Effectiveness of a cervical pessary for women who did not deliver 48 h after threatened preterm labor (Assessment of perinatal outcome after specific treatment in early labor: Apostel VI trial)

Background: Preterm birth is a major cause of neonatal mortality and morbidity. As preventive strategies are largely ineffective, threatened preterm labor is a frequent problem that affects approximately 10 % of pregnancies. In recent years, risk assessment in these women has incorporated cervical length measurement and fetal fibronectin testing, and this has improved the capacity to identify women at increased risk for delivery within 14 days. Despite these improvements, risk for preterm birth continues to be increased in women who did not deliver after an episode of threatened preterm labor, as indicated by a preterm birth rate between 30 to 60 % in this group of women. Currently no effective treatment is available. Studies on maintenance tocolysis and progesterone have shown ambiguous results. The pessary has not been evaluated in women with threatened preterm labor, however studies in asymptomatic women with a short cervix show reduced rates of preterm birth rates as well as perinatal complications. The APOSTEL VI trial aims to assess the effectiveness of a cervical pessary in women who did not deliver within 48 h after an episode of threatened preterm labor. Methods/Design: This is a nationwide multicenter open-label randomized clinical trial. Women with a singleton or twin gestation with intact membranes, who were admitted for threatened preterm labor, at a gestational age between 24 and 34 weeks, a cervical length between 15 and 30 mm and a positive fibronectin test or a cervical length below 15 mm, who did not deliver after 48 h will be eligible for inclusion. Women will be allocated to a pessary or no intervention (usual care). Primary outcome is preterm delivery <37 weeks. Secondary outcomes are amongst others a composite of perinatal morbidity and mortality. Sample size is based on an expected 50 % reduction of preterm birth before 37 weeks (two-sided test, a 0.05 and beta 0.2). Two hundred women with a singleton pregnancy need to be randomized. Analysis will be done by intention to treat. Discussion: The APOSTEL VI trial will provide evidence whether a pessary is effective in preventing preterm birth in women who did not deliver 48 h after admission for threatened pretermlabor and who remain at high risk for preterm birth

Severe metabolic ketoacidosis as a primary manifestation of SARS-CoV-2 infection in non-diabetic pregnancy

We present a case of a metabolic acidosis in a term-pregnant woman with SARS-CoV-2 infection. Our patient presented with dyspnoea, tachypnoea, thoracic pain and a 2-day history of vomiting, initially attributed to COVID-19 pneumonia. Differential diagnosis was expanded when arterial blood gas showed a high anion gap metabolic non-lactate acidosis without hypoxaemia. Most likely, the hypermetabolic state of pregnancy, in combination with maternal starvation and increased metabolic demand due to infection, had resulted in metabolic ketoacidosis. Despite supportive treatment and rapid induction of labour, maternal deterioration and fetal distress during labour necessitated an emergency caesarean section. The patient delivered a healthy neonate. Postpartum, after initial improvement in metabolic acidosis, viral and bacterial pneumonia with subsequent significant respiratory compromise were successfully managed with oxygen supplementation and corticosteroids. This case illustrates how the metabolic demands of pregnancy can result in an uncommon presentation of COVID-19

Progestogen maintenance therapy for prolongation of pregnancy after an episode of preterm labour: A systematic review and meta-analysis

