Revisions to mid-pregnancy cervical length reference range for preterm birth screening among singleton pregnancies in Taiwan - 10 years' experiences.

OBJECTIVE: Our study aimed to build a normal reference range for routine mid-pregnancy cervical length screening for preterm birth (PTB) based on a large cross-section of Taiwanese singleton pregnancies. Based on our reference range findings, we aim to develop a Z-score and centile calculator. MATERIALS AND METHODS: We performed a retrospective analysis of the routine mid-trimester cervical length measurement in low-risk singleton pregnancies (without known abnormal growth or karyotype, congenital malformation, history of preterm birth due to preterm premature rupture of the membranes, or history of cervical cerclage treatment). From November 2008 to June 2018, the cervical lengths of 51,644 Taiwanese low-risk pregnant women were measured by experienced sonographers via transvaginal ultrasound during second trimester fetal anatomical screening at 20-24 weeks of gestation. Kolmogorov-Smirnov test was used to assess the normality of the distribution. Cole's lambda, mu, sigma (LMS) method was applied to build mid-pregnancy cervical length reference range and calculate Z-scores. Cut-off values of 2.5, 2.0 and 1.5 cm were used to evaluate the number of pregnancies considered high-risk for PTB. RESULTS: Kolmogorov-Smirnov test showed that the cervical length measurements did not follow a normal distribution (<0.001). Reference range constructed by LMS method was presented in our study. Mean cervical length was 3.82 cm (SD = 0.62 cm). Overall, less than 0.3% of women had a cervical length shorter than 1.5 cm. CONCLUSION: We are providing an open access calculator for z-score and centile calculation for use in clinical practice for assessing how CL measurement compares in normally developing singleton pregnancies. Further investigation is needed to determine if Z-scores can better assess risk for PTB compared to fixed cut-offs. Since Z-scores are used to assess large deviations from normal development, they may be a useful tool for risk assessment and can be the basis for future standardized screening protocol in Taiwan.

Personalized assessment of cervical length improves prediction of spontaneous preterm birth: a standard and a percentile calculator.

BACKGROUND: A sonographic short cervix (length <25 mm during midgestation) is the most powerful predictor of preterm birth. Current clinical practice assumes that the same cervical length cutoff value should apply to all women when screening for spontaneous preterm birth, yet this approach may be suboptimal. OBJECTIVE: This study aimed to (1) create a customized cervical length standard that considers relevant maternal characteristics and gestational age at sonographic examination and (2) assess whether the customization of cervical length evaluation improves the prediction of spontaneous preterm birth. STUDY DESIGN: This retrospective analysis comprises a cohort of 7826 pregnant women enrolled in a longitudinal protocol between January 2006 and April 2017 at the Detroit Medical Center. Study participants met the following inclusion criteria: singleton pregnancy, ≥1 transvaginal sonographic measurements of the cervix, delivery after 20 weeks of gestation, and available relevant demographics and obstetrical history information. Data from women without a history of preterm birth or cervical surgery who delivered at term without progesterone treatment (N=5188) were used to create a customized standard of cervical length. The prediction of the primary outcome, spontaneous preterm birth at <37 weeks of gestation, was assessed in a subset of pregnancies (N=7336) that excluded cases with induced labor before 37 weeks of gestation. Area under the receiver operating characteristic curve and sensitivity at a fixed false-positive rate were calculated for screening at 20 to 23 6/7, 24 to 27 6/7, 28 to 31 6/7, and 32 to 35 6/7 weeks of gestation in asymptomatic patients. Survival analysis was used to determine which method is better at predicting imminent delivery among symptomatic women. RESULTS: The median cervical length remained fundamentally unchanged until 20 weeks of gestation and subsequently decreased nonlinearly with advancing gestational age among women who delivered at term. The effects of parity and maternal weight and height on the cervical length were dependent on the gestational age at ultrasound examination (interaction, P<.05 for all). Parous women had a longer cervix than nulliparous women, and the difference increased with advancing gestation after adjusting for maternal weight and height. Similarly, maternal weight was nonlinearly associated with a longer cervix, and the effect was greater later in gestation. The sensitivity at a 10% false-positive rate for prediction of spontaneous preterm birth at <37 weeks of gestation by a short cervix ranged from 29% to 40% throughout pregnancy, yet it increased to 50%, 50%, 53%, and 54% at 20 to 23 6/7, 24 to 27 6/7, 28 to 31 6/7, and 32 to 35 6/7 weeks of gestation, respectively, for a low, customized percentile (McNemar test, P<.001 for all). When a cervical length <25 mm was compared to the customized screening at 20 to 23 6/7 weeks of gestation by using a customized percentile cutoff value that ensured the same negative likelihood ratio for both screening methods, the customized approach had a significantly higher (about double) positive likelihood ratio in predicting spontaneous preterm birth at <33, <34, <35, <36, and <37 weeks of gestation. Among symptomatic women, the difference in survival between women with a customized cervical length percentile of ≥10th and those with a customized cervical length percentile of <10th was greater than the difference in survival between women with a cervical length ≥25 mm and those with a cervical length <25 mm. CONCLUSION: Compared to the use of a cervical length <25 mm, a customized cervical length assessment (1) identifies more women at risk of spontaneous preterm birth and (2) improves the distinction between patients at risk for impending preterm birth in those who have an episode of preterm labor.

