Preterm Birth, Cervical Insufficiency, Bed Rest, Pregnancy Complications, Immobilization, Depression, Postpartum, Pregnancy Outcome, Infant, Premature, Uterine Cervical Incompetence, Premature Birth, Obstetric Labor, Premature, Physical Activity, Bone Density
Conditions
Brief summary
Maternal AR has long been used to prevent PTB. However, definitions of AR vary widely, ranging from complete bed rest to partial limitation of physical activity for one or more hours daily. The use of maternal AR to prevent preterm birth is largely based on observational evidence linking strenuous physical activity to an increased risk of preterm birth, and the assumption that reduced activity may decrease myometrial activity. However, the existing evidence on the clinical effects of AR remains limited and has not demonstrated a reduction in preterm birth or a delay in deliv-ery. In contrast, some studies suggest a potential increase in preterm birth following AR and instead significant adverse maternal and fetal effects. The overall aim of this study is to compare gestational age at birth in women with a short cervix who are prescribed AR compared with women with a short cervix who are not prescribed AR (NAR). The primary hypothesis is that NAR is non-inferior to AR in prolonging pregnancy in women with a short cervix. Secondary hypotheses are that, compared with AR, NAR is associated with higher level of physical activity, lower risk of maternal depression, and reduced risk of loss of maternal bone mineral density. Through the BEWISE study, we wish to implement a change in the Danish national clinical practice regarding AR from recommending AR in risk groups (current practice) to no longer recommending AR as part as routine care (new practice). We will evaluate this change in clinical practice by prospectively collecting data from women both before and after implementation of the new recommendation. The transition from AR to NAR will be implemented sequentially in each Danish region using a randomised stepped-wedge (SW) cluster design, with each region constituting a cluster. The order in which regions transition is determined by randomisation. Each region will adopt the new recommendation at 3-month intervals, resulting in full national transition from AR to NAR within 12 months Eligible participants are pregnant women in gestational age 20+0 to 33+6 and cervical length \< 25 mm in singleton pregnancies and \< 30 mm in multiple pregnancies. Participants must be above 18 years of age and be able to read and understand Danish or English. There are no exclusion criteria. The primary outcome is gestational age in days (continuous).
Interventions
Recommendation to restrict physical activity in pregnant women with a short cervix. This may include increased rest or bed rest according to local clinical practice.
Recommendation to continue normal daily activity in pregnant women with a short cervix, without restricting physical activity.
Sponsors
Study design
Intervention model description
The BEWISE study is designed as a non-inferiority stepped-wedge cluster randomized controlled trial. The transition from activity restriction to no activity restriction is determined by a randomized sequence at cluster level and implemented stepwise across the Danish regions. The recommendation provided to each participant depends solely on the implementation phase of her region and is not influenced by individual participation or consent. Outcomes are measured across regions before and after implementation of the new recommendation.
Eligibility
Inclusion criteria
Pregnant women with gestational age 20+0 to 33+6 * Cervical length \< 25 mm in singleton pregnancies and \< 30 mm in multiple pregnancies * Above 18 years of age * Reads and understands Danish or English
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gestational age at birth | At birth (from inclusion until delivery) | Gestational age at birth measured in completed days of pregnancy. This is calculated based on the estimated due date from ultrasound (crown-rump lenght \<14weeks). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apgar score at 5 minutes | At birth (from inclusion until delivery) | — |
| Birth before 37 weeks of gestation | At birth | — |
| Gestational age at birth, pooled | At birth (from inclusion until delivery) | * 14+0-21+6 weeks * 22+0-27+6 weeks * 28+0-31+6 weeks * 32+0-36+6 weeks * Birth after 37+0 weeks of gestation |
| Latency from inclusion to birth (days) | At birth (from inclusion until delivery) | — |
| Onset of birth | At birth (from inclusion until delivery) | * Spontaneous * Induction * Caesarean section |
| Mode of birth | At birth (from inclusion until delivery) | * Vaginal * Assisted vaginal * Planned caesarean section * Non planned caesarean section |
| - Non-occipital presentation | At birth (from inclusion until delivery) | — |
| Interventions during birth | At birth (from inclusion until delivery) | * Oxytocin-infusion * Epidural anaesthesia |
| Degree of birth tear | At birth (from inclusion until delivery) | * No tear * 1\. or 2. degree tear * 3\. or 4. degree tear |
| Maternal serious morbidity | From inclusion to 42 days after delivery | Admission to an intensive care unit or a unit providing 24-hour medical supervision, mechanical ventilation, or continuous vasoactive drug support at any time during pregnancy and postpartum due to pregnancy- or childbirth-related complications |
| Umbilical cord arterial pH | At birth (from inclusion until delivery) | — |
| EPDS depression score | From inclusion to 8 weeks after due date | — |
| Bone turnover marker level | At inclusion and after 4 and 8 weeks. | * Procollagen type 1 N-propeptide (PINP) * Carboxy-terminal telopeptide of type I collagen (CTX) |
| Lumbar spine Z-score | 12 months after stopped breastfeeding | — |
| Data from SENS activity tracker | At birth (from inclusion until delivery) | Step count Time in supine position |
| Neonatal mortality | At birth (from inclusion until delivery) | — |
| Fetal loss | At birth (from inclusion until delivery) | — |
| Birth weight | At birth (from inclusion until delivery) | — |
| Neonatal admission, days | From inclusion until discharge or 44 postmenstrual weeks | — |
| CNS morbidity | From inclusion until discharge or 44 postmenstrual weeks | Intraventricular haemorrhage grade III or IV, Periventricular leukomalacia |
| Gastrointestinal morbidity | From inclusion until discharge or 44 postmenstrual weeks | Necrotizing enterocolitis (NEC) requiring surgery (Bell's stage 3), Spontaneous intestinal perfo-ration (SIP) requiring surgical treatment |
| Respiratory support | From inclusion until discharge or 44 postmenstrual weeks | Mechanical ventilation or non-invasive ventilation (NIV) |
| Early onset infection | From inclusion to 5 days after birth | Definition: \>5 days of i.v. antibiotics where the treatment starts within the first week after delivery. |
| Respiratory distress syndrome (RDS) | From inclusion until discharge or 44 postmenstrual weeks | — |
Contacts
Aarhus Univeristy Hospital, Department of Obstetrics and Gynecology