A Randomized Trial of Induction Versus Expectant Management

Study Overview
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Brief Summary
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A randomized clinical trial to assess whether elective induction of labor at 39 weeks of gestation compared with expectant management will improve outcomes.

Detailed Description
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Given the reported increased risks of adverse events in pregnancies extending beyond 39 weeks it has been hypothesized that a policy of planned elective induction at 39 weeks could improve outcomes for the infant and the mother. For multiparous patients, especially those with a favorable cervix, it is perhaps easy to justify an elective induction at 39 weeks given the low risk of cesarean section. However, for nulliparous patients the current evidence, derived mainly from retrospective observational studies, does not allow a clear recommendation. Nevertheless, a trend towards an increased rate of elective labor induction in pregnancies at 39 weeks has been reported, indicating that practitioners are more commonly using elective induction at this gestational age,even as others caution against routine elective induction prior to 41 weeks given the reported increased risk of cesarean delivery. Ultimately, a randomized controlled trial is necessary to satisfactorily understand whether elective induction of labor of nulliparas at 39 weeks improves neonatal and maternal outcomes.

Official Title
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Induction in Nulliparous Women at 39 Weeks to Prevent Adverse Outcomes: A Randomized Controlled Trial

Conditions
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Labor and Delivery

Intervention / Treatment
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* Procedure: Elective Induction of Labor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Nulliparous - no previous pregnancy beyond 20 weeks Singleton gestation. Twin gestation reduced to singleton, either spontaneously or therapeutically, is not eligible unless the reduction occurred before 14 weeks project gestational age. Gestational age at randomization between 38 weeks 0 days and 38 weeks 6 days inclusive based on clinical information and evaluation of the earliest ultrasound. Exclusion Criteria: Project gestational age at date of first ultrasound is > 20 weeks 6 days Plan for induction of labor prior to 40 weeks 5 days Plan for cesarean delivery or contraindication to labor Breech presentation Signs of labor (regular painful contractions with cervical change) Fetal demise or known major fetal anomaly Heparin or low-molecular weight heparin during the current pregnancy Placenta previa, accreta, vasa previa Active vaginal bleeding greater than bloody show Ruptured membranes Cerclage in current pregnancy Known oligohydramnios, defined as AFI < 5 or MVP < 2 Fetal growth restriction, defined as EFW < 10th percentile Known HIV positivity because of modified delivery plan Major maternal medical illness associated with increased risk for adverse pregnancy outcome (for example, any diabetes mellitus, lupus, any hypertensive disorder, cardiac disease, renal insufficiency) Refusal of blood products Participation in another interventional study that influences management of labor at delivery or perinatal morbidity or mortality Delivery planned elsewhere at a non-Network site
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized trial of 6000 women at 38 weeks 0 days to 38 weeks 6 days randomized to one of two arms: elective induction of labor between 39 weeks 0 days and 39 weeks 4 days; or expectant management (unless a medical indication arises) until at least 40 weeks 5 days.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Expectant Management<br>Expectant management (unless a medical indication arises) until at least 40 weeks 5 days. | |
| Other: Elective Induction of Labor<br>Elective induction of labor between 39 weeks 0 days and 39 weeks 4 days | Procedure: Elective Induction of Labor<br>* Women randomized to induction of labor will undergo induction via oxytocin at 39 weeks 0 days to 39 weeks 4 days. Those with an unfavorable cervix (modified Bishop score < 5) will first undergo cervical ripening (method left to the discretion of the patient's physician) in conjunction with or followed by oxytocin stimulation unless a contraindication arises.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of Severe Neonatal Morbidity and Perinatal Mortality | Includes any one of: Perinatal death Need for respiratory support within 72 hours after birth Apgar score of 3 or less at 5 minutes Hypoxic-ischemic encephalopathy Seizure Infection (confirmed sepsis or pneumonia) Meconium aspiration system Birth trauma (bone fracture, neurologic injury or retinal hemorrhage) Intracranial or subaleal hemorrhage Hypotension requiring vasopressor support | delivery through 72 hours after birth | 
| Perinatal Death (Component of Primary Outcome) | Perinatal death includes antepartum stillbirth, intrapartum stillbirth and neonatal death | antepartum pregnancy period through hospital discharge | 
| Number of Participant Infants Requiring Respiratory Support (Component of Primary Outcome) | Respiratory support includes mechanical ventilation, continuous positive airway pressure or high flow nasal cannula and cardiorespiratory resuscitation | Delivery through discharge | 
| Number of Infants With Apgar Score ≤3 at 5 Minutes (Component of Primary Outcome) | The Apgar score is based on a total score of 1 to 10. The higher the score, the better the baby is doing after birth. A score of 7, 8, or 9 is normal and is a sign that the newborn is in good health. | Delivery through 5 minutes after birth | 
