Urobilinogen, Maternal Weight Loss and Impending Parturition at Term
Condition: Increase in Urobilinogen in Urine Prior to Delivery; Weight Loss After 37 Weeks Gestation Prior to Delivery
MeSH terms: Body Weight; Weight Loss
Study type: Observational

Summary: 
      The purpose of this study, then, is to search existing clinic and hospital records for
      answers to the following two questions: (1) Do pregnant women who are at least 37 weeks
      gestation and who have an increase in urubilinogen on urine dipstick at a prenatal
      appointment have a statistically significant shorter average time before going into active
      labor than their negative counterparts? (2) Do pregnant women who are at least 37 weeks
      gestation and who show a modest weight loss between two prenatal appointments have a
      statistically significant shorter average time before going into active labor than their
      counterparts who did not lose weight?
    

Detailed description: 
      Rationale/Background:

      This study is a retrospective review of records which examines the possibility of two markers
      for the onset of active labor (contractions which result in a change in the uterine cervical
      dilatation) on routine clinical prenatal assessment. The markers in question are an elevation
      of urobilinogen on routine dipstick and slight maternal weight loss. An apparent clinical
      correlation between the presence of urobilinogen, maternal weight loss and onset of active
      labor has been observed in our patient population. Our hypothesis is that these markers in
      the term gravida are an indication of delivery within a week of their appearance on routine
      prenatal evaluation. Should a correlation exist, the clinician would have a relatively
      inexpensive way of identifying patients that could deliver within the week and could possibly
      predict those patients that would have success with induction, as the normal labor process
      may have begun. The purpose of this study, then, is to search existing clinic and hospital
      records for answers to the following two questions: (1) Do pregnant women who are at least 37
      weeks gestation and who have an increase in urobilinogen on urine dipstick at a prenatal
      appointment have a statistically significant shorter average time before going into active
      labor than their negative counterparts? (2) Do pregnant women who are at least 37 weeks
      gestation and who show a modest weight loss between two prenatal appointments have a
      statistically significant shorter average time before going into active labor than their
      counterparts who did not lose weight? In humans, the signals that initiate labor are not
      completely understood. While many theories have been explored, an exact pathway has not yet
      been determined. Urobilinogen is formed from conversion of conjugated bilirubin in the
      intestine by bacteria. A fraction of the urobiliogen is then reabsorbed into the bloodstream
      and filtered by the kidneys, becoming a colorless component of urine. Normally, only 1-4 mg
      of urobilinogen is excreted in the urine per day. Hemolytic processes, hepatocellular damage,
      and cholestasis can elevate urobilinogen in the urine. Routine dipstick tests have a normal
      urobilinogen range of 0.2 to 1 mg/dl (1). In this study, we will examine the urine dipsticks
      for an increased change in the urobilinogen levels within the last two prenatal appointments
      prior to delivery.

      No previous studies could be located regarding a link between an elevation in urobilinogen
      and/or minor maternal weight loss and parturition, labor, onset. There have been studies to
      suggest rationale for our clinical observation, however. Estrogens and progesterone both play
      a role in the growth and contractility of uterine myometrial cells. Progesterone tends to
      promote uterine relaxation, hence the name "pro-gest…". In most species, progesterone levels
      dramatically fall, a 'withdrawal', prior to the onset of labor. However, in human and higher
      level primates, the progesterone and estrogen levels are both elevated in later gestation and
      during parturition. The "withdrawal" in humans, therefore, may be mediated by changes in the
      myometrial responsiveness to progesterone (2).

      Estrogens induce myometrial contractility. Estriol is the most abundant estrogen during
      pregnancy and is produced by the placenta. It first appears at approximately the ninth week
      of gestation from the last menstrual period (3). Plasma concentrations of this estrogen
      increase throughout gestation along with those of estrone and estradiol (3,4,5). In the weeks
      preceding parturition, concentrations of estriol dramatically increase and continue to rise
      until birth (6). Estriol's roles include preparing uterine tissues for contraction and
      possibly signaling parturition in higher primates and humans (3,4,7,8,9,10). A rise in
      estriol, which can be monitored in saliva, has been shown to precede parturition, regardless
      of whether labor begins preterm, at term, or postterm (11,12).

