TVS-guided cervical strain elastography is more effective than measuring cervical length as an independent predictor of spontaneous preterm delivery in asymptomatic, high-risk women during the mid-trimester.

INTRODUCTION: TVS (Transvaginal Sonography) guided Cervical strain elastography (CSE) is now available in tertiary referral centers of LMICs (Low- and Middle-Income Countries). TVS cervical length (CL) assessment is being used routinely. Still, elastography is not used in clinical settings, although enough evidence suggests good predictive value towards sPTD (spontaneous Preterm Delivery). The clinical utility of elastography has not been tested among high-risk populations of LMICs for the prediction of sPTD. AIM: To test the performance of TVS-CSE in predicting sPTD among asymptomatic women in the mid-trimester at risk of sPTD either due to clinical factors or due to a short cervix. METHOD: Prospective observational study performed at a tertiary hospital in South India. Asymptomatic pregnant women between 16 and 24 weeks who had one or more clinical risk factors for sPTD or CL <2.5 cm were included. GE Voluson E-8 ultrasound machine was used. After CL measurement, elastography color coding was noted around the internal-os in the sagittal view. The strain ratio (SR) was calculated using the trace method on three ROIs (Region of Interest): Internal-os in sagittal view (IN), whole cervix in sagittal view (WN), and internal-os in axial view (AN). Reference Tissue (RT) of similar size and depth was chosen in the darkest blue region on elastography (stiffest area) outside the cervix, posterior/lateral to the cervix over the ligament insertion. Lower the SR - softer the cervix. Two trained fetal medicine consultants performed the initial 57 cases until intra/inter-observer correlation was satisfactory. Delivery before 37 weeks (after 26 weeks), in which the process of labor has begun spontaneously, or labor was induced after PPROM-was considered as sPTD. SRs were assessed to determine how well they could predict sPTD independently or combined with cervical length. RESULTS: Out of 221 recruited,17 were lost to follow-up after 32 weeks; 204 were delivered in our hospital. Irrespective of the route of delivery, 71 (34.8%) had sPTD. Of the remaining 133, 106 delivered at term, and 27 underwent medically indicated PTD. Apart from multiple pregnancies, no other preterm-related risk factors (including CL < 2.5 cm) showed significant association with sPTD. Red CSE pattern around internal-os was associated with a significantly higher (54.5%) incidence of sPTD. CLs were similar (3.63 ± 0.67 vs. 3.63 ± 0.80, p = .981) whereas SRs in all three ROIs were significantly lower among sPTD group versus no sPTD group (IN:0.65 ± 0.29 vs 0.79 ± 0.30 p = .001, WN:0.34 ± 0.13 vs 0.39 ± 0.15, p = .013, AN:0.37 ± 0.16 vs 0.48 ± 0.26, p = .002, respectively). Using ROC curves, while CL was not predictive (AUROC 0.49, p = .81), SRs showed moderate predictive value toward sPTD with the best AUC of 0.624 (p = .003) at IN. Prediction was slightly better for early sPTD <32 weeks (AUC 0.653 p = 0.03). The best cutoff for SR at IN was 0.72, below which there was a moderate accuracy in predicting sPTD (sensitivity 52.11%, specificity 60.9%, PPV 41.57%, NPV 70.44%, diagnostic OR 1.69 and overall accuracy of 57.84%). A weak positive correlation is seen between IN and CL (Pearson's correlation R = 0.181). Multi-variable binary logistic regression analysis suggested that SRs at IN (Adjusted OR - 0.259 CI 0.079-0.850), AN (Adjusted OR 0.182 CI 0.034-0.963), Multiple Pregnancy (Adjusted OR 3.5 CI 1.51-8.13) and previous sPTD/PPROM (Adjusted OR 2.72 CI 0.97-7.61) independently predicted sPTD. CONCLUSIONS: TVS CSE performed better than CL as an independent predictive tool toward sPTD, although predictive efficacy was modest at best. Since technology is now available in high-end USG machines in tertiary care centers, we propose optimal utilization of CSE in LMICs to triage at-risk populations since low SRs are strongly associated with sPTD.

Comparing cervical cerclage, pessary and vaginal progesterone for prevention of preterm birth in women with a short cervix (SuPPoRT): A multicentre randomised controlled trial.

