u003csub\u003e1\u0026minus;\u0026alpha;/2\u003c/sub\u003e\u003csub\u003e\u0026nbsp;\u003c/sub\u003e=1.96\u003c/li\u003e\n \u003cli\u003e\u0026beta; = 0.20 (80% power), corresponding to\u0026nbsp;Z\u003csub\u003e1\u0026minus;\u0026beta;\u003c/sub\u003e=0.842\u003c/li\u003e\n \u003cli\u003er = 0.43, based on the correlation between CL and gestational age reported by Fujita et al. (2002) [18].\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eThis yielded\u0026nbsp;n = 41. To account for design effect and potential attrition, the minimum required sample size was adjusted to 82. Ultimately, 110 women were enrolled.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy populatio\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003en\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll pregnant women aged 18-40 years with viable twin pregnancies at 14 weeks of gestation were enrolled and invited to participate in this study. They underwent serial transvaginal ultrasound assessments of CL and UCA every two weeks at the 14\u003csup\u003eth\u003c/sup\u003e, 16\u003csup\u003eth\u003c/sup\u003e, 18\u003csup\u003eth\u003c/sup\u003e, 20\u003csup\u003eth\u003c/sup\u003e, 22\u003csup\u003end\u003c/sup\u003e, and 24\u003csup\u003eth\u003c/sup\u003e weeks of gestation, performed by a certified sonographer, with close follow-up until delivery. Additionally, maternal blood samples were collected at 16 weeks of gestation to measure pro-inflammatory cytokines (IL-1\u0026beta;, IL-6, and TNF-\u0026alpha;).\u003c/p\u003e\n\u003cp\u003eGestational age was determined based on the first day of the last menstrual period, the date of embryo transfer (for assisted reproductive technology), or first-trimester ultrasound when the last menstrual period was unknown or irregular. Women were excluded if they had a history of cervical procedures (such as conisation or loop electrosurgical excision procedure - LEEP), intrauterine fetal demise of one or both fetuses during follow-up, fetal structural or chromosomal anomalies, medically indicated preterm birth, or missing ultrasound data at any scheduled time point.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA total of 110 twin pregnant women at 14\u003csup\u003eth\u003c/sup\u003e week of gestation voluntarily participated in the study. Demographic information was collected and documented at the time of recruitment through interviews, using self-designed records. Pregnancy and neonatal outcomes were recorded in electronic medical records. Women who delivered at hospitals other than the study site were contacted by phone.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter excluding 17 pregnant women who had a history of LEEP, missing ultrasound data, or medically indicated preterm birth, the final study population consisted of 93 twin pregnant women (Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAssessment of CL and UCA\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCL and UCA were assessed transvaginally by a single physician certified and supervised by the Fetal Medicine Foundation, using a GE HealthCare Voluson S8 ultrasound system with a 7.5-10 MHz vaginal probe. Participants were examined in the lithotomy position with an empty bladder. The probe was placed in the anterior vaginal fornix and adjusted to obtain a sagittal view of the cervix without excessive pressure, ensuring that the cervical canal occupied approximately 50\u0026ndash;75% of the image. For CL measurement, a straight line was drawn from the internal os to the external os along the cervical canal. Three measurements were obtained, and the shortest value was recorded (Figure 2a). The UCA was measured following the method described by Dziadosz et al. [19]. The first line was drawn along the cervical canal from the external os to the internal os, and the second line was drawn tangent to the anterior wall of the lower uterine segment, intersecting the internal os. Three measurements were performed, and the widest angle was used for analysis (Figure 2b).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAssessment of biochemical markers\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAt 16 weeks of gestation, blood samples were collected from all participants. Serum levels of IL-1\u0026beta;, IL-6, and TNF-\u0026alpha; were measured using the sandwich enzyme-linked immunosorbent assay (ELISA), following the manufacturer\u0026rsquo;s instructions. Concentrations were determined from optical absorbance values using a standardized calibration curve. Each assay was performed alongside negative, positive, and internal standards to account for potential technical variability.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSPSS version 26.0 (SPSS, Armonk, NY, USA) was used for the statistical analysis.\u003c/p\u003e\n\u003cp\u003eCategorical variables are presented as numbers and percentages, while continuous variables are expressed as means and standard deviations. The Chi-square test was used to compare the differences in rates. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association between outcomes and independent variables. A multivariate binary regression analysis was performed to examine the relationships among CL, UCA, and preterm birth. Receiver operating characteristic (ROC) curves were utilized to assess the predictive ability of CL and UCA for PTB. A p-value \u0026lt;0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eAmong the 93 women with twin pregnancies included in our study, preterm birth before 37 weeks occurred in 44.1% of cases, and before 34 weeks in 12.9%. The mean CL was significantly shorter in participants who delivered preterm compared to those who delivered at term, and the mean UCA was significantly larger in those who delivered preterm.