Biomarkers Associated With Spontaneous Preterm Birth Less Than 32 Wks Gestation
Condition: Preterm Labor; Preterm Birth
MeSH terms: Premature Birth; Obstetric Labor, Premature
Study type: Observational

Summary: 
      Preterm delivery (PTD) is a leading cause of neonatal mortality and continues to be a major
      public health concern, reaching 12.9% in 2006, despite intense research to reverse this
      trend. Currently, fetal fibronectin (fFN) screening and cervical length determined by
      ultrasound are two tests which are proven to have benefit in the identification of those at
      greatest risk for preterm delivery. However the benefit of these tests is limited to
      situations where a negative result can avoid unnecessary interventions. Currently, maternal
      fetal monitoring is limited, as it is difficult to "see" what is going on in the placenta
      (maternal-fetal interface) without invasive measures such as placental biopsy or
      amniocentesis. Our goal for this study is to identify a group of biomarkers in non-invasive
      compartments (such as saliva, blood, urine, and/or cervical and vaginal secretions) that are
      associated with preterm labor and birth. We hypothesize that preterm labor will display an
      inflammatory profile, which consists of unique inflammatory biomarkers from different
      non-invasive bodily fluid compartments (such as Il-10 in urine, VEGF in cervical secretions,
      and IP-10 in saliva), that correlates with a high incidence of preterm birth.
    

Detailed description: 
      Preterm delivery (PTD) is a leading cause of neonatal mortality and continues to be a major
      public health concern, reaching 12.9% in 2006, despite intense research to reverse this
      trend. Currently, fetal fibronectin (fFN) screening and cervical length determined by
      ultrasound are two tests which are proven to have benefit in the identification of those at
      greatest risk for preterm delivery. However the benefit of these tests is limited to
      situations where a negative result can avoid unnecessary interventions. The first goal of
      this study is to identify non-invasive predictor(s) that will increase the clinician's
      ability to identify patients who present with second trimester preterm labor (PTL) at risk
      for preterm delivery (PTD) ≤ 32 weeks gestation.

      Currently, maternal fetal monitoring is limited, as it is difficult to "see" what is going on
      in the placenta (maternal-fetal interface) without invasive measures such as placental biopsy
      or amniocentesis. Our preliminary study from term pregnancies has shown that a specific
      correlation of an intrauterine cytokine may be reflected in one noninvasive site but not
      another, depending upon the type of cytokine and the compartment from which it is secreted.
      Therefore, our second goal for this study is to identify inflammatory markers in non-invasive
      maternal compartments (such as saliva, blood, urine, and/or cervical and vaginal secretions)
      that have a strong association with placenta/fetal membranes at the time of preterm birth ≤
      32 weeks gestation.

      Pregnant women, under 32 weeks gestation, who are admitted to Winthrop University Hospital
      for evaluation of preterm labor will be eligible for this study. Women with indicated preterm
      births (i.e. pre-eclampsia), multiple pregnancies, known major fetal abnormality (ex. those
      that are known to be incompatible with life) and premature rupture of membranes will be
      excluded from this study. After consent is obtained, samples (blood, urine, saliva, vaginal,
      and cervical secretions) will be obtained and biomarkers will be identified using a Bio-Plex
      cytokine concentration assay. These women will than be followed until they deliver. Women who
      deliver after 32 weeks gestation will form our control group and women who deliver before 32
      weeks gestation will form our preterm birth group. Concentration of the biomarkers in the
      various maternal-fetal compartments will be analyzed and compared between the two groups. For
      all women who delivery ≤ 32 weeks gestation, non-invasive samples will also be collected
      around delivery and these cytokine levels will be compared to placenta/fetal membranes to
      access how well non-invasive fluids reflect the intrauterine environment.

      We hypothesize that preterm labor will display an inflammatory profile, which consists of
      unique inflammatory biomarkers from different non-invasive bodily fluid compartments (such as
      Il-10 in urine, VEGF in cervical secretions, and IP-10 in saliva), that correlates with a
      high incidence of preterm birth.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Pregnant females between the age of 18-40 who present in preterm labor will be asked to
        participate.
      
Biospecimen description: 
      1. Saliva - We will collect saliva in a sterile container.

        2. Maternal Blood - Blood samples will be collected during routine blood draws and into
           serum separator tubes, spun, and the serum stored at -80°C.

        3. Urine - Urine samples will be collected into a sterile container.

        4. Cervical and vaginal secretions - During speculum exam, we will simultaneously insert
           two Weck-Cell Sponges directly into the cervical os for collection of cervical
           secretions then another two sponges will be applied in the posterior fornix for
           collection of vaginal fluid.