Guideline No. 401: Sonographic Cervical Length in Singleton Pregnancies: Techniques and Clinical Applications.

OBJECTIVES: • To assess the association between sonography-derived cervical length measurement and preterm birth. • To describe the various techniques to measure cervical length using sonography. • To review the natural history of the short cervix. • To review the clinical uses, predictive ability, and utility of sonography-measured short cervix. OUTCOMES: Reduction in rates of prematurity and/or better identification of those at risk, as well as possible prevention of unnecessary interventions. INTENDED USERS: Clinicians involved in the obstetrical management or cervical imaging of patients at increased risk of a short cervix. TARGET POPULATION: Women at increased risk of a short cervix or at risk of preterm birth. EVIDENCE: Literature published up to June 2019 was retrieved through searches of PubMed and the Cochrane Library using appropriate controlled vocabulary and key words (preterm labour, ultrasound, cervix, cervical insufficiency, transvaginal, transperineal, cervical length, fibronectin). Results were restricted to general and systematic reviews, randomized controlled trials, controlled clinical trials, and observational studies. There were no date or language restrictions. Grey (unpublished) literature was identified through searching the websites of health technology assessment agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The evidence and this guideline were reviewed by the Diagnostic Imaging Committee of the Society of Obstetricians and Gynaecologists of Canada, and the recommendations were made and graded according to the rankings of the Canadian Task Force on Preventive Health Care (Online Appendix Table A1). BENEFITS, HARMS, COSTS: Preterm birth is a leading cause of perinatal morbidity and mortality. Use of the sonographic technique reviewed in this guideline may help identify women at risk of preterm birth and, in some circumstances, lead to interventions that may reduce the rate of preterm birth. SUMMARY STATEMENTS (CANADIAN TASK FORCE ON PREVENTIVE HEALTH CARE GRADING IN PARENTHESES): RECOMMENDATIONS (CANADIAN TASK FORCE ON PREVENTIVE HEALTH CARE GRADING IN PARENTHESES).

Comparison of reliability between uterocervical angle and cervical length measurements by various experienced operators using transvaginal ultrasound.

Purpose: To compare the reliability between uterocervical angle (UCA) and cervical length (CL) measurements by various experienced operators.Methods: Transvaginal ultrasonographies (TVS) were performed in 102 pregnant women between 16°/7-24°/7 gestational weeks by different levels of experienced operators. For both CL and UCA measurements, intraobserver variability was assessed for each operator by examining the range between maximum and minimum measurements in each participant, compared to the mean of all three measurements. Interobserver variabilities were explored using Bland-Altman analysis. Intraclass correlation coefficients were used for both intraobserver and interobserver reliability.Results: For intraobserver variability of the UCA, the ranges between maximum and minimum UCA measurements in operator 1 and 3 were 1.5º-34º and 2º-36º (n = 51), and in operators 2 and 3 were 0º-61º and 1º-25º (n = 51). Intraclass correlation coefficients (ICC) for intraobserver reliability were 0.90 for operator 1, 0.67 for operator 2 and 0.93 for operator 3. For interobserver variability of the UCA, the limits of agreement for mean UCA were -37.53º-38.41º and -36.27º-26.17º, and for maximum UCA were -39.47º-41.38º and -44.24º-22.9º in comparisons between operators 1 and 3, and operator 2 and 3, respectively. Intraclass correlation coefficients for mean UCA were 0.73 and 0.74, and for maximum UCA were 0.71 and 0.67 in comparisons between operators 1 and 3, and operator 2 and 3, respectively.Conclusions: The UCA measurements had a higher intra- and interobserver reliabilities than the CL measurements.

