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Maud D van Zijl,1 Bouchra Koullali,1 Ben WJ Mol,2 Eva Pajkrt,1 Martijn A Oudijk1 1Department of Obstetrics and Gynaecology, Academic Medical Center, Amsterdam, the Netherlands; 2The Robinson Research Institute, School for Reproductive Health and Pediatrics, University of Adelaide, Adelaide, SA, Australia Abstract: Preterm birth (PTB), defined as delivery at

Background: Progesterone is widely used in prenatal care. However, long‐term effects of prenatal progesterone treatment on child development are unclear. Objectives: To evaluate long‐term outcomes in children after prenatal progesterone treatment. Search strategy: MEDLINE, Embase and Cochrane Central Register of Controlled Trials from inception to 24 May 2020. Selection criteria: Randomised controlled trials (RCTs) reporting outcomes in children born to women who received progesterone treatment (compared with placebo or another intervention) during any trimester in pregnancy. Data collection and analysis: Two authors independently selected and extracted data. We used the Cochrane Risk of Bias tool for randomised trials and Quality In Prognosis Studies. Main results: Of 388 papers, we included seven articles based on five RCTs, comprising 4222 measurements of children aged 6 months to 8 years. All studies compared progesterone to placebo in second and/or third trimester for the prevention of preterm birth. Meta‐analysis (two studies, n = 890 children) showed no difference in neurodevelopment as assessed by the Bayley‐III Cognitive Composite score at 2 years between children exposed to progesterone versus placebo (Standardised Mean Difference −0.04, 95% Confidence Interval −0.26 to 0.19), I2 = 22%. Heterogeneity prohibited additional meta‐analyses. Other long‐term outcomes showed no differences. Conclusions: Our systematic review comprising a multitude of developmental measurements with a broad age range did not find evidence of benefit or harm in offspring prenatally exposed to progesterone treatment for the prevention of preterm birth. We identified an urgent need for follow‐up studies of prenatal progesterone administration in early pregnancy and effects in offspring beyond early childhood. Progesterone to prevent preterm birth: no effect on child development. Outcomes after first trimester progesterone are unclear. Progesterone to prevent preterm birth: no effect on child development. Outcomes after first trimester progesterone are unclear. [ABSTRACT FROM AUTHOR]

Objective: To assess the economic consequences of immediate delivery compared with expectant monitoring in women with preterm non-severe hypertensive disorders of pregnancy.Design: A cost-effectiveness analysis alongside a randomised controlled trial (HYPITAT-II).Setting: Obstetric departments of seven academic hospitals and 44 non-academic hospitals in the Netherlands.Population: Women diagnosed with non-severe hypertensive disorders of pregnancy between 340/7 and 370/7  weeks of gestation, randomly allocated to either immediate delivery or expectant monitoring.Methods: A trial-based cost-effectiveness analysis was performed from a healthcare perspective until final maternal and neonatal discharge.Main Outcome Measures: Health outcomes were expressed as the prevalence of respiratory distress syndrome, defined as the need for supplemental oxygen for >24 hours combined with radiographic findings typical for respiratory distress syndrome. Costs were estimated from a healthcare perspective until maternal and neonatal discharge.Results: The average costs of immediate delivery (n = 352) were €10 245 versus €9563 for expectant monitoring (n = 351), with an average difference of €682 (95% confidence interval, 95% CI -€618 to €2126). This 7% difference predominantly originated from the neonatal admissions, which were €5672 in the immediate delivery arm and €3929 in the expectant monitoring arm.Conclusion: In women with mild hypertensive disorders between 340/7 and 370/7  weeks of gestation, immediate delivery is more costly than expectant monitoring as a result of differences in neonatal admissions. These findings support expectant monitoring, as the clinical outcomes of the trial demonstrated that expectant monitoring reduced respiratory distress syndrome for a slightly increased risk of maternal complications.Tweetable Abstract: Expectant management in preterm hypertensive disorders is less costly compared with immediate delivery. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL.Design: Post hoc analysis of frozen fFN samples of a nationwide cohort study.Setting: Ten perinatal centres in the Netherlands.Population: Symptomatic women between 24 and 34 weeks of gestation.Methods: The risk of PTD <7 days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50 ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7 days using a reclassification table.Main Outcome Measures: Spontaneous delivery within 7 days after study entry.Results: We studied 350 women, of whom 69 (20%) delivered within 7 days. The risk of PTD in <7 days ranged from 2% in the lowest fFN group (<10 ng/ml) to 71% in the highest group (>500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7 days with rising fFN concentration [10-49 ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199 ng/ml: OR 3.2, 95% CI 0.79-13; 200-499 ng/ml: OR 9.0, 95% CI 2.3-35; >500 ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days.Conclusion: In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range.Tweetable Abstract: Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is the leading