Cervical Length Screening Research Articles

Early universal use of oral progesterone for prevention of preterm births in singleton pregnancy (SINPRO study): protocol of a multicenter, randomized, double-blind, placebo-controlled trial

BackgroundPreterm birth accounts for 75% of perinatal deaths and more than 50% of long-term neurological disabilities. For a singleton pregnancy, progesterone treatment is effective in prevention of preterm birth in women with an asymptomatic short cervix or a history of preterm birth. However, a large proportion of preterm births still is not currently preventable. The aim of this study is to determine whether early universal use of oral progesterone before 14 + 0 weeks of gestation can prevent preterm birth better than universal screening of cervical length at 18 + 0 to 23 + 6 weeks of gestation, followed by progesterone treatment in those with a short cervix in singleton pregnancy.MethodsThis is a multicenter, randomized, double-blind, placebo-controlled trial registered with ClinicalTrials.gov on 12 February 2018. Eligible consecutive pregnant women with singleton gestation attending antenatal outpatient clinics will be recruited after receiving counseling and signing the written consent form. Transvaginal cervical length measurement will be performed at recruitment (before 14 + 0 weeks of gestation) and between 18 + 0 and 23 + 6 weeks of gestation. After randomization, women will be randomly assigned to either the treatment group (oral dydrogesterone 10 mg three times daily) or the placebo group, and medication will be started before 14 + 0 weeks of gestation. Assigned groups will be unblinded if the cervical length is ≤ 25 mm between 18 + 0 and 23 + 6 weeks of gestation, and the management option for short cervix will be discussed (oral progesterone, vaginal progesterone, or cervical cerclage). The primary outcome is preterm birth before 37 + 0 weeks of gestation.DiscussionProgesterone is used extensively in part of the in vitro fertilization program as luteal phase support, and it is not associated with teratogenicity. Universal progesterone supplementation may be a better approach to prevent preterm birth. This large, multicenter, randomized, double-blind, placebo-controlled trial will provide the best evidence, leading to the best strategy for the prevention of preterm birth.Trial registrationClinicalTrials.gov, NCT03428685. Registered on 12 February 2018.

Current Approaches to Risk Assessment and Prevention of Preterm Birth-A Continuing Public Health Crisis.

Background: Preterm birth remains a major cause of neonatal morbidity and mortality. Several potential pathways and pathophysiologic processes can lead to preterm birth, complicating efforts to screen for the risk of preterm birth and making implementation of prevention strategies difficult.Methods: Based on a review of the literature, this article addresses screening strategies for preterm birth risk stratification and interventions for preterm birth prevention.Results: In women with a history of a prior spontaneous preterm birth, cervical cerclage placement in the setting of short cervix reduces the rate of recurrent spontaneous preterm birth. Weekly injections of 17-hydroxyprogesterone caproate (17-P) have been used as standard treatment for the prevention of recurrent preterm birth since 2011. However, results of a replication study of 17-P published in 2020 have raised questions regarding the effectiveness of this drug, and it is under review by the US Food and Drug Administration. Among women with no history of preterm birth, cervical length appears to be the best predictor of risk for preterm birth in asymptomatic women. In women with a cervical length <25 mm, vaginal progesterone has been demonstrated to reduce the risk of preterm birth.Conclusion: Strategies including cervical length screening, vaginal progesterone administration, cervical cerclage placement, and, potentially, 17-P administration may help reduce rates of preterm birth when used in the appropriate patient populations. Development of protocols for patient evaluation and risk stratification will help identify patients at highest risk for preterm birth and allow use of the best available therapeutic interventions.

1065: Are rates of spontaneous preterm birth stable across a range of normal cervical lengths?

Cervical length (CL) screening is an effective adjunct to reduce recurrent spontaneous preterm birth (sPTB) in high-risk women. While the efficacy of universal screening in women with no prior sPTB is debated, studies have shown benefit to identifying low-risk women with shortened CL ≤20 mm. In high-risk women a range of normal CLs (≥25 mm) has been associated with a stable risk of recurrent sPTB; however, it is unclear how rates of sPTB vary over a range of measured-normal CLs in low-risk women. Retrospective cohort of women with singletons and no prior sPTB who had universal mid-trimester transvaginal CL screening 1/2016-8/2018 and a measured (Normal) CL ≥25mm. We excluded fetal anomalies or an unmeasurable CL due to a poorly-developed lower uterine segment. The primary outcome was sPTB < 37 wk. We considered CL in interval groups: 25-29 mm, 30-34 mm, 35-39 mm, 30-44 mm, and ≥45 mm (χ2 test of trend) and as a continuum (logistic regression and ROC curve). A secondary outcome was the number of hospital evaluations for suspected preterm labor (PTL). 990 low-risk women were included. The incidence of sPTB < 37 wk was 3.6%; mean CL was 39.2±6.0 mm (interdecile range=31.6, 47.0), measured at 19.4±1.1 wk. The median number of PTL evaluations was 0 (range 0-4) and mean birth gestational age was 38±2.4 wk. There was a significant decreasing trend in rates of sPTB across increasing CL groups (p=0.001; Table). Increasing CL as a continuous variable was also associated with a significantly lower odds of sPTB (OR=0.92, 95% CI 0.87, 0.98). However, the number of evaluations for suspected PTL was not associated with CL (p=0.55). The ROC (Figure) AUC for sPTB was only 0.64, suggesting that a range of normal CLs in low-risk women was a poor predictor of sPTB. Among low-risk women with a normal CL observed during mid-trimester screening, there was only a modest effect of a range of measured-normal CLs on sPTB < 37 wk and no significant association with the number of hospital evaluations for PTL.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

