Clinical trial NCT05477381: Cervical Softening and the Prediction of Preterm Birth
Official title: Assessment of Cervical SofTening and the Prediction of Preterm Birth'
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Preterm Birth
Threatened Preterm Labor
Premature Birth
Premature Labor
Diagnosis
Cervical Incompetence, With Delivery
Cervical Incompetence in Pregnancy as Antepartum Condition
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Pregnolia AG
First posted: 2022-07-28
Enrollment: 390
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women with an increased risk of preterm birth. Women are eligible when they fall in one of following categories:

* Medical History of Spontaneous Preterm Birth before 34 weeks of gestation or
* Threatened Preterm Birth between 24 and 34 weeks of gestation

Brief summary: Currently, transvaginal cervical length measurement is used to screen in asymptomatic pregnant women with a history of PTB. In symptomatic women, presenting with threatened PTB cervical length in combination with the fibronectin test is used to identify women at high risk to deliver preterm. However, the predictive capacity of transvaginal cervical length measurement is limited. In pregnant women with a history of PTB, it only identifies a proportion of women who will have recurrent PTB. For symptomatic women, 30-60% of these women admitted to the hospital, do not deliver within seven days, leading to overtreatment of these women.

Cervical softening is precursor of cervical shortening, effacement and dilatation and therefore cervical softening is a promising new marker that is based on tissue elasticity. However, the predictive value of cervical softening and the relation with spontaneous PTB still has to be determined. With the newly developed Pregnolia® System cervical softness could be measured on a standardized and safe manner. This study could help to improve care for women with a history of spontaneous PTB.

Detailed description: Preterm birth (PTB) is amongst the leading causes of perinatal and childhood morbidity and mortality. Therefore, accurate identification of pregnant women at high risk of PTB is important. Identifying these women, enables obstetric healthcare professionals to apply interventions to postpone delivery and/or to prevent PTB to improve perinatal and childhood outcomes.

Currently, transvaginal cervical length measurement is used to screen asymptomatic pregnant women with a history of PTB to identify women requiring a cerclage. In symptomatic women, presenting with threatened (PTB), cervical length in combination with the fetal fibronectin(fFN) test is used to identify women at high risk to deliver within 7 days of presentation. However, the predictive capacity of transvaginal cervical length measurement is limited. In pregnant women with a history of PTB, it only identifies a proportion of women who will have recurrent PTB. For symptomatic women, 30-60% of these women admitted to the hospital, do not deliver within seven days, leading to overtreatment of these women.

Since cervical softening is a precursor of cervical shortening, effacement and dilatation, cervical softening is a promising new marker that is based on tissue elasticity. It can be measured with the CE-marked Pregnolia® System for accurate characterization of cervical softening status. It provides a value for tissue elasticity on a continuous scale.

A previous study has shown that softening of the cervix can be detected before shortening of the cervix. The Pregnolia® System may allow to detect women at risk for PTB earlier compared to traditional transvaginal ultrasound that measures shortening of the cervix, and therefore may prove useful for a more accurate risk assessment of PTB.

This current study is a single centre cohort study, where Two cohorts of women will be investigated. 1) Asymptomatic pregnant women with a history of spontaneous PTB before 34 weeks of gestation (Cohort A-STIPP). 2) Symptomatic women presenting with threatened PTB between 24 and 34 weeks (Cohort S-STIPP).

Objective: The aim of this study is to evaluate the predictive capacity of cervical softening and risk of PTB.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or above.
* Ability to understand Dutch or English (both spoken and written).
* Ultrasound-based gestational age determined by measurement of crown rump length (CRL) determined between 9 and 11 weeks of gestation.
* Singleton and twin pregnancies.

Cohort A-STIPP specific:

- Medical history of spontaneous preterm birth before 34 weeks of gestation

Cohort S-STIPP specific:

* Threatened Preterm birth between 24 and 34 weeks of gestation.
* Threatened preterm birth is defined as:

  * abdominal pain
  * (Braxton Hicks) contractions
  * vaginal blood loss.