BACKGROUND: Cervical cerclage, cervical pessary, and vaginal progesterone have each been shown to reduce preterm birth (PTB) in high-risk women, but to our knowledge, there has been no randomised comparison of the 3 interventions. The SuPPoRT "Stitch, Pessary, or Progesterone Randomised Trial" was designed to compare the rate of PTB <37 weeks between each intervention in women who develop a short cervix in pregnancy. METHODS AND FINDINGS: SuPPoRT was a multicentre, open label 3-arm randomised controlled trial designed to demonstrate equivalence (equivalence margin 20%) conducted from 1 July 2015 to 1 July 2021 in 19 obstetric units in the United Kingdom. Asymptomatic women with singleton pregnancies with transvaginal ultrasound cervical lengths measuring <25 mm between 14+0 and 23+6 weeks' gestation were eligible for randomisation (1:1:1) to receive either vaginal cervical cerclage (n = 128), cervical pessary (n = 126), or vaginal progesterone (n = 132). Minimisation variables were gestation at recruitment, body mass index (BMI), and risk factor for PTB. The primary outcome was PTB <37 weeks' gestation. Secondary outcomes included PTB <34 weeks', <30 weeks', and adverse perinatal outcome. Analysis was by intention to treat. A total of 386 pregnant women between 14+0 and 23+6 weeks' gestation with a cervical length <25 mm were randomised to one of the 3 interventions. Of these women, 67% were of white ethnicity, 18% black ethnicity, and 7.5% Asian ethnicity. Mean BMI was 25.6. Over 85% of women had prior risk factors for PTB; 39.1% had experienced a spontaneous PTB or midtrimester loss (>14 weeks gestation); and 45.8% had prior cervical surgery. Data from 381 women were available for outcome analysis. Using binary regression, randomised therapies (cerclage versus pessary versus vaginal progesterone) were found to have similar effects on the primary outcome PTB <37 weeks (39/127 versus 38/122 versus 32/132, p = 0.4, cerclage versus pessary risk difference (RD) -0.7% [-12.1 to 10.7], cerclage versus progesterone RD 6.2% [-5.0 to 17.0], and progesterone versus pessary RD -6.9% [-17.9 to 4.1]). Similarly, no difference was seen for PTB <34 and 30 weeks, nor adverse perinatal outcome. There were some differences in the mild side effect profile between interventions (vaginal discharge and bleeding) and women randomised to progesterone reported more severe abdominal pain. A small proportion of women did not receive the intervention as per protocol; however, per-protocol and as-treated analyses showed similar results. The main study limitation was that the trial was underpowered for neonatal outcomes and was stopped early due to the COVID-19 pandemic. CONCLUSIONS: In this study, we found that for women who develop a short cervix, cerclage, pessary, and vaginal progesterone were equally efficacious at preventing PTB, as judged with a 20% equivalence margin. Commencing with any of the therapies would be reasonable clinical management. These results can be used as a counselling tool for clinicians when managing women with a short cervix. TRIAL REGISTRATION: EU Clinical Trials register. EudraCT Number: 2015-000456-15, clinicaltrialsregister.eu., ISRCTN Registry: ISRCTN13364447, isrctn.com.

Pregnancy outcomes of cerclage in twin gestations: a multicenter retrospective cohort study.

OBJECTIVES: To determine the effects of cerclage on twin pregnancies. METHODS: A multicenter, retrospective, cohort study was conducted at 10 tertiary centers using a web-based data collection platform. The study population included twin pregnancies delivered after 20 weeks of gestation. Patients with one or two fetal deaths before 20 weeks of gestation were excluded. Maternal characteristics, including prenatal cervical length (CL) and obstetric outcomes, were retrieved from the electronic medical records. RESULTS: A total of 1,473 patients had available data regarding the CL measured before 24 weeks of gestation. Seven patients without CL data obtained prior to cerclage were excluded from the analysis. The study population was divided into two groups according to the CL measured during the mid-trimester: the CL ≤2.5 cm group (n = 127) and the CL >2.5 cm group (n = 1,339). A total of 127 patients (8.7%) were included in the CL ≤2.5 cm group, including 41.7% (53/127) who received cerclage. Patients in the CL >2.5 cm group who received cerclage had significantly lower gestational age at delivery than the control group (hazard ratio (HR): 1.8; 95% confidence interval (CI): 1.11-2.87; p = .016). Patients in the CL ≤2.5 cm group who received cerclage had a significantly higher gestational age at delivery than the control group (HR: 0.5; 95% CI: 0.30-0.82; p value = .006). CONCLUSIONS: In twin pregnancies with a CL ≤2.5 cm, cerclage significantly prolongs gestation. However, unnecessary cerclage in women with a CL >2.5 cm may result in a higher risk of preterm labor and histologic chorioamnionitis although this study has a limitation originated from retrospective design.

Prophylactic progesterone and preterm birth.

This review summarises the present knowledge of prophylactic progesterone and preterm birth. Preterm birth (less-than 37 weeks) is a leading cause of neonatal mortality and morbidity worldwide. The incidence varies globally but remains low in the Nordic countries (5-6%). Prediction and prevention are complicated due to diverse aetiology, but obstetric history and cervical length can improve prediction. Prophylactic vaginal progesterone initiated between 12 and 24 weeks of gestation is recommended to reduce preterm birth less-than 33-35 weeks in singleton pregnancies with a history of preterm birth or with a short cervix (less-than 25 mm) and can be considered for twin pregnancies with the same risk factors.

Cervical elastography in predicting spontaneous preterm birth in singleton pregnancy with a short cervix receiving progesterone treatment at 18 to 24 weeks' gestation.