931: Mid-trimester cervical length screening: effect of poorly-developed lower uterine segment on pregnancy outcome

Poorly developed lower segment (PDLUS) is characterized by a long “cervix” (> ∼5 cm), S-shaped canal, different echogenicties in the “cervix”, increased bladder-to-amniotic cavity distance, and “internal os” cephalad to the inferior edge of the bladder reflection (Figure). PDLUS precludes accurate CL measurement as the location of the true internal os is obscured. PDLUS is protective against sPTB in women with a prior sPTB < 34 weeks. Whether PDLUS affects gestational length in low-risk women is unknown. Retrospective cohort study of women with singletons and no prior sPTB who had mid-trimester transvaginal CL screening, 1/2016-8/2018; fetal anomalies were excluded. We compared birth gestational age (GA) between women with a measured (Normal) CL ≥ 25mm versus PDLUS. A sample of 1135 with a Normal:PDLUS ratio of 4:1 had 80% power to detect a 1/2-wk difference in birth GA (ɑ=.05, GA SD=2.4 wks). Secondary outcomes included sPTB < 37 wks, preterm labor (PTL) evaluations, and a Cox survival model that examined time from CL scan to delivery. Indicated PTBs were censored at birth, and to account for elective inductions ≥39 wks, we censored the time at 39.0 wks. 990 (79%) women with Normal CL and 265 (21%) with PDLUS were included. Characteristics were comparable (Table) but multiparity was more common in PDLUS; age and BMI were different but not clinically significant. Birth GA was 38.7±2.4 wks with Normal vs 38.9 ± 2.0 wks with PDLUS (p=0.10); 19% with Normal CL had ≥ 1 PTL evaluation vs. 17% with PDLUS (p=0.54), and at a similar GA for the initial visit (31±4.8 wks vs 30±5.4 wks, p=0.36). In the Cox model, PDLUS was found to have a significantly lower hazard ratio (HR) of 0.67 (95% CI 0.46, 0.98; p=0.04) for earlier birth. After controlling for parity, the HR fell to 0.64 (p=0.02). The incidence of sPTB < 37 wk was 3.6% for Normal CL and 1.1% for PDLUS (p=0.04). PDLUS observed at mid-trimester CL screening in low-risk women was associated with a significantly lower rate of sPTB < 37 wk and a lower HR for earlier birth.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

833: Incidentally found midtrimester shortened cervical length: Practice patterns among U.S. Maternal-fetal medicine specialists

The management of incidentally found short cervical length (CL) in a patient without history of prior spontaneous preterm birth (PTB) can vary. While most physicians agree on starting vaginal progesterone, management after CL shortens < 10mm can vary from expectant management with continued vaginal progesterone to cerclage placement with or without vaginal progesterone. The purpose of this study is to elucidate current practice patterns amongst Maternal-Fetal Medicine (MFM) specialists. We conducted an online survey of SMFM members in 2019. The primary outcome was management of varying CL measurements based on gestational age (GA). Variations in management of short CL were assessed descriptively. There were 204 respondents out of an estimated 1500 SMFM members. Practice type included academic (72.9%), private (12.8%) and community (12.8%). Region of practice included Northeast (37.8%), West (16.7%), South (19.2%), and Midwest (26.1%). Universal CL screening was reported by 93.1% (50.7% abdominal, 42.4% transvaginal), with 37.7% initiating screening at 16w0d to 18w0d, and 50.4% at 18w1d to 20w0d. Trends in management of short CL varied based on CL measurement, rather than GA at presentation. At CL < 10mm, management varied between cerclage, vaginal progesterone or cerclage plus vaginal progesterone. Between CL of 10-20mm, 74-91% would start vaginal progesterone. At CL 21-25mm, management varied between expectant management or vaginal progesterone (Figure 1). Suture material, use of preoperative antibiotics and postoperative tocolysis varied. After cerclage placement, 44.6% continued CL surveillance (Figure 2). Substantial differences of opinion exist amongst MFM physicians regarding management of incidentally found short CL in patients without history of PTB. The differences in responses obtained highlight the need for evidence-based guidelines for managing this frequently encountered clinical scenario.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The Effect of Intramuscular 17α-Hydroxyprogesterone in Women Screened for Shortened Cervical Length.

This article assesses the effect of weekly intramuscular 17α-hydroxyprogesterone caproate (17P) on midtrimester cervical length (CL) in patients with prior spontaneous preterm birth. Retrospective cohort study of all singletons that underwent CL screening at a single institution from 2011 to 2016. The timing of 17P exposure was assessed. The primary outcome was shortest midtrimester CL. Secondary outcomes included gestational age at delivery, rate of short cervix, cerclage, preterm labor admission, and preterm premature rupture of the membranes (PROM). Multivariable regression analysis was used to model the relationship between 17P exposure and shortest CL, controlling for selected covariates. Of 409 women who underwent screening, 211 received and 198 did not receive 17P prior to the last CL. Rates of short cervix and cerclage were similar between groups. After adjusting for covariates, the shortest CL was significantly shorter in the 17P group. In a secondary analysis, those who received any 17P (n = 293) versus those who did not (n = 116) had higher rates of preterm PROM, preterm labor admission, and cerclage. After controlling for covariates, gestational age at delivery was significantly lower in those receiving 17P. In high-risk patients undergoing CL screening for ultrasound-indicated cerclage, 17P did not prevent midtrimester cervical shortening or prolong gestation.