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInflammatory biomarkers (IL-1\u0026beta;, IL-6, TNF-\u0026alpha;) showed no significant associations with PTB (Table 1). \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e. Baseline characteristics of the study population (n=93).\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"700\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 199px;\"\u003e\u003cstrong\u003eCharacteristics\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003en (%) or median\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 252px;\"\u003e\u003cstrong\u003ePTB \u0026lt;34 weeks\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 249px;\"\u003e\u003cstrong\u003ePTB \u0026lt;37 weeks\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 91px;\"\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 113px;\"\u003eConception method\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003eNatural\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e22 (84.6)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e4 (15.4)\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 65px;\"\u003e0.733\u003csup\u003ea\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e8 (30.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e18 (69.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 65px;\"\u003e0.002\u003csup\u003ea\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003eIVF\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e59 (88.1)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e8 (11.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e44 (65.7)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e23 (34.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 113px;\"\u003eChorionicity\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003edichorionic\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e70 (88.6)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e9 (11.4)\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 65px;\"\u003e0.382\u003csup\u003eb\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e48 (60.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e31 (39.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 65px;\"\u003e0.039\u003csup\u003eb\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003eOthers\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e11 (78.6)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e3 (21.4)\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e4 (28.6)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e10 (71.4)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 113px;\"\u003ePTB Prevention\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003eNo\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e46 (93.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e3 (6.1)\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 65px;\"\u003e0.061\u003csup\u003eb\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e33 (67.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e16 (32.7)\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"3\" style=\"width: 65px;\"\u003e0.019\u003csup\u003ea\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003eYes\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e35 (79.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e9 (20.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e19 (43.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e25 (56.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003eYes\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e7 (87.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e1 (12.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e4 (50.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e5 (50.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 113px;\"\u003eObstetric history\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003eNulliparous\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e48 (84.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e9 (15.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 65px;\"\u003e0.357\u003csup\u003eb\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e32 (56.1)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e25 (43.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 65px;\"\u003e1.000\u003csup\u003ea\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003eMultiparous\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e33 (91.7)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e3 (8.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e20 (55.6)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e16 (44.4)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 113px;\"\u003eMother with a chronic illness\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003eNo\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e57 (85.1)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e10 (14.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 65px;\"\u003e0.499\u003csup\u003eb\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e39 (58.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e28 (41.8)\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 65px;\"\u003e0.474\u003csup\u003ea\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003eYes\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e24 (92.3)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e2 (7.1)\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e13 (50.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e13 (50.