Pessary Placement in the Prevention of Preterm Birth in Multiple Pregnancies : A Propensity Score Analysis

Preterm birth is the major contributor to perinatal mortality and serious neonatal morbidity, and approximately 30% of all patients admitted to a neonatal intensive care unit in the Netherlands are born from a multiple pregnancy. In asymptomatic women with a multiple pregnancy and short cervix, prophylactic use of a cervical pessary might reduce preterm birth. The aim of this study is to assess the possible treatment effects of pessary use in pregnancy duration and for poor perinatal outcome. This cohort study was performed between December 2012 and September 2014 in 44 hospitals in the Netherlands. Cervical length was measured between 16 and 22 weeks of gestation. When cervical length was below 38 mm, women were offered a cervical pessary. The pessaries were removed at 36 weeks of gestation or in case of premature rupture of the membranes, active vaginal bleeding, other signs of preterm labor, or severe patient discomfort. The course of pregnancy, including perinatal outcome in these women, was compared with the outcome of women from the placebo group of the AMPHIA trial (ISRCTN40512715) (historical cohort). Propensity score matching with replacement was used to create comparable baseline characteristics between both populations. The study included 63 women in the pessary group and 56 women as control subjects. Propensity score matching generated 57 women in the intervention group matched to 57 women (31 unique) in the control group. Gestational age at delivery was comparable between both groups (hazard ratio, 0.96; 95% confidence interval [CI], 0.46–1.46), as well as their delivery rates before 28, 32, and 37 weeks (RR, 0.68 [95% CI, 0.21–2.18]; RR, 0.54 [95% CI, 0.21–1.41]; and RR, 1.22 [95% CI, 0.47–3.15]), respectively. There was no difference in composite perinatal outcome (RR, 1.36 [95% CI, 0.53–3.51]) and perinatal mortality (RR, 0.89 [95% CI, 0.24–3.38]) either. Results of this cohort study with propensity score analysis could not confirm the positive effect of pessary therapy in the prevention of preterm birth in asymptomatic multiple pregnancies with a short cervix in this propensity score analysis. With ongoing studies on this subject, the definite answer whether pessaries are effective in the prevention of preterm birth will come. If effective, evaluation of implementation, similar to this study, is still necessary

Indicators for Cervical Length in Twin Pregnancies

Objective Cervical length (CL) is associated with the risk of preterm birth (PTB) in multiple pregnancies. However, the position of CL within the pathophysiological pathway of PTB is unclear, and it is unknown which factors are predictive for CL. This study aims to investigate whether in twin pregnancies baseline maternal and obstetrical characteristics are potential indicators for CL, to improve insight in the pathophysiological pathway of PTB. Study Design Secondary analysis of data on twin pregnancies and CL measurement between 16 and 22 weeks. A set of 10 potential indicators, known to be associated with an increased risk of PTB and/or which have a plausible mechanism resulting in a change of CL were selected. We used multivariable linear regression with backward selection to identify independent indicators for CL. Results A total of 1,447 women with twin pregnancies were included. Mean CL was 43.7 (+/- 8.9) mm. In multivariable analysis, age (0.27 mm/y; 95% confidence interval [Cl] 0.16 to 0.39), use of assisted reproductive technologies (ART) (-1.42 mm, 95% Cl -2.6 to -0.25), and having delivered at term in a previous pregnancy (1.32 mm, 95% Cl 0.25 to 2.39) were significantly associated with CL. Conclusion This study shows that in twin pregnancies, age, use of ART and having delivered term in a previous pregnancy has an association with CL

A multivariable model to guide the decision for pessary placement to prevent preterm birth in women with a multiple pregnancy : a secondary analysis of the ProTWIN trial

OBJECTIVE: The ProTWIN Trial (NTR1858) showed that in women with a multiple pregnancy and a cervical length less than the 25(th) percentile (38mm), prophylactic use of a cervical pessary reduced the risk of adverse perinatal outcome. We investigated whether other maternal or pregnancy characteristics collected at baseline can improve identification of women with the most probable benefit from pessary placement. METHODS: ProTWIN is a multicenter randomized trial in which 808 women with a multiple pregnancy were assigned to pessary or control. Using this data we developed a multivariable logistic model comprising treatment, cervical length, chorionicity, pregnancy history and number of fetuses and the interaction of these variables with treatment as predictors of adverse perinatal outcome. RESULTS: Short cervix, monochorionicity and nulliparity were predictive factors for a benefit from pessary insertion. History of previous preterm birth and triplet pregnancy were predictive factors of possible harm from pessary. The model identified 35% of women as benefiting (95% CI: 32% to 39%), which is 10% more than using cervical length only (25%) for pessary decisions. The model had acceptable calibration. We estimated that using the model to guide the choice of pessary would reduce the risk of adverse perinatal outcomes significantly from 13.5% when no pessary is inserted to 8.1% (absolute risk reduction 5.4%, 95% CI: 2.1% to 8.6%). CONCLUSIONS: We developed and internally validated a multivariable treatment selection rule, with cervical length, chorionicity, pregnancy history and number of fetuses. If externally validated, it can be used to identify women with a twin pregnancy who benefit from a pessary, and therefore a reduction in adverse perinatal outcomes in twin pregnancies can be anticipated

Pessary or Progesterone to Prevent Preterm delivery in women with short cervical length : the Quadruple P randomised controlled trial

