Atosiban versus placebo for threatened preterm birth (APOSTEL 8): a multicentre, randomised controlled trial.

Background: Tocolytics are recommended in international guidelines as treatment for threatened preterm birth. Atosiban, an oxytocin receptor antagonist, is a registered tocolytic drug specifically indicated for the treatment of threatened preterm birth. Although tocolytics have been shown to delay birth, benefits on neonatal outcomes have not been demonstrated.

The TANGO-DM randomized controlled trial study protocol: treatment outcomes for gestational diabetes diagnosed according to WHO 2013 or WHO 1999 thresholds.

Introduction: Gestational diabetes mellitus (GDM), or hyperglycemia first diagnosed in pregnancy, affects 7-10% of all pregnancies worldwide. Perinatal risk rises with increasing glycemia at oral glucose tolerance test (OGTT). The new (2013) WHO criteria recommend a lower fasting, and a higher post-load threshold for GDM diagnosis in comparison to the old (1999) WHO criteria.

Which variables are associated with recruitment failure? A nationwide review on obstetrical and gynaecological multicentre RCTs (2003-2023).

Objective: We aim to assess which variables are associated with recruitment failure of obstetrical and gynaecological randomised controlled trials (RCTs), leading to an extension of the study period.

Design: Nationwide study.

Setting: A cohort of RCTs supported by the trial centre of the Dutch Consortium of Obstetrics and Gynaecology.

Oral Glucose-Lowering Agents vs Insulin for Gestational Diabetes: A Randomized Clinical Trial.

Importance: Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown.

Objective: To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants.

The UPDATE trial (UVB Phototherapy in Dermatology for ATopic Eczema): study protocol for a randomized controlled trial of narrowband UVB with optimal topical therapy versus optimal topical therapy in patients with atopic eczema.

Background: Narrowband ultraviolet B (NB-UVB) phototherapy is commonly prescribed for patients with moderate-to-severe atopic eczema (AE). The efficacy of NB-UVB, however, has not yet properly been established, as current evidence is of low certainty. Our aim is to assess the short-term and long-term (cost-)effectiveness and safety of NB-UVB in adult AE patients by performing a pragmatic, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) trial.

Procedural sedation and analgesia versus general anesthesia for hysteroscopic myomectomy (PROSECCO trial): A multicenter randomized controlled trial.

Background: Hysteroscopic resection is the first-choice treatment for symptomatic type 0 and 1 fibroids. Traditionally, this was performed under general anesthesia. Over the last decade, surgical procedures are increasingly being performed in an outpatient setting under procedural sedation and analgesia.

Effect of Pessary vs Surgery on Patient-Reported Improvement in Patients With Symptomatic Pelvic Organ Prolapse: A Randomized Clinical Trial.

Importance: Pelvic organ prolapse is a prevalent condition among women that negatively affects their quality of life. With increasing life expectancy, the global need for cost-effective care for women with pelvic organ prolapse will continue to increase.

Objective: To investigate whether treatment with a pessary is noninferior to surgery among patients with symptomatic pelvic organ prolapse.

Working conditions in women with multiple pregnancy-the impact on preterm birth and adherence to guidelines: a prospective cohort study.

Background: Women with multiple pregnancies are at risk for maternal complications such as preterm birth. Hazardous working conditions, such as physically demanding work and long and irregular working hours, might increase the risk of preterm birth.

Objective: This study primarily aimed to determine whether certain working conditions up to 20 weeks of pregnancy increase the risk of preterm birth in multiple pregnancies.

Elective induction of labour and expectant management in late-term pregnancy: A prospective cohort study alongside the INDEX randomised controlled trial.

Objective: To assess adverse perinatal outcomes and caesarean section of low-risk women receiving elective induction of labour at 41 weeks or expectant management until 42 weeks according to their preferred and actual management strategy.

Design: Multicentre prospective cohort study alongside RCT.

Setting: 90 midwifery practices and 12 hospitals in the Netherlands.

Study protocol for a randomized trial on timely delivery versus expectant management in late preterm small for gestational age pregnancies with an abnormal umbilicocerebral ratio (UCR): the DRIGITAT study.

Background: The clinical inability to correctly identify late fetal growth restriction (FGR) within a group of fetuses who are identified as small for gestational age (SGA) is an everyday problem for all obstetrician-gynecologists. This leads to substantial overtreatment of healthy small fetuses but also inadequate detection of the growth-restricted fetuses that may benefit from timely delivery. Redistribution of the fetal circulation, signaled by an abnormal ratio of the Doppler velocity flow profiles of the umbilical artery and the middle cerebral artery, more specifically an increased umbilicocerebral ratio (UCR) (or its inverse: a decreased cerebroplacental ratio (CPR)), is an adaptation to chronic hypoxemia and nutritional scarcity with long-term consequences in survivors.

Endometrial ablation plus levonorgestrel releasing intrauterine system versus endometrial ablation alone in women with heavy menstrual bleeding: study protocol of a multicentre randomised controlled trial; MIRA2 trial.

Background: It is estimated that between 12 to 25% of women who undergo an endometrial ablation for heavy menstrual bleeding (HMB) are dissatisfied after two years because of recurrent menstrual bleeding and/or cyclical pelvic pain, with around 15% of these women ultimately having a hysterectomy. The insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) immediately after endometrial ablation may inactivate residual untreated endometrium and/or inhibit the regeneration of endometrial tissue. Furthermore, the LNG-IUS may prevent agglutination of the uterine walls preventing intrauterine adhesion formation associated with endometrial ablation.