BACKGROUND: A short cervix in the second trimester is known to increase the risk of preterm birth, which can be reduced with the administration of vaginal progesterone. However, some studies have suggested that a significant number of cases still experience preterm birth despite progesterone treatment. OBJECTIVE: This study was aimed to investigate the potential value of transvaginal cervical elasticity measured by E-Cervix as a predictor for spontaneous preterm birth (sPTB) in singleton pregnancies receiving progesterone treatment for a short cervix (CL ≤ 2.5 cm) diagnosed at 18 to 24 weeks' gestation. STUDY DESIGN: This prospective study was conducted at a single center premature high-risk clinic from January 2020 to July 2022. Singleton pregnancies with a short cervix at 18 to 24 weeks' gestation were enrolled. Cervical elastography using E-Cervix was performed, and maternal and neonatal demographic characteristics, cervical length (CL), elasticity contrast index (ECI), cervical hardness ratio, mean internal os strain (IOS), and mean external os strain (EOS) were compared before and after progesterone treatment in sPTB and term birth groups. Multivariate logistic regression was used to analyze the association between elasticity parameters and spontaneous preterm birth. The screening performance of CL and optimal cervical elasticity parameters in predicting sPTB was evaluated using receiver-operating characteristic (ROC) curve analysis. RESULTS: A total of 228 singleton pregnant women were included in the study, among which 26 (11.4%) had sPTB. There were no significant differences in maternal characteristics and gestational age at enrollment between women with and without sPTB. At the start of progesterone treatment, there were no significant differences in cervical elasticity parameters between the two groups. After two weeks of progesterone treatment, women who had sPTB showed significantly higher levels of ECI, IOS, EOS (p = 0.0108, 0.0001, 0.016), and lower hardness ratio (p = 0.011) compared to those who had a full-term birth. Cervical length did not show significant differences between the two groups, regardless of whether progesterone treatment was administered before or after. Among the post-treatment cervical elasticity parameters, IOS and EOS were associated with a 3.38-fold and 2.29-fold increase in the risk of sPTB before 37 weeks (p = 0.032, 0.047, respectively). The AUROC of the combined model including CL, IOS, and EOS (0.761, 95% CI0.589-0.833) was significantly higher than the AUROC of CL alone (0.618, 95% CI 0.359-0.876). At a fixed false-positive of 13%, the addition of IOS and EOS in the CL model increased sensitivity from 34.6% to 57.6%, PPV from 25.7% to 36.5%, and NPV from 91.1% to 94.1%. CONCLUSION: When assessing the risk of sPTB in singleton pregnancies with a short cervix receiving progesterone therapy, relying solely on cervical length is insufficient. It is crucial to also evaluate cervical stiffness, particularly the strain of the internal and external os, using cervical elastography.

Cervical length screening among low-risk women; relationship of body mass index on cervical length and risk of preterm birth.

BACKGROUND: Preterm birth (PTB) contributes to nearly 11% of all deliveries in the world. The majority of spontaneous preterm birth (sPTB) remains unexplained. Risk factors include abnormal body mass index (BMI), short cervical length, comorbidities and many more. However, there is limited study on the association between body mass index, cervical length and preterm birth in Malaysia among low-risk women. Hence, we aim to examine the relationship between body mass index, cervical length and the risk of spontaneous preterm birth. METHOD: In this prospective cohort study, pregnant women between 16 and 24 weeks who fulfilled the criteria were recruited. Women with history of preterm birth were excluded. Demographic and clinical data (age, BMI, ethnicity, education level and parity) were obtained. Cervical length was measured using transvaginal scan. Patients were then followed up till delivery to determine their delivery gestation and outcome of delivery. RESULTS: Out of 153 women who participated in this study, 146 women had cervical length of more than 30 mm, six had cervical length between 25 mm and 30 mm and one had cervical length of 24 mm. There were nine (9) cases of sPTB, with all of them being late preterm with normal midtrimester cervical length. Almost half of them (44%) were overweight/obese. A significant association was found between age, cervical length, and parity compared to BMI. Nevertheless, no significant association was seen between the BMI and risk of sPTB. CONCLUSION: This study demonstrates a higher BMI is associated with longer cervical length, but it is not necessarily protective against sPTB. Hence, we concluded there is a limited role in cervical length screening among low-risk women regardless of their BMI in predicting sPTB.

Assessing the multifaceted cervix: examining cervical gland area at cervical length screening to predict spontaneous preterm birth.

BACKGROUND: Biologically active cervical glands provide a mucous barrier while influencing the composition and biomechanical strength of the cervical extracellular matrix. Cervical remodeling during ripening may be reflected as loss of the sonographic cervical gland area. As sonographic cervical length remains suboptimal for universal screening, adjunctive evaluation of other facets of the mid-trimester cervix may impart additional screening benefit. OBJECTIVE: To sonographically assess the cervical gland area at universal cervical length screening for preterm birth. STUDY DESIGN: We performed a retrospective cohort study of singletons with transvaginal cervical length screening universally performed during anatomic survey between 18 0/7 and 23 6/7 weeks and subsequent live delivery at a single institution in 2018. Uterine anomalies, cerclage, suboptimal imaging, or medically indicated preterm birth were excluded. Ultrasound images were assessed for cervical length and cervical gland area (with quantitative measurements when present). The primary outcome was spontaneous preterm birth <37 weeks. Absent and present gland groups were compared using χ2, Fisher's exact, T-test, and multivariate logistic regression (adjusting for parity and progesterone use, as well as the gestational age, cervical length, and gland absence at screening ultrasound). Gland measurements were evaluated using the Mann-Whitney-U Test and Spearman's correlation. RESULTS: Among the cohort of 772 patients, absent and present CGA groups were overall similar. Patients were on average 33 years old, ∼20 weeks gestation at screening ultrasound, and overall, 2.5% had history of prior spontaneous preterm birth. The absent gland group was more likely to have been taking progesterone (17% vs 4%, P=.04). Overall rate of preterm birth was 2.6%. However, the 2.3% of patients with absent cervical gland area were significantly more likely to deliver <37 weeks (aOR 23.9, 95% CI 6.4-89, P<.001). Multivariate logistic regression demonstrated better performance of a cervical length screening model for preterm birth prediction with the addition of qualitative gland evaluation (P<.001). Qualitative gland assessment was reproducible (PABAK 0.89), but quantitative gland measurements did not correlate with preterm birth. CONCLUSION: Qualitative gland absence at mid-gestation cervical length screening was associated with subsequent spontaneous preterm birth, whereas quantitative gland measurements were not. Multifaceted ultrasound screening may be needed to adequately evaluate the multiple biologic functions of the cervix.