Uterocervical angle: an ultrasound screening tool to predict satisfactory response to labor induction.

Background: A wide uterocervical angle >95° detected during the second trimester was associated with an increased risk for spontaneous preterm birth.Objective: We aimed to determine whether an ultrasonographic marker, uterocervical angle, correlates with satisfactory response to labor induction.Study design: We conducted a prospective cohort study from May 2016 through December 2017 of singleton term gestations undergoing transvaginal ultrasound for cervical length screening and uterocervical angle measurement. Uterocervical angle was measured between the lower uterine segment and the cervical canal. Latent phase duration >720 min was accepted to be a prolonged latent phase. The primary outcome was a prediction of satisfactory response to labor induction (latent phase duration <720 min).Results: Both anterior uterocervical angle (AUC = 0.802, p < .001) and the cervical length (AUC = 0.679, p < .05) significantly predicted satisfactory response to labor induction. Optimal cutoff value was obtained at the value of 97° (64% sensitivity, 91% specificity) for anterior uterocervical angle and 27 mm (64% sensitivity, 64% specificity) for the cervical length. Kaplan-Meier survival analysis showed that duration from labor induction to delivery was significantly higher in a group with longer cervical length (p = .04), additionally labor induction to delivery time was significantly higher in a group with lower UCA (p = .04).Conclusions: Both the cervical length and anterior uterocervical length were predictors for the satisfactory response to labor induction, and both parameters were found to be significantly associated with time from induction to delivery in survival analysis.

Cervical pathways for racial disparities in preterm births: the Preterm Prediction Study.

Purpose: Racial disparities in preterm birth have been long recognized, but the social and biological mechanisms for these differences are unclear. Our analysis had three goals: (1) to determine the relation between race and other social risk factors and cervical structure; (2) to determine whether social factors mediate the relation between race and cervical structure; and (3) to determine whether racial disparities in preterm birth (PTB) are mediated through changes in cervical structure observed earlier in pregnancy. Materials and methods: Data from the Maternal Fetal Medicine Unit network Preterm Prediction Study were used to examine the relation between race and other social factors and cervical properties throughout pregnancy in 2920 black and white women. Outcomes included cervical length and dilation; cervical score (cervical length-internal dilation); and whether membranes protruded at 22-24 and 26-29 weeks. Race, education, income, insurance type, and marital status were examined as predictors of the outcomes using linear and logistic regression, adjusting for age, BMI, parity, and smoking. Mediation analysis was used to examine whether (a) any social factors explained racial differences in cervical properties, and (b) whether cervical properties mediated racial differences in risk for preterm birth. Results: Shorter cervical length, especially at a subject's first visit, was associated with black race (adjusted beta -1.56 mm, p < .01) and lower income (adjusted beta -1.48, p =.05). External dilation was not associated with social factors, while internal dilation was associated with black race and lower education. Black race and marital status were associated with lower cervical score. There was no evidence of mediation of the racial effect on cervical properties by any social factor. Shorter cervical length, dilation, and score were all associated with preterm birth (p < .01). Mediation analysis indicated that each of these mediated the effect of race, but explained a small proportion of the total effect (15-25%). Conclusions: Race, and, to a lesser extent, other social factors are correlated with adverse cervical properties. This pathway could explain a proportion of the racial disparity in preterm birth.

Clinical guidelines for prevention and management of preterm birth: a systematic review.