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 199px;\"\u003eMaternal age (years)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e32.6\u0026plusmn;4.3\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e28.8\u0026plusmn;5.4\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e0.008\u003csup\u003ec\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e32.9\u0026plusmn;4.3\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e31.1\u0026plusmn;4.9\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e0.056\u003csup\u003ec\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 199px;\"\u003eBMI (kg/ m\u003csup\u003e2\u003c/sup\u003e)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e21.2\u0026plusmn;2.3\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e20.3\u0026plusmn;2.0\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e0.195\u003csup\u003ec\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e21.1\u0026plusmn;1.9\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e21.1\u0026plusmn;2.7\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e0.961\u003csup\u003ec\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 199px;\"\u003eCL (mm)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e37.2 \u0026plusmn; 5.6\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e32.1 \u0026plusmn; 6.7\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\u0026lt;0.001\u003csup\u003ec\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e38.0 \u0026plusmn; 5.4\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e34.7 \u0026plusmn; 6.2\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e\u0026lt;0.001\u003csup\u003ec\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 199px;\"\u003eUCA (degree)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e99.2 \u0026plusmn; 21.9\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e102.7 \u0026plusmn; 22.1\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e0.210\u003csup\u003ec\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e97.0 \u0026plusmn; 21.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e103.0 \u0026plusmn; 21.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e0.001\u003csup\u003ec\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 199px;\"\u003eIL1 (median, IQR)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e197.0(50.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e190.4(115.2)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e0.814\u003csup\u003ed\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e197.2(47.1)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e195.3(78.7)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e0.736\u003csup\u003ed\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 199px;\"\u003eIL6 (median, IQR)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e19.6(20.0)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e29.4(29.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e0.590\u003csup\u003ed\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e19.4(19.1)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e23.6(19.1)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e0.612\u003csup\u003ed\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 199px;\"\u003eTNF (median, IQR)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e15.5(8.5)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 93px;\"\u003e14.1(11.4)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e0.393\u003csup\u003ed\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 95px;\"\u003e15.3(7.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e14.4(7.9)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 65px;\"\u003e0.160\u003csup\u003ed\u003c/sup\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 3px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e\u003cem\u003eChi-square test, \u003csup\u003eb\u0026nbsp;\u003c/sup\u003eFisher\u0026rsquo;s exact test, \u003csup\u003ec\u0026nbsp;\u003c/sup\u003eT-test, \u003csup\u003ed\u0026nbsp;\u003c/sup\u003eMann-Whitney U test.\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAbbreviations: IVF, in vitro fertilization; BMI, body mass index;\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003cem\u003eIL-1\u0026beta;, interleukin-1\u0026beta;; IL-6, interleukin-6;\u0026nbsp;\u003c/em\u003e\u003cem\u003eTNF-\u0026alpha;,\u0026nbsp;\u003c/em\u003e\u003cem\u003etumor necrosis factor-\u0026alpha;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eBeginning from the 16\u003csup\u003eth\u003c/sup\u003e week, a difference in CL was observed between the PTB and non-PTB groups, with the PTB group showing a shorter CL. Starting from the 22\u003csup\u003end\u0026nbsp;\u003c/sup\u003eweek, a difference in UCA was noted, with the PTB group having a larger UCA (Table 2).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eCharacteristics of longitudinal CL and UCA in the study population.\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"695\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 66px;\"\u003e\u003cstrong\u003eTimes (Weeks)\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 86px;\"\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e(mean\u0026plusmn;SD)\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 96px;\"\u003e\u003cstrong\u003eOverall\u003c/strong\u003e\u003cbr\u003e\u003cstrong\u003e(mm/ degree)\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 224px;\"\u003e\u003cstrong\u003ePTB \u0026lt;34 weeks\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 223px;\"\u003e\u003cstrong\u003ePTB \u0026lt;37 weeks\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 85px;\"\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\u003cstrong\u003epd\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\u003cstrong\u003eNo\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e\u003cstrong\u003eYes\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\u003cstrong\u003epd\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 66px;\"\u003e14 weeks\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003eCL\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e36.8\u0026plusmn;5.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e36.9\u0026plusmn;5.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e36.1\u0026plusmn;6.1\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e0.517\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e37.2\u0026plusmn;5.6\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e36.4\u0026plusmn;6.1\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e0.479\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003eUCA\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e96.4\u0026plusmn;24.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e97.5\u0026plusmn;23.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e88.6\u0026plusmn;30.3\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e0.154\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e98.6\u0026plusmn;24.2\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e93.6\u0026plusmn;25.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e0.479\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 66px;\"\u003e16 weeks\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003eCL\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e26.1\u0026plusmn;5.6\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e36.4\u0026plusmn;5.6\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e34.0\u0026plusmn;4.9\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e0.094\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e37.2\u0026plusmn;5.7\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e34.7\u0026plusmn;5.0\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e0.046\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003eUCA\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e100.2\u0026plusmn;22.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e101.4\u0026plusmn;22.4\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e92.3\u0026plusmn;22.6\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e0.142\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e101.3\u0026plusmn;22.9\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e98.9\u0026plusmn;22.3\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e0.580\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 66px;\"\u003e18 weeks\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003eCL\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e37.2\u0026plusmn;4.7\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e37.7\u0026plusmn;4.6\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e33.5\u0026plusmn;3.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e0.004\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e38.1\u0026plusmn;4.7\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e35.9\u0026plusmn;4.4\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e0.038\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003eUCA\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e102.6\u0026plusmn;18.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e103.0\u0026plusmn;18.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e99.5\u0026plusmn;16.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e0.406\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e101.8\u0026plusmn;18.1\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e103.5\u0026plusmn;19.1\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e0.716\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 66px;\"\u003e20 weeks\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003eCL\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e36.4\u0026plusmn;5.4\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e37.2\u0026plusmn;4.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e31.0\u0026plusmn;6.3\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e37.8\u0026plusmn;4.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e34.6\u0026plusmn;5.7\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e0.004\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003eUCA\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e102.1\u0026plusmn;20.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e101.5\u0026plusmn;21.1\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e105.8\u0026plusmn;18.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e0.663\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e98.4\u0026plusmn;20.7\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e106.7\u0026plusmn;20.2\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e0.090\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 66px;\"\u003e22 weeks\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003eCL\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e36.5\u0026plusmn;6.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e37.7\u0026plusmn;5.5\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e28.9\u0026plusmn;7.6\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e38.6\u0026plusmn;5.3\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e33.9\u0026plusmn;6.8\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003eUCA\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e99.6\u0026plusmn;19.9\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e97.6\u0026plusmn;20.2\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e112.9\u0026plusmn;10.7\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e0.007\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e94.6\u0026plusmn;19.2\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e105.9\u0026plusmn;19.2\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e0.002\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 66px;\"\u003e24 weeks\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 86px;\"\u003eCL\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e36.4\u0026plusmn;7.6\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e37.5\u0026plusmn;7.0\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e29.2\u0026plusmn;7.9\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e39.2\u0026plusmn;6.1\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e32.9\u0026plusmn;8.0\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 86px;\"\u003eUCA\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e97.1\u0026plusmn;24.4\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e94.1\u0026plusmn;24.1\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e117.0\u0026plusmn;16.6\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 54px;\"\u003e0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e87.4\u0026plusmn;22.6\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 81px;\"\u003e109.4\u0026plusmn;21.1\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\u0026lt;0.001\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 2px;\"\u003e\u0026nbsp;\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ed\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e\u003cem\u003eMann-Whitney U test.\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eFor PTB \u0026lt;34 weeks, at 20 weeks, CL was associated with PTB with an OR (95% CI) of 0.783 (0.633-0.970). At 22 weeks, both CL and UCA were associated with PTB, with ORs of 0.797 (0.647-0.982) and 1.086 (1.000-1.179), respectively. In contrast, for PTB \u0026lt;37 weeks, the UCA was associated with PTB starting from 20 weeks, with ORs (95% CI) at 20, 22, and 24 weeks being 1.027 (1.000-1.055), 1.038 (1.007-1.070), and 1.044 (1.015-1.073), respectively. Additionally, at 22 weeks of gestation, there was also an association between CL and PTB with an OR (95% CI) of 0.906 (0.822-1.000) (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u0026nbsp;\u003c/strong\u003eAssociation between CL, UCA, and preterm birth\u003csup\u003ee\u003c/sup\u003e.\u003c/p\u003e\n\u003cdiv align=\"\"\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"676\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 101px;\"\u003e\u003cstrong\u003ePreterm birth\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 83px;\"\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 231px;\"\u003e\u003cstrong\u003ePreterm birth \u0026lt;34 weeks\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 261px;\"\u003e\u003cstrong\u003ePreterm birth \u0026lt;37 weeks\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 162px;\"\u003e\u003cstrong\u003eOR (95% CI)\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e\u003cstrong\u003eOR (95% CI)\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 101px;\"\u003e14 weeks\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003eCL\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e1.089 (0.934-1.270)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e0.274\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e1.009 (0.925-1.101)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e0.837\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003eUCA\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e0.982 (0.948-1.016)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e0.291\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e0.997 (0.978-1.017)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e0.796\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 101px;\"\u003e16 weeks\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003eCL\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e0.968 (0.795-1.178)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e0.742\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e0.932 (0.842-1.032)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e0.176\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003eUCA\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e0.996 (0.959-1.035)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e0.850\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e1.001 (0.980-1.023)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e0.911\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 101px;\"\u003e18 weeks\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003eCL\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e0.755 (0.552-1.034)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e0.079\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e0.919 (0.819-1.031)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e0.150\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003eUCA\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e0.965 (0.916-1.016)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e0.175\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e1.005 (0.979-1.032)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e0.709\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 101px;\"\u003e20 weeks\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003eCL\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e0.783 (0.633-0.970)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e0.025\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e0.897 (0.803-1.001)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e0.052\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003eUCA\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e0.998 (0.953-1.045)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e0.940\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e1.027 (1.000-1.055)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e0.050\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 101px;\"\u003e22 weeks\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003eCL\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e0.797 (0.647-0.982)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e0.033\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e0.906 (0.822-1.000)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e0.049\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003eUCA\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e1.086 (1.000-1.179)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e0.049\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e1.038 (1.007-1.070)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e0.016\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 101px;\"\u003e24 weeks\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 83px;\"\u003eCL\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e0.968 (0.841-1.113)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e0.646\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e0.912 (0.830-1.003)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e0.058\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 83px;\"\u003eUCA\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 162px;\"\u003e1.050 (0.986-1.117)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e0.128\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 180px;\"\u003e1.044 (1.015-1.073)\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e0.002\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cem\u003e\u003csup\u003ee\u003c/sup\u003e\u003c/em\u003e\u003cem\u003eAdjusted for: Maternal age, BMI, Conception method, Chorionicity,\u0026nbsp;\u003c/em\u003e\u003cem\u003ePTB prevention\u003c/em\u003e\u003cem\u003e,\u0026nbsp;\u003c/em\u003e\u003cem\u003eObstetric history\u003c/em\u003e\u003cem\u003e, Mother with a chronic illness,\u0026nbsp;\u003c/em\u003e\u003cem\u003eand\u0026nbsp;\u003c/em\u003e\u003cem\u003eInterleukin\u003c/em\u003e\u003cem\u003es.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAt 22 weeks, the combination of CL and UCA showed good predictive value for PTB \u0026lt;34 weeks for PTB \u0026lt;34 weeks, with an AUC of 0.886 (95% CI: 0.809-0.963) (Figure 3a).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt 24 weeks, the combination of CL and UCA demonstrated good predictive value for PTB \u0026lt;37 weeks, with an AUC of 0.825 (95% CI: 0.743-0.907) (Figure 3b). ]\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study on 93 women with twin pregnancies found a significant and independent association between CL, UCA, and PTB \u0026lt;37 weeks, as well as PTB \u0026lt;34 weeks, at 22 weeks of gestation. Furthermore, at the aforementioned gestational age, the combination of CL and UCA yielded the highest predictive ability for PTB.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAs shown in Table 1, women who delivered preterm had a significantly higher mean UCA than those who delivered at term, suggesting that UCA may be a predictor of PTB in twin pregnancies. This finding supports previous studies in twins: Benito Vielba et al. (2021) demonstrated that at 20 weeks, a UCA \u0026gt;120\u0026deg; was a strong predictor of PTB, with an OR of 2.66 (p \u0026lt;0.01) [20]. Similarly, Ponce et al. (2025) found that the preterm group had a significantly wider UCA compared with the term group (137\u0026deg; vs. 120\u0026deg;, p = 0.004) [14]. Additionally, the mean CL was shorter in participants who delivered preterm. These results are consistent with prior studies showing that a shorter CL is strongly associated with PTB [21]. PTB poses significant risks in twin pregnancies, especially with a short CL or dilated cervix, although CL alone has low sensitivity as a screening test. Current guidelines recommend transvaginal ultrasound CL measurement as the routine method for screening for PTB in twins, with a cutoff of 25 mm between 18 and 24 weeks of gestation; however, these parameters (CL and UCA) have been measured only at specific gestational ages [8]. In contrast, in our study, CL and UCA were assessed every two weeks from 14 to 24 weeks of gestation to monitor their changes over time in women with twin pregnancies, beginning at 14 weeks, in accordance with guidelines that recommend starting cervical length screening to evaluate the risk of preterm birth in twin pregnancies. Still, from 16 weeks onward, CL was significantly shorter in the preterm group, indicating that cervical shortening begins early in the second trimester. Fujita et al. previously reported that CL decreases from 47 mm at 13 weeks to 32 mm at 32 weeks [18]. Bergelin et al. observed a weekly decline of 1.8 mm in term twin pregnancies compared with 2.9 mm in preterm cases [22]. Other meta-analyses also confirmed that CL measured at 20\u0026ndash;24 weeks is a reliable predictor of PTB \u0026nbsp;[23]. In a large individual patient data meta-analysis, Hughes et al. found that each 1 mm increase in CL reduced the risk of PTB \u0026lt;37 weeks by approximately 4% (HR = 0.96; 95% CI 0.95\u0026ndash;0.97) and PTB \u0026lt;34 weeks by 6.8% (HR = 0.93; 95% CI 0.92\u0026ndash;0.95) [24]. These findings emphasize that early CL reduction is a sensitive indicator of PTB risk in twin gestations in the early second trimester. In contrast, UCA widened later, with significant divergence only from 22 weeks (p \u0026lt; 0.05), suggesting that UCA reflects PTB risk primarily during the mid-to-late second trimester. Lynch et al. (2020) similarly reported that women with PTB had a mean UCA of 133\u0026deg; compared with 118\u0026deg; in those delivering at term (p = 0.002), and a UCA \u0026gt;110\u0026deg; could be a significant predictor of PTB \u0026lt;37 weeks [25]. However, its predictive strength for earlier PTB (\u0026lt;34 weeks) was limited, underscoring that UCA may be most informative in the second half of the second trimester.\u003c/p\u003e\n\u003cp\u003ePhysiological mechanisms may explain these differing trajectories of CL and UCA. CL shortening reflects early biochemical remodeling and softening of cervical connective tissue. At the same time, UCA widening occurs later as a mechanical consequence of increasing uterine mass and intrauterine pressure on a progressively weakened cervix. An obtuse UCA may exert a direct force on the cervical canal, increasing the risk of cervical shortening and dilation, while an acute UCA may help preserve cervical strength. Zhang et al. also observed that CL decreases while UCA increases throughout mid-gestation, with both parameters diverging significantly between preterm and term groups only after 20 weeks [21]. This aligns with our observation that CL changes become evident earlier, whereas UCA becomes a significant marker from approximately 22 weeks onward. Together, these findings highlight the dynamic and sequential nature of cervical remodeling in twin pregnancies, supporting the use of longitudinal sonographic assessment to capture these time-dependent changes.