cause of neonatal mortality and morbidity in developed countries. Whether continued tocolysis after 48 hours of rescue tocolysis improves neonatal outcome is unproven.Objectives: To evaluate the effectiveness of maintenance tocolytic therapy with oral nifedipine on the reduction of adverse neonatal outcomes and the prolongation of pregnancy by performing an individual patient data meta-analysis (IPDMA).Search Strategy: We searched PubMed, Embase, and Cochrane databases for randomised controlled trials of maintenance tocolysis therapy with nifedipine in preterm labour.Selection Criteria: We selected trials including pregnant women between 24 and 36(6/7)  weeks of gestation (gestational age, GA) with imminent preterm labour who had not delivered after 48 hours of initial tocolysis, and compared maintenance nifedipine tocolysis with placebo/no treatment.Data Collection and Analysis: The primary outcome was perinatal mortality. Secondary outcome measures were intraventricular haemorrhage (IVH), necrotising enterocolitis (NEC), infant respiratory distress syndrome (IRDS), prolongation of pregnancy, GA at delivery, birthweight, neonatal intensive care unit admission, and number of days on ventilation support. Pre-specified subgroup analyses were performed.Main Results: Six randomised controlled trials were included in this IPDMA, encompassing data from 787 patients (n = 390 for nifedipine; n = 397 for placebo/no treatment). There was no difference between the groups for the incidence of perinatal death (risk ratio, RR 1.36; 95% confidence interval, 95% CI 0.35-5.33), intraventricular haemorrhage (IVH) ≥ grade II (RR 0.65; 95% CI 0.16-2.67), necrotising enterocolitis (NEC) (RR 1.15; 95% CI 0.50-2.65), infant respiratory distress syndrome (IRDS) (RR 0.98; 95% CI 0.51-1.85), and prolongation of pregnancy (hazard ratio, HR 0.74; 95% CI 0.55-1.01).Conclusion: Maintenance tocolysis is not associated with improved perinatal outcome and is therefore not recommended for routine practice.Tweetable Abstract: Nifedipine maintenance tocolysis is not associated with improved perinatal outcome or pregnancy prolongation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate long-term effects of maintenance tocolysis with nifedipine on neurodevelopmental outcome of the infant.Design, Setting and Population: Follow up of infants of women who participated in a multicentre randomised controlled trial on maintenance tocolysis with nifedipine versus placebo.Methods: Two years after the APOSTEL II trial on maintenance tocolysis with nifedipine versus placebo, we asked participants to complete the Ages and Stages Questionnaire.Main Outcome Measures: Infant development was measured in five domains. Developmental delay was defined as a score of ≤1 SD in one or more developmental domains. We performed exploratory subgroup analysis in women with preterm prolonged rupture of the membranes, and in women with a cervical length <10 mm at study entry.Results: Of the 276 women eligible for follow up, 135 (52.5%) returned the questionnaire, encompassing data of 170 infants. At 2 years of age, infants of women with nifedipine maintenance tocolysis compared with placebo had a higher overall incidence of fine motor problems (22.2 versus 7.6%, OR 3.43, 95% CI 1.29-9.14, P = 0.01), and a lower incidence of poor problem-solving (21.1 versus 29.1%, OR 0.27, 95% CI 0.08-0.95, P = 0.04).Conclusions: This follow-up study revealed no clear benefit of nifedipine maintenance tocolysis at 2 years of age. As short-term adverse perinatal outcome was not reduced in the original APOSTEL II trial, we conclude that maintenance tocolysis does not appear to be beneficial at this time.Tweetable Abstract: No clear benefit of nifedipine maintenance tocolysis in preterm labour on 2-year infant outcome. [ABSTRACT FROM AUTHOR]

The decision to initiate pharmacological intervention in case of fetal tachycardia depends on several factors and must be weighed against possible maternal and/or fetal adverse effects inherent to the use of antiarrhythmics. First, the seriousness of the fetal condition must be recognized. Many studies have shown that in case of fetal tachycardia, there is a significant predisposition to congestive heart failure and subsequent development of fetal hydrops and even sudden cardiac death1,2,3 Secondly, predictors of congestive heart failure have been suggested in several studies, such as the percentage of time that the tachycardia is present, the gestational age at which the tachycardia occurs4, the ventricular rate5 and the site of origin of the tachycardia6. However, the sensitivity of these predictors is low and they are therefore clinically not very useful. In addition, hemodynamic compromise may occur in less than 24 - 48 hours as has been shown in the fetal lamb7 and in tachycardic fetuses8,9. On the other hand, spontaneous resolution of the tachycardia has also been described10. Thirdly, transplacental management of fetuses with tricuspid regurgitation11, congestive heart failure or fetal hydrops is difficult12,13, probably as a result of limited transplacental transfer of the antiarrhythmic drug14,15. In case of fetal hydrops, conversion rates are decreased and time to conversion is increased13. Treatment of sustained fetal tachycardia is therefore to be preferred above expectant management, although some centers oppose this regimen and suggest that in cases with (intermittent) fetal SVT not complicated by congestive heart failure or fetal hydrops, conservative management and close surveillance might be a reasonable alternative16,17,18.

