Preterm Delivery, Short Cervix
Conditions
Keywords
Short cervix, Preterm delivery, Singletons, Pregnancy, Pessary
Brief summary
The purpose of the study is to determine whether the Arabin pessary is a useful intervention of preterm birth at less than 37 weeks in women with a singleton gestation and a short cervix.
Detailed description
While cervical length is one of the most powerful predictors of subsequent preterm birth, the best treatment to reduce subsequent preterm birth remains unknown. This study is a randomized trial of women who have a singleton pregnancy and a short cervical length on transvaginal ultrasound as determined by a study-certified sonographer. It is being conducted at 12 clinical centers across the country and the recruitment target is enrollment of 850 pregnant women. Participants will be randomized to 1) Arabin pessary or 2) usual care as per by local hospital protocol. Pessary is a promising low-cost, non-surgical intervention that appears to be well-tolerated. The pessary will be placed by obstetric providers trained in appropriate placement of the Arabin pessary. The primary outcome of the study is delivery or fetal death prior to 37 weeks 0 days gestational age. In the literature, there are two large trials that have produced conflicting results (M Goya et al, 2012, K Nicolaides et al, 2016). Thus, the results of an adequately powered and appropriately conducted trial from the United States will be important in determining whether pessary is a useful intervention for the prevention of subsequent preterm birth in women with singleton gestation.
Interventions
DEVICEArabin Cervical Pessary
The Arabin cervical pessary is a soft, flexible silicone pessary and fits high around the cervix with no rigid metal framework or inflexible edges that put increase pressure on the vaginal wall. It is available in a variety of sizes however three sizes will be used in this study: Pessary Size upper diameter, lower diameter 1. Nulliparous 65 mm, 32 mm 2. Multiparous 70 mm, 32 mm 3. Alternative 70 mm, 35 mm
Sponsors
The George Washington University Biostatistics Center
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Intervention model description
The study is an unblinded randomized controlled trial. Participants will receive usual care (vaginal progesterone if they meet criteria per local standard of care) or an Arabin cervical pessary (plus progesterone if the local usual care is to receive vaginal progesterone for a short cervix).
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
Yes
Inclusion criteria
* Singleton gestation. Twin gestation reduced to singleton either spontaneously or therapeutically, is not eligible unless the reduction occurred before 13 weeks 6 days project gestational age. Higher order multifetal gestations reduced to singletons are not eligible. * Gestational age at randomization between 16 weeks 0 days and 23 weeks 6 days based on clinical information and evaluation of the earliest ultrasound. * Cervical length on transvaginal examination of less than or equal to 20 mm by a study certified sonographer. There is no lower cervical length threshold.
Exclusion criteria
* Cervical dilation (internal os) 3 cm or greater on digital examination or evidence of prolapsed membranes beyond the external cervical os either at the time of the qualifying cervical ultrasound examination or at a cervical exam immediately before randomization. * Fetal anomaly or imminent fetal demise. This includes lethal anomalies, or anomalies that may lead to early delivery or increased risk of neonatal death e.g., gastroschisis, spina bifida, serious karyotypic abnormalities. An ultrasound examination from 14 weeks 0 days to 23 weeks 6 days by project Estimated Date of Confinement (EDC) must be performed prior to randomization to evaluate the fetus for anomalies. * Previous spontaneous preterm birth between 16 weeks 0 days and 36 weeks 6 days. This includes induction for pPROM in a prior pregnancy. * Planned treatment with intramuscular 17-α hydroxy-progesterone caproate. * Placenta previa, because of risk of bleeding and high potential for indicated preterm birth. A low lying placenta is acceptable. * Active vaginal bleeding greater than spotting at the time of randomization, because of potential exacerbation due to pessary placement. * Symptomatic, untreated vaginal or cervical infection because of potential exacerbation due to pessary placement. Patients may be treated and if subsequently asymptomatic, randomized. However, if it is more than 10 days since the cervical length measurement, a new cervical length measurement must be obtained. * Active, unhealed herpetic lesion on labia minora, vagina, or cervix due to the potential for significant patient discomfort or increasing genital tract viral spread. Once lesion(s) heal and the patient is asymptomatic, she may be randomized. History of herpes is not an exclusion. * Rupture of membranes due to likelihood of pregnancy loss and preterm delivery as well as the risk of ascending infection which could be increased with pessary placement. * More than six contractions per hour reported or documented prior