Prediction of Preterm Delivery With Serial Cervical Length Measurements After Threatened Preterm Labor

May 20, 2026 updated by: Giuseppe Chiossi, University of Modena and Reggio Emilia

Serial Cervical Length Measurements After the 1st Episode of Threatened Preterm Labor to Improve Prediction of Spontaneous Preterm Delivery: Prospective Cohort Study

Prospective cohort study on pregnant women discharged from the hospital after the first episode of threatened preterm labor. Cervical length (CL) will be measured with transvaginal US upon initial presentation (i.e at the time of hospital admission), at the time of hospital discharge, and respectively 2, 4, 8 and 12 weeks later. Pregnant women undelivered after the 1st episode of threatened preterm labor will be invited to participate in the study if CL upon discharge is < 25 mm. The study will investigate the potential association between cervical shortening over time and time of delivery, to assess if spontaneous preterm delivery can be predicted by CL.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Preterm labor is the result of labor occurring prior to 36 6/7 weeks' gestation (i.e spontaneous preterm labor) leading to delivery. Preterm labor is a clinical diagnosis, defined as the appearance of regular contractions accompanied by a change in cervical dilation, effacement, or both, or initial presentation with regular contractions and cervical dilation of at least 2 cm prior to 36 6/7 weeks' gestation.

The pathogenesis of preterm labor has not yet been fully understood, but it has been hypothesized that it could be caused by early idiopathic activation of the normal process of labor or instead, that it could be the result of pathological insults (Goldenberg 2008, Hamilton 2013, Slattery 2002). In Western countries, spontaneous PTB is responsible for 75% of perinatal mortality and more than half of long-term morbidity (McCormick 1985). Although most preterm newborns survive, they have an increased risk of neuro-behavioral disability, cerebral palsy, mental and developmental retardation. Moreover, spontaneous PTB also represents an important cause of chronic broncho pneumopathies, visual and auditory abnormalities and other chronic diseases of the pediatric age including school failure.

As contractions are the most commonly recognized antecedent of preterm birth, cessation of uterine contractions has been the primary focus of therapeutic intervention to prevent the burden of prematurity.

Preterm labor is currently considered a syndrome with a multifactorial etiology, among which inflammation, uteroplacental ischemia or hemorrhage, uterine overdistension, stress and other immune-mediated processes certainly play a role (Romero 2006): these factors do not necessarily represent a direct cause, but contribute to a transition from uterine quiescence to preterm labor or preterm premature rupture of membranes (pPROM) (Goldenberg 2005).

There are many maternal and fetal conditions that have been associated with PTB, including maternal demographic characteristics (such as low socio-economic status, race), nutritional status, obstetric history (history of prior spontaneous PTB), psychological aspects, risk behaviors (such as drug and tobacco use), infections, short CL, as well as biological and genetic markers (Goldenberg 2008, Andrews 2000).

Cervical length is measured with a 7-9 MHz transvaginal probe by trained obstetricians-gynecologists following the same standardized approach (Berghella 2003). Short CL (< 20 mm) prior to 24 weeks' gestation has been recognized as a risk factor for preterm delivery among asymptomatic women; furthermore, short CL (< 25 mm) has also been identified as a risk factor for spontaneous preterm delivery among patients presenting with painful uterine contractions (ACOG 2012).

Threatened preterm labor (TPL) is the most common diagnosis that leads to hospitalization during pregnancy (Bennet 1998) and its annual costs exceed $800 million in the USA (Nicholson 2000). The association between preterm labor and preterm delivery is weak, as less than 10% of women diagnosed preterm labor actually give birth within 7 days of presentation (Fucks 2004). Therefore, clinicians define as threatened preterm labor a condition characterized by uterine contractions associated with cervical changes, that does not lead to preterm delivery, due a spontaneous resolution of the labor process, interventions aimed at possible causes of the labor process (such as treatment of a concomitant infection), or symptomatic therapeutic interventions (such as administration of tocolytics).

Although approximately 75% of women presenting with TPL remain undelivered after a 48-hours course of tocolytics, their risk of preterm delivery remains high, as approximately 30% of them deliver before 37 weeks (Simhan 2007). However, it is a challenge for clinicians to identify who will deliver prematurely after an episode of threatened preterm labor.