Cervicovaginal fluid proteomic analysis to identify potential biomarkers for preterm birth

Spontaneous preterm birth is a leading cause of neonatal morbidity and mortality. Early identification of at-risk women by reliable screening tests could reduce the spontaneous preterm birth rate, but conventional methods such as obstetrical history and maternal cervical length screening identify only a minority of spontaneous preterm birth cases. Cervicovaginal fluid might prove to be a useful, readily available biological fluid for identifying spontaneous preterm birth biomarkers. The objective of the study was to identify cervicovaginal fluid biomarkers of early spontaneous preterm birth in a high-risk cohort of pregnant women with a history of spontaneous preterm birth using targeted and shotgun proteomic analyses. A nested case control study (cases were spontaneous preterm birth <34 weeks in the current pregnancy; controls were spontaneous labor and delivery at 39-41 weeks) was performed using cervicovaginal fluid samples collected at 3 study visits (100/7 to 186/7 weeks, 190/7 to 236/7 weeks, and 280/7 to 316/7 weeks). All participants had a history of at least 1 prior spontaneous preterm birth. Targeted proteomic analysis was performed using a stable isotope-labeled proteome derived from endocervical and vaginal mucosal cells. This served as a standard to quantitate candidate protein levels in individual cervicovaginal fluid samples from the second and third study visits using liquid chromatography-multiple reaction monitoring mass spectrometry. The ratio of endogenous peptide area/stable isotope-labeled proteome-derived peptide area was used to measure levels of 42 peptides in 22 proteins. To maximize biomarker discovery in the cervicovaginal fluid samples, shotgun proteomic analysis also was performed utilizing liquid chromatography and ion trap mass spectrometry. A validation study was performed in second-trimester cervicovaginal fluid samples from an independent study group (12 spontaneous preterm birth cases, 19 term delivery controls) using enzyme-linked immunosorbent assay for 5 proteins expressed at higher levels in spontaneous preterm birth cases compared with controls in targeted or shotgun proteomic analyses. For targeted proteomics, cervicovaginal fluid samples from 33 cases and 32 controls at 190/7 to 236/7 weeks and 16 cases and 14 controls at 280/7 to 316/7 weeks from the same pregnancies were analyzed. When samples were compared between cases and controls, the relative abundance of 5 proteins was greater (P= .02-.05) in cases at both visits, while the relative abundance of 1 protein was lower (P= .03) in cases at both visits. For shotgun proteomics analyses, cervicovaginal fluid samples were pooled for 9 spontaneous preterm birth cases and 9 term delivery controls at each study visit. Shotgun proteomics yielded 28 proteins that were detected at levels >2 times higher and 1 protein that was detected at a level <0.5 times lower in spontaneous preterm birth cases compared with controls at all 3 study visits. Validation enzyme-linked immunosorbent assay for 5 proteins that were detected at higher levels in cervicovaginal fluid samples from spontaneous preterm birth cases compared with term delivery controls in proteomics analyses did not demonstrate statistically significant differences between spontaneous preterm birth cases and controls. Potential biomarkers of spontaneous preterm birth were identified by targeted and shotgun proteomics analyses in cervicovaginal fluid samples from high-risk, asymptomatic women. Many of the proteins detected at higher levels in cervicovaginal fluid samples from spontaneous preterm birth cases are extracellular matrix proteins and/or regulate cell membrane physiology. These proteins have substantial biological interest, but validation enzyme-linked immunosorbent assay for 5 of these proteins did not yield clinically useful biomarkers for spontaneous preterm birth.

Correlation of transabdominal and transvaginal sonography for the assessment of uterocervical angle at 16–24 weeks’ gestation

The objective of this study was to determine the correlation between transabdominal (TAS) and transvaginal sonography (TVS) uterocervical angle (UCA) measurement in pregnant women with no history of previous preterm birth. A cross-sectional study involving singleton pregnancies between 16 and 24 weeks of gestation who underwent routine foetal anatomical scan was conducted. The TAS-UCA measurement was performed before voiding and with an empty bladder. A total of 256 women completed the sonography. The mean maternal age was 32 ± 6.68 years. The mean gestation age at the time of ultrasound assessment was 19 ± 1.71 weeks. The mean prevoid TAS-UCA was 119.74 ± 33.12° and the mean postvoid TAS-UCA was 110.73 ± 25.30°. There was a significant difference between prevoid and postvoid TAS-UCA measurement (p < .05). The mean TVS-UCA was 103.91 ± 26.42°. The Pearson correlation coefficients of prevoid and postvoid TAS-UCA with TVS-UCA were 0.438 and 0.601, respectively. In conclusion, the postvoid TAS-UCA has moderate correlation with TVS-UCA measurement and is better than the prevoid TAS-UCA in women with low risk for preterm birth.IMPACT STATEMENTWhat is already known on this subject? TVS is the gold standard for cervical length (CL) assessment for prediction preterm birth. However, TVS requires an experienced or trained sonographer and some women decline TVS because of the embarrassment and discomfort during examination. Several studies have demonstrated the correlation between TAS and TVS and suggested that TAS could be an alternative for CL screening. UCA has been reported as a new predictor of spontaneous preterm birth and is usually performed by TVS. Thus, it is interesting to evaluate whether TAS can be a substitute procedure for TVS in UCA measurement.What the results of this study add? TAS may be used as a substitute procedure for TVS and the postvoid TAS is more appropriate than prevoid TAS for UCA measurement.What the implications are of these findings for clinical practice and/or further research? TAS may be an alternative method for UCA measurement when TVS is unavailable or in pregnant women who decline TVS-UCA measurement. However, further study should be conducted to confirm the association between TVS-UCA and postvoid TAS-UCA before deciding to use postvoid TAS-UCA as a screening tool for preterm prediction.