to randomization. It is not necessary to place the patient on a tocodynamometer. * Known major Mullerian anomaly of the uterus (specifically bicornuate, unicornuate, or uterine septum not resected) due to increased risk of preterm delivery which is unlikely to be affected by progesterone. * Any fetal/maternal condition which would require invasive in-utero assessment or treatment, for example significant red cell antigen sensitization or neonatal alloimmune thrombocytopenia. * Major maternal medical illness associated with increased risk for adverse pregnancy outcome or indicated preterm birth (treated hypertension requiring more than one agent, treatment for diabetes prior to pregnancy, chronic renal insufficiency defined by creatinine \>1.4 mg/dL, carcinoma of the breast, conditions treated with chronic oral glucocorticoid therapy). Lupus, uncontrolled thyroid disease, and New York Heart Association(NYHA) stage II or greater cardiac disease are also excluded. Patients with seizure disorders, HIV, and other medical conditions not specifically associated with an increased risk of indicated preterm birth are not excluded. Prior cervical cone/LOOP/Loop Electrocautery Excision Procedure (LEEP) is not an exclusion criterion. * Planned cerclage or cerclage already in place since it would preclude placement of a pessary. * Planned indicated delivery prior to 37 weeks. * Allergy to silicone. * Participation in another interventional study that influences gestational age at delivery or neonatal morbidity or mortality. * Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, may be included. * Prenatal care or delivery planned elsewhere unless the study visits can be made as scheduled and complete outcome information can be obtained.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Preterm Delivery or Fetal Death at Less Than 37 Weeks. | Before 37 weeks 0 days gestation, a period of up to 21 weeks from enrollment. | Participants who either delivered or experienced a fetal death prior to 37 weeks gestation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Interval From Randomization to Delivery or Fetal Death | from randomization to delivery or fetal death (up to a length of 189 days) | The median interval between randomization to delivery or death of the fetus. |
| Gestational Age at Delivery | From randomization to delivery (up to a length of 189 days) | Median gestational age (in weeks) at the time of delivery |
| Number of Participants With Preterm Delivery or Fetal Death at Less Than 28 Weeks Gestation | from randomization to less than 28 weeks gestation (a period of less than 91 days) | The number of participants who either delivered or experienced a fetal death prior to 28 weeks gestation. |
| Number of Participants With Preterm Delivery or Fetal Death at Less Than 32 Weeks Gestation | from randomization to less than 32 weeks gestation (a period of less than 119 days) | The number of participants who either delivered or experienced a fetal death prior to 32 weeks gestation. |
| Number of Participants With Preterm Delivery or Fetal Death at Less Than 35 Weeks Gestation | from randomization to less than 35 weeks gestation (a period of less than 140 days) | The number of participants who either delivered or experienced a fetal death prior to 35 weeks gestation. |
| Number of Participants With Preterm Premature Rupture of Membranes | Before 37 weeks 0 days gestation, a period of up to 21 weeks from enrollment | Participants were categorized as yes if the amniotic membranes ruptured prior to labor onset and before 37 weeks gestation. |
| Number of Participants With Spontaneous Preterm Delivery. | From randomization to delivery (up to a length of 189 days) | The number of participants who experienced spontaneous onset of labor and had an unassisted vaginal delivery prior to 37 weeks gestation. Induction for delivery was not performed and operative techniques such as forceps or vacuum were not used. |
| Number of Participants With Indicated Preterm Delivery | from randomization to delivery (up to a length of 189 days) | The number of participants who underwent labor induction or had an assisted vaginal delivery with forceps or vacuum or cesarean delivery prior to 37 weeks gestation. |
| Number of Participants With Cesarean Delivery | From randomization to delivery (up to a length of 189 days) | The number of participants who underwent a surgical procedure for delivery (cesarean) at any gestational age. |
| Number of Participants With Chorioamnionitis | From randomization to delivery (up to a length of 189 days) | The number of participants who had a clinical diagnosis of chorioamnionitis and a body temperature of at least 100.0° F (38° C) and no other defined infection. |
| Median Length of Maternal Antepartum Hospital Stay Before Delivery | from date of admission for delivery up to delivery date (up to 5 days) | Median number of days from maternal hospital admission for delivery and the date of delivery. |
| Number of Participants With Vaginal Infection | From randomization to delivery (up to a length of 189 days) | The number of participants with a clinical diagnosis of a vaginal infection. Includes participants with at least one study visit. |
