Dataset Information

Effectiveness of cervical pessary compared to cervical cerclage with or without vaginal progesterone for the prevention of preterm birth in women with twin pregnancies and a short cervix: study protocol for a two-by-two factorial randomised clinical trial.

ABSTRACT:

Introduction

Women with twin pregnancies and a short cervix are at increased risk for preterm birth (PTB). Given the burden of prematurity and its attendant risks, the quest for effective interventions in twins has been an area of considerable research. Studies investigating the effectiveness of cervical cerclage, cervical pessary and vaginal progesterone in preventing PTB have yielded conflicting results. The aim of this study is to compare the effectiveness of cervical pessary and cervical cerclage with or without vaginal progesterone to prevent PTB in women with twin pregnancies and a cervical length (CL) ≤ 28 mm.

Methods and analysis

This multicentre, randomised clinical trial will be conducted at My Duc Hospital and My Duc Phu Nhuan Hospital, Vietnam. Asymptomatic women with twin pregnancies and a CL ≤28 mm, measured at 16-22 weeks' gestation, will be randomised in a 1:1:1:1 ratio to receive a cerclage, pessary, cerclage plus progesterone or pessary plus progesterone. Primary outcome will be PTB <34 weeks. Secondary outcomes will be maternal and neonatal complications. We preplanned a subgroup analysis according to CL from all women after randomisation and divided into four quartiles. Analysis will be conducted on an intention-to-treat basis. The rate of PTB <34 weeks' gestation in women with twin pregnancies and a cervix ≤28 mm and treated with pessary in our previous study at My Duc Hospital was 24.2%. A sample size of 340 women will be required to show or refute that cervical cerclage decreases the rate of PTB <34 weeks by 50% compared with pessary (from 24.2% to 12.1%, α level 0.05, power 80%, 5% lost to follow-up and protocol deviation). This study is not to be powered to assess interactions between interventions.

Ethics and dissemination

Ethical approval was obtained from the Institutional Ethics Committee of My Duc Hospital and informed patient consent was obtained before study enrolment. Results of the study will be submitted for publication in a peer-reviewed journal.

Trial registration number

NCT03863613 (date of registration: 4 March 2019).

SUBMITTER: Dang VQ

PROVIDER: S-EPMC7304826 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Effectiveness of cervical pessary compared to cervical cerclage with or without vaginal progesterone for the prevention of preterm birth in women with twin pregnancies and a short cervix: study protocol for a two-by-two factorial randomised clinical trial.

Dang Vinh Q VQ He Yen Tn YT Pham Ha Nh HN Trieu Tuyen Tt TT Bui Trung Q TQ Vuong Nhu T NT Nguyen Loc Mt LM Nguyen Diem Tn DT Le Thanh V TV Li Wentao W Le Cam H CH Mol Ben W BW Vuong Lan N LN

BMJ open 20200616 6

<h4>Introduction</h4>Women with twin pregnancies and a short cervix are at increased risk for preterm birth (PTB). Given the burden of prematurity and its attendant risks, the quest for effective interventions in twins has been an area of considerable research. Studies investigating the effectiveness of cervical cerclage, cervical pessary and vaginal progesterone in preventing PTB have yielded conflicting results. The aim of this study is to compare the effectiveness of cervical pessary and cerv ...[more]

PMID: 32554744

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Project description:IntroductionPreterm birth is the most common cause of neonatal morbidity and mortality. Women with twin pregnancies and a short cervical length are at high risk for preterm birth. Vaginal progesterone and cervical pessary have been proposed as potential strategies to reduce preterm birth in this high-risk population. Therefore, we aimed to compare the effectiveness of cervical pessary and vaginal progesterone in improving developmental outcomes of children born to women with twin pregnancies and mid-trimester short cervical length.Material and methodsThis was a follow-up study (NCT04295187) of all children at 24 months of age, born from women treated with cervical pessary or progesterone to prevent preterm birth in a randomized controlled trial (NCT02623881). We used a validated Vietnamese version of Ages & Stages Third Edition Questionnaires (ASQ-3) and a red flag questionnaire. In surviving children, we compared the mean ASQ-3 scores, abnormal ASQ-3 scores, the number of children with any abnormal ASQ-3 scores and red flag signs between the two groups. We reported the composite outcome of perinatal death or survival with any abnormal ASQ-3 score in offspring. These outcomes were also calculated in a subgroup of women with a cervical length ≤28 mm (<25th percentile).ResultsIn the original randomized controlled trial, we randomized 300 women to pessary or progesterone. After counting the number of perinatal deaths and lost to follow-up, 82.8% parents in the pessary group and 82.5% parents in progesterone group returned the questionnaire. The mean ASQ-3 scores of the five skills and red flag signs did not differ significantly between the two groups. However, the percentage of children having abnormal ASQ-3 scores in fine motor skills was significantly lower in the progesterone group (6.1% vs 1.3%, P = 0.01). There were no significant differences in the composite outcome of perinatal death or survival with any abnormal ASQ-3 score in unselected women and in those with cervical length ≤28 mm.ConclusionsCervical pessary and vaginal progesterone may have comparable effects on developmental outcomes in children at ≥24 months of age, born to women with twin pregnancies and short cervical length. However, this finding could be likely due to a lack of study power.