Background: Evidence for progestogen maintenance therapy after an episode of preterm labour (PTL) is contradictory. Objectives: To assess effectiveness of progestogen maintenance therapy after an episode of PTL. Search Strategy: An electronic search in Central Cochrane, Ovid Embase, Ovid Medline and clinical trial databases was performed. Selection Criteria: Randomised controlled trials (RCT) investigating women between 16+0 and 37+0 weeks of gestation with an episode of PTL who were treated with progestogen maintenance therapy compared with a control group. Data Collection and Analysis: Systematic review and meta-analysis were conducted. The primary outcome was latency time in days. Secondary neonatal and maternal outcomes are consistent with the core outcome set for preterm birth studies. Studies were extensively assessed for data trustworthiness (integrity) and risk of bias. Main Results: Thirteen RCT (1722 women) were included. Progestogen maintenance therapy demonstrated a longer latency time of 4.32 days compared with controls (mean difference [MD] 4.32, 95% CI 0.40–8.24) and neonates were born with a higher birthweight (MD 124.25 g, 95% CI 8.99–239.51). No differences were found for other perinatal outcomes. However, when analysing studies with low risk of bias only (five RCT, 591 women), a significantly longer latency time could not be shown (MD 2.44 days; 95% CI −4.55 to 9.42). Conclusions: Progestogen maintenance therapy after PTL might have a modest effect on prolongation of latency time. When analysing low risk of bias studies only, this effect was not demonstrated. Validation through further research, preferably by an individual patient data meta-analysis is highly recommended

Cervical Pessary After Arrested Preterm Labor : A Randomized Controlled Trial

OBJECTIVE: To assess the effectiveness of cervical pessary in reducing the rate of preterm birth in women at high risk for preterm birth who did not deliver after an episode of threatened preterm labor. METHODS: In a multicenter open-label randomized controlled trial, a cervical pessary was compared with no intervention (control group) (one-to-one ratio). Women between 24 and 34 weeks of gestation at high risk for preterm birth based on a short cervical length (less than 15 mm) or an intermediate cervical length (between 15 and 30 mm) with a positive fetal fibronectin test who did not deliver after an episode of threatened preterm labor were eligible. The primary outcome was birth before 37 weeks of gestation. Secondary outcomes were a composite adverse neonatal outcome, preterm birth before 34 and 32 weeks of gestation, and side effects. A total sample size of 200 women carrying singletons was planned so as to have adequate statistical power to detect a reduction in the rate of preterm birth from 40% to 20%. Women with twin gestations were also enrolled but were considered only in secondary analyses. After a planned interim analysis, the trial was stopped for futility. RESULTS: From November 2013 through September 2016, 130 women with a singleton pregnancy (65 pessary, 65 no treatment) were recruited. The groups had comparable baseline characteristics. In the cervical pessary group, 31 (48%) women delivered before 37 weeks of gestation compared with 25 (39%) in the no-treatment group (relative risk 1.2, 95% CI 0.83-1.8). Nine (15%) children in the cervical pessary group had the composite adverse perinatal outcome compared with eight (13%) in the control group (relative risk 1.2, 95% CI 0.49-2.9). CONCLUSION: In women at high risk for preterm birth who did not deliver after an episode of threatened preterm labor, treatment with a cervical pessary is not effective. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register, NTR4210

Three-dimensional saline infusion sonography compared to two-dimensional saline infusion sonography for the diagnosis of focal intracavitary lesions

