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

ObjectiveOur 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 methodsWe 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.ResultsKolmogorov–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.ConclusionWe 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.     

Predictors of preterm birth

Cervical length (CL) measured by transvaginal ultrasound examination (TVUE) best identifies the risk for preterm birth (PTB). It identifies women at risk who can benefit from corticosteroids or in utero transfer. Early screening improves effectiveness of tocolysis. It reduces iatrogenicity and cost. In preterm premature rupture of membranes (PPROM), CL is devoid of infectious risk and predicts duration of the latency phase but not the risk of perinatal sepsis.Asymptomatic women at risk should be screened at a 2-week interval starting from 16 to 18 weeks, up to 24 weeks. CLs <10th centile are at risk of PTB, especially with decrease in CL after 16 weeks. Repeat ultrasound improves predictive values. Stable CL calls for term delivery. Funneling does not improve predictivity of CL. In twin pregnancies, CL reduces unnecessary interventions. In symptomatic women, fetal fibronectin performs less than CL. Its combination with inconclusive CL has not emerged productive through randomized controlled trials (RCTs), and studies with homogeneous management for preterm labor (PTL) suggest that up to 15% of unjustified hospitalizations and treatment could be avoided.     

Risk of spontaneous preterm birth in IVF-conceived twin pregnancies

Objective: To compare the mean transvaginal ultrasound (TVU) cervical length (CL) at midtrimester in screening for preterm birth in in vitro (IVF)-conceived twin pregnancies versus spontaneously-conceived twin pregnancies.

Methods: This was a retrospective cohort study. Potential study subjects were identified at the time of a routine second trimester fetal ultrasound exam at 18 0/7 to 23 6/7-week gestation. All women with twin diamniotic pregnancies screened with a single TVU CL for this trial were included. Mean TVU CLs were compared between IVF-conceived twin pregnancies and spontaneously-conceived twin pregnancies. The relationship of TVU CL with gestational age at delivery was assessed. Incidence of short TVU CL, defined as TVU CL ≤30?mm, was also calculated in the two groups. The primary outcome was the mean of TVU CL. Distribution of CL was determined and normality was examined in both groups

Results: A total of 668 women with diamniotic twin pregnancies who underwent TVU CL screening between 18 0/6 and 23 6/7 weeks were included. 158 (23.7%) were IVF-conceived pregnancies, and 510 (76.3%) were spontaneously-conceived pregnancies. No women received progesterone, pessary, or cerclage for preterm birth prevention during pregnancy. The mean TVU CL was significantly lower in the IVF-conceived group (32.2?±?10.5?mm) compared to the spontaneously-conceived group (34.1?±?9.1?mm) (mean difference (MD)???1.90?mm, 95%CI ?3.72 to ?0.08). The incidence of TVU CL ≤30?mm was 30.4% in the IVF-conceived group and 21.6% in the spontaneously-conceived group (adjusted odds ratio (aOR) 1.59, 95%CI 1.06–2.37). IVF-conceived twins had a significantly higher risk of spontaneous preterm birth <34 weeks (32.9 versus 21.2%; aOR 1.83, 95% confidence interval (CI) 1.23–2.71) and higher rate of delivery due to spontaneous onset of labor (64.5 versus 54.9%; aOR 1.50, 95%CI 1.03–2.17). For any given TVU CL measured between 18 0–7 and 23 6/7 weeks, gestational age at delivery for IVF-conceived twins was earlier by about 1 week on average compared with spontaneously-conceived twins.

Conclusions: The higher rate of spontaneous preterm birth in IVF-conceived twin pregnancies is predicted by lower midtrimester TVU CL, as well as by the lower gestational age at birth per any given CL in the IVF-conceived compared to the spontaneously-conceived twin pregnancies.     

Contemporary use of cervical cerclage

Although it was devised over 50 years ago, only recently controlled randomized trials have evaluated the efficacy of cervical cerclage. Cerclage was originally devised for women with both prior preterm birth (PTB) and cervical changes in the current pregnancy. Evidence suggests that transvaginal cerclage probably prevents second trimester loss/PTB in women with >or=3 PTB/second trimester loss (history-indicated cerclage best placed at 12 to 14 wk); and in women with a prior PTB 16 to 36 weeks and transvaginal ultrasound cervical length<25 mm in the current pregnancy (ultrasound-indicated cerclage at 14 to 23 6/7 wk).     

Clinical management of the short cervix

Cervical cerclage is associated with prolongation of gestation in singleton pregnancies with prior spontaneous preterm delivery and a short cervix on vaginal ultrasonography in the mid-trimester. Ultrasound screening of cervical length is not indicated in low-risk singleton pregnancies and in women with multiple gestations. 17α-Hydroxyprogesterone does not prevent preterm delivery in twin gestations with a short cervix. Cervical cerclage may cause detrimental effects in twin gestations. Vaginal pessary for the prevention of preterm birth in women with a short cervix is currently under active investigation.     

The utility of screening for historical risk factors for preterm birth in women with known second trimester cervical length

Abstract

Objective: To evaluate for the presence of risk factors (RFs) for preterm birth (PTB) in women without prior PTB having second trimester cervical length (CL) screening, and to estimate the utility of RF screening.

Methods: “Low-risk” singletons were prospectively screened with midtrimester transvaginal ultrasound CL. Prior PTB, intrauterine fetal demise and lethal anomalies were excluded. Women were analyzed based on second trimester CL (<25?mm versus ≥25?mm) and the presence of RFs for PTB. A p-value of < 0.05 was considered significant.

Results: A total of 639 women were screened; 8% had CL <25?mm. Ninety-eight percent of women with CL <25?mm and 95% of women with CL ≥25?mm had RFs for PTB. Five percent of women with a CL ≥25?mm delivered preterm as compared to 18% with CL <25?mm (p?<?0.01). Treatment of cervical dysplasia, drug use during the pregnancy and unmarried status were significantly more common in women with CL <25?mm than CL ≥25?mm. When data were analyzed by CL, the presence of additional RFs did not add to the prediction of PTB <37 weeks.

Discussion: Over 95% of singleton gestations without prior PTB have ≥1 other RF for PTB. In women without prior PTB, assessment of other PTB RFs does not add to prediction of PTB provided by CL alone.     

Cervical incompetence: a reappraisal of an obstetric controversy

Cervical incompetence is not a categoric but rather a continuous variable, meaning that there are various degrees in the competency of the cervix. Furthermore, a certain degree of competency of the cervix can be expressed differently in subsequent pregnancies. Women with risk factors for cervical incompetence in their gynecological/obstetric history should be followed by transvaginal ultrasonography. History alone is not an indication for a prophylactic cerclage. Although transvaginal ultrasonography identifies women at high risk of preterm delivery, it does not discriminate between different underlying pathologies. Short cervical length alone is not an indication for a therapeutic cerclage. Serial transvaginal ultrasonographic measurements of cervical length in women with risk factors can identify those women truly at high risk of preterm delivery. A transvaginal cervical cerclage with bed rest reduces preterm delivery and improves perinatal outcome in women with a short cervical length and risk factors for cervical incompetence. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader will be able to define cervical incompetence, explain the role of transvaginal ultrasonography in the prediction of preterm delivery, and summarize the data on the use of transvaginal cervical cerclage.     

Novel developments on cervical length screening and progesterone for preventing preterm birth

Cervical length (CL) measured by transvaginal ultrasound is an effective screening test for the prevention of preterm birth (PTB). The criteria for an effective screening test are all met by CL. It studies an important condition (PTB); it is safe and acceptable by >99% of women; it recognises an early asymptomatic phase that precedes PTB by many weeks; it has a well-described technique, is reproducible, is predictive of PTB in all populations studies so far; and, perhaps most importantly, it has been shown that 'early' treatment is effective in prevention. These two interventions, effective only in specific populations, are ultrasound-indicated cerclage and vaginal progesterone.     

Risk of intrapartum cervical lacerations in women with cerclage

Objective: The aim of our study was to estimate whether the placement of cerclage in pregnancy to prevent preterm birth (PTB) is associated with higher incidence of intrapartum cervical lacerations. Methods: A retrospective cohort study was conducted on singleton pregnancies with risk factors for PTB. The study group consisted of women with either a history- or ultrasound-indicated cerclage placed between 12 and 24 weeks of gestation, while the control group consisted of women with similar risk factors for PTB but who did not receive a cerclage. Primary outcome was the incidence of intrapartum cervical lacerations. A sample size calculation was performed on the basis of the results of previous studies on cervical lacerations. Results: We identified 134 women who had a cerclage placed in pregnancy. They were compared with 236 controls with no cerclage. Cases and controls had similar risk factors for cervical lacerations. Cervical lacerations occurred with similar frequencies in the cerclage and no-cerclage group (2.2 vs 1.3%, p = 0.78). There was no significant difference between the two groups for the risk of cervical lacerations (RR 1.76, 95% CI: 0.36–8.60). Conclusions: Cerclage placement during pregnancy is not associated with an increased risk of intrapartum cervical lacerations.     