Project description:BackgroundClinically, once a woman has been identified as being at risk of spontaneous preterm birth (sPTB) due to a short cervical length, a decision regarding prophylactic treatment must be made. Three interventions have the potential to improve outcomes: cervical cerclage (stitch), vaginal progesterone and cervical pessary. Each has been shown to have similar benefit in reduction of sPTB, but there have been no randomised control trials (RCTs) to compare them.MethodsThis open label multi-centre UK RCT trial, will evaluate whether the three interventions are equally efficacious to prevent premature birth in women who develop a short cervix (<25 mm on transvaginal ultrasound). Participants will be asymptomatic and between 14+0 and 23+6 weeks' gestation in singleton pregnancies. Eligible women will be randomised to cervical cerclage, Arabin pessary or vaginal progesterone (200 mg once daily) (n = 170 women per group). The obstetric endpoints are premature birth rate <37 weeks' of gestation (primary), 34 weeks and 30 weeks (secondary outcomes) and short-term neonatal outcomes (a composite of death and major morbidity). It will also explore whether intervention success can be predicted by pre-intervention biomarker status.DiscussionPreterm birth is the leading cause of perinatal morbidity and mortality and a short cervix is a useful way of identifying those most at risk. However, best management of these women has presented a clinical conundrum for decades. Given the promise offered by cerclage, Arabin pessary and vaginal progesterone for prevention of preterm birth in individual trials, direct comparison of these prophylactic interventions is now essential to establish whether one treatment is superior. If, as we hypothesise, the three interventions are equally efficacious, this study will empower women to make a choice of treatments based on personal preference and quality of life issues also explored by the study. Our exploratory analysis into whether the response to intervention is related to the pre-intervention biomarker status further our understanding of the pathophysiology of spontaneous preterm birth and help focus future research questions.Trial registrationEudraCT Number: 2015-000456-15 . Registered 11th March 2015.

Project description:BackgroundPreterm birth is the leading cause of childhood mortality and morbidity. We aimed to provide a comprehensive systematic review on randomized controlled trials (RCTs) on progesterone, cerclage, pessary, and acetylsalicylic acid (ASA) to prevent preterm birth in asymptomatic women with singleton pregnancies defined as risk of preterm birth and multifetal pregnancies.MethodsSix databases (including PubMed, Embase, Medline, the Cochrane Library) were searched up to February 2022. RCTs published in English or Scandinavian languages were included through a consensus process. Abstracts and duplicates were excluded. The trials were critically appraised by pairs of reviewers. The Cochrane risk-of-bias tool was used for risk of bias assessment. Predefined outcomes including preterm birth, perinatal/neonatal/maternal mortality and morbidity, were pooled in meta-analyses using RevMan 5.4, stratified for high and low risk of bias trials. The certainty of evidence was assessed using the GRADE approach. The systematic review followed the PRISMA guideline.ResultsThe search identified 2,309 articles, of which 87 were included in the assessment: 71 original RCTs and 16 secondary publications with 23,886 women and 32,893 offspring. Conclusions were based solely on trials with low risk of bias (n = 50).Singleton pregnancies: Progesterone compared with placebo, reduced the risk of preterm birth <37 gestational weeks: 26.8% vs. 30.2% (Risk Ratio [RR] 0.82 [95% Confidence Interval [CI] 0.71 to 0.95]) (high certainty of evidence, 14 trials) thereby reducing neonatal mortality and respiratory distress syndrome. Cerclage probably reduced the risk of preterm birth <37 gestational weeks: 29.0% vs. 37.6% (RR 0.78 [95% CI 0.69 to 0.88]) (moderate certainty of evidence, four open trials). In addition, perinatal mortality may be reduced by cerclage. Pessary did not demonstrate any overall effect. ASA did not affect any outcome, but evidence was based on one underpowered study.Multifetal pregnancies: The effect of progesterone, cerclage, or pessary was minimal, if any. No study supported improved long-term outcome of the children.ConclusionProgesterone and probably also cerclage have a protective effect against preterm birth in asymptomatic women with a singleton pregnancy at risk of preterm birth. Further trials of ASA are needed. Prevention of preterm birth requires screening programs to identify women at risk of preterm birth.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021234946].