| The Number of Participants Who Had a Vaginal Infection and Received Antibiotic Treatment, Among All Persons Enrolled With at Least One Study Visit | From randomization to delivery (up to a length of 189 days) | The number of participants who received antibiotics or antifungal medication for a vaginal infection (out of the total sample for which data is available) |
| Number of Participants Treated for Preterm Labor Including Placement of Cerclage | From randomization to delivery (up to a length of 189 days) | The number of participants who received any one of the following treatments for preterm labor: tocolysis, cerclage, bedrest, antenatal corticosteroids for fetal lung maturity, or magnesium sulfate for neuroprotection. |
| Median Duration of Neonatal Ventilator or Continuous Positive Airway Pressure Use | delivery through hospital discharge (up to a length of 435 days) | Median number of days a neonate or infant was on a ventilator or received continuous positive airway pressure. |
| Number of Neonates Requiring Ventilator or Continuous Positive Airway Pressure Use | delivery through hospital discharge (up to a length of 435 days) | The number of neonates or infants who required ventilator support or received continuous positive airway pressure. |
| Median Duration (in Days) of Neonatal Supplemental Oxygen Use | delivery through hospital discharge (up to a length of 435 days) | Median number of days a neonate received supplemental oxygen after admission to the NICU or intermediate nursery. Supplemental oxygen is defined as FiO2 \> 0.21. |
| Number of Neonates With Seizures Requiring Treatment | delivery through hospital discharge (up to a length of 435 days) | The number of neonates with a clinical diagnosis of seizures who received anti-seizure medication. |
| Number of Neonates Small for Gestational Age < 5th Percentile | delivery through hospital discharge (up to a length of 435 days) | The number of neonates whose birthweight compared with gestational age at delivery was less than the 5th percentile, as assessed by sex and race, using United States birth certificate data. |
| Number of Neonates With Intraventricular Hemorrhage (IVH) Grades III or IV | delivery through hospital discharge (up to a length of 435 days) | IVH grades III or IV are as determined by cranial ultrasounds performed as part of routine clinical care and classified based on the Papile classification system |
| Number of Neonates With Retinopathy of Prematurity (ROP) | delivery through hospital discharge (up to a length of 435 days) | The number of neonates with a clinical diagnosis of retinopathy of prematurity where an ophthalmologic examination of the retina was performed. |
| Number of Neonates Experiencing Respiratory Distress Syndrome (RDS) | delivery through hospital discharge (up to a length of 435 days) | The number of neonates with a diagnosis of respiratory distress syndrome defined as the presence of clinical signs of respiratory distress (tachypnea, retractions, flaring, grunting, or cyanosis), with oxygen requirement and a chest x-ray that show hypoaeration and reticulogranular infiltrates. |
| Number of Neonates With Bronchopulmonary Dysplasia (BPD) | Delivery through 28 days of life if delivered at or after 32 weeks. Delivery through 36 weeks gestation if delivered before 32 weeks. | The number of neonates with a clinical diagnosis of bronchopulmonary dysplasia defined as oxygen requirement at 28 days of life if delivered at or after 32 weeks gestation, or at 36 weeks project gestational age if delivered before 32 weeks gestation. |
| Number of Neonates With Necrotizing Enterocolitis (NEC) Stage 2 or 3 | delivery through hospital discharge (up to a length of 435 days) | The number of neonates diagnosed with NEC, defined as modified Bell Stage 2 or 3 where stage 2 represents clinical signs and symptoms with pneumatosis intestinalis on radiographs and stage 3 is defined as advanced clinical signs and symptoms, pneumatosis, impending or proven intestinal perforation. |
| Number of Neonates With Hyperbilirubinemia | delivery through hospital discharge (up to a length of 435 days) | The number of neonates diagnosed with hyperbilirubinemia, defined as peak total bilirubin of at least 15 mg% or the use of phototherapy |
| Neonatal Infectious Morbidity Including Sepsis, Suspected Sepsis and Pneumonia | delivery through hospital discharge (up to a length of 435 days) | The number of neonates diagnosed with any one of the following: * Sepsis (within 72 hours and \> 72 hours after birth) defined as a clinically ill infant in whom systemic infection is suspected with a positive blood, CSF, or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal radiograph confirming infection. * Suspected sepsis. The diagnosis of suspected sepsis will include infants with suspicious clinical findings of infection, but no positive cultures or radiographs. * Pneumonia. The diagnosis of pneumonia will be confirmed by radiograph or positive blood culture. |