Cervical elastography using E-Cervix™ for prediction of preterm birth in twin pregnancies with threatened preterm labor.

OBJECTIVE: To evaluate the prediction performance of E-Cervix™ for preterm birth in twin pregnancies with threatened preterm labor. METHODS: This was a single-center retrospective cohort study of twin pregnancies presenting to obstetrics triage for threatened preterm labor (PTL) between 23 0/7 - 33 6/7 weeks who received screening for PTL with transvaginal ultrasound cervical length (TVU CL) and cervical elastography with E-Cervix™ at the time of triage. Cervical elastography parameters were examined and compared between women who delivered preterm and those who did not. The quantification of cervical strain was calculated by a data analysis system that directly analyzes raw data from the region of interest (ROI) and described as hardness ratio (HR), mean strain level within 1 cm from internal (IOS) and external (EOS) os. RESULTS: 63 twin gestations without prior preterm birth and with threatened PTL between 23 0/7 - 33 6/7 weeks of gestation were included in the study. 27 (42.9 %) had cervical length < 25 mm, and were admitted for true PLT. Out of the 36 women with cervical length ≥ 25 mm, 6 (16.7 %) were admitted. Women with threatened PTL had significantly higher HR compared to those with true PTL (p < 0.01), and significantly lower IOS and EOS. Women who delivered preterm had significantly higher HR compared to those who did not delivery preterm and significantly lower IOS and EOS, in overall cohort, and in the subset of women with true PTL. Incidences of HR < 50 % and < 35 % were statistically significantly higher in women who delivered preterm compared to those who did not (p < 0.01). CONCLUSION: Cervical elastography with E-Cervix™ may be useful for assessment of twin gestations presenting to obstetrics triage for threatened PTL.

SMFM Consult Series #70: Management of short cervix in individuals without a history of spontaneous preterm birth.

Most deliveries before 34 weeks of gestation occur in individuals with no previous history of preterm birth. Midtrimester cervical length assessment using transvaginal ultrasound is one of the best clinical predictors of spontaneous preterm birth. This Consult provides guidance for the diagnosis and management of a short cervix in an individual without a history of preterm birth. The following are Society for Maternal-Fetal Medicine recommendations: (1) we recommend that all cervical length measurements used to guide therapeutic recommendations be performed using a transvaginal approach and in accordance with standardized procedures as described by organizations such as the Perinatal Quality Foundation or the Fetal Medicine Foundation (GRADE 1C); (2) we recommend using a midtrimester cervical length of ≤25 mm to diagnose a short cervix in individuals with a singleton gestation and no previous history of spontaneous preterm birth (GRADE 1C); (3) we recommend that asymptomatic individuals with a singleton gestation and a transvaginal cervical length of ≤20 mm diagnosed before 24 weeks of gestation be prescribed vaginal progesterone to reduce the risk of preterm birth (GRADE 1A); (4) we recommend that treatment with vaginal progesterone be considered at a cervical length of 21 to 25 mm based on shared decision-making (GRADE 1B); (5) we recommend that 17-alpha hydroxyprogesterone caproate, including compounded formulations, not be prescribed for the treatment of a short cervix (GRADE 1B); (6) in individuals without a history of preterm birth who have a sonographic short cervix (10-25 mm), we recommend against cerclage placement in the absence of cervical dilation (GRADE 1B); (7) we recommend that cervical pessary not be placed for the prevention of preterm birth in individuals with a singleton gestation and a short cervix (GRADE 1B); and (8) we recommend against routine use of progesterone, pessary, or cerclage for the treatment of cervical shortening in twin gestations outside the context of a clinical trial (GRADE 1B).

Longitudinal Cervical Length Measurements and Spontaneous Preterm Birth in Singleton and Twin Pregnancies.

Importance: Changes in cervical length in twin pregnancies exhibit various patterns, but it is unclear whether the mechanism underlying spontaneous preterm birth (sPTB) is consistent. The existence of detailed phenomena in singleton pregnancies is also unclear. Objectives: To explore the different patterns in cervical length trajectories in singleton and twin pregnancies and to analyze whether the immunological mechanisms of sPTB are consistent among these cervical length patterns. Design, Setting, and Participants: This cohort study recruited pregnant individuals who received antenatal care and delivered at Peking University Third Hospital in Beijing, China, between January 1, 2014, and December 31, 2022. Individuals with singleton and twin pregnancies were included. Exposures: Cervical length measurements and white blood cell (WBC) indicators. Main Outcomes and Measures: The primary outcome was sPTB. Longitudinal trajectory cluster analysis was used to identify patterns of changes in cervical length in singleton and twin pregnancies. A random-effects model with cubic spline was used to fit and compare the longitudinal trajectory of WBC indicators among early preterm birth, moderate to late preterm birth, and term birth. Results: A total of 43 559 pregnant individuals were included; of these, 41 706 had singleton pregnancies (mean [SD)] maternal age, 33.0 [4.0] years) and 1853 had twin pregnancies (mean [SD] maternal age, 33.3 [3.6] years). Two distinct patterns of cervical length changes were observed in both singleton and twin pregnancies: shortened (21 366 singletons and 546 twins) and stable (20 340 singletons and 1307 twins). In singleton pregnancies, WBC count was associated with early sPTB in individuals with both shortened cervix (odds ratio [OR], 1.35; 95% CI, 1.00-1.82) and stable cervix (OR, 1.64; 95% CI, 1.07-2.50). However, for twin pregnancies, the association of WBC count (OR, 3.13; 95% CI, 1.58-6.18) with the risk of early sPTB was observed only in individuals with a shortened cervix. Conclusions and Relevance: This study identified 2 distinct cervical length patterns: shortened and stable. These patterns revealed 2 preterm birth mechanisms in twin pregnancies, with the immunopathogenesis of sPTB found only in the shortened cervix pattern; in singleton pregnancies, maternal immune response was associated with a higher risk of sPTB regardless of a shortened or stable cervix.

Vaginal Progesterone to Prevent Spontaneous Preterm Birth in Women With a Sonographic Short Cervix: The Story of the PREGNANT Trial.

The PREGNANT trial was a randomized, placebo-controlled, multicenter trial designed to determine the efficacy and safety of vaginal progesterone (VP) to reduce the risk of birth < 33 weeks and of neonatal complications in women with a sonographic short cervix (10 to 20 mm) in the mid-trimester (19 to 23 6/7 wk). Patients allocated to receive VP had a 45% lower rate of preterm birth (8.9% vs 16.1%; relative risk = 0.55; 95% CI: 0.33-0.92). Neonates born to mothers allocated to VP had a 60% reduction in the rate of respiratory distress syndrome. This article reviews the background, design, execution, interpretation, and impact of the PREGNANT Trial.

Universal cervical length screening and risk of spontaneous preterm birth: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the risk of spontaneous preterm birth with or without universal transvaginal ultrasound cervical length screening at the time of midtrimester scan. DATA SOURCES: Medline, Embase, ClinicalTrials.gov, and Web of Science were systematically searched from the inception of the databases to November 12, 2023, using combinations of the relevant medical subject heading terms, key words, and word variants that were considered suitable for the topic. STUDY ELIGIBILITY CRITERIA: Studies including individuals with singleton gestations at 16-25 weeks of gestation screened or not screened with universal transvaginal ultrasound cervical length screening were considered eligible. Primary outcome was spontaneous preterm birth <37 weeks; secondary outcomes were spontaneous preterm birth <34 and <32 weeks. METHODS: Random effect head-to-head analyses were used to directly compare each outcome, expressing the results as summary odds ratio and relative 95% confidence interval. The quality of the included studies was independently assessed by 2 reviewers, using the Newcastle-Ottawa scale for cohort studies and the Cochrane risk-of-bias tool for randomized controlled studies. The study was registered on the prospective register of systematic reviews database (PROSPERO) (registration number: CRD42022385325). RESULTS: Eight studies, including 447,864 pregnancies, were included in the meta-analysis (213,064 screened with transvaginal ultrasound cervical length and 234,800 unscreened). In the overall analysis, universal transvaginal ultrasound cervical length did not significantly decrease the spontaneous preterm birth rates <37 weeks (odds ratio, 0.92 [95% confidence interval, 0.84-1.01], P=.07) and <34 weeks (odds ratio, 0.87 [95% confidence interval, 0.73-1.04], P=.12), but was significantly associated with a lower risk of spontaneous preterm birth <32 weeks (odds ratio, 0.84 [95% confidence interval, 0.76-0.94], P=.002). Individuals without a prior spontaneous preterm birth had a significantly lower risk of spontaneous preterm birth <37 weeks (odds ratio, 0.88 [95% confidence interval, 0.79-0.97], P=.01) and a lower trend of spontaneous preterm birth <32 weeks (odds ratio, 0.82 [95% confidence interval, 0.66-1.01], P=.06) when screened with transvaginal ultrasound cervical length, compared with no screening. CONCLUSION: Universal transvaginal ultrasound cervical length screening usually <24 weeks in singletons without a prior spontaneous preterm birth, is associated with a significant reduction in spontaneous preterm birth <37 weeks, compared with no screening.

Cost-effectiveness of universal routine sonographic cervical-length measurement at 19 to 25 weeks' gestation.