Controversies regarding cervical incompetence, short cervix, and the need for cerclage

Cervical incompetence (CI) is not an all or nothing phenomenon but a continuous variable. CI and preterm labor are not distinct entities but rather part of a spectrum leading to preterm delivery. Cervical length (CL) is an independent variable in the prediction of preterm delivery, to which it is inversely related. Application of a primary transvaginal cervical cerclage appears to be an unnecessary intervention in about 50% of women presenting with a history suggesting cervical incompetence. A better alternative for women with a history of or risk factors for CI is transvaginal ultrasonographic follow-up of CL. To facilitate the comparison of studies of CI, the authors suggest a nomenclature reflecting the different stages of prevention: primary, secondary, and tertiary transvaginal cervical cerclage.     

Effect of cerclage on obstetrical outcome in twin gestations with a shortened cervical length

OBJECTIVE: Our purpose was to determine the impact of cerclage placement on obstetric outcome in twin gestations with a shortened cervical length. STUDY DESIGN: A prospective cohort study of 147 consecutive twin pregnancies (July 1994 to March 2001) who underwent transvaginal ultrasonographic cervical length measurement between 18 and 26 weeks' gestation. Cerclage was offered to women with cervical lengths < or = 25 mm. Patients were segregated into quartiles by cervical length. Regression analysis and chi(2) tests were used to determine the effect of cervical length and cerclage on parameters of prematurity. RESULTS: One hundred twenty-eight twin gestations met inclusion criteria, including 21 (16.4%) who underwent cerclage for a cervical length < or = 25 mm. Decreasing cervical length was significantly associated with a shorter length of gestation, lower combined birth weight, delivery at < or = 34 weeks, preterm premature rupture of fetal membranes, and very low birth weight. None of these outcomes was altered by cerclage placement. CONCLUSION: Midtrimester cerclage does not alter the risks of prematurity associated with a shortened cervical length in twin gestations.     

Outcomes of ultrasound-indicated cerclage in twin pregnancies with a short cervical length

ObjectiveTo investigate the outcomes of ultrasound-indicated cerclage in dichorionic-diamniotic (DCDA) twin pregnancies with a short cervical length.Materials and methodsThis was a retrospective cohort study of DCDA twin pregnancies with a short cervical length (≤25 mm) from January 2000 to July 2017 to compare maternal and neonatal outcomes. Additional sub-analysis was performed by dividing the patients into two subgroups by a cervical length ≤15 mm and between 16 and 25 mm.ResultsOne hundred and eight women were initially diagnosed with twin pregnancies and cervical insufficiency. After excluding cases not meeting the study criteria, 46 women were recruited for analysis, of whom 33 underwent ultrasound-indicated cerclage. The delivery age of the cerclage group was significantly later than the non-cerclage group (34.85 ± 3.91 versus 31.08 ± 5.25 weeks, p = 0.011), and the latency was significantly longer in the cerclage group than in the non-cerclage group (86.09 ± 41.32 versus 52.31 ± 33.24 days, p = 0.014). Sub-analysis revealed that these benefits were significant in the subgroup of a cervical length ≤15 mm. Both first twin (twin A) and second twin (twin B) had a significantly decreased rate of neonatal intensive care unit admission in the cerclage group. However, twin A had more promising outcomes with significantly decreased rates of neonatal respiratory distress syndrome (6.7% versus 50.0%, p = 0.004) and sepsis (0% versus 25.0%, p = 0.019).ConclusionUltrasound-indicated cerclage in DCDA twin pregnancies can decrease preterm birth and prolong the latency. It also decreases neonatal morbidity, and is especially beneficial for twin A.     

Abdominal cerclage after failed transvaginal cervical cerclage

This study aimed to evaluate the efficacy of abdominal cerclage by laparotomy and by laparoscopy among women who had failed transvaginal cerclage. We evaluated all women with cervical insufficiency that underwent abdominal cerclage between the years 2000 and 2010. Of a total of 20 patients, 12 patients underwent abdominal cerclage by laparoscopy and 8 others by laparotomy. The procedure was done in the pregnant state in four patients in the laparoscopy group and in all patients in the laparotomy group. There was no significant difference in the operative time between the laparoscopy and the laparotomy group. The median duration of hospitalization in the laparoscopy group was 6 h and in the laparotomy group was 96 h. Of 18 pregnancies, 16 resulted in a live birth (88.9%). Abdominal cerclage in women who have failed a transvaginal cervical cerclage is associated with a high live birth rate.     