Background Focal abnormalities most commonly acquired within the uterine cavity include endometrial polyps (arising from the endometrium) and submucous fibroids (arising from the myometrium). These benign abnormalities can cause several problems, including abnormal uterine bleeding (AUB) and subfertility. Two-dimensional saline infusion sonography (2D SIS) is a minimally invasive test that can be used to diagnose these pathologies, but it is less accurate than hysteroscopy, which is a more invasive procedure by which an endoscope allows direct visualisation of the uterine cavity. Three-dimensional (3D) SIS appears to enhance sonographic visualisation within the uterine cavity, thereby offering a potentially more accurate minimally invasive diagnostic test. Objectives Primary objectives To evaluate the diagnostic accuracy of 3D SIS (index test 1) compared with 2D SIS for the diagnosis of focally growing lesions (presence or not) in women with AUB or subfertility, with hysteroscopy performed as the reference test. To evaluate the diagnostic accuracy of 2D+3D SIS (index test 2) compared with 2D SIS for the diagnosis of focally growing lesions (presence or not) in women with AUB or subfertility, with hysteroscopy performed as the reference test. In this case, any abnormality on either modality was regarded as a positive result ('OR' approach). Secondary objectives To evaluate the diagnostic accuracy of 3DSIS (index test 1) compared with 2D SIS according to type of abnormality and discrimination between uterine polyps and submucous fibroids in women with AUB or subfertility, with hysteroscopy and histology used as the reference. To evaluate the diagnostic accuracy of 2D+3D SIS (index test 2) compared with 2D SIS according to type of abnormality and discrimination between uterine polyps and submucous fibroids in women with AUB or subfertility, with hysteroscopy and histology used as the reference. Search methods We searched the following databases: Cochrane Central Register of Studies Online (CENTRAL CRSO), MEDLINE, Embase, PubMed, Cochrane Gynaecology and Fertility Group (CGF) Specialised Register and CGFG Diagnostic Test Accuracy (DTA) Specialised Register, clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). Screening reference lists of appropriate studies was also performed. We screened for eligibility all studies identified from inception until March 2016. We performed searches with no date or language restrictions. Selection criteria The population of interest consisted of premenopausal women with AUB or subfertility and postmenopausal women with AUB. Diagnostic test accuracy studies, randomised controlled trials (RCTs) and prospective cohort studies were eligible for inclusion if they evaluated the accuracy of both 2D SIS and 3D SIS for the diagnosis of acquired intracavitary abnormalities with hysteroscopy used as the reference standard. In light of the lack of data for 3D SIS, we also included studies that evaluated the accuracy of 3D SIS alone. Data collection and analysis Two review authors read all potentially eligible references after performing a first screening by title and abstract (LLN and FJRH). They independently extracted data to construct 2x2 tables from eligible studies and assessed studies for methodological quality using the QUADAS-2 tool (revised tool for quality assessment of diagnostic accuracy studies). To describe and visually present results, we produced in RevMan forest plots showing pairs of sensitivity and specificity together with 95% confidence intervals from each study, as well as raw receiver operating characteristic (ROC) plots. We displayed paired analyses in an ROC plot by linking sensitivity-specificity pairs from each study by using a dashed line. To compare 3D SIS versus 2D SIS, we restricted analyses to studies that provided 2x2 tables for both tests and used the bivariate meta-analysis of sensitivity and specificity. Main results Thirteen studies (1053 women) reported the accuracy of 3D SIS for focal uterine abnormalities; 11 of these (846 women) were suitable for meta-analysis, and eight reported accuracy according to the type of focal abnormality. The design of the included studies seems applicable. The main problem involving the quality of included studies is insufficient reporting of study methods, resulting in unclear risk of bias for several of the quality domains assessed. Therefore, we considered the overall quality of the evidence as low. The summary estimate (11 studies reporting absence or presence of abnormality at 3D SIS) for sensitivity was 94.5% (95% confidence interval (CI) 90.6% to 96.9%) and for specificity 99.4%(95% CI 96.2% to 99.9%). Meta-analysis of the eight studies (N = 716) directly comparing 2D SIS versus 3D SIS showed summary sensitivity of 96.9% (95% CI 91.9% to 98.8%) and summary specificity of 99.5% (95% CI 96.1% to 100%) for 3D SIS. For 2D SIS, summary sensitivity was 90.9% (95% CI 81.2% to 95.8%) and summary specificity was 96.3% (95% CI 86.1% to 99.1%). The difference in accuracy between 2D SIS and 3D SIS was non-significant (P values of 0.07 for sensitivity and 0.10 for specificity). Authors' conclusions Low-quality evidence suggests that 3D SIS may be very accurate in detecting intracavitary abnormalities. Meta-analysis revealed no statistically significant differences between 2D SIS and 3D SIS. Summary sensitivity and summary specificity are higher for 3D SIS, but margins of improvement are limited because 2D SIS is already very accurate. When the technology and appropriate expertise are available, 3D SIS offers an alternative to 2D SIS. Both 2D SIS and 3D SIS should be considered alternatives to diagnostic hysteroscopy when intracavitary pathology is suspected in subfertile women and in those with abnormal uterine bleedin

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