BACKGROUND: National second-trimester scanning of cervical length was introduced in Israel in 2010, and in the decade thereafter, a significant systematic reduction in preterm birth and in the delivery of low birthweight babies was found among singletons. OBJECTIVE: In this study, we sought to estimate the cost-effectiveness of a national policy mandating second-trimester cervical length screening by ultrasound, followed by vaginal progesterone treatment for short cervical length in comparison with no screening strategy. STUDY DESIGN: We constructed a decision model comparing 2 strategies, namely (1) universal cervical length screening, and (2) no screening strategy. This study used the national delivery registry of Israel's Ministry of Health. All women diagnosed with a second-trimester cervical length <25 mm were treated with vaginal progesterone and were monitored with a bimonthly ultrasound scan for cervical dynamics and threat of early delivery. Preterm birth prevalence associated with short cervical length, the efficacy of progesterone in preterm birth prevention, and the accuracy of cervical length measurements were derived from previous studies. The cost of progesterone and bimonthly sonographic surveillance, low birthweight delivery, newborn admission to intensive care units, the first-year costs of managing preterm birth and low birthweight, and instances of handicaps and the cost of their follow-up were extracted from the publicly posted registry of Israel's Ministry of Health and Israel Social Securities data. Monte Carlo simulations decision tree mode, Tornado diagrams, and 1- and 2-way sensitivity analyses were implemented and the base case and sensitivity to parameters that were predicted to influence cost-effectiveness were calculated. RESULTS: Without cervical length screening, the discounted quality-adjusted life years were 30.179, and with universal cervical length screening, it increased to 30.198 (difference of 0.018 quality-adjusted life years). The average cost of no screening for cervical length strategy was $1047, and for universal cervical length screening, it was reduced to $998. The calculated incremental cost-effectiveness ratio was -$2676 per quality-adjusted life year (dividing the difference in costs by the difference in quality-adjusted life years). Monte Carlo simulation of cervical length screening of 170,000 singleton newborns (rounded large number close to the number of singleton newborns in Israel) showed that 95.17% of all babies were delivered at gestational week ≥37 in comparison with 94.46% of babies with the no screening strategy. Given 170,000 singleton births, the national savings of screening for short cervical length when compared with no cervical length screening amounted to $8.31M annually, equating to $48.84 for a base case, and the incremental cost-effectiveness ratio for each case of low birthweight or very low birthweight avoided was -$14,718. A cervical length <25 mm was measured for 30,090 women, and of those, 24,650 were false positives. The major parameters that affected the incremental cost-effectiveness ratio were the incidence of preterm birth, the specificity of cervical length measurements, and the efficacy of progesterone treatment. At a preterm birth incidence of <3%, universal screening does not lead to a cost saving. CONCLUSION: National universal cervical length screening should be incorporated into the routine anomaly scan in the second trimester, because it leads to a drop in the incidence of preterm birth and low birthweight babies in singleton pregnancies, thereby saving costs related to the newborn and gaining quality-adjusted life years.

Longitudinal evaluation of cervical length and shear wave elastography in women with spontaneous preterm birth.

OBJECTIVE: To evaluate longitudinal changes in cervical length (CL) and mean cervical shear wave elastography (CSWE) score in women with a singleton or twin pregnancy who undergo spontaneous preterm birth (sPTB) compared with those who deliver at term. METHODS: This was a prospective longitudinal study of unselected women with a singleton or twin pregnancy attending a dedicated research clinic for screening for sPTB at four timepoints during pregnancy: 11 + 0 to 15 + 6 weeks, 16 + 0 to 20 + 6 weeks, 21 + 0 to 24 + 6 weeks and 28 + 0 to 32 + 6 weeks. At each visit, a transvaginal ultrasound scan was conducted to measure the CL and the CSWE scores in six regions of interest (ROI) (inner, middle and external parts of anterior and posterior cervical lips). The mean CSWE score from the six ROIs was calculated for analysis. Log10 transformation was applied to data to produce a Gaussian distribution prior to statistical analysis. A multilevel mixed-effects analysis was performed to compare longitudinally CL and CSWE between the sPTB and term-delivery groups. RESULTS: The final cohort consisted of 1264 women, including 1143 singleton pregnancies, of which 57 (5.0%) were complicated by sPTB, and 121 twin pregnancies, of which 33 (27.3%) were complicated by sPTB. Compared to those who delivered at term, women with sPTB had a lower CL across gestation when controlling for history of cervical surgery, number of fetuses, gestational age (GA) at cervical assessment and the interaction between GA at cervical assessment and sPTB (P < 0.001). Specifically, CL in the sPTB group was significantly lower at 21 + 0 to 24 + 6 weeks (P = 0.039) and 28 + 0 to 32 + 6 weeks (P < 0.001). Twin pregnancies had significantly greater CL throughout pregnancy compared with singleton pregnancies (regression coefficient, 0.01864; P < 0.001). After adjusting for maternal age, weight, height, body mass index and GA at cervical assessment, CSWE score in the sPTB group was significantly lower compared with that in the term-delivery group across gestation (P = 0.013). However, on analysis of individual visits, CSWE score in the sPTB group was significantly lower than that in the term-delivery group only at 11 + 0 to 15 + 6 weeks (P = 0.036). There was no difference in CSWE score between singleton and twin pregnancies throughout gestation (regression coefficient, -0.00128; P = 0.937). CONCLUSIONS: Women with sPTB have a shorter and softer cervix across gestation compared with those who deliver at term. A shorter cervix in the sPTB group is observed from the late second trimester onwards, while lower cervical stiffness in the sPTB group is observed primarily in the first trimester. CL is significantly lower in singleton pregnancies compared with twin pregnancies, while cervical stiffness does not differ between the two. Our findings indicate that the cervix tends to undergo a softening process prior to shortening in sPTB cases. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of spontaneous preterm birth in women with previous full dilatation cesarean delivery.