Cervical assessment by ultrasound for preventing preterm delivery.

Measurement of cervical length by ultrasound is predictive of preterm birth (PTB). There are three methods of ultrasound cervical assessment: transvaginal (TVU), transabdominal (TAU), and transperineal (TPU, also called translabial). Cervical length measured by TVU is a relatively new screening test, and has been associated with better prediction of PTB than previously available tests. It is unclear if cervical length measured by ultrasound is effective for preventing PTB. This is an update of a review last published in 2013. To assess the effectiveness of antenatal management based on transvaginal, transabdominal, and transperineal (also called translabial) ultrasound screening of cervical length for preventing preterm birth. For this update, we searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform (ICTRP) to 30 August 2018; reviewed the reference lists of all articles, and contacted experts in the field for additional and ongoing trials. We included published and unpublished randomised controlled trials (RCT) including pregnant women between the gestational ages of 14 to 32 weeks, for whom the cervical length was screened for risk of PTB with TVU, TAU, or TPU. This review focused on studies based on knowledge versus no knowledge of cervical length results, or ultrasound versus no ultrasound for cervical length. We excluded studies based on interventions (e.g. progesterone, cerclage) for short cervical length. We followed standard Cochrane methods. We included seven RCTs (N = 923): one examined asymptomatic women with twin pregnancies; four included women with singleton pregnancies and symptoms of preterm labour (PTL); one included women with singleton pregnancies and symptoms of preterm premature rupture of membranes (PPROM); and one included asymptomatic singletons. All trials used TVU for screening.We assessed the risk of bias of the included studies as mixed, and the quality of the evidence for primary outcomes as very low for all populations.For asymptomatic women with twin pregnancies, it is uncertain whether knowledge of TVU-measured cervical length compared to no knowledge reduces PTB at less than 34 weeks (risk ratio (RR) 0.62, 95% confidence intervals (CI) 0.30 to 1.25; 1 study, 125 participants) because the quality of the evidence is very low. The results were also inconclusive for preterm birth at 36, 32, or 30 weeks; gestational age at birth, and other maternal and perinatal outcomes.Four trials examined knowledge of TVU-measured cervical length of singletons with symptoms of PTL versus no knowledge. We are uncertain of the effects because of inconclusive results and very low-quality evidence for: preterm births at less than 37 weeks (average RR 0.59, 95% CI 0.26 to 1.32; 2 studies, 242 participants; I² = 66%; Tau² = 0.23). Birth occurred about four days later in the knowledge groups (mean difference (MD) 0.64 weeks, 95% CI 0.03 to 1.25; 3 trials, 290 women). The results were inconclusive for the other outcomes for which there were available data: PTB at less than 34 or 28 weeks; birthweight less than 2500 g; perinatal death; maternal hospitalisation; tocolysis; and steroids for fetal lung maturity.The trial of singletons with PPROM (N = 92) evaluated safety of using TVU to measure cervical length in this population as its primary outcome, not its effect on management. The results were inconclusive for incidence of maternal and neonatal infections between the TVU and no ultrasound groups.In the trial of asymptomatic singletons (N = 296), in which women either received TVU or not, the results were inconclusive for preterm birth at less than 37 weeks (RR 1.27, 95% CI 0.61 to 2.61; I² = 0%), gestational age at birth, and other perinatal and maternal outcomes.We downgraded evidence for limitations in study design, inconsistency between the trials, and imprecision, due to small sample size and wide confidence intervals crossing the line of no effect.No trial compared the effect of knowledge of the CL with no knowledge of CL in other populations, such as asymptomatic women with singleton pregnancies, or symptomatic women with twin pregnancies. There are limited data on the effects of knowing the cervical length, measured by ultrasound, for preventing preterm births, which preclude us from drawing any conclusions for women with asymptomatic twin or singleton pregnancies, singleton pregnancies with PPROM, or other populations and clinical scenarios.Limited evidence suggests that knowledge of transvaginal ultrasound-measured cervical length, used to inform the management of women with singleton pregnancies and symptoms of preterm labour, appears to prolong pregnancy by about four days over women in the no knowledge groups.Future studies could look at specific populations separately (e.g. singleton versus twins; symptoms versus no symptoms of PTL), report on all pertinent maternal and perinatal outcomes, and include cost-effectiveness analyses. Most importantly, future studies should include a clear protocol for management of women based on TVU-measured cervical length.

