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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]

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]

Abstract Background The prevalence of asymptomatic bacteriuria (ASB) in pregnancy is 2-10% and is associated with both maternal and neonatal adverse outcomes as pyelonephritis and preterm delivery. Antibiotic treatment is reported to decrease these adverse outcomes although the existing evidence is of poor quality. Methods/Design We plan a combined screen and treat study in women with a singleton pregnancy. We will screen women between 16 and 22 weeks of gestation for ASB using the urine dipslide technique. The dipslide is considered positive when colony concentration ≥105 colony forming units (CFU)/mL of a single microorganism or two different colonies but one ≥105 CFU/mL is found, or when Group B Streptococcus bacteriuria is found in any colony concentration. Women with a positive dipslide will be randomly allocated to receive nitrofurantoin or placebo 100 mg twice a day for 5 consecutive days (double blind). Primary outcomes of this trial are maternal pyelonephritis and/or preterm delivery before 34 weeks. Secondary outcomes are neonatal and maternal morbidity, neonatal weight, time to delivery, preterm delivery rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal admission days and costs. Discussion This trial will provide evidence for the benefit and cost-effectiveness of dipslide screening for ASB among low risk women at 16–22 weeks of pregnancy and subsequent nitrofurantoin treatment. Trial registration Dutch trial registry: NTR-3068

Abstract 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. Discussion This study will provide evidence for the usefulness and cost-effectiveness of screening for short cervical length at the 18-22 weeks and subsequent progesterone treatment among low risk women. Trial registration Netherlands Trial Register (NTR): NTR207

Abstract Background Gestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term. Methods/Design Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised. Discussion This trial will provide insight as to whether in women with hypertensive disorders late pre-term, induction of labour is an effective treatment to prevent severe maternal complications without compromising the neonatal morbidity. Trial Registration NTR1792 Clinical trial registration: http://www.trialregister.nl

Abstract 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 Background Hypoxic-ischaemic encephalopathy is associated with development of cerebral palsy and cognitive disability later in life and is therefore one of the fundamental problems in perinatal medicine. The xanthine-oxidase inhibitor allopurinol reduces the formation of free radicals, thereby limiting the amount of hypoxia-reperfusion damage. In case of suspected intra-uterine hypoxia, both animal and human studies suggest that maternal administration of allopurinol immediately prior to delivery reduces hypoxic-ischaemic encephalopathy. Methods/Design The proposed trial is a randomized double blind placebo controlled multicenter study in pregnant women at term in whom the foetus is suspected of intra-uterine hypoxia. Allopurinol 500 mg IV or placebo will be administered antenatally to the pregnant woman when foetal hypoxia is suspected. Foetal distress is being diagnosed by the clinician as an abnormal or non-reassuring foetal heart rate trace, preferably accompanied by either significant ST-wave abnormalities (as detected by the STAN-monitor) or an abnormal foetal blood scalp sampling (pH < 7.20). Primary outcome measures are the amount of S100B (a marker for brain tissue damage) and the severity of oxidative stress (measured by isoprostane, neuroprostane, non protein bound iron and hypoxanthine), both measured in umbilical cord blood. Secondary outcome measures are neonatal mortality, serious composite neonatal morbidity and long-term neurological outcome. Furthermore pharmacokinetics and pharmacodynamics will be investigated. We expect an inclusion of 220 patients (110 per group) to be feasible in an inclusion period of two years. Given a suspected mean value of S100B of 1.05 ug/L (SD 0.37 ug/L) in the placebo group this trial has a power of 90% (alpha 0.05) to detect a mean value of S100B of 0.89 ug/L (SD 0.37 ug/L) in the 'allopurinol-treated' group (z-test2-sided). Analysis will be by intention to treat and it allows for one interim analysis. Discussion In this trial we aim to answer the question whether antenatal allopurinol administration reduces hypoxic-ischaemic encephalopathy in neonates exposed to foetal hypoxia. Trial registration number Clinical Trials, protocol registration system: NCT00189007

Abstract 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 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, β 0.2, α 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.

