CellulaR Injury and Preterm Birth
Condition: Preterm Birth
MeSH terms: Premature Birth
Study type: Observational

Summary: 
      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: 
      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.
    

Observational model: Case-Control
Time perspective: Prospective
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.
      
Biospecimen description: 
      1. Collect blood, urine and cervicovaginal cells from women with preterm labor and term labor
      in order to investigate:

        1. What is the role of bioenergetics in pregnancy and what are the pertubations in cell
           metabolism that lead to spontaneous preterm birth

        2. What are the interactions between the microbiome (oral, gut, cervicovaginal, and
           placental) and host metabolic function in pregnancy

        3. How do interactions between cell metabolism and the microbiome influence cervical
           remodeling and placental function leading to spontaneous preterm delivery

        4. What genetic and environmental factors influence the metabolic function of reproductive
           tissues leading to spontaneous preterm delivery