BACKGROUND: A previous term (≥37 weeks' gestation), full-dilatation cesarean delivery is associated with an increased risk for a subsequent spontaneous preterm birth. The mechanism is unknown. We hypothesized that the cesarean delivery scar characteristics and scar position relative to the internal cervical os may compromise cervical function, thereby leading to shortening of the cervical length and spontaneous preterm birth. OBJECTIVE: This study aimed to determine the relationship of cesarean delivery scar characteristics and position, assessed by transvaginal ultrasound, in pregnant women with previous full-dilatation cesarean delivery with the risk of shortening cervical length and spontaneous preterm birth. STUDY DESIGN: This was a single-center, prospective cohort study of singleton pregnant women (14 to 24 weeks' gestation) with a previous term full-dilatation cesarean delivery who attended a high-risk preterm birth surveillance clinic (2017-2021). Women underwent transvaginal ultrasound assessment of cervical length, cesarean delivery scar distance relative to the internal cervical os, and scar niche parameters using a reproducible transvaginal ultrasound technique. Spontaneous preterm birth prophylactic interventions (vaginal cervical cerclage or vaginal progesterone) were offered for short cervical length (≤25 mm) and to women with a history of spontaneous preterm birth or late miscarriage after full-dilatation cesarean delivery. The primary outcome was spontaneous preterm birth; secondary outcomes included short cervical length and a need for prophylactic interventions. A multivariable logistic regression analysis was used to develop multiparameter models that combined cesarean delivery scar parameters, cervical length, history of full-dilatation cesarean delivery, and maternal characteristics. The predictive performance of models was examined using the area under the receiver operating characteristics curve and the detection rate at various fixed false positive rates. The optimal cutoff for cesarean delivery scar distance to best predict a short cervical length and spontaneous preterm birth was analyzed. RESULTS: Cesarean delivery scars were visualized in 90.5% (220/243) of the included women. The spontaneous preterm birth rate was 4.1% (10/243), and 12.8% (31/243) of women developed a short cervical length. A history- (n=4) or ultrasound-indicated (n=19) cervical cerclage was performed in 23 of 243 (9.5%) women; among those, 2 (8.7%) spontaneously delivered prematurely. A multiparameter model based on absolute scar distance from the internal os best predicted spontaneous preterm birth (area under the receiver operating characteristics curve, 0.73; 95% confidence interval, 0.57-0.89; detection rate of 60% for a fixed 25% false positive rate). Models based on the relative anatomic position of the cesarean delivery scar to the internal os and the cesarean delivery scar position with niche parameters (length, depth, and width) best predicted the development of a short cervical length (area under the receiver operating characteristics curve, 0.79 [95% confidence interval, 0.71-0.87]; and 0.81 [95% confidence interval, 0.73-0.89], respectively; detection rate of 73% at a fixed 25% false positive rate). Spontaneous preterm birth was significantly more likely when the cesarean delivery scar was <5.0 mm above or below the internal os (adjusted odds ratio, 6.87; 95% confidence interval, 1.34-58; P =.035). CONCLUSION: In pregnancies following a full-dilatation cesarean delivery, cesarean delivery scar characteristics and distance from the internal os identified women who were at risk for spontaneous preterm birth and developing short cervical length. Overall, the spontaneous preterm birth rate was low, but it was significantly increased among women with a scar located <5.0 mm above or below the internal cervical os. Shortening of cervical length was strongly associated with a low scar position. Our novel findings indicate that a low cesarean delivery scar can compromise the functional integrity of the internal cervical os, leading to cervical shortening and/or spontaneous preterm birth. Assessment of the cesarean delivery scar characteristics and position seem to have use in preterm birth clinical surveillance among women with a previous, full-dilatation cesarean delivery and could better identify women who would benefit from prophylactic interventions.

The uterocervical angle-cervical length ratio: A promising predictor of preterm birth?

OBJECTIVE: To predict spontaneous preterm birth (sPTB) (labor before 37 weeks of pregnancy) in low-risk singleton pregnancies during the second trimester, using ultrasound markers: uterocervical angle (UCA) and cervical length (CL). METHODS: In a prospective observational cohort study, we followed primigravid women with singleton pregnancies without known risk factors for sPTB from 16+0-23+6 weeks of pregnancy until birth. Transvaginal ultrasonography on admission revealed the UCA and CL, and maternal history was obtained from submitted patient profiles. Logistic regression models disclosed significant predictive variables, and receiver operating curves (ROCs) demonstrated optimal cut-offs and test accuracy indices. Predictive functions of variables were compared using positive and negative likelihood ratios. RESULTS: In a sample of 357 participants, 41 (11.5%) experienced sPTB. UCA and CL were significantly associated with sPTB when adjusting for other variables (adjusted odds ratio: UCA 1.05, 95% confidence interval [CI] 1.02-1.07 and CL 0.82, 95% CI 0.75-0.90). Optimal cut-offs were estimated to be 106° and 33 mm for UCA and CL, respectively. We devised the novel index UCA/CL with an area under the ROC of 0.781 (95% CI 0.734-0.823), cut-off = 3.09°/mm, and improved likelihood ratios (positive: 3.18, 2.47, and 4.22; negative: 0.63, 0.52, and 0.51 for UCA, CL, and UCA/CL, respectively). CONCLUSION: The second-trimester UCA/CL was found to be a promising index to predict sPTB in low-risk singleton pregnancies. Further multicenter studies may generalize this conclusion to other gestational ages or risk groups and make it more comprehensive by considering other risk factors.

Reliability of the sonographic evaluation for cervical length and elastography with pelvic parameters in term pregnancy by experienced operators with varying levels of experience.