BACKGROUND: Clinical practice guidelines (CPG) endorse multiple strategies to prevent or manage preterm birth (PTB). OBJECTIVES: To summarise CPG recommendations for PTB and identify areas of international consensus. SEARCH STRATEGY: In May 2017 we searched for all CPG relevant to PTB without language restrictions. SELECTION CRITERIA: CPG were eligible if the following criteria were met: (1) the guideline was published or current from June 2013; (2) the guideline recommended practices for the prevention or management of PTB relevant to our prespecified clinical questions for screening, medications or surgery and other interventions; (3) publications on methods of guideline development for eligible CPG were included to enable quality assessment. DATA COLLECTION AND ANALYSIS: Two authors classified CPG recommendations relevant to prespecified clinical questions. When more than 70% of CPGs reporting on a topic recommended or rejected an intervention, we regarded this as consensus. We summarised recommendations in tables. MAIN RESULTS: We identified 49 guidelines from 16 guideline developers. We found consensus for several clinical practices: cervical length screening for high-risk women; short-term tocolysis; steroids for fetal lung maturation; and magnesium sulphate for fetal neuroprotection. We found discrepant recommendations for progesterone and fibronectin. No guideline identified an effective strategy for women with multiple pregnancy. CONCLUSIONS: We identified interventions for which there is an international consensus on benefit for PTB. Systematic reviews of CPG using standardised methodology will help avoid duplication and target scarce resources for guideline developers globally. TWEETABLE ABSTRACT: International clinical guidelines agree on the benefits and harmful effects of several important interventions to prevent preterm birth.

Assessment of Transvaginal Ultrasound Cervical Length Image Quality.

OBJECTIVE: To use data from the Cervical Length Education and Review program to evaluate the quality of transvaginal cervical length ultrasonography by trained imagers (ie, ultrasonographers, radiologists, perinatologists). METHODS: This is a retrospective observational study of data from the Cervical Length Education and Review program. Candidates underwent an online lecture series, examination, and submitted a batch of images for review. For a candidate's batch of images to pass, all images must meet at least seven of the nine criteria assessed, the overall batch score needs to be 80% or greater, correct caliper placement must be met for all images, and the same criterion cannot be consistently missed. We also examined a subset of these criteria-appropriate image acquisitions, defined as an image that demonstrated both internal and external os and visualization of the entire endocervical canal. Primary outcome was the overall initial candidate pass rate; secondary outcomes included distribution of criteria missed in images and percentage of images that was inadequately acquired. RESULTS: Six hundred eighty-seven candidates submitted 3,748 images between June 10, 2012, and August 18, 2016. Eighty-five percent of candidates were ultrasonographers. Of the 687 initial batches submitted, 105 (15%) did not pass. Eight hundred thirty-seven images (22%) of all images failed at least one criterion; the most common image deficiencies were in "anterior width of cervix equals the posterior width" (33%), "failure to visualize" the internal or external os (29%), "cervix occupies 75% of image and bladder area visible" (33%), and incorrect caliper placement (24%). Two hundred fifty-six (7%) of all images failed to meet our criteria for adequate image acquisition. CONCLUSION: Fifteen percent of trained imagers failed to obtain appropriate cervical length imaging. This highlights the importance of a standardized cervical length training and certification program.

Universal cervical length screening in singleton gestations without a previous preterm birth: ten reasons why it should be implemented.

A short cervix is associated strongly with preterm birth. Pharmacologic intervention with vaginal progesterone in women with a singleton pregnancy and a short cervix in the second trimester decreases the incidence of preterm birth. We explore the evidence that universal cervical length screening in women with a singleton pregnancy meets the criteria for an effective screening test for preterm birth prevention, driving it towards becoming routinely offered in prenatal care.

Effect of e-learning on quality of cervical-length measurements.

