CellulaR Injury and Preterm Birth (CRIB)

The goal of this study is to examine how cellular dysfunction can lead to preterm birth. Women with singleton pregnancies with spontaneous preterm labor, preterm premature rupture of membranes, and cervical insufficiency (20 to 36-6/7 weeks gestation), and term deliveries (greater than 38 weeks) will be enrolled. Medical/obstetric history and pregnancy outcomes will be recorded. Maternal blood, urine and cervical cells (enrollment); cord blood and placental biopsy (delivery) will be collected.

Study Overview

• Status: Completed
• Conditions: Preterm Birth

Detailed Description

Despite improvements in prenatal care, preterm birth (PTB) remains a leading contributor to perinatal morbidity and mortality. Several genetic and environmental factors have been associated with spontaneous preterm birth, but the pathways by which these factors induce preterm delivery have not been defined. The March of Dimes CPR at the University of Pennsylvania was created to help elucidate the pathogenesis of preterm birth by bringing together a diverse team of investigators with expertise in preterm birth, cellular metabolism, genetics, mitochondrial functional analyses, genome, epigenome, and transcriptome profiling, integrated bioinformatics analyses, and microbiome research. The center will focus on addressing the interactions between bioenergetics, genetics, microbiome, abnormal cervical remodeling and placental dysfunction. Each one of these factors will be studied independently and in relation to the other factors. In order to study metabolic processes in relation to spontaneous PTB, a prospective case-control study will be performed. This study will involve women with singleton pregnancies with spontaneous preterm labor (PTL), preterm premature rupture of membranes (PPROM), and cervical insufficiency, between 20-0/7 and 36-6/7 weeks gestational age (cases), and women with term deliveries (38 to 41 weeks gestation, controls). The investigators will obtain information regarding the patients' pertinent past medical and obstetric histories, and the following specimens will be collected: maternal blood, maternal urine, and cervical epithelial cells at enrollment; and umbilical cord blood and placental biopsies at delivery. We will follow and record each of these patients' pregnancy outcomes.

• Study Type: Observational
• Enrollment (Actual): 705

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

At HUP, there are approximately 4,200 deliveries a year, of which approximately 10 percent (420) deliver preterm. Among these preterm births, two-thirds (280) are spontaneous, which is the focus of our research. Many women who ultimately have a preterm birth, first present with preterm labor. Women who have advanced dilatation, preterm rupture of membranes, etc are at high risk for having a preterm birth. The investigators anticipate, based on the number of spontaneous preterm births at HUP per year, enrolling about 40-50% of those eligible and understanding that about 40% of those enrolled will have a preterm birth, we should be able to enroll about 112 women per year over 5 years. The coordinators will enroll cases who are admitted to the hospital with PTL, PPROM, or cervical insufficiency at 20-0/7 to 36-6/7 weeks.

Description

Cases:

Inclusion Criteria:

• 18-45 years of age
• Singleton pregnancy between 20 0/7 and 36 6/7 weeks gestational age who is admitted with preterm labor or cervical insufficiency (greater than 2 cm dilation) or Preterm Premature Rupture of Membranes

Exclusion Criteria:

• Multiple gestation
• Fetal chromosomal abnormality
• Major fetal anomaly
• Intra-uterine fetal demise
• Gestational hypertension/preeclampsia

Controls:

Inclusion Criteria:

• 18-45 years of age
• Singleton pregnancy that delivers at term (38 to 41 weeks gestational age)
• Admitted to the hospital with spontaneous labor (regular contractions, cervical dilation) or spontaneous rupture of membranes

Exclusion Criteria:

• Multiple gestation
• Fetal chromosomal abnormality
• Major fetal anomaly
• Intra-uterine fetal demise
• Intra-uterine growth restriction
• Gestational hypertension/preeclampsia
• Clinical chorioaminionitis
• Induction of labor
• Elective c-section

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Group 1 (Preterm labor, PPROM, cervical insufficiency); Singleton pregnancy between 20 0/7 36 6/7 weeks gestational age who is admitted with PTL or cervical insufficiency (Equal or greater than 2 cm dilated) or PPROM
Group 2 (Term labor); Admitted to the hospital with spontaneous labor (regular contractions, cervical dilation) or spontaneous rupture of membranes
Group 3 (PTB-medically indicated); Singleton pregnancy between 20 0/7 34 5/6 weeks gestational age who is admitted with a medically indicated preterm birth (IOL for abruption, non reassuring fetal heart tones, intrauterine growth restriction, preeclampsia, trauma, etc.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biogenetics	The role of biogenetics in pregnancy and what are the perturbations in cell metabolism that lead to spontaneous preterm birth.	5 years
Microbiome	The interactions between the microbiome (oral, gut, cervicovaginal, and placental) and host metabolic function in pregnancy.	5 years
Cervical remodeling	How the interactions between cell metabolism and the microbiome influence cervical remodeling and placental function leading to spontaneous preterm delivery.	5 years
Genetics and Environmental factors	How genetic and environmental factors influence the metabolic function of reproductive tissues leading to spontaneous preterm delivery.	5 years

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: March of Dimes
• Investigators: Principal Investigator: Michal Elovitz, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): August 1, 2019
• Study Completion (Actual): August 1, 2019

Study Registration Dates

• First Submitted: April 6, 2015
• First Submitted That Met QC Criteria: May 7, 2015
• First Posted (Estimate): May 12, 2015

Study Record Updates

• Last Update Posted (Actual): October 7, 2019
• Last Update Submitted That Met QC Criteria: October 2, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth
• Other Study ID Numbers: 821376