\u003c/p\u003e\n\u003cp\u003eOur results showed that 22 weeks of gestation is the best time to assess CL and UCA for predicting PTB. At this point, both parameters remain significant independent predictors for PTB \u0026lt;34 weeks and \u0026lt;37 weeks in multivariate models (Table 3), with the highest predictive accuracy (Figure 3). Previous studies have generally suggested that mid-trimester cervical assessment improves the prediction of PTB\u0026nbsp;in twins. Still, most reported a relatively broad screening interval or relied on cross-sectional or meta-analytic data rather than serial measurements in the same cohort. Lim et al. reported that CL measured within 4 weeks (20\u0026ndash;24 weeks) provides better predictive value for PTB than earlier or later assessments [26], while Benito Vielba et al. found that both CL and UCA measured at 19\u0026ndash;22 weeks predicted PTB, with UCA showing more substantial predictive value [27]. Our longitudinal observations show that 22\u0026ndash;24 weeks provide the optimal balance between structural cervical change and mechanical load, which likely explains the peak predictive accuracy we observed.\u003c/p\u003e\n\u003cp\u003eMoreover, this timing aligns with recommendations for routine CL screening between 16 and 24 weeks to identify women at risk and start preventive measures such as vaginal progesterone or cerclage [28]. Detecting high-risk patients at 22\u0026ndash;24 weeks allows intervention before the threshold of viability, especially for those at risk of early PTB before 34 weeks. Biologically, this period corresponds to the onset of cervical remodeling, during which UCA widening and CL shortening accelerate in women predisposed to preterm labor [21]. The optimal timing of 22 weeks may therefore reflect the point at which these structural and mechanical differences between preterm and term groups are maximal. Earlier assessments capture insufficient change, while later evaluations may be confounded by interventions or early deliveries [29].\u003c/p\u003e\n\u003cp\u003eBased on current knowledge, this is the first longitudinal serial assessment of combined CL-UCA in twin pregnancies, providing valuable data from a Vietnamese cohort. However, the modest sample size may limit generalizability, and inflammatory biomarkers were measured only once at 16 weeks, potentially underestimating their predictive value. Future research should validate these findings in larger multicenter cohorts and explore integrated predictive models combining CL, UCA, maternal factors, and biomarkers, as well as the impact of targeted preventive interventions.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThe results of this study indicated that the 22-week assessment had the highest predictive ability for combined CL and UCA screening, suggesting it is the best timing for mid-trimester screening for PTB in twin pregnancies.\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was in accordance with the Declaration of Helsinki, has been approved by the Ethics Committee in Biomedical Research of Hue University (approval No. H2023/461), the Ethics Committee of Hai Phong University of Medicine and Pharmacy (approval No. 206/QD-DHYDHP, dated October 21, 2023), and the Scientific Council of Hai Phong University of Medicine and Pharmacy Hospital. Written informed consent was obtained from all participants before enrollment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConsent for publication\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAvailability of data and materials\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe dataset used and/or analyzed in the current study is available in the supplementary file.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eCompeting interests\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eFunding\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research did not receive specific grants from funding agencies in the public, commercial, or nonprofit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eA\u003c/strong\u003e\u003c/em\u003e\u003cem\u003e\u003cstrong\u003euthors contributions \u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eB.V.H., N.V.Q.H., L.M.T., and N.T.H.T. designed the study. B.V.H., T.K.Q., and N.T.H.T. collected the data. B.V.H., N.V.Q.H., N.T.H.T., and T.K.Q. performed statistical analyses and wrote the first manuscript. B.V.H., N.V.Q.H., N.T.H.T, T.K.Q., V.V.T., N.T.H.T., and N.T.T.N. critically revised successive drafts of the paper. All the authors have read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the pregnant women who participated in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLanglois EV, Reid A, Lawn JE, Kinney M, Bizri ME, Beliz\u0026aacute;n JM, Gruending A, Jacobsson B: \u003cstrong\u003eBorn Too Soon: Priorities to improve the prevention and care of preterm birth\u003c/strong\u003e. \u003cem\u003eReprod Health \u003c/em\u003e2025, \u003cstrong\u003e22\u003c/strong\u003e(Suppl 2):110.\u003c/li\u003e\n\u003cli\u003eOsterman MJK, Hamilton BE, Martin JA, Driscoll AK, Valenzuela CP: \u003cstrong\u003eBirths: Final Data for 2022\u003c/strong\u003e. \u003cem\u003eNatl Vital Stat Rep \u003c/em\u003e2024, \u003cstrong\u003e73\u003c/strong\u003e(2):1-56.\u003c/li\u003e\n\u003cli\u003eElliott JP: 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data\u003c/strong\u003e. \u003cem\u003eBMJ Med \u003c/em\u003e2025, \u003cstrong\u003e4\u003c/strong\u003e(1):e000877.