Project description:ObjectiveTo investigate whether the classification of a previous spontaneous preterm birth (sPTB) as preterm labor (PTL) with intact membranes (IM) or as preterm prelabor rupture of membranes (PPROM) impacts the efficacy of cervical pessary or vaginal progesterone for prevention of sPTB in pregnant women with short cervix on transvaginal ultrasound.MethodsThis was a retrospective cohort study of asymptomatic high-risk singleton pregnancies with a short cervix and history of sPTB, treated using Arabin pessary or vaginal progesterone for primary PTB prevention, conducted at four European hospitals. A log-rank test on Kaplan-Meier curves was used to assess the difference in performance of pessary and progesterone, according to history of PTL-IM or PPROM. Linear regression analysis was used to evaluate significant predictors of gestational age at delivery.ResultsBetween 2008 and 2015, 170 women were treated with a pessary and 88 with vaginal progesterone. In women treated with a pessary, rate of sPTB < 34 weeks was 16% in those with a history of PTL-IM and 55% in those with a history of PPROM. In women treated with progesterone, rate of sPTB < 34 weeks was 13% in those with a history of PTL-IM and 21% in those with a history of PPROM. Treatment with a pessary resulted in earlier delivery in women with previous PPROM than in any other subgroup (P < 0.0001). Linear regression analysis showed a clear effect of PPROM history (P < 0.0001), combination of PPROM history and treatment (P = 0.0003) and cervical length (P = 0.0004) on gestational age at birth.ConclusionsCervical pessary may be a less efficacious treatment option for women with previous PPROM; however, these results require prospective validation before change in practice is recommended. Phenotype of previous preterm birth may be an important risk predictor and treatment effect modifier; this information should be reported in future clinical trials. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Project description:IntroductionOur objective was to compare the vaginal microbiome in low-risk and high-risk pregnant women and to explore a potential association between vaginal microbiome and preterm birth.Material and methodsA pilot, consecutive, longitudinal, multicenter study was conducted in pregnant women at 18-22 weeks of gestation. Participants were assigned to one of three groups: control (normal cervix), pessary (cervical length ≤25 mm) and cerclage (cervical length ≤25 mm or history of preterm birth). Analysis and comparison of vaginal microbiota as a primary outcome was performed at inclusion and at 30 weeks of gestation, along with a follow-up of pregnancy and perinatal outcomes. We assessed the vaginal microbiome of pregnant women presenting a short cervix with that of pregnant women having a normal cervix, and compared the vaginal microbiome of women with a short cervix before and after placement of a cervical pessary or a cervical cerclage.ResultsThe microbiome of our control cohort was dominated by Lactobacillus crispatus and inners. Five community state types were identified and microbiome diversity did not change significantly over 10 weeks in controls. On the other hand, a short cervix was associated with a lower microbial load and higher microbial richness, and was not correlated with Lactobacillus relative abundance. After intervention, the cerclage group (n = 19) had a significant increase in microbial richness and a shift towards community state types driven by various bacterial species, including Lactobacillus mulieris, unidentified Bifidobacterium or Enterococcus. These changes were not significantly observed in the pessary (n = 26) and control (n = 35) groups. The cerclage group had more threatened preterm labor episodes and poorer outcomes than the control and pessary groups.ConclusionsThese findings indicate that a short cervix is associated with an altered vaginal microbiome community structure. The use of a cerclage for preterm birth prevention, as compared with a pessary, was associated with a microbial community harboring a relatively low abundance of Lactobacillus, with more threatened preterm labor episodes, and with poorer clinical outcomes.