Among women with congenital uterine anomalies, is a short cervix predictive of preterm birth

Cervical length measurements are used to assess risk for preterm birth in women with normal uterine architecture. The utility of this measurement in women with congenital uterine anomalies is not known. The objective of this study was to describe pregnancy outcomes among women with known congenital uterine anomalies based on cervical length. A retrospective cohort of pregnant women with a congenital uterine anomaly (CUA) that delivered at a single tertiary academic center and its affiliated community hospital between June 1, 2013 and August 1, 2018 who underwent cervical length screening. Women were identified using ICD9 codes for both congenital uterine anomalies as well as for delivery. Prenatal records were reviewed to obtain demographic variables, obstetrics and gynecology history, ultrasound measurement of cervical length (CL) and delivery and neonatal outcomes. Short cervix was defined as a transvaginal cervical length of <25mm. The primary outcome was gestational age at delivery. Secondary outcomes included delivery at <37 weeks, delivery at <34 weeks, mode of delivery and neonatal death. Women with a short cervix were compared to those with CL≥25mm using Wilcoxon rank sum, Fisher’s exact and chi squared tests. 95 women with congenital uterine anomalies delivered between June 1, 2013 and August 1, 2018 and were included in analysis. 10 women had a short cervix. Median cervical length in the short cervix group was 22mm (IQR 12,14) as compared to 39mm (IQR 35, 42) in the long CL cohort (p < 0.001). No significant difference in parity, prior preterm birth, history of abnormal pap smears, prior cervical surgery, tobacco use or infertility treatment was seen between groups. Women with a short cervix delivered at a median of 28.6 weeks (IQR 21.4, 34.1) as compared to 38.1 weeks (IQR 35.9, 39.4) in the long cervix cohort (p < 0.001). Delivery at less than 37 weeks (90% vs 38%, p = 0.002) and less than 34 weeks (70% vs 14%, p < 0.001) were also more common among women with a short cervix. Though mode of delivery did not differ, neonatal demise was ten times more common in the short cervix group (40% vs 4.7%, p = 0.004). Among women with a CUA, short cervix may portend a more ominous outcome than among women with normal uterine architecture. Larger studies are needed to corroborate this data.

Predictive Value of Midtrimester Universal Cervical Length Screening Based on Parity.

To evaluate the effect of parity on performance characteristics of midtrimester cervical length (CL) in predicting spontaneous preterm birth (sPTB) before 37 weeks. This was a retrospective cohort study of 13,508 women with no history of sPTB undergoing universal transvaginal CL screening at 17 to 23 weeks' gestation from 2011 to 2016. Patients who declined screening or with unknown delivery outcomes were excluded. Areas under the receiver operator characteristic curves were used to assess and compare the predictive ability of CL screening for sPTB. The sensitivity, specificity, and positive and negative predictive values were estimated for specific CL cutoffs for prediction of sPTB. There were 20,100 patients, of whom 2087 (10%) declined screening and 4505 (22%) did not meet inclusion criteria. Of the remaining 13,508 patients, 43% were nulliparous. The incidence rates of sPTB were 6.5% in nulliparas and 4.9% in multiparas (P < .001). The mean CLs were 39.9 mm in nulliparas and 41.8 mm in multiparas (P < .001), and those of the first percentiles were 19.0 mm in nulliparas and 24.0 mm in multiparas. Cervical length was significantly more predictive of sPTB in nulliparas (area under the curve, 0.67; 95% confidence interval, 0.63-0.70; versus 0.61, 95% confidence interval, 0.57-0.63; P = .008). At CL cutoffs of 10, 15, 20, and 25 mm or less, the sensitivity was lower in multiparas, and the specificity was comparable between the groups. Midtrimester CL is less predictive of sPTB in multiparas compared to nulliparas. The poor predictive ability, especially in multiparas, calls into question the value of universal CL screening in this population.

Cervical Length Screening: Barriers to, and Patient Perception of, Cervical Length Measurement [31J

INTRODUCTION: Universal cervical length screening is not yet the standard of care in the United States, but meta-analyses suggest that such a practice could reduce the incidence of preterm delivery and is cost-effective. The objectives of this study were to 1) determine the prevalence of cervical length screenings among users of the mobile app, Ovia Pregnancy, and 2) identify barriers to receiving a cervical length measurement. METHODS: A survey about experience with cervical length measurement and barriers to receiving a measurement was sent to users of a pregnancy mobile app. Respondents were age 18 or older, United States residents, and pregnant (n=2,145). RESULTS: A total of 796 (37%) of respondents indicated that their healthcare provider measured the length of their cervix. Among 1,349 (63%) women who have not had a cervical length measurement, 349 (26%) reported that they would be unlikely to ask their healthcare provider to measure their cervical length, 727 (54%) reported that they would be likely to ask, and the remaining 273 (20%) were neutral on the topic. The most frequently reported barriers to a cervical length measurement were that their healthcare provider had not suggested it (44%), they had never heard of a cervical length measurement prior to taking the survey (21%), and concerns that the screening would not be covered by insurance (15%). CONCLUSION: Survey results indicate that more can be done to educate patients about the importance of cervical insufficiency during pregnancy, as well as to encourage providers to regularly measure their patients' cervical length.