BACKGROUND: Preterm birth is in quantity and in severity the most important topic in obstetric care in the developed world. Progestogens and cervical pessaries have been studied as potential preventive treatments with conflicting results. So far, no study has compared both treatments. METHODS/DESIGN: The Quadruple P study aims to compare the efficacy of vaginal progesterone and cervical pessary in the prevention of adverse perinatal outcome associated with preterm birth in asymptomatic women with a short cervix, in singleton and multiple pregnancies separately. It is a nationwide open-label multicentre randomized clinical trial (RCT) with a superiority design and will be accompanied by an economic analysis. Pregnant women undergoing the routine anomaly scan will be offered cervical length measurement between 18 and 22 weeks in a singleton and at 16-22 weeks in a multiple pregnancy. Women with a short cervix, defined as less than, or equal to 35 mm in a singleton and less than 38 mm in a multiple pregnancy, will be invited to participate in the study. Eligible women will be randomly allocated to receive either progesterone or a cervical pessary. Following randomization, the silicone cervical pessary will be placed during vaginal examination or 200 mg progesterone capsules will be daily self-administered vaginally. Both interventions will be continued until 36 weeks gestation or until delivery, whichever comes first. Primary outcome will be composite adverse perinatal outcome of perinatal mortality and perinatal morbidity including bronchopulmonary dysplasia, intraventricular haemorrhage grade III and IV, periventricular leukomalacia higher than grade I, necrotizing enterocolitis higher than stage I, Retinopathy of prematurity (ROP) or culture proven sepsis. These outcomes will be measured up until 10 weeks after the expected due date. Secondary outcomes will be, among others, time to delivery, preterm birth rate before 28, 32, 34 and 37 weeks, admission to neonatal intensive care unit, maternal morbidity, maternal admission days for threatened preterm labour and costs. DISCUSSION: This trial will provide evidence on whether vaginal progesterone or a cervical pessary is more effective in decreasing adverse perinatal outcome in both singletons and multiples. TRIAL REGISTRATION: Trial registration number: NTR 4414 . Date of registration January 29th 2014

Continuous glucose monitoring during diabetic pregnancy (GlucoMOMS): A multicentre randomized controlled trial

Aim: Diabetes is associated with a high risk of adverse pregnancy outcomes. Optimal glycaemic control is fundamental and is traditionally monitored with self-measured glucose profiles and periodic HbA1c measurements. We investigated the effectiveness of additional use of retrospective continuous glucose monitoring (CGM) in diabetic pregnancies. Material and methods: We performed a nationwide multicentre, open label, randomized, controlled trial to study pregnant women with type 1 or type 2 diabetes who were undergoing insulin therapy at gestational age < 16 weeks, or women who were undergoing insulin treatment for gestational diabetes at gestational age < 30 weeks. Women were randomly allocated (1:1) to intermittent use of retrospective CGM or to standard treatment. Glycaemic control was assessed by CGM for 5-7 days every 6 weeks in the CGM group, while self-monitoring of blood glucose and HbA1c measurements were applied in both groups. Primary outcome was macrosomia, defined as birth weight above the 90th percentile. Secondary outcomes were glycaemic control and maternal and neonatal complications. Results: Between July 2011 and September 2015, we randomized 300 pregnant women with type 1 (n = 109), type 2 (n = 82) or with gestational (n = 109) diabetes to either CGM (n = 147) or standard treatment (n = 153). The incidence of macrosomia was 31.0% in the CGM group and 28.4% in the standard treatment group (relative risk [RR], 1.06; 95% CI, 0.83-1.37). HbA1c levels were similar between treatment groups. Conclusions: In diabetic pregnancy, use of intermittent retrospective CGM did not reduce the risk of macrosomia. CGM provides detailed information concerning glycaemic fluctuations but, as a treatment strategy, does not translate into improved pregnancy outcome

A multi-centre, non-inferiority, randomised controlled trial to compare a cervical pessary with a cervical cerclage in the prevention of preterm delivery in women with short cervical length and a history of preterm birth - PC study

Background Preterm birth is in quantity and in severity the most important contributor of perinatal morbidity and mortality both in well- and low-resource countries. Cervical pessary and cervical cerclage are both considered as preventive treatments in women at risk for preterm birth. We aim to evaluate whether a cervical pessary can replace cervical cerclage for preventing recurrent preterm birth in women with a prior preterm birth due to cervical insufficiency or in women with a prior preterm birth and a short cervix in the current pregnancy. Methods/design A nationwide open-label multicentre randomised clinical trial will be set up to study women with a singleton pregnancy and a prior preterm birth before 34 weeks of gestation. Women are eligible in case of previous preterm birth based on cervical insufficiency (primary intervention, <16 weeks) or in case of previous preterm birth and a short cervical length in current pregnancy ≤25 mm (secondary intervention, <24 weeks). Eligible women will be randomised to either cervical pessary or cervical cerclage. Both interventions will be removed at labour or at 36 weeks of gestational age, whatever comes first. The primary outcome will be delivery before 32 weeks. Secondary outcomes will be gestational age at birth, preterm birth rate before 24, 28, 34 and 37 weeks of gestation (overall and stratified by spontaneous or indicated delivery), premature rupture of membranes, use of tocolysis and/or corticosteroids during pregnancy, mode of delivery, maternal infections, maternal side effects, neonatal and maternal hospital admissions, and a composite of adverse perinatal outcomes including both morbidity and mortality. We assume an event rate of 20% preterm birth before 32 weeks for cerclage and use a non-inferiority margin of 10% for the cervical pessary. Using an alpha of 0.05 and power of 0.80 we need 2 groups of 200 women each. Discussion The outcome of this study will indicate the effectiveness and the cost-effectiveness of a cervical cerclage and of a cervical pessary