OBJECTIVES: To assess the effect of implementation of a newly developed e-learning module on the quality of cervical-length measurements. METHODS: With the introduction of cervical-length (CL) measurement in a research setting, a CL measurement e-learning module (CLEM) was developed with the purpose to enhance the knowledge and skills of experienced ultrasonographers. CLEM was designed specifically for ultrasonographers who perform ultrasound in a general obstetrical practice but who do not regularly perform CL measurements. CLEM consists of five theoretical questions and three caliper-placement tests to learn the CL measurement technique. The quality of the CL measurements of CLEM participants was compared with images of non-participants using a CL measurement image score (CIS), defined as the sum of six items which assess the quality of the image. Each CLEM participant submitted five CL images and the images of non-CLEM participants were selected randomly from an ultrasound database. RESULTS: The CIS of the CLEM participants (n = 61) were significantly higher than those of non-CLEM participants (n = 23) (164.9 vs 155.6, respectively; P = 0.03). Visualization of the internal os and positioning of the calipers on the internal and external ora were found to have significantly higher CIS among the CLEM participants than among the non-CLEM participants (P = 0.001 and P < 0.001, respectively). CONCLUSIONS: Introducing CLEM may improve the quality of CL measurements obtained by trained and untrained sonographers.

Adherence to criteria for transvaginal ultrasound imaging and measurement of cervical length.

OBJECTIVE: Adherence to published criteria for transvaginal imaging and measurement of cervical length is uncertain. We sought to assess adherence by evaluating images submitted to certify research sonographers for participation in a clinical trial. STUDY DESIGN: We reviewed qualifying test results of sonographers seeking certification to image and measure cervical length in a clinical trial. Participating sonographers were required to access training materials and submit 15 images, 3 each from 5 pregnant women not enrolled in the trial. One of 2 sonologists reviewed all qualifying images. We recorded the proportion of images that did not meet standard criteria (excess compression, landmarks not seen, improper image size, or full maternal bladder) and the proportion in which the cervical length was measured incorrectly. Failure for a given patient was defined as >1 unacceptable image, or >2 acceptable images with incorrect caliper placement or erroneous choice of the "shortest best" cervical length. Certification required satisfactory images and cervical length measurement from ≥4 patients. RESULTS: A total of 327 sonographers submitted 4905 images. A total of 271 sonographers (83%) were certified on the first, 41 (13%) on the second, and 2 (0.6%) on the third submission. Thirteen never achieved certification. Of 314 who passed, 196 submitted 15 acceptable images that were appropriately measured for all 5 women. There were 1277 deficient images: 493 were acceptable but incorrectly measured images from sonographers who passed certification because mismeasurement occurred no more than twice. Of 784 deficient images submitted by sonographers who failed the certification, 471 were rejected because of improper measurement (caliper placement and/or failure to identify the shortest best image), and 313 because of failure to obtain a satisfactory image (excessive compression, required landmarks not visible, incorrect image size, brief examination, and/or full maternal bladder). CONCLUSION: Although 83% of sonographers were certified on their first submission, >1 in 4 ultrasound images submitted did not meet published quality criteria. Increased attention to standardized education and credentials is warranted for persons who perform ultrasound examinations of the cervix in pregnancy.

The role of cervical length measurement at 11-14 weeks for the prediction of preterm delivery.

OBJECTIVE: To determine whether cervical length (CL) measurement at 11?14 weeks is predictive of preterm delivery (PTD). METHODS: This was a prospective study of a low-risk population of 1113 women, who underwent CL measurement at 11-14 weeks. Mean CL was calculated for deliveries at >37, <37 and <34 weeks. Cut-off limits of 27 mm and 30 mm were used to examine the predictive value of CL. RESULTS: Mean +/- SD CL for the entire study population was 40.6 +/- 5.5 mm. CL was analyzed for term and PTD (<37 weeks) and further analyzed for deliveries at 34-37 and <34 weeks. Mean CL was 38.9 +/- 5.5 mm for PTD and 40.8 +/- 5.5 mm for deliveries >37 weeks (p=0.001). Receiver operating characteristic analysis showed small predictive value of CL for PTD <37 weeks (sensitivity = 63.3% and specificity = 51.1%, area under the curve (AUC)=0.60, 95% CI: 0.54-0.66) (p=0.001) and did not show any predictive value for PTD <35 weeks (AUC=0.55, 95% CI: 0.43-0.67, p=0.355) or PTD <32 weeks (AUC=0.51, 95% CI: 0.30-0.74, p=0.851). CONCLUSION: CL at 11-14 weeks does not appear to be predictive of PTD. Statistical analysis of CL did not show any predictive value for PTD <35 weeks, or <32 weeks and although it showed a predictive value for PTD at <37 weeks, the sensitivity was very low.