Working conditions in low risk nulliparous women in The Netherlands: are legislation and guidelines a guarantee for a healthy working environment? A cohort study.

Objective: Hazardous working conditions increase the risk of adverse pregnancy outcomes. In this study, we examine adherence to legislation and guidelines aimed at improving working conditions in pregnancy.

Methods: Between 2014 and 2016, we recruited a prospective cohort of low-risk nulliparous pregnant women in paid employment or self-employed in 16 community midwifery practices in The Netherlands.

Marketing Authorization Applications Made to the European Medicines Agency in 2018-2019: What was the Contribution of Real-World Evidence?

Information derived from routinely collected real-world data has for a long time been used to support regulatory decision making on the safety of drugs and has more recently been used to support marketing authorization submissions to regulators. There is a lack of detailed information on the use and types of this real-world evidence (RWE) as submitted to regulators. We used resources held by the European Medicines Agency (EMA) to describe the characteristics of RWE included in new marketing authorization applications (MAAs) and extensions of indication (EOIs) for already authorized products submitted to the EMA in 2018 and 2019.

Pessary or surgery for a symptomatic pelvic organ prolapse: the PEOPLE study, a multicentre prospective cohort study.

Objective: To compare the 24-month efficacy of pessary or surgery as the primary treatment for symptomatic pelvic organ prolapse (POP).

Design: Multicentre prospective comparative cohort study.

Setting: Twenty-two Dutch hospitals.

Evaluation of a blended care programme for caregivers and working pregnant women to prevent adverse pregnancy outcomes: an intervention study.

Objective: Work-related activities can be a risk factor for pregnancy complications such as preterm birth. This study evaluates the effectiveness of a blended care programme, Pregnancy and Work, that provides pregnant workers and their obstetrical caregivers with advice on work adjustment.

Methods: Women less than 20 weeks of gestation, in paid employment or self-employed, in the care of four participating hospitals and their referring midwifery practices in the Netherlands received either the blended care programme (n=119), consisting of a training for professionals and a mobile health application, or care as usual (n=122) in a controlled intervention study with a follow-up in intervention and control populations.

The CErebro Placental RAtio as indicator for delivery following perception of reduced fetal movements, protocol for an international cluster randomised clinical trial; the CEPRA study.

Background: Routine assessment in (near) term pregnancy is often inaccurate for the identification of fetuses who are mild to moderately compromised due to placental insufficiency and are at risk of adverse outcomes, especially when fetal size is seemingly within normal range for gestational age. Although biometric measurements and cardiotocography are frequently used, it is known that these techniques have low sensitivity and specificity. In clinical practice this diagnostic uncertainty results in considerable 'over treatment' of women with healthy fetuses whilst truly compromised fetuses remain unidentified.

Predictive factors for failure of the levonorgestrel releasing intrauterine system in women with heavy menstrual bleeding.

Background: This study was conducted to identify factors that are associated with failure of treatment using the levonorgestrel releasing intrauterine system (LNG-IUS) in women with heavy menstrual bleeding.

Methods: For this study, data of a cohort of women treated with an LNG-IUS was used. Women who suffered from heavy menstrual bleeding, aged 34 years and older, without intracavitary pathology and without a future child wish, were recruited in hospitals and general practices in the Netherlands.

Temporizing management vs immediate delivery in early-onset severe preeclampsia between 28 and 34 weeks of gestation (TOTEM study): An open-label randomized controlled trial.

Introduction: There is little evidence to guide the timing of delivery of women with early-onset severe preeclampsia. We hypothesize that immediate delivery is not inferior for neonatal outcome but reduces maternal complications compared with temporizing management.

Material And Methods: This Dutch multicenter open-label randomized clinical trial investigated non-inferiority for neonatal outcome of temporizing management as compared with immediate delivery (TOTEM NTR 2986) in women between 27 and 33 weeks of gestation admitted for early-onset severe preeclampsia with or without HELLP syndrome.

Treatment of women with heavy menstrual bleeding: Results of a prospective cohort study alongside a randomised controlled trial.

Objective: The objective of this study was to compare the reintervention rate of women who opted for treatment with the levonorgestrel-releasing intrauterine system (LNG-IUS) to women who opted for endometrial ablation. Furthermore, the difference in reintervention rate between women in this observational cohort and women who were randomised was compared, with the hypothesis that women who actively decide on treatment have lower reintervention rates compared to women in a RCT.

Study Design: An observational cohort study alongside a multicentre randomised controlled trial (RCT) was conducted between April 2012 and January 2016, with a follow-up time of 24 months, in 26 hospitals and nearby general practices in the Netherlands.

Induction of labour at 41 weeks or expectant management until 42 weeks: A systematic review and an individual participant data meta-analysis of randomised trials.

Background: The risk of perinatal death and severe neonatal morbidity increases gradually after 41 weeks of pregnancy. Several randomised controlled trials (RCTs) have assessed if induction of labour (IOL) in uncomplicated pregnancies at 41 weeks will improve perinatal outcomes. We performed an individual participant data meta-analysis (IPD-MA) on this subject.

Effect of single- versus double-layer uterine closure during caesarean section on postmenstrual spotting (2Close): multicentre, double-blind, randomised controlled superiority trial.

Objective: To evaluate whether double-layer uterine closure after a first caesarean section (CS) is superior compared with single-layer uterine closure in terms of postmenstrual spotting and niche development in the uterine caesarean scar.

Design: Multicentre, double-blind, randomised controlled superiority trial.

Setting: Thirty-two hospitals in the Netherlands.