Cerclage for the prevention of preterm birth in high risk women receiving intramuscular 17-α-hydroxyprogesterone caproate

Objective: To assess cerclage benefit in women with short cervix also receiving 17-α-hydroxyprogesterone caproate (17P) to prevent recurrent preterm birth (PTB). Methods: Secondary analysis of a multicenter trial of ultrasound-indicated cerclage for shortened cervical length (CL). Women with prior spontaneous PTB at 16–33 6/7 weeks, singleton gestation and CL < 25?mm between 16 and 22 6/7 weeks were counseled on use of 17P and randomized to cerclage or no cerclage. Outcomes of women who received 17P were analyzed by randomization group. Primary outcome was PTB < 35 weeks. Results: 99 women received 17P: 47 cerclage; 52 no cerclage. Rates of PTB < 35 weeks were similar, 30% for cerclage and 38% for no cerclage (aOR 0.64 (0.27–1.52)). In women with CL < 15?mm, PTB < 35 weeks was reduced for the cerclage group (17% vs. 75%, p = 0.02). However, this difference was nullified after controlling for total progesterone doses received (p = 0.40). Conclusions: Cerclage was shown not to offer additional benefit for the prevention of recurrent PTB in women with short CL < 25?mm receiving 17P, but the sample size is insufficient for a definite conclusion given the 36% nonsignificant decrease in the odds of PTB < 35 weeks. Cerclage may further offer substantial benefit to women with very short CL < 15?mm and further study is needed.     

Shirodkar versus McDonald cerclage for the prevention of preterm birth in women with short cervical length

The efficacy of Shirodkar cerclage was compared with that of the McDonald procedure for the prevention of preterm birth (PTB) in women with a short cervix. Secondary analysis using data from all published randomized trials including women with a short cervical length (CL) was performed comparing the use of Shirodkar versus McDonald sutures. Analysis was limited to singletons with short CL on transvaginal ultrasound. The primary outcome measure was PTB < 33 weeks. Statistical analysis was performed using bivariate and multivariable techniques. From 607 women randomly assigned in the study, 277 met our inclusion criteria; 127 received Shirodkar and 150 women received McDonald sutures. The mean ( +/- standard deviation) gestational age at delivery was 35.0 +/- 5.3 versus 36.3 +/- 4.7 for the Shirodkar versus McDonald groups, respectively ( p< 0.02). PTB < 33 weeks was seen in 61 (22%) of 277 women; 26 (20%) of 127 in the Shirodkar and 35 (23%) of 150 in the McDonald groups, respectively (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.5 to 1.6). On adjusting for confounders using logistic regression modeling, no significant difference in PTB < 33 weeks was found between the two groups (OR, 0.55; 95% CI, 0.2 to 1.3). In women with short cervical length randomly assigned to receiving cerclage, no significant difference in prevention of PTB was observed using Shirodkar or McDonald's procedures.     

Current Practice of Maternal–Fetal Medicine Specialists Regarding the Prevention and Management of Preterm Birth in Twin Gestations

ObjectiveTo investigate the current practices of maternal–fetal medicine (MFM) specialists regarding the prevention and management of preterm birth (PTB) in twin pregnancies.MethodsThis was a cross-sectional study of Canadian MFM specialists. Participants responded to an anonymous survey regarding the prevention and management of PTB in twins, including lifestyle and gestational weight gain recommendations, cervical length screening, PTB prevention, and labour and delivery practices.ResultsOf 137 MFM specialists surveyed, 95 (69%) responded. Most MFM specialists recommend against activity restriction (77.9%), avoidance of sexual activity (96.7%), routine progesterone (97.8%), routine prophylactic cerclage (98.9%), and routine administration of antenatal corticosteroids (95.6%). There were considerable inconsistencies with respect to gestational weight gain management. Despite lack of support by guidelines, most MFM specialists reported using routine cervical length screening (97.8%) and progesterone for short cervix (92.3%). Over half (52.7%) of MFM specialists recommend cervical cerclage when the cervix is <15mm. In cases of PTB, most MFM specialists recommend vaginal delivery when twins are in vertex presentation (63%–75%). MFM specialists are less likely to recommend vaginal delivery when twin B is non-vertex (35%–41%).ConclusionThere is a considerable variation among MFM specialists regarding the prevention and management of PTB in twins, and the practice of many MFM specialists differs from that recommended by professional societies’ guidelines. These findings underscore the necessity for high-quality studies and up-to-date recommendations.     