Project description:BackgroundThe optimal approach to prevent preterm birth (PTB) in twins has not been fully established yet. Recent evidence suggests that placement of cervical cerclage in twin pregnancies with short cervical length at ultrasound or cervical dilatation at physical examination might be associated with a reduced risk of PTB. However, such evidence is based mainly on small studies thus questioning the robustness of these findings. The aim of this systematic review was to determine the role of cervical cerclage in preventing PTB and adverse maternal or perinatal outcomes in twin pregnancies.Methods and findingsKey databases searched and date of last search: MEDLINE, Embase, and CINAHL were searched electronically on 20 April 2023. Eligibility criteria: Inclusion criteria were observational studies assessing the risk of PTB among twin pregnancies undergoing cerclage versus no cerclage and randomized trials in which twin pregnancies were allocated to cerclage for the prevention of PTB or to a control group (e.g., placebo or treatment as usual). The primary outcome was PTB <34 weeks of gestation. The secondary outcomes were PTB <37, 32, 28, 24 weeks of gestation, gestational age at birth, the interval between diagnosis and birth, preterm prelabor rupture of the membranes (pPROM), chorioamnionitis, perinatal loss, and perinatal morbidity. Subgroup analyses according to the indication for cerclage (short cervical length or cervical dilatation) were also performed. Risk of bias assessment: The risk of bias of the included randomized controlled trials (RCTs) was assessed using the Revised Cochrane risk-of-bias tool for randomized trials, while that of the observational studies using the Newcastle-Ottawa scale (NOS). Statistical analysis: Summary risk ratios (RRs) of the likelihood of detecting each categorical outcome in exposed versus unexposed women, and (b) summary mean differences (MDs) between exposed and unexposed women (for each continuous outcome), with their 95% confidence intervals (CIs) were computed using head-to-head meta-analyses. Synthesis of the results: Eighteen studies (1,465 twin pregnancies) were included. Placement of cervical cerclage in women with a twin pregnancy with a short cervix at ultrasound or cervical dilatation at physical examination was associated with a reduced risk of PTB <34 weeks of gestation (RR: 0.73, 95% CI [0.59, 0.91], p = 0.005 corresponding to a 16% difference in the absolute risk, AR), <32 (RR: 0.69, 95% CI [0.57, 0.84], p < 0.001; AR: 16.92%), <28 (RR: 0.54, 95% [CI 0.43, 0.67], 0.001; AR: 18.29%), and <24 (RR: 0.48, 95% CI [0.23, 0.97], p = 0.04; AR: 15.57%) weeks of gestation and a prolonged gestational age at birth (MD: 2.32 weeks, 95% [CI 0.99, 3.66], p < 0.001). Cerclage in twin pregnancy with short cervical length or cervical dilatation was also associated with a reduced risk of perinatal loss (RR: 0.38, 95% CI [0.25, 0.60], p < 0.001; AR: 19.62%) and composite adverse outcome (RR: 0.69, 95% CI [0.53, 0.90], p = 0.007; AR: 11.75%). Cervical cerclage was associated with a reduced risk of PTB <34 weeks both in women with cervical length <15 mm (RR: 0.74, 95% CI [0.58, 0.95], p = 0.02; AR: 29.17%) and in those with cervical dilatation (RR: 0.68, 95% CI [0.57, 0.80], p < 0.001; AR: 35.02%). The association between cerclage and prevention of PTB and adverse perinatal outcomes was exclusively due to the inclusion of observational studies. The quality of retrieved evidence at GRADE assessment was low.ConclusionsEmergency cerclage for cervical dilation or short cervical length <15 mm may be potentially associated with a reduction in PTB and improved perinatal outcomes. However, these findings are mainly based upon observational studies and require confirmation in large and adequately powered RCTs.

Dataset Information

Effectiveness of cervical pessary compared to cervical cerclage with or without vaginal progesterone for the prevention of preterm birth in women with twin pregnancies and a short cervix: study protocol for a two-by-two factorial randomised clinical trial.

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Publications

Effectiveness of cervical pessary compared to cervical cerclage with or without vaginal progesterone for the prevention of preterm birth in women with twin pregnancies and a short cervix: study protocol for a two-by-two factorial randomised clinical trial.

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