| Number of Neonates With Early Onset Sepsis | within 72 hours of birth | The number of neonates with a clinical diagnosis of sepsis within 72 hours of life, defined as a clinically ill infant in whom systemic infection is suspected with a positive blood, cerebrospinal fluid, or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal radiograph confirming infection. |
| Number of Neonates With Late Onset Sepsis | 72 hours of birth or later (up to hospital discharge - a maximum of 435 days) | The number of neonates with a clinical diagnosis of sepsis at or after 72 hours of life, defined as the presence of a clinically ill infant in whom systemic infection is suspected with a positive blood, cerebrospinal fluid, or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal radiograph confirming infection. |
| Number of Neonates With Suspected Sepsis | delivery through hospital discharge (up to a length of 435 days) | The number of neonates with suspicious clinical findings of infection, but no positive cultures or radiographs. |
| Number of Neonates With Pneumonia | delivery through hospital discharge (up to a length of 435 days) | The number of neonates with a clinical diagnosis of pneumonia within 72 hours of birth and confirmed by either an x-ray demonstrating consolidation with air bronchograms, or a positive blood culture performed at the time of clinical diagnosis. |
| Number of Neonates With Composite Outcome | delivery through hospital discharge (up to a length of 435 days) | The number of neonates diagnosed with any one of fetal or neonatal death or Respiratory Distress Syndrome, Grade 3 or 4 Intraventricular Hemorrhage, Periventricular Leukomalacia, Stage 2 or 3 Nectrotizing Enterocolitis, Bronchopulmonary Dysplasia, Stage III or higher Retinopathy of Prematurity, or early onset sepsis. |
| Median Length of Neonatal Hospital Stay | delivery through hospital discharge (up to a length of 435 days) | Median number of days the neonate/infant remained in hospital. |
| Median Number of Days in Neonatal Intensive Care Unit (NICU) | delivery through hospital discharge (up to a length of 435 days) | Median number of days the neonate/infant remained in the neonatal intensive care unit or special care nursery. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRebecca Clifton, Ph.D.
George Washington University Biostatistics Center
STUDY_DIRECTORMonica Longo, MD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
STUDY_CHAIRMatthew Hoffman, MD
Christiana Care Health Services
Participant flow
Recruitment details
From February 2017 through November 5, 2021 we conducted a multicenter randomized trial comparing the Arabin pessary versus usual care at 12 clinical centers. Individuals with asymptomatic singleton pregnancies who had a transvaginal cervical length \<20mm between 16 weeks 0 days and 23 weeks 6 days were identified per the local protocol for assessment of cervical length. People meeting eligibility requirements and accepting trial participation were randomized to either pessary or usual care.
Participants by arm
| Arm | Count |
|---|---|
| Cervical Arabin Pessary Arabin pessary. Participants will also receive vaginal progesterone to be administered daily, if it is the local standard of care.
Pessary: The Arabin cervical pessary is a soft, flexible silicone pessary and fits high around the cervix with no rigid metal framework or inflexible edges that put increase pressure on the vaginal wall. It is available in a variety of sizes however three sizes will be used in this study:
Pessary Size upper diameter, lower diameter
1. Nulliparous 65 mm, 32 mm
2. Multiparous 70 mm, 32 mm
3. Alternative 70 mm, 35 mm | 280 |
| No Pessary Participants will also receive vaginal progesterone to be administered daily, if it is the local standard of care. | 264 |
| Total | 544 |
Baseline characteristics
| Characteristic | Cervical Arabin Pessary | No Pessary | Total |
|---|---|---|---|
| Age, Continuous | 29.9 years STANDARD_DEVIATION 6 | 29.1 years STANDARD_DEVIATION 5.9 | 29.5 years STANDARD_DEVIATION 6 |
| Cervical length at screening (mm) | 12.7 mm STANDARD_DEVIATION 5.2 | 12.7 mm STANDARD_DEVIATION 5.3 | 12.7 mm STANDARD_DEVIATION 5.3 |
| Gestational age at enrollment (weeks) | 21.7 weeks | 21.9 weeks | 21.7 weeks |
| Race/Ethnicity, Customized American Indian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 12 Participants | 16 Participants | 28 Participants |
| Race/Ethnicity, Customized Hispanic | 62 Participants | 56 Participants | 118 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Non-Hispanic Black | 132 Participants | 127 Participants | 259 Participants |
| Race/Ethnicity, Customized Non-Hispanic White | 61 Participants | 53 Participants | 114 Participants |
| Race/Ethnicity, Customized Other/not reported/unknown | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Female | 280 Participants | 264 Participants | 544 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 37 / 280 | 18 / 264 |
| other Total, other adverse events | 248 / 280 | 200 / 264 |
| serious Total, serious adverse events | 13 / 280 | 17 / 264 |
Outcome results
Primary
Number of Participants With Preterm Delivery or Fetal Death at Less Than 37 Weeks.