OBJECTIVE: To assess the reliability of sonographic measurements of six cervical and pelvic parameters by three sonographers with varying levels of experience. METHODS: A cross-sectional study was conducted in pregnant women with a gestational age of ≥39 weeks. Each pregnant woman was examined by two sonographers with different levels of experience. Six parameters were measured: cervical length (CL), cervical strain elastography (extrinsic type), posterior cervical angle (PCA), fetal head-to-perineum distance (FHPD), fetal head-to-pubic symphysis distance (FHSD), and angle of progression (AOP). Intra- and interobserver reliabilities were assessed using the intraclass correlation coefficient with a 95% confidence interval. Pearson pairwise correlation coefficients were used to analyze the correlation between the parameter values. RESULTS: In all, 66 pregnant women were enrolled in this study. We found excellent intraobserver reliability for measurements of CL, PCA, FHPD, FHSD, and AOP and good-to-excellent intraobserver reliability for cervical strain values in the cross-sectional view of the endocervix in the internal os area and cross-sectional view of the entire cervix in the internal os area. Interobserver reliability was excellent for all pelvic parameters, except for the FHPD. Strain values were moderate to excellent in the area of the internal os. A significant negative correlation between CL and strain values at the internal os was observed. CONCLUSIONS: Pelvic parameters, except for FHPD, have excellent intra- and interobserver reliabilities. The high reproducibility of CL and cervical strain elastography at the internal os level, with a negative correlation between these two parameters, may play an important role in predicting successful induction of labor.

First-trimester and early-second-trimester transvaginal cervical length before 16 weeks among women with preterm and term birth: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the differences in first-trimester and early-second-trimester transvaginal cervical length between patients with spontaneous preterm birth and those with term birth. DATA SOURCES: PubMed, MEDLINE, Embase, and the Cochrane Library were systematically searched through August 2023. STUDY ELIGIBILITY CRITERIA: Studies had to include (1) transvaginal cervical length measurement before 16+0 weeks of gestation and (2) transvaginal cervical length measurement in a population of patients who delivered preterm and at term. Abstracts, studies with duplicated data, and those with cervical length measured by transabdominal ultrasound scan were excluded. METHODS: K.W.C. and J.L. searched for, screened, and reviewed the articles independently. The quality of the studies was assessed using the Newcastle-Ottawa scale. Mean differences were calculated using a random-effects model and pooled through a meta-analysis. RESULTS: A total of 5727 published articles were identified. Only 10 studies (which analyzed 22,151 pregnancies) met the inclusion criteria. All studies excluded iatrogenic preterm birth. Transvaginal cervical length was significantly shorter in women with spontaneous preterm birth than in those who delivered at term (mean difference, -0.97; 95% confidence interval, -1.65 to -0.29; P=.005; I2=69%). When a linear technique was used to measure transvaginal cervical length, a significantly shorter transvaginal cervical length was associated with spontaneous preterm birth as opposed to term birth (mean difference, -1.09; 95% confidence interval, -1.96 to -0.21; P=.02; I2=77%). A shorter transvaginal cervical length measured by other techniques was also associated with spontaneous preterm birth before 34 to 35 weeks (mean difference, -1.87; 95% confidence interval, -3.04 to -0.70; P=.002; I2=0%). When studies where interventions were given for a "short" cervix or studies with a mean transvaginal cervical length ≥40 mm were excluded, a significantly shorter transvaginal cervical length was observed among those with spontaneous preterm birth (mean difference, -1.13; 95% confidence interval, -1.89 to -0.37; P=.004; mean difference, -0.86; 95% confidence interval, -1.67 to -0.04; P=.04; respectively). The optimal transvaginal cervical length cutoff was 38 to 39 mm, yielding pooled sensitivity of 0.80, specificity of 0.45, positive likelihood ratio of 1.16, negative likelihood ratio of 0.33, diagnostic odds ratio of 5.12, and an area under the curve of 0.75. CONCLUSION: Women with spontaneous preterm birth had significantly shorter transvaginal cervical length before 16 weeks of gestation compared with those who delivered at term. The linear method and the 2-line method are acceptable techniques for measuring transvaginal cervical length.

A pragmatic evaluation of the implementation and acceptance of a universal second trimester cervical length screening program in an un-selected population.

PURPOSE: To evaluate patients' acceptance of a universal transvaginal ultrasound cervical length (CL) screening program and the feasibility of initiating treatment with progesterone in a clinical setting in women found to have a short cervix. METHODS: An observational, pragmatic cohort study was conducted at one tertiary care facility from 2012-2015, involving eligible women with singleton pregnancies who accepted and underwent second-trimester CL screening. The primary outcomes were the percentage of women who were eligible and accepting of screening, compliance with progesterone treatment, and the screening value of TVCL in predicting SPTB. Secondary outcomes were the number of women who received progesterone treatment and the rates of SPTB. RESULTS: Overall cervical length screening acceptance rate was found to be 82.5%. Of the 797 women that underwent screening, 21 women (2.6%) had a TVCL < 25 mm, of whom nine had a TVCL < 20.0 mm. Nineteen of the 21 women with a TVCL < 25 mm were treated with progesterone, with a 94.7% compliance rate. Delivery outcomes were obtained for 767 women. Of those with a TVCL < 25 mm, there was a 35% rate of SPTB as opposed to a 6.3% SPTB rate in those with TVCL > 25 mm. The negative predictive value for SPTB with a TVCL 25 mm or greater was 94.0%. CONCLUSION: Universal cervical length screening was successfully implemented in 82.5% of the patient population with a high compliance rate with progesterone treatment. Furthermore, there was a higher rate of SPTB in those with a shorter cervix. Based on our outcomes obtained in an observational and pragmatic manner, we showed that incorporating second trimester transvaginal cervical length screening into routine clinical practice is readily accepted and, with the addition of vaginal progesterone treatment, may reduce the rate of prematurity.