| Number of Infants With Neonatal Hypoxic-ischemic Encelphalopathy (Component of Primary Outcome) |  | delivery through discharge | 
| Number of Infants With Neonatal Seizure (Component of Primary Outcome) |  | Delivery through discharge | 
| Number of Infants With Neonatal Infection (Component of Primary Outcome) | Neonatal infection includes confirmed sepsis and/or confirmed pneumonia | delivery through discharge | 
| Number of Infants With Meconium Aspiration Syndrome (Component of Primary Outcome) |  | Delivery through discharge | 
| Number of Infants With Birth Trauma (Component of Primary Outcome) | Birth trauma includes clavicular, skull or other fracture; brachial plexus palsy, facial nerve palsy, retinal hemorrhage or vocal cord paralysis | During the Delivery process | 
| Number of Infants With Intracranial or Subgaleal Hemorrhage (Component of Primary Outcome) | Intracranial or subgaleal hemorrhage includes Intraventricular hemorrhage grades III or IV, subdural hematoma, subarachnoid hematoma, and subgaleal hematoma | delivery through disharge | 
| Hypotension Requiring Vasopressor Support (Component of Primary Outcome) |  | delivery through discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Cesarean Delivery |  | delivery | 
| Number of Participants Who Had Uterine Incisional Extension at Cesarean Delivery | Incisional extensions at cesarean section, including J shape or T shape; or cervical traumas | delivery | 
| Participants Who Had Operative Vaginal Delivery |  | delivery | 
| Number of Participants Who Had Chorioamnionitis | Chorioamnionitis, defined as a clinical diagnosis before delivery | at any time from randomization through delivery | 
| Number of Participants With Third or Fourth Degree Perineal Laceration |  | delivery | 
| Number of Maternal Deaths | Maternal death at anytime between randomization and hospital discharge. | from randomization to hospital discharge | 
| Number of Participants Admitted to Intensive Care Unit (ICU) | Admission of the participant to the intensive care unit (ICU) | delivery through hospital discharge | 
| Number of Participants Experiencing Hypertensive Disorder of Pregnancy |  | Randomization to hospital discharge | 
| Number of Participants With Postpartum Hemorrhage | defined as any of the following: Transfusion Non-elective hysterectomy Use of two or more uterotonics other than oxytocin Other surgical interventions such as uterine compression sutures, uterine artery ligation, embolization, hypogastric ligation, or balloon tamponade Curettage | delivery through hospital discharge | 
| Labor Agentry Scale Scores | Scores on the Labor Agentry Scale range from 29 to 203, with higher scores indicating greater perceived control during childbirth; included are women who had spontaneous labor, labor that started spontaneously but then was augmented, or induced labor. | Between 6 hours after delivery and 8 weeks after delivery | 
| Labor Pain Scores | Labor pain was scored according to a 10-point Likert scale, with higher scores indicating greater pain; included are women who had spontaneous labor, labor that started spontaneously but then was augmented, or induced labor. | During labor and delivery | 
| Number of Participants With Maternal Postpartum Infection | Defined as any of the following: Clinical diagnosis of endometritis Wound reopened for hematoma, seroma, infection or other reasons Cellulitis requiring antibiotics Pneumonia Pyelonephritis Bacteremia - unknown source Septic pelvic thrombosis | delivery through discharge | 
| Number of Participants With Venous Thromboembolism | Maternal deep venous thrombosis or pulmonary embolism | delivery through discharge | 
| Number of Participants With Indications for Cesarean Delivery | Number of participants with indications for cesarean delivery including dystocia, non-reassuring fetal status or other indication | Labor and delivery | 
| Duration of Respiratory Support | including ventilator, CPAP, high-flow nasal cannula (HFNC) | delivery through hospital discharge | 
| Number of Infants With Cephalohematoma |  | delivery through hospital discharge | 
| Shoulder Dystocia |  | delivery | 
| Number of Infants Who Had Transfusion of Blood Products or Blood |  | delivery through hospital discharge | 
| Number of Infants With Hyperbilirubinemia | Hyperbilirubinemia requiring phototherapy or exchange transfusion | delivery through discharge | 
| Number of Infants With Neonatal Hypoglycemia | glucose < 35 mg/dl and requiring IV therapy | delivery through discharge | 
| Number Infants Admitted to NICU or Intermediate Care | Number infants admitted to intensive care unit (NICU) or intermediate care unit | delivery through hospital discharge | 
| Number of Hours on the Labor and Delivery Unit | Median duration of stay in labor and delivery unit | Hours from admission to L&D to discharge from L&D | 
| Maternal Postpartum Length of Hospital Stay |  | delivery through hospital discharge | 
| Neonatal Length of Hospital Stay |  | delivery through hospital discharge | 
| Number of Participants With Indications for Operative Vaginal Delivery | Number of participants with indications for operative vaginal delivery including dystocia, non-reassuring fetal status and other indications | Labor and delivery | 
| Number of Participants and Breastfeeding Status at 4-8 Weeks After Delivery | Breastfeeding status includes breastfeeding, breastfeeding and formula feeding, or formula feeding | 4-8 weeks after delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Induction of labor, Expectant management of labor, 39 weeks gestation