Fetal tachycardia, first recognized in 1930 by Hyman et al1, is a condition occurring in approximately 0.4-0.6% of all pregnancies2. A subset of these cases with more sustained periods of tachycardia is clinically relevant. The necessity of therapeutic intervention in this condition is still a matter of discussion focused on the natural history of the disease. The spectrum of opinions varies from non-intervention3,4,5 based on a number of cases in which the tachycardia subsided spontaneously6, to aggressive pharmacotherapeutic intervention7,8 based on reports of deterioration of the fetal condition ultimately ending in significant neurological morbidity9,10,11, or fetal demise12,13,14. Prenatal treatment through indirect, maternally administered drug therapy seems to be the preference of most centers15,16,17,18,19,20,21. This matter will be discussed further in Fetal Tachyarrhythmia, Part II, Treatment.

Objective To investigate whether vaginal Group B Streptococcus ( GBS) colonisation or other baseline characteristics of women with preterm premature rupture of membranes ( PPROM) can help in identifying subgroups of women who would benefit from immediate delivery. Design Secondary analysis of the PPROMEXIL trials. Setting Sixty hospitals in the Netherlands. Population Women with PPROM between 34 and 37 weeks of gestation. Methods Random assignment of 723 women to immediate delivery or expectant management. Main outcome measures Early onset neonatal sepsis. Results Vaginal GBS colonisation status was the only marker which was significantly associated with the benefit of immediate delivery ( P for interaction: 0.04). GBS colonisation was observed in 14% of women. The risk of early onset neonatal sepsis in GBS-positive women was high (15.2%) when they were managed expectantly but this risk was reduced to 1.8% with immediate delivery. The early onset neonatal sepsis risk was much lower in neonates of GBS-negative women: 2.6% after expectant management and 2.9% with immediate delivery. We estimated that by inducing labour only in GBS-positive women, there would be a 10.4% increase in term delivery rate, while keeping neonatal sepsis and caesarean delivery rates comparable to a strategy of labour induction for all. Conclusions Our post hoc findings suggest that women with PROM between 34 and 37 weeks might benefit from immediate delivery if they have GBS vaginal colonisation, while in GBS-negative women labour induction could be delayed until 37 weeks. [ABSTRACT FROM AUTHOR]

Importance: In threatened preterm labor, maintenance tocolysis with nifedipine, after an initial course of tocolysis and corticosteroids for 48 hours, may improve perinatal outcome.Objective: To determine whether maintenance tocolysis with nifedipine will reduce adverse perinatal outcomes due to premature birth.Design, Setting, and Participants: APOSTEL-II (Assessment of Perinatal Outcome with Sustained Tocolysis in Early Labor) is a double-blind, placebo-controlled trial performed in 11 perinatal units including all tertiary centers in The Netherlands. From June 2008 to February 2010, women with threatened preterm labor between 26 weeks (plus 0 days) and 32 weeks (plus 2 days) gestation, who had not delivered after 48 hours of tocolysis and a completed course of corticosteroids, were enrolled. Surviving infants were followed up until 6 months after birth (ended August 2010).Intervention: Randomization assigned 406 women to maintenance tocolysis with nifedipine orally (80 mg/d; n = 201) or placebo (n = 205) for 12 days. Assigned treatment was masked from investigators, participants, clinicians, and research nurses.Main Outcome Measures: Primary outcome was a composite of adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage >grade 2, periventricular leukomalacia >grade 1, or necrotizing enterocolitis). Analyses were completed on an intention-to-treat basis.Results: Mean (SD) gestational age at randomization was 29.2 (1.7) weeks for both groups. Adverse perinatal outcome was not significantly different between groups: 11.9% (24/201; 95% CI, 7.5%-16.4%) for nifedipine vs 13.7% (28/205; 95% CI, 9.0%-18.4%) for placebo (relative risk, 0.87; 95% CI, 0.53-1.45).Conclusions and Relevance: In patients with threatened preterm labor, nifedipine-maintained tocolysis did not result in a statistically significant reduction in adverse perinatal outcomes when compared with placebo. Although the lower than anticipated rate of adverse perinatal outcomes in the control group indicates that a benefit of nifedipine cannot completely be excluded, its use for maintenance tocolysis does not appear beneficial at this time.Trial Registration: trialregister.nl Identifier: NTR1336. [ABSTRACT FROM AUTHOR]