Participants who either delivered or experienced a fetal death prior to 37 weeks gestation.
Time frame: Before 37 weeks 0 days gestation, a period of up to 21 weeks from enrollment.
Population: 1 participant in each group was lost to follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Participants With Preterm Delivery or Fetal Death at Less Than 37 Weeks. | 127 Participants |
| No Pessary | Number of Participants With Preterm Delivery or Fetal Death at Less Than 37 Weeks. | 120 Participants |
95% CI: [0.83, 1.2]
Secondary
Gestational Age at Delivery
Median gestational age (in weeks) at the time of delivery
Time frame: From randomization to delivery (up to a length of 189 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cervical Arabin Pessary | Gestational Age at Delivery | 37.3 weeks |
| No Pessary | Gestational Age at Delivery | 37.4 weeks |
95% CI: [-1.06, 0.8]
Secondary
Interval From Randomization to Delivery or Fetal Death
The median interval between randomization to delivery or death of the fetus.
Time frame: from randomization to delivery or fetal death (up to a length of 189 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cervical Arabin Pessary | Interval From Randomization to Delivery or Fetal Death | 105 days |
| No Pessary | Interval From Randomization to Delivery or Fetal Death | 103 days |
95% CI: [-4, 8]
Secondary
Median Duration (in Days) of Neonatal Supplemental Oxygen Use
Median number of days a neonate received supplemental oxygen after admission to the NICU or intermediate nursery. Supplemental oxygen is defined as FiO2 \> 0.21.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cervical Arabin Pessary | Median Duration (in Days) of Neonatal Supplemental Oxygen Use | 7 days |
| No Pessary | Median Duration (in Days) of Neonatal Supplemental Oxygen Use | 6 days |
95% CI: [-12, 14]
Secondary
Median Duration of Neonatal Ventilator or Continuous Positive Airway Pressure Use
Median number of days a neonate or infant was on a ventilator or received continuous positive airway pressure.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cervical Arabin Pessary | Median Duration of Neonatal Ventilator or Continuous Positive Airway Pressure Use | 6 days |
| No Pessary | Median Duration of Neonatal Ventilator or Continuous Positive Airway Pressure Use | 5 days |
95% CI: [-12, 12]
Secondary
Median Length of Maternal Antepartum Hospital Stay Before Delivery
Median number of days from maternal hospital admission for delivery and the date of delivery.
Time frame: from date of admission for delivery up to delivery date (up to 5 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cervical Arabin Pessary | Median Length of Maternal Antepartum Hospital Stay Before Delivery | 1 days |
| No Pessary | Median Length of Maternal Antepartum Hospital Stay Before Delivery | 1 days |
95% CI: [0, 0]
Secondary
Median Length of Neonatal Hospital Stay
Median number of days the neonate/infant remained in hospital.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cervical Arabin Pessary | Median Length of Neonatal Hospital Stay | 3 days |
| No Pessary | Median Length of Neonatal Hospital Stay | 3 days |
95% CI: [0, 0]
Secondary
Median Number of Days in Neonatal Intensive Care Unit (NICU)
Median number of days the neonate/infant remained in the neonatal intensive care unit or special care nursery.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cervical Arabin Pessary | Median Number of Days in Neonatal Intensive Care Unit (NICU) | 50 days |
| No Pessary | Median Number of Days in Neonatal Intensive Care Unit (NICU) | 37 days |
95% CI: [-16, 36]
Secondary
Neonatal Infectious Morbidity Including Sepsis, Suspected Sepsis and Pneumonia
The number of neonates diagnosed with any one of the following: * Sepsis (within 72 hours and \> 72 hours after birth) defined as a clinically ill infant in whom systemic infection is suspected with a positive blood, CSF, or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal radiograph confirming infection. * Suspected sepsis. The diagnosis of suspected sepsis will include infants with suspicious clinical findings of infection, but no positive cultures or radiographs. * Pneumonia. The diagnosis of pneumonia will be confirmed by radiograph or positive blood culture.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9). 2 neonates missing data in the pessary group
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Neonatal Infectious Morbidity Including Sepsis, Suspected Sepsis and Pneumonia | 53 Participants |
| No Pessary | Neonatal Infectious Morbidity Including Sepsis, Suspected Sepsis and Pneumonia | 65 Participants |
95% CI: [0.58, 1.1]
Secondary
Number of Neonates Experiencing Respiratory Distress Syndrome (RDS)
The number of neonates with a diagnosis of respiratory distress syndrome defined as the presence of clinical signs of respiratory distress (tachypnea, retractions, flaring, grunting, or cyanosis), with oxygen requirement and a chest x-ray that show hypoaeration and reticulogranular infiltrates.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9). 2 neonates in the pessary group are missing data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates Experiencing Respiratory Distress Syndrome (RDS) | 67 Participants |
