Prospective Evaluation of Pathways for Preterm Birth (PEPP)

Prospective Evaluation of Pathways for Preterm Birth: The PEPP Study

This is a single center, prospective cohort study of pregnant patients at high risk for spontaneous preterm birth: patient's with history of spontaneous preterm birth, patient's with a short cervix and patient's symptomatic for preterm birth will be included. A control cohort of nulliparous patients without a short cervix will be recruited to provide baseline data. Plan to enroll 240 patients identified through our ultrasound unit with goal of 60 patients in each group.

Study Overview

• Status: Recruiting
• Conditions: Preterm Birth; Cervix; Pregnancy

Detailed Description

Patients will be approached for potential enrollment at the time of their anatomy ultrasound 18+0 and 23+6 weeks' gestation pending their obstetric history or if a transabdominal ultrasound evaluation or past transvaginal examination suggests the cervical length is less than 30 mm. Exclusion criteria will be reviewed and if none are present and the patient is considered a candidate for enrollment, informed consent will be performed. A 10-ml serum sample obtained. Before the transvaginal ultrasound, the patient will be asked to undergo a cervical washing of 3 cc of normal saline to obtain inflammatory cells followed by placement of a swab into the posterior fornix for 30 seconds. Patients who are found to have a short cervix will be prescribed standard of care medication (progesterone). Standard practice at our institution is to perform a cervical cerclage for women with a history of spontaneous preterm birth and a cervical length of =25mm at 16+0-23+6 weeks' gestation and this intervention will be continued regardless of enrollment. In addition, it is our standard to perform a cervical cerclage in women with progressive cervical change reaching a cervical length of <10 mm prior to 24+0 weeks regardless of obstetrical history. These standard practices will continue regardless of study participation.

Follow-Up Testing Visits. Additional study interventions will be collection of biomarker specimens and biophysical data. At 28 and 34 weeks gestation, the patient will undergo repeat TVU and 10-ml serum sample collection. A CRF will record the cervical length and the sonographer will be blinded to any prior cervical length measurement. A different sonographer will be utilized from the immediately preceding exam. All sonographers will complete the coursework for assessment of cervical length from either the Perinatal Quality Foundation CLEAR program or the Fetal Medicine Foundation.

• Study Type: Observational
• Enrollment (Estimated): 240

Contacts and Locations

• Study Contact: Name: Cynthia Cockerham; Phone Number: 859-629-2015; Email: cynthia.cockerham@uky.edu
• Study Contact Backup: Name: Ashley Boerrigter, MD; Phone Number: 859-257-2321; Email: ashley.boerrigter@uky.edu

Study Locations

• United States
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • Recruiting
      • University of Kentucky
      • Contact: Cynthia Cockerham; Email: ctcock2@uky.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

• Subpopulation 1: Asymptomatic women with or without a history of spontaneous preterm birth who undergo screening for preterm birth with transvaginal sonography between 18-24 weeks of gestation with a cervical length =5mm and up to and including 30mm will be eligible for enrollment.
• Subpopulation 2: Asymptomatic with a history of early spontaneous (PTL or PROM as etiology) occurring in a prior pregnancy at 20-34 weeks' gestation.
• Subpopulation 3: Patients with symptoms of preterm birth: preterm contractions or preterm premature rupture of membranes at less than 34 weeks.
• Control Subpopulation: Nulliparous women with a cervical length of >30 mm

Description

Inclusion Criteria:

• Maternal age from 18 to 45 years of age.
• Singleton gestation.

Exclusion Criteria:

• Treatment with vaginal progesterone or intramuscular progestogen within the previous 4 weeks.
• History of congestive heart failure, chronic renal failure, or uncontrolled diabetes mellitus, or diabetes mellitus with evidence of end organ dysfunction secondary to vascular disease.
• Current pregnancy with a major fetal anomaly or known chromosomal abnormality.
• The subject has a marked uterine anatomic malformation that may alter pregnancy duration such as a septated uterus, unicornuate uterus, or uterine didelphys.
• The subject is considered not capable or unwilling to undergo study procedures and requirements.
• The subject is symptomatic with vaginal bleeding at enrollment visit.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Patients with a history of spontaneous preterm birth; Patients with a history of spontaneous preterm birth (<34 weeks)
Control/Nulliparous; Nulliparous patients
Patients with short cervix; Patients with a short cervix identified on transvaginal ultrasound <30 mm
Patients with symptoms of preterm birth; Patients with preterm premature rupture of membranes or </=2 cm dilated before 34 weeks gestation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory Cytokine Profile	Serum and Cervicovaginal cytokine profile (CRP, ICAM-1, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, MCP-1, PIGF, TNFα, TNFβ)	18-24 weeks gestation
Inflammatory Cytokine Profile	Serum and Cervicovaginal cytokine profile (CRP, ICAM-1, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, MCP-1, PIGF, TNFα, TNFβ)	28 weeks gestation
Inflammatory Cytokine Profile	Serum and Cervicovaginal cytokine profile (CRP, ICAM-1, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, MCP-1, PIGF, TNFα, TNFβ)	34 weeks gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progesterone Cytokine Response	Serum and cervicovaginal cytokine profiles of those patients receiving progesterone for short cervix before and after exposure. (CRP, ICAM-1, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, MCP-1, PIGF, TNFα, TNFβ)	18-24 weeks gestation
Progesterone Cytokine Response	Serum and cervicovaginal cytokine profiles of those patients receiving progesterone for short cervix before and after exposure. (CRP, ICAM-1, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, MCP-1, PIGF, TNFα, TNFβ)	28 weeks gestation
Progesterone Cytokine Response	Serum and cervicovaginal cytokine profiles of those patients receiving progesterone for short cervix before and after exposure. (CRP, ICAM-1, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-8 (HA), IL-10, MCP-1, PIGF, TNFα, TNFβ)	34 weeks gestation

Collaborators and Investigators

• Sponsor: John O'Brien, MD
• Investigators: Principal Investigator: Calvin Ward, MD, University of Kentucky; Principal Investigator: Ashley Boerrigter, MD, University of Kentucky; Principal Investigator: John O'Brien, MD, University of Kentucky

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: January 31, 2022
• First Submitted That Met QC Criteria: February 8, 2022
• First Posted (Actual): February 18, 2022

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; Cervical Length; Preterm Birth
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth
• Other Study ID Numbers: 73519

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