Cervical cerclage in twin pregnancy

Cervical cerclage in women with twin pregnancy is not routinely indicated but appears to be beneficial in subjects with a history of preterm birth or very short cervix or dilated cervix. There is a paucity of literature data regarding transabdominal or laparoscopic cervical cerclage (LCC) in twin pregnancy. It is uncertain whether LCC is more effective than transvaginal cerclage. Our own experience of 24 cases of LCC in twin pregnancy showed encouraging results. Further, well-planned studies are required to answer whether, when, and how cervical cerclage should be performed in women with twin pregnancy.     

Physical examination-indicated cerclage in singleton and twin pregnancies: maternal–fetal outcomes

Objectives: To study maternal and perinatal outcomes after physical examination-indicated cerclage in both singleton and twin pregnancies and evaluate the possible risk factors associated.

Study design: Retrospective review of all women undergoing physical examination-indicated cerclage at the Hospital Vall d’Hebro, Barcelona from January 2009 to December 2012 after being diagnosed with cervical incompetence and risk of premature birth.

Results: During the study period, 60 cases of women diagnosed with cervical incompetence who were carrying live and morphologically-normal fetuses (53 singleton and 7 twin pregnancies), and who had an imminent risk of premature birth were evaluated. Mean gestational age until birth was 35 weeks in singleton and 32 weeks in twin pregnancies. Four cases (7.5%) of immature births and one case (2.0%) of neonatal death were recorded in singleton pregnancies. No cases of immature births or neonatal deaths were recorded in twin pregnancies. Diagnostic amniocentesis was performed IN all cases to rule out possible chorioamnionitis.

Conclusions: Physical examination-indicated cerclage for cervical incompetence in women at risk for immature or preterm birth demonstrates good perinatal prognosis without increasing maternal morbidity in either singleton or twin pregnancies. The increase in gestation time in our study may also have been due to the fact that patients with subclinical chorioamnionitis were excluded by diagnostic amniocentesis.     

Cervical assessment in women with threatened preterm labor.

OBJECTIVE: The aim of the study was to examine the clinical value of cervical assessment by transvaginal ultrasonography in women with symptoms of preterm labor. METHODS: We prospectively evaluated 172 women with singleton pregnancies and symptoms of preterm labor. Seventy of them were nulliparas, while 102 were multiparas. Gestational age ranged between 24 and 34 wks. All women underwent cervical assessment with transvaginal ultrasonography and were given intravenous tocolytics. The only parameter evaluated was cervical length. Women with multiple pregnancies, gestational age <24 wks or >34 wks, cervical dilatation >2 cm, placenta praevia, premature rupture of membranes, or cervical cerclage were excluded from the study. The outcome measure was delivery before 34 wks gestation. RESULTS: The preterm delivery rate before 34 wks was 37%. The sensitivity and the specificity of a cervical length of less than 20 mm was 60 and 53.8% and 97.7 and 95.2% for nulliparas and multiparas, respectively. A cervical length <20 mm was also 93.7% predictive of preterm delivery in nulliparas and 87.5% in multiparas, while the corresponding numbers for its negative predictive value (NPV) were 81.4 and 76.9%, respectively. CONCLUSIONS: Cervical assessment in women with symptoms of preterm labor can distinguish those at high risk for preterm delivery. Cervical sonography can be a valuable adjunct to the clinical evaluation of these patients.     

Relationship between interpregnancy interval and cervical length in high-risk women

Objective: Our objective was to evaluate the relationship between the interpregnancy interval (IPI) and next-pregnancy mid-trimester cervical length (CL) in women at high risk for recurrent spontaneous preterm birth (SPTB).

Methods: Retrospective review identified high-risk women, defined as a prior SPTB <36 weeks, who began scheduled serial transvaginal sonographic CL screening at 16–18 weeks gestation between December 2008 and November 2010. All CL assessment ended by 22^6/7 weeks, and weekly 17-α hydroxyprogesterone caproate, 250?mg IM, was recommended to all patients. Details of the prior and current pregnancy were collected, and regression models were used to evaluate the relationship between IPI and CL shortening.

Results: One hundred and eight women with singleton gestations and a qualifying SPTB underwent CL screening. The mean (SD) birth gestational age (GA) of the last pregnancy was 25 (10) weeks, the median IPI was 613 (range 49–6038) days, and the mean (SD) delivery GA in the current pregnancy was 36 (5.3) weeks. Linear regression found no significant relationship between the IPI and the GA of the current birth (p?=?0.98). There was a weak significant relationship between IPI and shortest CL (p?=?0.04). However, after controlling for the GA of the prior pregnancy, this relationship was non-significant (p?=?0.13).

Conclusions: IPI does not predict next birth outcome or next-pregnancy mid-trimester CL in high-risk women managed with progesterone and ultrasound-indicated cerclage.