Does Implementation of Universal Cervical Length Screening Increase Antepartum Resource Utilization? [15E

INTRODUCTION: Concern has been raised regarding “intention creep” and increased resource utilization with implementation of universal cervical length (CL) screening. We compared the incidence of antepartum interventions before and after implementation of screening. METHODS: Retrospective cohort study of singleton gestations who underwent anatomic ultrasound between 16w0d and 20w6d for two years pre and post implementation of screening. Excluded multiples, fetal anomalies, aneuploidy, and missing records. Interventions included ≥2 repeat CL measurements, vaginal progesterone, 17-OHP, cerclage, pessary, admission for preterm labor, betamethasone administration, and NICU consultation. Multivariable logistic regression was used. RESULTS: There were 8309 patients- 4350 before (unexposed) vs. 3959 after (exposed). In the unexposed group 94 (0.87%) patients had a CL of ≤3 cm vs. 56 (1.41%) in the exposed group (p=0.02). There were no differences in demographics between groups. Of those with short cervix, the median CL was 2.4 cm (unexposed) vs. 2.5 cm (exposed). The exposed were less likely to undergo ≥1 antepartum intervention (58.9% vs. 80.0%, aRR 0.68, 95% CI 0.34, 0.99). There were no differences in the rates of individual interventions (cerclage placement, vaginal progesterone, 17-OHP, PTL admission, NICU consultation or administration of steroids). Chorioamnionitis was less frequent in the exposed (8.9 vs. 26.3%, p=0.02). There were no differences in neonatal outcomes or the rate of preterm birth. CONCLUSION: Implementation of universal CL screening identified more people with a short cervix with no difference in the rate of individual interventions. The exposed were less likely to undergo ≥one intervention. Universal CL screening does not unduly increase antepartum resource utilization.

The Role of Digital Cervical Examination in the Setting of a Sonographically Short Cervix [23T

INTRODUCTION: Many practices that have instituted universal cervical length (CL) screening have not included digital cervical examination in their process. Our objective was to investigate the incidence of cervical dilatation (CD) at various midtrimester CL thresholds as well as characteristics associated with CD that may inform who would benefit from digital examination in the setting of a short CL. METHODS: This retrospective IRB-approved cohort study included women with a singleton gestation with a midtrimester CL ≤ 2.5 cm who subsequently had a digital cervical examination within a week. The primary outcome was any CD on digital examination. Maternal sociodemographic, clinical, and sonographic characteristics were abstracted from the medical record. Bivariable and multivariable analyses were used to determine the relationship between these characteristics and CD. Receiver operating curves were developed to assess the predictive capacity of these characteristics to identify CD or CD ≥1 cm. RESULTS: Of the 256 women who met eligibility criteria, 103 (40.2%) were found to have any CD; 87 (34.0%) were at least 1 cm dilated and 8 (3.1%) were at least 2 cm dilated. While race/ethnicity, insurance status, nulliparity, a prior cervical excisional procedure, funneling on ultrasound, and the sonographic CL were each associated with CD, including all of these variables into a regression yielded a model with only fair predictive capacity to identify CD or CD ≥ 1 cm [AUC = 0.77 (95% CI 0.71-0.83) and 0.76 (0.70-0.82), respectively]. CONCLUSION: As prediction of CD is limited, consideration should be given to performing a digital cervical exam in the setting of a sonographically short cervix.

Does Universal Cervical Length Screening Impact Cerclage Practice Patterns? [36I

INTRODUCTION: We sought to evaluate the impact of universal cervical length screening (UCLS) on the placement rate of history-indicated (HIC), ultrasound (USIC)-indicated, & physical exam (PEIC)-indicated cerclages. METHODS: A retrospective cohort study compared women with a CL of <3 cm on US between 16 and 20 weeks for 2 years before and after implementation of UCLS at a single institution from April 2013 to April 2017. Multivariable logistic regression was used to evaluate the changes in the rate of overall cerclage placement and types of cerclages along with impact on preterm birth (PTB) rates. RESULTS: 4350 were evaluated in the pre-screening period and 3959 in the post-screening period. Detection rate of short cervix was increased after implementation of screening, but rates of cerclage placement were similar (P=0.11). Among 67 patients with cerclages, demographics (race, BMI, prior PTB, CL, tobacco use) were similar. There was decrease in HIC placement post implementation (RR 0.6 95% CI 0.4-0.9) and a non-significant trend toward an increased placement rate of USIC (RR 1.9 95% CI 0.9-3.9). The rate of PE-indicated cerclages was similar. Among women with cerclage, there were no differences in PTB before and after screening implementation. CONCLUSION: Cerclage placement rate was unchanged with UCLS. Rates of USIC and PEIC were unchanged, while the rate of HIC was significantly decreased. This was likely related to increased reliance on US screening. While this may have increased utilization of ultrasound, this change in practice pattern did not impact rates of PTB.