\u003c/li\u003e\n\u003cli\u003eLynch TA, Szlachetka K, Seligman NS: \u003cstrong\u003eSecond trimester uterocervical angle and spontaneous preterm birth in twins\u003c/strong\u003e. \u003cem\u003eJ Matern Fetal Neonatal Med \u003c/em\u003e2020, \u003cstrong\u003e33\u003c/strong\u003e(18):3125-3131.\u003c/li\u003e\n\u003cli\u003eLim AC, Hegeman MA, Huis In TVMA, Opmeer BC, Bruinse HW, Mol BW: \u003cstrong\u003eCervical length measurement for the prediction of preterm birth in multiple pregnancies: a systematic review and bivariate meta-analysis\u003c/strong\u003e. \u003cem\u003eUltrasound Obstet Gynecol \u003c/em\u003e2011, \u003cstrong\u003e38\u003c/strong\u003e(1):10-17.\u003c/li\u003e\n\u003cli\u003eBenito Vielba M, De Bonrostro Torralba C, Espiau Romera A, Roca Arquillue M, Campillos Maza JM, Cast\u0026aacute;n Mateo S: \u003cstrong\u003eUterocervical angle as a predictor of spontaneous preterm birth in twin pregnancies\u003c/strong\u003e. \u003cem\u003eJ Matern Fetal Neonatal Med \u003c/em\u003e2022, \u003cstrong\u003e35\u003c/strong\u003e(10):1878-1885.\u003c/li\u003e\n\u003cli\u003e\u003cstrong\u003ePrediction and Prevention of Spontaneous Preterm Birth: ACOG Practice Bulletin, Number 234\u003c/strong\u003e. \u003cem\u003eObstet Gynecol \u003c/em\u003e2021, \u003cstrong\u003e138\u003c/strong\u003e(2):e65-e90.\u003c/li\u003e\n\u003cli\u003eFerro J, Diago V, Diago DM, Pellicer N, Olmo I, V\u0026aacute;zquez S, Lara C, Perales A, Serra V: \u003cstrong\u003eThe effectiveness of cervical cerclage in twin pregnancies with a mid-trimester short cervix: A retrospective cohort study\u003c/strong\u003e. \u003cem\u003eEur J Obstet Gynecol Reprod Biol \u003c/em\u003e2024, \u003cstrong\u003e294\u003c/strong\u003e:33-38.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Preterm birth, cervical length, uterocervical angle, twin pregnancy, inflammatory markers","lastPublishedDoi":"10.21203/rs.3.rs-8505360/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8505360/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eTwin pregnancies carry a significantly higher risk of preterm birth; however, measuring cervical length with sonography during the mid-trimester provided limited predictive accuracy when used as a standalone test. This study aimed to investigate the relationship between cervical length (CL) and uterocervical angle (UCA) for predicting preterm birth in twins, and to determinethe gestational age at which the combined CL-UCA measurement offers the best predictive ability.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eA prospective longitudinal cohort study involving 93 twin pregnancies at 14 weeks of gestation was conducted at Haiphong Medical University Hospital, from 09/2023 to 08/2025. Each patient underwent a transvaginal ultrasound to measure CL and UCA every 2 weeks from 14 to 24 weeks, performed by a certified sonographer. Blood samples for interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) testing were collected at 16 weeks. Patients were followed until delivery to determine pregnancy outcomes, including spontaneous preterm birth (PTB) before 37 weeks and before 34 weeks of gestation. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association between CL-UCA and PTB. A multivariate binary regression model was used to analyze the relationship between CL-UCA and PTB, with p-values \u0026lt;0.05 considered significant. Receiver operating characteristic (ROC) curves assessed the ability of CL-UCA to predict PTB.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e At 22 weeks of gestation, significant associations were found between both CL and UCA with PTB \u0026lt;34 weeks, with ORs (95% CI) of 0.797 (0.647-0.982) and 1.086 (1.000-1.179), respectively, as well as with PTB \u0026lt;37 weeks, with ORs (95% CI) of 0.906 (0.822-1.000) and 1.038 (1.007-1.070). Combined CL and UCA showed good predictive value for PTB \u0026lt;34 weeks, with an AUC of 0.886 (95% CI: 0.809-0.963) at 22 weeks of gestation, and also demonstrated good predictive value for PTB \u0026lt;37 weeks, with an AUC of 0.825 (95% CI: 0.743-0.907) at 24 weeks of gestation. Inflammatory markers at 16 weeks were not associated with PTB (p \u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eThe study's findings show that the 22-week assessment has the highest predictive ability for combined CL and UCA screening for PTB, making it the best timing for mid-trimester screening in twin pregnancies.\u003c/p\u003e","manuscriptTitle":"Cervical Length and Uterocervical Angle for Optimal Timing in Predicting Preterm Birth among Twin Pregnancies: A Longitudinal Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-16 09:02:06","doi":"10.21203/rs.3.rs-8505360/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"258805349993470711520117118733305205","date":"2026-04-29T14:38:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-12T11:28:22+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-07T07:13:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-06T10:08:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-06T10:08:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2026-01-03T08:02:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"be707f1e-45dd-430e-a9b9-242810b64d7c","owner":[],"postedDate":"January 16th, 2026","published":true,"recentEditorialEvents":[{"type":"reviewerAgreed","content":"258805349993470711520117118733305205","date":"2026-04-29T14:38:29+00:00","index":100,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-01-16T09:02:06+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-16 09:02:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8505360","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8505360","identity":"rs-8505360","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}