Background: One of the most commonly reported problems of randomised trials is that recruitment is usually slower than expected. Trials will cost more and take longer, thus delaying the use of the results in clinical practice, and incomplete samples imply decreased statistical power and usefulness of its results. We aim to identify barriers and facilitators for successful patient recruitment at the level of the patient, the doctor and the hospital organization as well as the organization and design of trials over a broad range of studies.Methods/design: We will perform two cohort studies and a case-control study in The Netherlands. The first cohort study will report on a series of multicenter trials performed in a nationwide network of clinical trials in obstetrics and gynaecology. A questionnaire will be sent to all clinicians recruiting for these trials to identify determinants--aggregated at centre level--for the recruitment rate. In a case control-study nested in this cohort we will interview patients who refused or consented participation to identify factors associated with patients' consent or refusal. In a second cohort study, we will study trials that were prospectively registered in the Netherlands Trial Register. Using a questionnaire survey we will assess whether issues on hospital organization, trial organization, planning and trial design were associated with successful recruitment, i.e. 80% of the predefined number of patients recruited within the planned time.Discussion: This study will provide insight in barriers and facilitators for successful patient recruitment in trials. The results will be used to provide recommendations and a checklist for individual trialists to identify potential pitfalls for recruitment and judge the feasibility prior to the start of the study. Identified barriers and motivators coupled to evidence-based interventions can improve recruitment of patients in clinical trials. [ABSTRACT FROM AUTHOR]

Background: At present, women with threatened preterm labor before 32 weeks of gestation are, after transfer to a perinatal center, treated with tocolytics and corticosteroids. Many of these women are treated unnecessarily. Fibronectin is an accurate predictor for the occurrence of preterm birth among women with threatened preterm labor. We will assess whether triage of these women with fibronectin testing, cervical length or their combination is cost-effective.Methods/design: We will investigate a prospective cohort of women referred to a perinatal centre for spontaneous threatened preterm labor between 24 and 34 weeks with intact membranes. All women will be tested for fibronectin and cervical length. Women with a cervical length <10 mm and women with a cervical length between 10-30 mm in combination with a positive fibronectin test will be treated with tocolytics according to local protocol. Women with a cervical length between 10-30 mm in combination with a negative fibronectin test will be randomised between treatment with nifedipine (intervention) and placebo (control) for 48 hours. Women with a cervical length > 30 mm will be managed according to local protocol. Corticosteroids may be given to all women at the discretion of the attending physician. Primary outcome measure will be delivery within 7 days. Secondary outcome measures will be neonatal morbidity and mortality, complications of tocolytics, costs and health related quality of life. The analysis will be according to the intention to treat principle. We anticipate the probability on preterm birth within 7 days in the group of women with a negative fibronectine test to be 5%. Two groups of 110 women will be needed to assure that in case of non-inferiority the difference in the proportion of preterm deliveries < 7 days will be within a prespecified boundary of 7.5% (one sided test, beta 0.2, alpha 0.05). Data obtained from women with a positive and negative fibronectin tests in both the cohort study and the trial will be integrated in a cost-effectiveness analysis that will assess economic consequences of the use of fibronectin.Discussion: This study will provide evidence for the use of fibronectin testing as safe and cost-effective method in a triage for threatened preterm labor.Trial Registration: Nederlands Trial Register (NTR) number 1857, http://www.trialregister.nl. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the effectiveness of cervical cerclage in women with a twin pregnancy and a midpregnancy asymptomatic short cervix (≤25 mm), in preventing preterm birth and improving neonatal outcomes., Data Sources: Systematic searches were conducted in MEDLINE, Embase, Web of Science, Scopus, and Cochrane Library up to April 17, 2023, updated in September and February 2024., Study Eligibility Criteria: Included were randomized controlled trials, cohort studies, and case-control studies comparing cerclage with expectant management in twin pregnancies and an asymptomatic short cervix (≤25 mm)., Methods: Risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale and the Risk of Bias 2 tool. Data were analyzed using RevMan 5.4 using a random-effects model., Results: Three randomized controlled trials and 13 cohort studies, involving 696 cerclage patients and 595 controls, were analyzed. Combined randomized controlled trial findings (N=49) found no significant difference in preterm birth occurrence after adjustment for preterm birth history and gestational age. Neonates from cerclage-treated mothers exhibited significantly higher rates of respiratory distress syndrome (adjusted odds ratio, 3.88; 95% confidence interval, 1.09-21.03) and very low birthweight (adjusted odds ratio, 2.22; 95% confidence interval, 1.07-5.73). In contrast, pooled cohort data indicated significantly less preterm birth rates in women with a cerclage: at 34 weeks (relative risk, 0.75; 95% confidence interval, 0.63-0.90), 32 weeks (relative risk, 0.67; 95% confidence interval, 0.49-0.90), and 28 weeks (relative risk, 0.572; 95% confidence interval, 0.39-0.83). Cerclage also reduced risk for infants <1500 g, respiratory distress syndrome, admission at the neonatal intensive care unit, and sepsis. Women with cervical length <15 mm and a cerclage experienced fewer preterm birth rates at <37 weeks (relative risk, 0.88; 95% confidence interval, 0.81-0.94), 34 weeks (relative risk, 0.70; 95% confidence interval, 0.57-0.87), 32 weeks (relative risk, 0.63; 95% confidence interval, 0.50-0.80), and 28 weeks (relative risk, 0.43; 95% confidence interval, 0.32-0.59). Perinatal mortality risk was significant lower in neonates born to mothers with a cerclage. For women with cervical length between 16 and 25 mm, no significant differences in outcomes were observed., Conclusion: Based on our meta-analysis, cerclage may benefit women with a twin pregnancy with an asymptomatic midpregnancy short cervix <25 mm, especially in women with a cervix <15 mm, by reducing preterm birth and improving neonatal outcomes. However, the differences between randomized controlled trials and recent cohort studies emphasize the need for well-powered randomized controlled trials on neonatal outcomes before introducing cerclage in clinical practice for these women., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: After a previous caesarean section, morbidity in the subsequent delivery in general is considered to depend on the probability of a vaginal birth after caesarean. However counselling could be improved by adding individualized probability of serious morbidity following either trial of labour or elective repeat caesarean section. The objective of this study was to develop prediction models for morbidity for both a repeat caesarean section and a trial of labor for a Dutch population., Material and Methods: In this cohort study, data were joined from three previous studies (SIMPLE 1, SIMPLE 2 and SIMPLE 2-implementation study). A cohort of 2592 women with one previous caesarean section and a singleton pregnancy who delivered ≥37 weeks, without a contraindication for vaginal delivery was formed. Maternal morbidity was defined as postpartum hemorrhage, blood transfusion, uterine rupture, ICU admittance or death. Neonatal morbidity was defined as asphyxia, NICU-admittance or death. Potential predictors for morbidity were chosen based on literature and expert opinion. Logistic regression was used to develop the models. Internal validation was intended using bootstrapping techniques. Main outcome measures were predictors for morbidity and for validation of the model we used the area under the receiver operating characteristic curve for discriminative capacity and calibration for accuracy., Results: In 324 out of the 2592 cases (12.7 %) maternal or fetal complications occurred. In general total morbidity was higher in women choosing TOL as compared to ERCS (p < 0.001). The performance of the several developed models was insufficient, the area under the receiver operating characteristic curve did not rise above 0.6. Due to poor model performance, before correction for overfitting, interval validation was not conducted., Conclusion: In this large cohort, developing a Dutch population based prediction model that aimed to improve