Cervical length (CL) measured by transvaginal sonography has been shown to be an accurate predictor of spontaneous preterm delivery among women presenting with painful uterine contractions (Berghella 2017, Sotiriadis 2016). However, studies have mainly focused on the role of a single CL measure collected at the time of the initial presentation instead of evaluating the predictive value of serial CL evaluations as threatened preterm labor resolves. We have previously showed in a secondary analysis of a RCT that serial CL evaluations may help identify those who will deliver prematurely after their first episode of threatened preterm labor (Chiossi 2020). We now intend to validate these findings prospectively, with a cohort study on the role of serial CL measures among women who remained undelivered after their first episode threatened preterm labor. Transvaginal CL measure has the potential to promptly identify shortening of the uterine cervix, a condition associated with preterm delivery. Such evaluation could be included in the antenatal care of women discharged from the hospital after an episode of threatened preterm labor to stratify their risk of preterm birth, to rationalize care and resource-utilization, as well as to improve pregnancy outcome.

Pregnant women admitted to the hospital with the diagnosis of threatened preterm labor (regular contractions accompanied a change in cervical dilation, effacement, or both, or initial presentation with regular contractions and cervical dilation of at least 2 cm), who remained undelivered, will be invited to participate if CL upon discharge is < 25 mm. Cervical length will be evaluated at follow up appointments 2, 4, 8 and 12 weeks after discharge and linked to the actual gestational age at delivery.

Using a CL threshold of 10 mm we will estimate the risk of preterm delivery at different time points: each risk assessment will be based on the CL measured from hospital admission up to that time. At hospital discharge, patients will be classified at "low risk" of preterm delivery if their CL will be > 10 mm, while "high risk" subjects will have a shorter CL. The risk of preterm birth will then be assessed on all the women who will remain undelivered until the 1st follow up appointment, 2 weeks later: pregnancies with CL measurements > 10 mm from hospital discharge up to 2 weeks later will be considered "low risk", while those with CL < 10 mm on at least one assessment will be classified as "high risk". If delivery will not occur after 4 weeks (2nd follow up visit), pregnancies who will maintain CL measurement > 10 mm from hospital admission through the following 2 visits will be classified as "low risk", while "high risk" women will have a shorter CL on at least one of the 4 assessments. Risk estimates will be calculated in a similar fashion on women still pregnant 8 and 12 weeks after hospital discharge (3rd and 4th follow up visits). Cervical length will also be evaluated upon hospital admission, and the risk of preterm delivery will also be assessed taking into account such value.

Descriptive statistics will be used to characterize the socio-demographic features and the obstetric characteristics of women categorized as "low risk" (i.e pregnancies whose CL persistently remains above 10 mm) or high risk (i.e those with at least one CL measurement < 10 mm): categorical variables will be presented as absolute and percentage frequencies, they will be tested with Chi square test or Fisher's exact test as appropriate. Continuous variables will be summarized as mean +/- SD and compared with Student's t test. A level of statistical significance of p < 0.05 will be considered.

To control for confounding, multivariate logistic regression models will be used to describe the association between delivery prior to 37 weeks' gestation and CL (measured from hospital admission to each subsequent evaluation). Socio-demographic variables such as maternal age, BMI at entry to care, ethnicity, smoking, and education will be considered as potential confounders. Similarly, obstetric features such as parity, tocolysis at the initial hospitalization or at any subsequent hospital admission, urine culture collected on the initial hospitalization, and gestational age at enrolment will also be tested as potential.

Study Type

Observational

Enrollment (Actual)

303

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Ancona, Italy
        • Facoltà di Medicina e Chirurgia, università politecnica delle Marche
      • Florence, Italy
        • Mariarosaria Di Tommaso, Divisione di Ginecologia ed Ostetricia, Dipartimento Assistenziale Integrato Materno Infantile, Azienda Ospedaliero-Universitaria Careggi
      • Milan, Italy
        • Divisione di Ginecolgia ed stetricia, Azienda Ospedaliera Vimercate-Desio presidio di Carate Brianza Giussano, e Università di Milano Bicocca
      • Milan, Italy
        • Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Clinica Mangiagalli, Università di Milano
      • Monza, Italy
        • Department of Obstetrics and Gynecology, Foundation MBBM at San Gerardo Hospital, University of Milan-Bicocca School of Medicine and Surgery
      • Reggio Emilia, Italy
        • Divisione di Ginecologia ed Ostetricia, Dipartimento Materno infantile, Arcispedale Santa Maria Nuova, IRCCS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 41 years (Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Women who remained undelivered after their first episode of threatened preterm labor, whose cervical length upon hospital discharge is < 25 mm

Description

Inclusion Criteria:

  • Singleton pregnancy at 23+0 - 33+6 weeks' gestation
  • Age > 18 years old
  • Patients should be capable of providing consent to participate in the study

Exclusion Criteria:

  • Previous spontaneous preterm (20+0 - 36+6 weeks' gestation) delivery (including history of pregnancy loss due to cervical incompetence, i.e painless cervical dilatation prior to 24 weeks' gestation)
  • Treatment with 17 hydroxyprogesterone caproate due to a previous spontaneous preterm delivery
  • Detection of a cervical length < 25 mm during routine ultrasound < 24 weeks' gestation in asymptomatic patients (i.e patients that do not complain of uterine contractions or patients with no uterine contractions documented on tocometry)
  • Treatment with vaginal progesterone or micronized progesterone due to a cervical length < 25 mm
  • Cerclace placement in the current or in a previous pregnancy
  • Multiple pregnancy
  • Age < 18 years old
  • Preterm premature rupture of membranes (pPROM) upon initial presentation
  • Müllerian malformations
  • Prior cervical surgery

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Women who remained undelivered after their first episode of threatened preterm labor
Women admitted to the hospital due to their first episode of threatened preterm labor (i.e onset of spontaneous labor < 34 weeks gestation), who did not deliver prematurely as labor stopped (with or without interventions such as tocolysis). Those with a cervical length < 25 mm at the time of hospital discharge are eligible to participate in the study
Other: Monitoring the length of the uterine cervix using transvaginal ultrasound
Cervical length is measured with a 7-9 MHz transvaginal probe by trained obstetricians-gynecologists following the same standardized approach (Berghella 2003). Transvaginal CL measurement is largely used in current obstetric practice, and it is considered the 'gold standard' measurement when assessing the uterine cervix. In contrast to transabdominal US, the transvaginal approach is highly reproducible, and measurements are unaffected by maternal obesity, cervical position, and shadowing from fetal parts (Berghella 2003, Hassan 2000, ACOG 2012, Berghella 2012).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To investigate the association between cervical length measured at different time points and the risk of spontaneous preterm birth < 37 weeks' gestation
Time Frame: At the time of delivery
The risk of spontaneous preterm birth < 37 weeks' gestation will be compared among women with at least a cervical length < 10 mm as opposed to those whose cervix will remain persistently > 10 mm. A relationship between gestational age at delivery and cervical length will also be investigate considering the two variables as continuous
At the time of delivery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To assess a possible association between cervical length and adverse neonatal outcomes
Time Frame: At the time of delivery
Adverse neonatal outcomes will be summarized as a composite of neonatal death, neonatal resuscitation, non-invasive (cPAP) or invasive (mechanical ventilation) respiratory support, hypoglycemia (< 44 mg/dl needing therapy), newborn sepsis, confirmed seizures, stroke, intraventricular hemorrhage (IVH), basal nuclei anomalies, cardiopulmonary resuscitation, umbilical-cord-blood arterial pH < 7.0 or base excess < -12.5, prolonged hospitalization (> 5 days), or shoulder dystocia.
At the time of delivery
To assess a possible association between cervical length and adverse maternal outcomes.
Time Frame: At the time of delivery
Adverse maternal outcomes will be summarized as a composite of blood loss > 1000 ml, maternal sepsis, post-partum endometritis, hysterectomy, bowel or urinary tract injuries, uterine rupture, wound (either perineal or abdominal) complications (i.e abscess, hematoma or disruption), 3rd and 4th degree perineal lacerations, blood transfusion, maternal admission to the ICU, laparotomy, and death.
At the time of delivery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Modena and Reggio Emilia

Investigators

  • Principal Investigator: Giuseppe Chiossi, MD, Dept of Ob/Gyn, Modena Policlinico Hospital, University of Modena and Reggio Emilia

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 20, 2021

Primary Completion (Actual)

December 28, 2024

Study Completion (Actual)

December 28, 2024

Study Registration Dates

First Submitted

September 3, 2021

First Submitted That Met QC Criteria

September 4, 2021

First Posted (Actual)

September 14, 2021

Study Record Updates

Last Update Posted (Actual)

May 26, 2026

Last Update Submitted That Met QC Criteria

May 20, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Università di Modena

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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