CellulaR Injury and Preterm Birth

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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CellulaR Injury and Preterm Birth

Conditions
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Preterm Birth

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group 1 (Preterm labor, PPROM, cervical insufficiency)<br>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)<br>Admitted to the hospital with spontaneous labor (regular contractions, cervical dilation) or spontaneous rupture of membranes | |
| Group 3 (PTB-medically indicated)<br>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?
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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 |