Universal cervical length screening with a cervicometer to prevent preterm birth

Background: Preterm birth is a leading cause of neonatal morbidity and mortality worldwide; evidence-based strategies to decrease preterm birth are desperately needed.Objective: The purpose of this study was to estimate which of three strategies for screening for shortened cervix in asymptomatic low-risk women is the most cost-effective in terms of prevention of preterm birth and associated morbidity.Study design: A decision analysis model was developed from available published evidence comparing three strategies in screening asymptomatic low-risk women for shortened cervix: (1) cervicometer with subsequent referral for transvaginal ultrasound, (2) transvaginal ultrasound screening, and (3) no screening. The cost and effectiveness of each strategy was assessed in terms of quality-adjusted life-years (QALYs), and cost in US dollars.Results: Screening with a cervicometer with referral was the most cost-effective strategy and represented a savings of $999.65 ($11,617.28 versus $12,616.93) over screening with ultrasound, and a savings of $15,601.62 ($11,617.28 versus $27,218.90) over no screening. Costs for outcomes ranged from $3528 for a healthy neonate ≥34 weeks to $717,467.5 for a neonate <34 weeks with severe morbidity. The cervicometer strategy avoided 11.68 neonatal deaths per 1000 deliveries (3.59 deaths versus 15.27 deaths) compared with no screening, and avoided 0.73 neonatal deaths per 1000 deliveries (3.59 deaths versus 4.32 deaths) compared with ultrasound strategy. The cervicometer strategy prevented 82.44 preterm births per 1000 deliveries (22.56 versus 105.00) compared with no screening, and 5.10 preterm births per 1000 deliveries (22.56 versus 27.66) compared with ultrasound strategy. Per QALY, cervicometer screening cost $386.57, transvaginal ultrasound cost $420.31, and no screening cost $922.73. Sensitivity analyses confirmed the robustness of these findings, including evaluation across the range of quoted transvaginal ultrasound costs ($43–$300).Conclusion: A simulation of universal screening of asymptomatic low-risk women with a cervicometer with subsequent referral for ultrasound for those with a cervix <25 mm is cost-effective and yields the greatest reduction in preterm births at <34 weeks. A risk simulation trial noted that a cervicometer strategy may be more expensive than a universal transvaginal ultrasound strategy, but both are less expensive than a no screening strategy.

Second trimester uterocervical angle and spontaneous preterm birth in twins

Objective: To determine if there is an association between uterocervical angle (UCA) and spontaneous preterm birth (sPTB) < 37 weeks for women with twins. Materials and methods: Retrospective cohort study from 2014 to 2017 of twin pregnancies with cervical length (CL) screening between 15 0/7 and 24 6/7 weeks. Monochorionic-monoamniotic twins were excluded. Post-hoc UCA measurements were analyzed as a continuous variable and a wide UCA was also defined as an angle >95° and >110°. The primary outcome was sPTB < 37 weeks. Secondary outcomes were sPTB <34 weeks, <32 weeks, CL, and performance metrics for UCA. Binary logistic regression controlled for age, tobacco use, prior sPTB, CL, and gestational age at CL measurement. Results: A total of 114 women were studied. The rate of sPTB <37 weeks was 35.0%, <34 weeks was 21.4%, and <32 weeks was 17.1%. As a continuous variable, mean UCA was 117.9° (SD 27.1°) for delivery ≥37 weeks and 133.1° (SD 23.1°) <37 weeks (p = .002). A wider mean UCA was also associated with sPTB <34 weeks (sPTB ≥34 weeks: 120.9° [SD 26.5°] vs. <34 weeks: 133.0° [SD 22.8°], p = .025) and sPTB <32 weeks (sPTB ≥32 weeks: 121.2° [SD 25.9°] vs. <32 weeks: 135.0° [SD 24.0°], p = .018). However, after controlling for age, prior sPTB, tobacco use, CL measurement, and gestational age at CL measurement, UCA was not associated with sPTB <37 weeks, <34 weeks, or <32 weeks. UCA >110° was associated with sPTB <37 weeks after controlling for confounders (aOR 3.6 [95% CI 1.2–10.5], p = 0.02). There was no association between UCA >110° and sPTB <34 or <32 weeks. Furthermore, a UCA >95° was not associated with sPTB <37, <34, or <32 weeks. As a screening tool for sPTB <37 weeks, a UCA of >110° had a sensitivity of 85.7%, specificity of 43.1%, positive predictive value of 53.2%, negative predictive value of 80.0%, positive likelihood ratio of 1.5, and negative likelihood ratio of 0.3. Conclusions: In a cohort of dichorionic-diamniotic and monochroionic-diamniotic twins, UCA >110° was associated with sPTB <37 weeks. However, second trimester UCA had a low positive likelihood ratio and was not a robust marker for the prediction of sPTB in twins.

Evaluation of additive effect of quantitative fetal fibronectin to cervical length for prediction of spontaneous preterm birth among asymptomatic high-risk women