Exclusion Criteria:

* Under 18 years of age.
* Signs of intrauterine infection.
* Obstetric indication for immediate delivery (advanced labor, cord prolapse, abruption, signs of fetal distress).
* Confirmed fetal abnormality.
* Confirmed preterm rupture of membranes.
* Confirmed vasa / placenta praevia.
* Severe vaginal bleeding and light bleeding that cannot be stopped.
* Signs of imminent labor such as blood loss, regular contractions.

Primary outcomes:
measure: Spontaneous Preterm Birth < 34 weeks
timeFrame: Maximum time frame up to 28 weeks: from inclusion at 14 weeks of gestational age until delivery, with a maximum of 42 weeks of gestational age.
measure: Delivery within seven days after inclusion
timeFrame: From inclusion until 7 days later
Secondary outcomes:
measure: Spontaneous preterm birth <37 weeks
timeFrame: From inclusion (symptomatic cohort 24-34 weeks, asymptomatic cohort 14 weeks) until delivery with a maximum of 42 weeks of gestational age
measure: Spontaneous preterm birth <34 weeks
timeFrame: From inclusion (symptomatic cohort 24-34 weeks, asymptomatic cohort 14 weeks) until delivery with a maximum of 42 weeks of gestational age
measure: Spontaneous preterm birth <32 weeks
timeFrame: From inclusion (symptomatic cohort 24-34 weeks, asymptomatic cohort 14 weeks) until delivery with a maximum of 42 weeks of gestational age
measure: Spontaneous preterm birth <28 weeks
timeFrame: From inclusion (symptomatic cohort 24-34 weeks, asymptomatic cohort 14 weeks) until delivery with a maximum of 42 weeks of gestational age
measure: Prediction of preterm birth using cervical softening.
timeFrame: From inclusion (symptomatic cohort 24-34 weeks, asymptomatic cohort 14 weeks) until delivery with a maximum of 42 weeks of gestational age
measure: Prediction of preterm birth using the combination of cervical softening and transvaginal cervical length measurement.
timeFrame: From inclusion (symptomatic cohort 24-34 weeks, asymptomatic cohort 14 weeks) until delivery with a maximum of 42 weeks of gestational age
measure: Prediction of preterm birth using the combination of cervical softening, transvaginal cervical length measurement, and fetal fibronectin.
timeFrame: From inclusion (symptomatic cohort 24-34 weeks) until delivery with a maximum of 42 weeks of gestational age
measure: Prediction of latency time using cervical softening.
timeFrame: From inclusion (symptomatic cohort 24-34 weeks, asymptomatic cohort 14 weeks) until delivery with a maximum of 42 weeks of gestational age
measure: Prediction of latency time using the combination of cervical softening and transvaginal cervical length measurement.
timeFrame: From inclusion (symptomatic cohort 24-34 weeks, asymptomatic cohort 14 weeks) until delivery with a maximum of 42 weeks of gestational age.
measure: Prediction of latency time using the combination of cervical softening, transvaginal cervical length measurement, and fetal fibronectin
timeFrame: From inclusion (symptomatic cohort 24-34 weeks) until delivery with a maximum of 42 weeks of gestational age.
Other outcomes:
measure: Patient discomfort of Pregnolia measurement
timeFrame: In asymptomatic cohort at 14, 16, 18, 20, 22 and 24 weeks of gestational age, in the symptomatic cohort at moment of inclusion
measure: Vaginal or Cervical blood loss (directly after measurement)
timeFrame: In asymptomatic cohort at 14, 16, 18, 20, 22 and 24 weeks of gestational age, in the symptomatic cohort at moment of inclusion
measure: Infections within seven days of measurement
timeFrame: From inclusion up to 1 week
measure: Preterm Prelabour Rupture of membranes at moment of measurement
timeFrame: Within 1 hour after measurement
measure: Irritation and sensitization of mucosal tissue
timeFrame: Within 1 hour after measurement
measure: Superficial lacerations or minor tissue abrasions
timeFrame: Within 1 hour after measurement
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location AMC
state: North-Holland
Study officials:
affiliation: Amsterdam UMC, location AMC
name: Eva Pajkrt, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Amsterdam UMC, location AMC
name: Martijn Oudijk, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References: