Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length: the Quadruple P randomised controlled trial (original) (raw)
Related papers
BMC Pregnancy and Childbirth
Background Preterm birth is the leading cause of mortality and disability in newborn and infants. Having a short cervix increases the risk of preterm birth, which can be accessed by a transvaginal ultrasound scan during the second trimester. In women with a short cervix, vaginal progesterone and pessary can both reduce this risk, which progesterone more established than cervical pessary. The aim of this study is to compare the use of vaginal progesterone alone versus the association of progesterone plus pessary to prevent preterm birth in women with a short cervix. Methods This is a pragmatic open-label randomized controlled trial that will take place in 17 health facilities in Brazil. Pregnant women will be screened for a short cervix with a transvaginal ultrasound between 18 0/7 until 22 6/7 weeks of gestational age. Women with a cervical length below or equal to 30 mm will be randomized to the combination of progesterone (200 mg) and pessary or progesterone (200 mg) alone until 3...
BMJ Open
IntroductionVaginal progesterone and a cervical pessary are both interventions that are investigated for the prevention of preterm birth (PTB). Thus far, beneficial or harmful effects of these interventions on long-term child health and development are described, but evidence is not robust enough to draw firm conclusions. With this follow-up study, we intent to investigate if progesterone or a pessary is superior for the prevention of PTB considering the child’s health at 4–6 years of corrected age.Methods and analysisThis study is a follow-up study of the Quadruple-P trial; a multicentre, randomised clinical trial (NL42926.018.13, Eudractnumber 2013-002884-24) which randomises women with an asymptomatic midtrimester short cervix to daily progesterone or a pessary for the prevention of PTB. All children born to mothers who participated in the Quadruple-P study (n=628 singletons and n=332 multiples) will be eligible for follow-up at 4–6 years of corrected age. Children will be assess...
BMC Pregnancy and Childbirth, 2011
Background: Women with a short cervical length in mid-trimester pregnancy have a higher risk of preterm birth and therefore a higher rate of neonatal mortality and morbidity. Progesterone can potentially decrease the number of preterm births and lower neonatal mortality and morbidity. Previous studies showed good results of progesterone in women with either a history of preterm birth or a short cervix. However, it is unknown whether screening for a short cervix and subsequent treatment in mid trimester pregnancy is effective in low risk women. Methods/Design: We plan a combined screen and treat study among women with a singleton pregnancy without a previous preterm birth. In these women, we will measure cervical length at the standard anomaly scan performed between 18 and 22 weeks. Women with cervical length ≤ 30 mm at two independent measurements will be randomly allocated to receive either vaginal progesterone tablets or placebo between 22 and 34 weeks. The primary outcome of this trial is adverse neonatal condition, defined as a composite outcome of neonatal mortality and severe morbidity. Secondary outcomes are time to delivery, preterm birth rate before 32, 34 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We will assess growth, physical condition and neurodevelopmental outcome of the children at two years of age.
Journal of Obstetrics and Gynaecology Research, 2016
Aim: We compared the effectiveness of a combined treatment involving cervical pessary plus vaginal progesterone to vaginal progesterone alone in decreasing the rate of preterm birth in women with short cervix in the second gestational trimester. Methods: This prospective, open-label, randomized clinical trial was conducted on 144 pregnant women with singleton pregnancy who had a cervical length ≤ 25 mm, at 18-22 gestational weeks (GW). Seventythree patients were assigned to receive 400 mg of daily vaginal progesterone (group A), and 73 to receive cervical pessary plus 400 mg of daily vaginal progesterone (group B), until the 37th GW. The patients were then followed until delivery. Results: The rates of preterm birth were 16.4% in group A and 19.7% in group B, which were not statistically different (P = 0.6). There were no statistically significant differences in the rates of preterm birth at <37, <34, <32, and ≤26 GW between participants randomized to each group (P = 0.55). The rates of low-birthweight delivery were 17.8% in group A, and 23.9% in group B, which were not statistically different (P = 0.36). The rates of premature rupture of membranes, chorioamnionitis, the requirement for neonatal intensive care unit admission, and fetal and neonatal deaths were similar between the two groups. Conclusion: In pregnancies with short cervix at mid-pregnancy, combination therapy of cervical pessary plus daily vaginal progesterone does not have any additional benefit over daily vaginal progesterone alone in reducing the rate of preterm birth and adverse pregnancy outcomes.