| No Pessary | Number of Neonates Experiencing Respiratory Distress Syndrome (RDS) | 69 Participants |
95% CI: [0.71, 1.27]
Secondary
Number of Neonates Requiring Ventilator or Continuous Positive Airway Pressure Use
The number of neonates or infants who required ventilator support or received continuous positive airway pressure.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9). 2 neonates missing date in the pessary group
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates Requiring Ventilator or Continuous Positive Airway Pressure Use | 75 Participants |
| No Pessary | Number of Neonates Requiring Ventilator or Continuous Positive Airway Pressure Use | 82 Participants |
95% CI: [0.69, 1.17]
Secondary
Number of Neonates Small for Gestational Age < 5th Percentile
The number of neonates whose birthweight compared with gestational age at delivery was less than the 5th percentile, as assessed by sex and race, using United States birth certificate data.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates Small for Gestational Age < 5th Percentile | 5 Participants |
| No Pessary | Number of Neonates Small for Gestational Age < 5th Percentile | 6 Participants |
95% CI: [0.25, 2.65]
Secondary
Number of Neonates With Bronchopulmonary Dysplasia (BPD)
The number of neonates with a clinical diagnosis of bronchopulmonary dysplasia defined as oxygen requirement at 28 days of life if delivered at or after 32 weeks gestation, or at 36 weeks project gestational age if delivered before 32 weeks gestation.
Time frame: Delivery through 28 days of life if delivered at or after 32 weeks. Delivery through 36 weeks gestation if delivered before 32 weeks.
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates With Bronchopulmonary Dysplasia (BPD) | 14 Participants |
| No Pessary | Number of Neonates With Bronchopulmonary Dysplasia (BPD) | 19 Participants |
95% CI: [0.37, 1.41]
Secondary
Number of Neonates With Composite Outcome
The number of neonates diagnosed with any one of fetal or neonatal death or Respiratory Distress Syndrome, Grade 3 or 4 Intraventricular Hemorrhage, Periventricular Leukomalacia, Stage 2 or 3 Nectrotizing Enterocolitis, Bronchopulmonary Dysplasia, Stage III or higher Retinopathy of Prematurity, or early onset sepsis.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9). 1 neonate missing data in the pessary group
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates With Composite Outcome | 81 Participants |
| No Pessary | Number of Neonates With Composite Outcome | 74 Participants |
95% CI: [0.81, 1.37]
Secondary
Number of Neonates With Early Onset Sepsis
The number of neonates with a clinical diagnosis of sepsis within 72 hours of life, defined as a clinically ill infant in whom systemic infection is suspected with a positive blood, cerebrospinal fluid, or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal radiograph confirming infection.
Time frame: within 72 hours of birth
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates With Early Onset Sepsis | 5 Participants |
| No Pessary | Number of Neonates With Early Onset Sepsis | 2 Participants |
95% CI: [0.48, 12.57]
Secondary
Number of Neonates With Hyperbilirubinemia
The number of neonates diagnosed with hyperbilirubinemia, defined as peak total bilirubin of at least 15 mg% or the use of phototherapy
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9). 2 neonates missing data in the pessary group. 1 neonate missing data in the no pessary group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates With Hyperbilirubinemia | 84 Participants |
| No Pessary | Number of Neonates With Hyperbilirubinemia | 82 Participants |
95% CI: [0.78, 1.29]
Secondary
Number of Neonates With Intraventricular Hemorrhage (IVH) Grades III or IV
IVH grades III or IV are as determined by cranial ultrasounds performed as part of routine clinical care and classified based on the Papile classification system
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9). there are 3 neonates with missing data in the pessary group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates With Intraventricular Hemorrhage (IVH) Grades III or IV | 4 Participants |
| No Pessary | Number of Neonates With Intraventricular Hemorrhage (IVH) Grades III or IV | 7 Participants |
95% CI: [0.17, 1.9]
Secondary
Number of Neonates With Late Onset Sepsis
The number of neonates with a clinical diagnosis of sepsis at or after 72 hours of life, defined as the presence of a clinically ill infant in whom systemic infection is suspected with a positive blood, cerebrospinal fluid, or catheterized/suprapubic urine culture; or, in the absence of positive cultures, clinical evidence of cardiovascular collapse or an unequivocal radiograph confirming infection.