counselling on the mode of delivery, by predicting individual chances of morbidity for different delivery modes was not possible, due to lack of performance. Further study could be directed to cut off on VBAC success rates to a more general advice regarding the safest mode of delivery., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To assess the variation between countries for routine transvaginal ultrasound assessment of the cervical length and interventions offered to prevent preterm birth (PTB)., Study Design: An anonymous digital questionnaire was sent out between August and October 2023 to delegates of the European Spontaneous Preterm Birth Congress. Outcomes assessed included method, indications (i.e. singleton pregnancy in women with or without a history of PTB, or a multiple pregnancy), timing and frequency of routine cervical length measurement, interventions offered to pregnant women with a short cervix or a history of PTB, and advice on physical- and sexual activity., Results: In total, 247 visitors of the European Spontaneous Preterm Birth Congress were approached for this study and 103 (42 %) participants completed the questionnaire representing 15 countries. Most participants worked in a Public/University hospital (n = 54, 53 %) and worked as a specialist (registrar or consultant; n = 84, 82 %). In most countries, the cervix was measured via a straight-line method without the cervical isthmus, but variety existed also within countries. Routine cervical length measurement in women with no prior PTB or a multiple pregnancy is rarely performed in the first trimester. For women with a history of PTB, 39 (38 %) respondents from six countries reported to start serial cervical measurement in the first trimester and 99 (96 %) from 14 countries in the second trimester. Follow-up for women at risk for PTB mainly occurs fortnightly (n = 40, 39 %) or monthly (n = 14, 14 %). However, follow-up is often individualized according to patient's history and/or cervical length. In women with a history of PTB or a short cervix progesterone is administered vaginally (n = 99, 96 %), however dosage vary between 100 mg and 400 mg daily. The timing and gestational age at which a (primary/secondary/tertiary) vaginal cerclage is offered widely differ between countries (e.g. up to 24-28 weeks of gestation for a secondary cerclage). Advice on restrictions regarding sexual activity in pregnancy is frequently prescribed for women with a short cervix (n = 38, 37 %)., Conclusion: Substantial variation exist between and within countries regarding the indications and timing of cervical length measurement and interventions offered. There is a need for a more universal approach to manage patients at risk for PTB based on the existing evidence., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

To assess the cost-effectiveness of low-dose aspirin compared to placebo for the prevention of recurrent preterm birth from a healthcare perspective. This was a cost-effectiveness analysis alongside a multicenter, randomized, double-blinded, placebo-controlled trial. We included women with a singleton pregnancy and a previous spontaneous preterm birth <37 weeks of gestation of a singleton. Women were randomized between aspirin 80 mg daily and placebo, initiated between 8 and 16 weeks of gestation. We estimated the difference in preterm births (<37 weeks of gestation), and maternal and neonatal healthcare costs using seemingly unrelated linear regression analyses. Bootstrapping was performed to estimate statistical uncertainty. A total of 387 women were included: 194 in the aspirin group and 193 in the placebo group. We observed a small, statistically non-significant difference in preterm birth (21.2% vs. 25.4%; risk difference -4.3%; 95% CI: -12.7% to 4.1%) and healthcare costs (mean -€99; 95% CI: -€2385 to €2325) in the aspirin group compared to placebo. The cost-effectiveness acceptability curve showed that the probability of aspirin being cost-effective was 54% for a willingness to pay threshold of €0 for one prevented preterm birth and 78% for €50 000 for one prevented preterm birth. Our findings suggest that aspirin is the dominant strategy over placebo for the prevention of preterm birth. However, there was substantial uncertainty around the results and definite conclusions regarding the cost-effectiveness of aspirin cannot be drawn., (© 2024 The Author(s). International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: Previous spontaneous preterm birth (sPTB) is a strong risk indicator for recurrent preterm birth (PTB). Cervical cerclage is an accepted intervention to prevent recurrent PTB in