IMPORTANCE: Spontaneous preterm birth is a major cause of perinatal morbidity and mortality. It is unclear if a cervical pessary can reduce the risk of spontaneous preterm delivery. OBJECTIVE: To test whether in asymptomatic women with singleton pregnancies and no prior spontaneous preterm birth but with short cervical length on transvaginal ultrasound, use of a cervical pessary would reduce the rate of spontaneous preterm birth at less than 34 weeks of gestation. DESIGN, SETTING, AND PARTICIPANTS: Parallel-group, nonblinded, randomized clinical trial conducted from March 1, 2016, to May 25, 2017, at a single center in Italy. Asymptomatic women with singleton gestations, no previous spontaneous preterm births, and cervical lengths of 25 mm or less at 18 weeks 0 days to 23 weeks 6 days of gestation were eligible. INTERVENTIONS: Patients were randomized 1:1 to receive either cervical pessary (n = 150) or no pessary (n = 150). The pessary was removed between 37 weeks 0 days and 37 weeks 6 days of gestation or earlier if clinically indicated. The control group received standard care. For cervical length of 20 mm or shorter, women in both groups were prescribed vaginal progesterone, 200 mg/d, until 36 weeks 6 days of gestation. No bed rest or activity restriction was recommended. MAIN OUTCOMES AND MEASURES: The primary end point was spontaneous preterm birth at less than 34 weeks of gestation. Secondary outcomes were adverse events. RESULTS: Among 300 women who were randomized (mean age, 29 [SD, 6.3] years; mean gestational age, 22 [SD, 1.3] weeks), 100% completed the trial. The primary end point occurred in 11 women (7.3%) in the pessary group and 23 women (15.3%) in the control group (between-group difference, -8.0% [95% CI, -15.7% to -0.4]; relative risk, 0.48 [95% CI, 0.24-0.95]). During follow-up, the pessary group had a higher rate of increased or new vaginal discharge (86.7% vs 46.0%; between-group difference, +40.7% [95% CI, +30.1%-+50.3%]; relative risk, 1.88 [95% CI, 1.57-2.27]). CONCLUSIONS AND RELEVANCE: Among women without prior spontaneous preterm birth who had asymptomatic singleton pregnancies and short transvaginal cervical length, use of a cervical pessary, compared with no pessary use, resulted in a lower rate of spontaneous preterm birth at less than 34 weeks of gestation. The results of this single-center, nonblinded study among selected pregnant women require confirmation in multicenter clinical trials.
Cervical Pessary and Vaginal Progesterone in Twin Pregnancies With a Short Cervix
OBJECTIVE: To evaluate cervical pessary as an intervention to prevent preterm birth in twin pregnancies with a short cervix. METHODS: This was a retrospective cohort study of twin pregnancies managed by a single maternal-fetal medicine practice from 2005 to 2015. We included patients at 28 weeks of gestation or less who were diagnosed with a cervical length less than 20 mm. At the time of diagnosis, all patients were prescribed vaginal progesterone. Starting in 2013, they were also offered pessary placement in addition to vaginal progesterone. We compared outcomes between patients who received a pessary and matched women in a control group in a one-to-three ratio. Women in the control group were matched to women in the case group according to cervical length and gestational age (within 5 mm and 1 week, respectively, of the case patient at the time of pessary placement). We excluded patients with cerclage, monochorionic–monoamniotic placentation, major fetal congenital anomalies discovered before or after birth, patients with twin-twin transfusion syndrome, and patients for whom there were no appropriate controls. Chi-square, Fisher exact, and Student's t tests were used, as appropriate. Regression analysis was performed to control for significant differences at baseline. RESULTS: Twenty-one patients received a cervical pessary, and they were compared with 63 matched women in the control group. As expected (as a result of matching), baseline gestational age (25.7±2.1 compared with 25.9±2.1 weeks of gestation, P=.671) and cervical length (10.9±3.6 mm compared with 11.9±4.5 mm, P=.327) were similar between the groups. Patients with a pessary had a significantly lower incidence of delivery at less than 32 weeks of gestation (1/21 [4.8%] compared with 18/63 [28.6%], adjusted P=.05), longer interval to delivery (65.2±16.8 compared with 52.1±24.3 days, adjusted P=.025), and a lower incidence of severe neonatal morbidity (2/21 [9.5%] compared with 22/63 [34.9%], adjusted P=.04). CONCLUSION: For twin pregnancies with a short cervix, the addition of a cervical pessary to vaginal progesterone is associated with prolonged pregnancy and reduced risk of adverse neonatal outcomes. A large randomized trial should be performed to verify these retrospective findings.