Time frame: 72 hours of birth or later (up to hospital discharge - a maximum of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates With Late Onset Sepsis | 8 Participants |
| No Pessary | Number of Neonates With Late Onset Sepsis | 12 Participants |
95% CI: [0.27, 1.58]
Secondary
Number of Neonates With Necrotizing Enterocolitis (NEC) Stage 2 or 3
The number of neonates diagnosed with NEC, defined as modified Bell Stage 2 or 3 where stage 2 represents clinical signs and symptoms with pneumatosis intestinalis on radiographs and stage 3 is defined as advanced clinical signs and symptoms, pneumatosis, impending or proven intestinal perforation.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates With Necrotizing Enterocolitis (NEC) Stage 2 or 3 | 7 Participants |
| No Pessary | Number of Neonates With Necrotizing Enterocolitis (NEC) Stage 2 or 3 | 6 Participants |
95% CI: [0.39, 3.37]
Secondary
Number of Neonates With Pneumonia
The number of neonates with a clinical diagnosis of pneumonia within 72 hours of birth and confirmed by either an x-ray demonstrating consolidation with air bronchograms, or a positive blood culture performed at the time of clinical diagnosis.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates With Pneumonia | 2 Participants |
| No Pessary | Number of Neonates With Pneumonia | 4 Participants |
95% CI: [0.09, 2.66]
Secondary
Number of Neonates With Retinopathy of Prematurity (ROP)
The number of neonates with a clinical diagnosis of retinopathy of prematurity where an ophthalmologic examination of the retina was performed.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9). 2 neonates in the pessary group are missing data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates With Retinopathy of Prematurity (ROP) | 27 Participants |
| No Pessary | Number of Neonates With Retinopathy of Prematurity (ROP) | 23 Participants |
95% CI: [0.68, 1.96]
Secondary
Number of Neonates With Seizures Requiring Treatment
The number of neonates with a clinical diagnosis of seizures who received anti-seizure medication.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates With Seizures Requiring Treatment | 1 Participants |
| No Pessary | Number of Neonates With Seizures Requiring Treatment | 1 Participants |
95% CI: [0.06, 15.7]
Secondary
Number of Neonates With Suspected Sepsis
The number of neonates with suspicious clinical findings of infection, but no positive cultures or radiographs.
Time frame: delivery through hospital discharge (up to a length of 435 days)
Population: among livebirth deliveries (excludes fetal deaths - pessary 18, no pessary 9). 2 neonates missing data in the pessary group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Neonates With Suspected Sepsis | 38 Participants |
| No Pessary | Number of Neonates With Suspected Sepsis | 51 Participants |
95% CI: [0.47, 0.97]
Secondary
Number of Participants Treated for Preterm Labor Including Placement of Cerclage
The number of participants who received any one of the following treatments for preterm labor: tocolysis, cerclage, bedrest, antenatal corticosteroids for fetal lung maturity, or magnesium sulfate for neuroprotection.
Time frame: From randomization to delivery (up to a length of 189 days)
Population: Data missing for 21 participants in the pessary group and 13 participants in the no pessary group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Participants Treated for Preterm Labor Including Placement of Cerclage | 150 Participants |
| No Pessary | Number of Participants Treated for Preterm Labor Including Placement of Cerclage | 143 Participants |
95% CI: [0.88, 1.18]
Secondary
Number of Participants With Cesarean Delivery
The number of participants who underwent a surgical procedure for delivery (cesarean) at any gestational age.
Time frame: From randomization to delivery (up to a length of 189 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Participants With Cesarean Delivery | 86 Participants |
| No Pessary | Number of Participants With Cesarean Delivery | 80 Participants |
95% CI: [0.79, 1.31]
Secondary
Number of Participants With Chorioamnionitis
The number of participants who had a clinical diagnosis of chorioamnionitis and a body temperature of at least 100.0° F (38° C) and no other defined infection.
Time frame: From randomization to delivery (up to a length of 189 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Participants With Chorioamnionitis | 18 Participants |
| No Pessary | Number of Participants With Chorioamnionitis | 16 Participants |
95% CI: [0.55, 2.04]
Secondary
Number of Participants With Indicated Preterm Delivery
The number of participants who underwent labor induction or had an assisted vaginal delivery with forceps or vacuum or cesarean delivery prior to 37 weeks gestation.