Objective: To determine if quantitative fetal fibronectin (qFFN) in addition to transvaginal ultrasound (TVU) cervical length (CL) measurement between 180/7 and 236/7 weeks would be predictive of spontaneous preterm birth (sPTB) at <350/7 weeks among asymptomatic high-risk women as defined by those with prior sPTB > 200/7 weeks.Material and methods: A prospective observational study of asymptomatic women with singleton gestations between 180/7 and 236/7weeks and one or more prior SPTB was performed. Women at their anatomy scan who opted into universal CL screening were enrolled. At enrollment, a vaginal speculum exam was performed to collect cervico-vaginal fluid from the posterior fornix using fetal fibronectin (FFN) swab. These women were then followed until delivery. Women with multiple gestations, rupture of membranes, vaginal bleeding, intercourse, or vaginal exam within 48 h of enrollment were excluded. Physicians were blinded to the qFFN levels, but the CL measurements were made available. The primary outcome was sPTB < 350/7 weeks.Results: Of the 105 asymptomatic women with prior sPTB who were prospectively enrolled, 19 (18.1%) had recurrent sPTB < 370/7 weeks. None of the sPTB were iatrogenic. Using receiver-operating characteristic curves, qFFN ≥ 10 ng/mL had the highest sensitivity with subsequent lowest false negative rate, while FFN ≥ 50 ng/mL was identified as being the best balance of sensitivity and false positive rate for predicting sPTB < 350/7 weeks. As compared with CL ≤ 25 mm alone, with the use of CL ≤ 25 mm or qFFN ≥ 50 ng/mL as screening criteria for prediction of SPTB < 350/7 weeks, sensitivity improved from 18.2 to 63.6%, specificity decreased from 96.8 to 82.1%, positive predictive value (PPV) decreased from 40.0 to 29.2%, negative predictive value (NPV) marginally improved from 91.1 to 95.1%.Conclusion: In women with singleton gestations with prior SPTB, qFFN can be used as an adjunct to triage patients who are found to have a shortened cervix. Sensitivity and NPVs improved with the addition of qFFN to TVU CL screening alone in women with singleton gestations with prior SPTB. However, specificity and PPVs decreased.

Cervical length, cervical dilation, and gestational age at cerclage placement and the risk of preterm birth in women undergoing ultrasound or exam indicated Shirodkar cerclage

Background: Preterm birth is a major cause of neonatal morbidity and mortality in the USA. In many patients at risk for preterm birth, cervical length (CL) screening is used to guide decisions regarding cerclage placement. Quality evidence shows that cerclage prolongs pregnancy in high-risk women with a short CL in women with a history of preterm birth and in women with painless cervical dilation in the second trimester, though the degree of cervical shortening, dilation, or gestational age at cerclage placement are not consistently associated with the subsequent rate of preterm birth. Our objective was to determine if cervical length (CL), cervical dilation or gestational age (GA) at the time of cerclage placement are associated with preterm birth among women undergoing ultrasound-indicated or exam-indicated cerclage.Study design: This was a retrospective cohort study of all patients with a singleton pregnancy who underwent ultrasound-indicated or exam-indicated Shirodkar cerclage placement at a single maternal-fetal medicine practice in New York City between November 2005 and May 2017. All patients included in the study had previously undergone CL screening for an increased risk of preterm birth (for example, prior spontaneous preterm birth or mid-trimester loss, prior cervical excision). The cervical length or dilation and GA at the time of cerclage placement were collected, as were demographic and obstetric outcome data for the current pregnancy. The primary outcome was delivery <36 or ≥36 weeks. Planned subgroup analyses of the primary outcome were performed based on CL at the time of ultrasound-indicated cerclage (0–9 mm, 10–19 mm, ≥20 mm), cervical dilation at the time of physical exam-indicated cerclage (<2 cm vs. ≥2 cm), and gestational age at cerclage placement (<20 weeks vs. ≥20 weeks). Data were analyzed using the Student’s t-test and chi-square test for trend.Results: There were 123 and 39 patients in the ultrasound- and exam-indicated cerclage groups, respectively. Twenty six (21.2%) patients in the ultrasound-indicated subgroup and 24 patients (61.5%) in the exam-indicated subgroup delivered <36 weeks. CL (16.4 versus 17.6 mm, p = .28) and GA (19.7 versus 20.0 weeks, p = .58) at the time of ultrasound-indicated cerclage placement were not significantly different in patients who delivered <36 and ≥36 weeks’ gestation, respectively. Women with cervical dilation ≥2 cm prior to exam-indicated cerclage placement were significantly more likely to deliver <36 weeks when compared to women with cervical dilation <2 cm (77.8 versus 47.6%, p = .05); however, there were no significant differences in rates of preterm birth <28 and <32 weeks between these two groups (38.9 versus 23.8%, p = .31 and 50.0% versus 28.6%, p = .17, respectively).Conclusions: Cervical length and GA at the time of ultrasound-indicated Shirodkar cerclage placement do not appear to impact the likelihood of preterm birth <36 weeks, while cervical dilation ≥2 cm at the time of exam-indicated Shirodkar cerclage is associated with an increased rate of preterm birth <36 weeks, but not earlier gestational ages at delivery.

Follow-up of dichorionic twins

Only once chorionicity is correctly assigned can appropriate follow up be planned for a twin pregnancy. Dichorionic twins, considered the ‘safest’ type of twin pregnancy, remain at increased risk of preterm birth, structural abnormalities, and intra-uterine fetal death. Second trimester ultrasound can screen for these complications, enabling best practice management. But should we always screen, just because we can? The pros and cons of cervical length screening in asymptomatic twin pregnancies will be discussed. Third trimester ultrasound follow-up is centered around the detection of fetal growth restriction, which has additional challenges in twin pregnancies compared to singletons. Which measurements give the most accurate estimated fetal weights? Should specific twin growth charts be used? Do the changes in Doppler studies mirror those of singleton pregnancies? Understanding the answers to these questions will guide the most appropriate third trimester follow-up of dichorionic twin pregnancies.