The Lancet, 2012
Background Most previous studies of the use of cervical pessaries were either retrospective or case controlled and their results showed that this intervention might be a preventive strategy for women at risk of preterm birth; no randomised controlled trials have been undertaken. We therefore undertook a randomised, controlled trial to investigate whether the insertion of a cervical pessary in women with a short cervix identifi ed by use of routine transvaginal scanning at 20-23 weeks of gestation reduces the rate of early preterm delivery. Methods The Pesario Cervical para Evitar Prematuridad (PECEP) trial was undertaken in fi ve hospitals in Spain. Pregnant women (aged 18-43 years) with a cervical length of 25 mm or less were randomly assigned according to a computer-generated allocation sequence by use of central telephone in a 1:1 ratio to the cervical pessary or expectant management (without a cervical pessary) group. Because of the nature of the intervention, this study was not masked. The primary outcome was spontaneous delivery before 34 weeks of gestation. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00706264. Findings 385 pregnant women with a short cervix were assigned to the pessary (n=192) and expectant management groups (n=193), and 190 were analysed in each group. Spontaneous delivery before 34 weeks of gestation was signifi cantly less frequent in the pessary group than in the expectant management group (12 [6%] vs 51 [27%], odds ratio 0•18, 95% CI 0•08-0•37; p<0•0001). No serious adverse eff ects associated with the use of a cervical pessary were reported. Interpretation Cervical pessary use could prevent preterm birth in a population of appropriately selected at-risk women previously screened for cervical length assessment at the midtrimester scan.
A blueprint for the prevention of preterm birth: vaginal progesterone in women with a short cervix
Journal of Perinatal Medicine, 2000
Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and is the most important challenge to modern obstetrics. A major obstacle has been that preterm birth is treated (implicitly or explicitly) as a single condition. Two thirds of preterm births occur after the spontaneous onset of labor, and the remaining one third after " indicated " preterm birth; however, the causes of spontaneous preterm labor and " indicated " preterm birth are different. Spontaneous preterm birth is a syndrome caused by multiple etiologies, one of which is a decline in progesterone action, which induces cervical ripening. A sonographic short cervix (identifi ed in the midtrimester) is a powerful predictor of spontaneous preterm delivery. Randomized clinical trials and individual patient meta-analyses have shown that vaginal progesterone reduces the rate of preterm delivery at < 33 weeks of gestation by 44 % , along with the rate of admission to the neonatal intensive care unit, respiratory distress syndrome, requirement for mechanical ventilation, and composite neonatal morbidity/mortality score. There is no evidence that 17-α-hydroxyprogesterone caproate can reduce the rate of preterm delivery in women with a short cervix, and therefore, the compound of choice is natural progesterone (not the synthetic progestin). Routine assessment of the risk of preterm birth with cervical ultrasound coupled with vaginal progesterone for women with a short cervix is cost-effective, and the implementation of such a policy is urgently needed. Vaginal progesterone is as effective as cervical cerclage in reducing the rate of preterm delivery in women with a singleton gestation, history of preterm birth, and a short cervix (< 25 mm).