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: Data and guidelines are lacking, so implantable cardioverter-defibrillators (ICDs) are often deactivated during labour to prevent inappropriate shocks. This study aimed to ascertain the safety of an activated ICD during labour., Design: An observational study was performed., Setting: Dutch hospitals., Population or Sample: A total of 41 childbirths were included of 26 patients who gave birth between February 2009 and November 2018 after receiving an ICD in our tertiary hospital. Five of these childbirths were attended by the research team between December 2018 and August 2020, during which the ICD remained active., Methods: Groups were made based on ICD status during labour. Patients who gave birth with an activated ICD at least once were stratified to the activated ICD group. Patients' files were checked and patients received a questionnaire about childbirth perceptions and treatment preferences. The differences in ordinal data resulting from the questionnaire were calculated using a chi-square or Fisher's exact test., Main Outcome Measures: Primary outcome was inappropriate ICD therapy and occurrence of ventricular arrhythmias requiring treatment., Results: During the 41 childbirths, no inappropriate shocks or ventricular arrhythmias occurred during labour. All patients in the activated ICD group (n = 13) preferred this setting, while 8 of the 13 patients in the deactivated ICD group preferred activation (p = 0.002). Reasons included avoiding hemodynamic monitoring, magnet placement, or labour induction to facilitate technician availability., Conclusions: This study shows no evidence that labour and birth in women with an activated ICD are unsafe, as there were no ventricular arrhythmias or inappropriate therapy. In addition, most patients prefer an activated ICD during labour., (© 2024 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Aim: This qualitative focus group study aims to asses cerclage-related symptoms, the impact of a cerclage on daily functioning and patient perspectives of their healthcare experience. This study extends beyond the current focus on surgical and obstetric outcomes of a cerclage, thereby contributing to a more comprehensive understanding of the challenges faced by individuals in the context of extreme preterm birth and fetal loss and the impact of a cerclage on multiple facets in life., Methods: Participants were recruited from the Amsterdam University Medical Center, Amsterdam, the Netherlands or via the website of a Dutch patient organization for (extreme) preterm birth. Eligible participants were ≥ 18 years old with a previous vaginal and/or abdominal cerclage with a subsequent delivery at ≥ 34 weeks of gestation with neonatal survival. Two focus group discussions (FGD) were performed. A predefined format was used, which was identical for both the vaginal and abdominal cerclage group. The International Classification of Functioning, Disability and Health (ICF-DH) was used to provide structure. Outcomes were a broad range of participants reported perspectives on physical, emotional, and social-related quality of life., Results: In the Vaginal Cerclage Group (VCG) and Abdominal Cerclage Group (ACG), respectively, 11 and 8 participants were included. Fear for a subsequent pregnancy loss was the most limiting factor to perform daily activities during pregnancy in all participants with a cerclage. Fear to conceive again because of prior second-trimester fetal loss was experienced by 27% in the VCG and 13% in the ACG. The majority of participants experienced a reduction in anxiety after placement of their cerclage (VCG = 64%, ACG = 75%). Decreased mobility/bedrest (VCG = 100%, ACG = 75%) and blood loss (VCG = 55%, ACG = 13%) were frequently mentioned complaints during pregnancy with cerclage. Other aspects mentioned in both groups were social isolation, the lack of societal participation, and the perceived need to quit work and sports. All participants in the abdominal cerclage group reported a lack of comprehensible and unambiguous information about obstetric management and expectations during pregnancy in secondary care hospitals. Clear communication between secondary and tertiary care hospitals about obstetric management following an abdominal cerclage, for example, about the need for cervical length measurements by ultrasound, the need for bedrest or advice concerning sexual activity was missing (63%). Psychologic support was desired in half of all participants, but was not offered to them., Conclusions: The fear of a subsequent pregnancy loss was reported as the most limiting factor in daily life by all participants. Cerclage placement resulted in the reduction of anxiety. Participants mentioned a significant impact of bedrest and activity restriction during pregnancy with cerclage on social participation and daily activities. Unfortunately, no high level evidence is available on this matter. Patients might even benefit from appropriate levels of physical activity throughout their pregnancy to promote their overall well-being. More evidence is needed to determine the optimal level of physical activity. There is a need for clear and unambiguous patient information about obstetric management., (© 2024. The Author(s).)

Introduction: Currently, the majority of women worldwide with threatened preterm birth are treated with tocolytics. Although tocolytics can effectively delay birth for 48 hours, no tocolytic drug has convincingly been shown to improve neonatal outcomes and effects on long-term child development are unknown. The aim of this follow-up study of a placebo controlled randomised trial is to investigate the long-term effects of atosiban administration in case of threatened preterm birth on child's neurodevelopment and behaviour development, overall health and mortality., Methods and Analysis: This protocol concerns a follow-up study of the multicentre randomised double-blind placebo controlled APOSTEL 8 trial (NL61439.018.17, EudraCT-number 2017-001007-72). In this trial, women with threatened preterm birth (between 30 and 34 weeks of gestation) defined as uterine contractions with (1) a cervical length of <15 mm or (2) a cervical length of 15-30 mm and a positive fibronectin test or (3) in centres where cervical length measurement is not part of the local protocol: a positive fibronectin test or Actim-Partus test or (4) ruptured membranes, are randomised to atosiban or placebo for 48 hours. The primary outcome is a composite of perinatal mortality and severe neonatal morbidity. Children born to mothers who participated in the APOSTEL 8 study (n=760) will be eligible for follow-up at 4 years of corrected age and assessed using four parent-reported questionnaires. Primary outcomes are neurodevelopment and behaviour problems. Secondary outcomes are on child growth and general health. All outcomes will be compared between the atosiban and placebo group with OR and corresponding 95% CI. Analyses will be performed using the intention-to-treat approach., Ethics and Dissemination: The Medical Research Ethics Committee from Amsterdam UMC confirmed that de Medical Research Involving Human Subjects Act (Dutch WMO-law) did not apply to our study (W21&#95;386 # 21.431). Results will be published in a peer-reviewed journal and shared with stakeholders and participants. This protocol is published before analysis of the results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)