high risk patients. Cervical pessary might be a less invasive alternative. The objective of this study is to determine whether a cervical pessary is non-inferior to cerclage in the prevention of recurrent PTB., Methods: We performed an international, open-label, non-inferiority, randomised controlled trial in 21 hospitals between March 2014 and December 2022. We included singleton pregnancies with an indication for cerclage based on either multiple previous sPTBs <34 weeks or with a previous sPTB <34 weeks and an asymptomatic mid-trimester short cervix (≤25 mm). Randomisation was 1:1, stratified by centre and indication, to cervical pessary or vaginal cerclage. Primary outcome was PTB <32 weeks. Secondary outcomes included (s)PTB rates, obstetric, and maternal outcomes and a composite of adverse perinatal outcomes including perinatal mortality and severe neonatal morbidity. Analysis was by intention-to-treat. Treatment effect was expressed as relative risk (RR), absolute risk difference (aRD) and 95% confidence intervals (CI). Sample size was calculated at 400 participants with a non-inferiority margin for pessary of 10%, meaning that non-inferiority is proven if the upper limit of the CI of the risk difference is <10%. Trial registration at ICTRP: NL-OMON26958., Findings: We randomised 261 participants to pessary (n = 133) or cerclage (n = 128). After the third interim analysis (n = 228 participants), recruitment was halted due to safety concerns and the apparent challenge in establishing non-inferiority of pessary treatment. PTB <32 weeks occurred in 44/130 cases after pessary vs 30/125 cases after cerclage (33.8% vs 24.0% aRR 1.4, 95% CI 0.95-2.1, p = 0.09, aRD 9.8% 95% CI -1.2 to 20.9). The composite of adverse perinatal outcomes occurred in 42 cases after pessary compared to 29 cases in cerclage (32.2% vs 23.2%; RR 1.4 95% CI 0.93-2.1 p = 0.1) and consisted mainly of perinatal death (22.3% vs 14.4% RR 1.5 95% CI 0.9-2.6 p = 0.1)., Interpretation: Non-inferiority of cervical pessary compared to cerclage in preventing recurrent PTB <32 weeks was not proven. Cerclage is the recommended treatment., Funding: ZonMw (#837002406), a Dutch Organisation for Health Research and Development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. BMT reports receiving consulting fees for participation to the advisory board of Effik, Pierre-Favre and Sanofy, received payment for legal expert testimonies in malpractice cases in obstetrics and received a device to measure cervical softening from Pregnolia. BWM received an investigator grant from NHMRC. MAO received research grants for studies on the prevention of preterm birth, reports expenses paid for organization of preterm birth symposium, is chairman of the Fetal-Maternal Medicine board of the Dutch society of Obstetrics & Gynecology and chairman of the scientific committee of the Fetal-Maternal-Medicine Board. MAO and EP are board members of Stichting Stoptevroegbevallen, a non-profit organization supporting preterm birth research and received payments to the institution. EP received research grants for studies on prevention and treatment of preterm birth and the fetal microbiome., (© 2024 The Author(s).)

Objective: To assess the risk of recurrent preterm birth following spontaneous extreme preterm birth between 16 +0 - 27 +6 weeks., Methods: A nationwide retrospective cohort study was conducted with data from the Perinatal Registry of the Netherlands. We included nulliparous women with a singleton pregnancy that ended in spontaneous preterm birth between 16 +0 and 27 +6 weeks of gestation without congenital anomalies or antenatal death between 2010-2014 and had a subsequent pregnancy in the 5 years following (2010-2019). The primary outcome of this study was recurrent preterm birth < 37 weeks., Results: In total, 1011 women with linked pregnancies were included. The risk of preterm birth < 37 weeks with prior spontaneous birth between 16 +0 -19 +6 , 20 +0 -23 +6 , and 24 +0 -27 +6 weeks was respectively 19.0 %, 29.5 % and 27.6 %. The risk of subsequent preterm birth < 24 weeks was 5.8 %, 7.2 % and 4.3 %. A short interpregnancy interval of 0-3 months was associated with increased odds for recurrent preterm birth < 32 weeks (OR 2.3 95 % CI 1.4-3.7) and preterm birth < 37 weeks (OR 1.8 95 % CI 1.2-2.6)., Conclusion: Patients with previous spontaneous preterm birth from 16 weeks GA onwards are at high risk for recurrent preterm birth and should be regarded as such in the consideration of preventive measures to prevent recurrent adverse pregnancy outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article’., (© 2024 The Authors.)