Time frame: from randomization to delivery (up to a length of 189 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Participants With Indicated Preterm Delivery | 18 Participants |
| No Pessary | Number of Participants With Indicated Preterm Delivery | 14 Participants |
95% CI: [0.61, 2.39]
Secondary
Number of Participants With Preterm Delivery or Fetal Death at Less Than 28 Weeks Gestation
The number of participants who either delivered or experienced a fetal death prior to 28 weeks gestation.
Time frame: from randomization to less than 28 weeks gestation (a period of less than 91 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Participants With Preterm Delivery or Fetal Death at Less Than 28 Weeks Gestation | 72 Participants |
| No Pessary | Number of Participants With Preterm Delivery or Fetal Death at Less Than 28 Weeks Gestation | 54 Participants |
95% CI: [0.92, 1.71]
Secondary
Number of Participants With Preterm Delivery or Fetal Death at Less Than 32 Weeks Gestation
The number of participants who either delivered or experienced a fetal death prior to 32 weeks gestation.
Time frame: from randomization to less than 32 weeks gestation (a period of less than 119 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Participants With Preterm Delivery or Fetal Death at Less Than 32 Weeks Gestation | 93 Participants |
| No Pessary | Number of Participants With Preterm Delivery or Fetal Death at Less Than 32 Weeks Gestation | 73 Participants |
95% CI: [0.93, 1.55]
Secondary
Number of Participants With Preterm Delivery or Fetal Death at Less Than 35 Weeks Gestation
The number of participants who either delivered or experienced a fetal death prior to 35 weeks gestation.
Time frame: from randomization to less than 35 weeks gestation (a period of less than 140 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Participants With Preterm Delivery or Fetal Death at Less Than 35 Weeks Gestation | 111 Participants |
| No Pessary | Number of Participants With Preterm Delivery or Fetal Death at Less Than 35 Weeks Gestation | 90 Participants |
95% CI: [0.93, 1.45]
Secondary
Number of Participants With Preterm Premature Rupture of Membranes
Participants were categorized as yes if the amniotic membranes ruptured prior to labor onset and before 37 weeks gestation.
Time frame: Before 37 weeks 0 days gestation, a period of up to 21 weeks from enrollment
Population: Data is missing for 2 participants in the pessary group and 5 participants in the no pessary group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Participants With Preterm Premature Rupture of Membranes | 64 Participants |
| No Pessary | Number of Participants With Preterm Premature Rupture of Membranes | 46 Participants |
95% CI: [0.92, 1.82]
Secondary
Number of Participants With Spontaneous Preterm Delivery.
The number of participants who experienced spontaneous onset of labor and had an unassisted vaginal delivery prior to 37 weeks gestation. Induction for delivery was not performed and operative techniques such as forceps or vacuum were not used.
Time frame: From randomization to delivery (up to a length of 189 days)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Participants With Spontaneous Preterm Delivery. | 109 Participants |
| No Pessary | Number of Participants With Spontaneous Preterm Delivery. | 106 Participants |
95% CI: [0.79, 1.19]
Secondary
Number of Participants With Vaginal Infection
The number of participants with a clinical diagnosis of a vaginal infection. Includes participants with at least one study visit.
Time frame: From randomization to delivery (up to a length of 189 days)
Population: Data missing for 53 participants in the pessary group and 43 participants in the no pessary group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | Number of Participants With Vaginal Infection | 57 Participants |
| No Pessary | Number of Participants With Vaginal Infection | 41 Participants |
95% CI: [0.95, 1.94]
Secondary
The Number of Participants Who Had a Vaginal Infection and Received Antibiotic Treatment, Among All Persons Enrolled With at Least One Study Visit
The number of participants who received antibiotics or antifungal medication for a vaginal infection (out of the total sample for which data is available)
Time frame: From randomization to delivery (up to a length of 189 days)
Population: Data missing for 53 participants in the pessary group and 43 participants in the no pessary group.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cervical Arabin Pessary | The Number of Participants Who Had a Vaginal Infection and Received Antibiotic Treatment, Among All Persons Enrolled With at Least One Study Visit | 55 Participants |
| No Pessary | The Number of Participants Who Had a Vaginal Infection and Received Antibiotic Treatment, Among All Persons Enrolled With at Least One Study Visit | 37 Participants |
95% CI: [1, 2.11]