      Estrogens' effect on the liver has been studied extensively. The active transport of biliary
      components in the canaliculi is impaired by estrogen (13). The pregnant state can cause some
      changes in bile acid production and secretion, presumably due to the higher levels of
      estrogen, but also because of progesterone's effect on GI motility. This can lead to a mild
      subclinical cholestasis. Studies have shown conflicting evidence as to whether there is an
      increase in bile acid levels during pregnancy. As estrogen increases are known to induce a
      cholestasis, and urobilinogen levels increase in cholestasis, our hypothesis is that the
      increase in estrogen levels within the last week of pregnancy may slow the clearance of bile
      even further yielding the rise in urobilinogen levels noticed on routine dipstick.

      An in depth literature review was performed in an effort to find a correlation between
      maternal weight loss and the onset of labor. No supporting literature validated or explained
      our clinical observation.

      Methodology This study will be a retrospective chart review of all eligible patients who
      presented to labor and delivery at Oklahoma State University Medical Center between the dates
      of January 1, 2002 and December 31, 2006. We selected this particular time period of charts
      to review, because they are recent enough to be accessible, and we estimate they will yield
      usable data for about 200 women.

      The study population will include mothers between the ages of 18 and 34 years of age with a
      single intrauterine pregnancy between 37 weeks and 41 weeks gestational age. (Both very young
      mothers and women 35 and older have increased risk of premature delivery.) The patients will
      have an admission diagnosis of either active labor or spontaneous rupture of membranes.
      Active labor is defined as uterine contractions resulting in changes either in the cervical
      dilatation, the effacement of the cervix and/or descent of the fetal head in the pelvis.

      This study will review chart data collected from our obstetrical clinic, OSU Obstetrics and
      Gynecology, as well as OSU Medical Center records. We will first search the hospital's
      records for patients admitted with the diagnosis of active labor. These charts will be
      examined for inclusion/exclusion criteria and entered into the study if they are eligible (as
      later defined). Once these charts have been obtained, we will then search their corresponding
      clinic chart for the defined parameters of our study.

      Eligibility Criteria:

      Our study population will consist of women between the ages of 18 and 34 who delivered a
      single, viable, term infant at OSU Medical Center between January 1, 2002 and December 31,
      2006. Gestational age must be greater than 37 weeks and less than 41 weeks, as ascertained by
      certain last menstrual period and/or first trimester ultrasound. The chart must include a
      diagnosis of active labor or spontaneous rupture of membranes, and the patient must have had
      at least two third-trimester prenatal checkups at OSU Houston Center OB/GYN, including one
      during the last two weeks of gestation. We will define a term infant as 37 weeks gestation or
      greater (3). Our study population will consist of mainly Medicaid patients. The ethnic blend
      of our study population will include Caucasian, African-American, Hispanic, American Indian,
      and Asian women.

      We will exclude women with multiple gestation, because they are at risk of preterm labor. We
      will also exclude anyone else who had preterm delivery. In addition, we will exclude women
      with a diagnosis of liver disease, including intrahepatic cholestasis and hepatitis, chronic
      hypertension, intraamniotic infection, preeclampsia or its variant, HELLP syndrome,
      cholelithiasis, inadequate prenatal care, preterm labor, or induction of labor (other than
      due to premature rupture of membranes).

      Data Collection Only the investigators will have access to the patients' data collection
      sheet. Individual physicians involved in the care of a specific patient will have access to
      that patient's information. All individuals will be in compliance with HIPPA guidelines as
      set forth by the university and the medical center. Patient records will be locked in a file
      cabinet or kept with their regular charts in the patient records department of the OSU
      Houston Center OB/GYN clinic. Any information obtained from hospital labor and delivery
      charts will be collected by Dr. Harris. It will be directly transported from the hospital to
      the clinic only by her, will be kept on her person at all times en route, and will be stored
      in a locked folder while in transit.

      The following data will be collected from the patients' hospital record.

        1. Name

        2. Birthdate

        3. Age of patient (years)

        4. Medical Record Number (MRN)

        5. Gestational age (in weeks and days)/Determined by:

        6. Initial sterile vaginal exam results (normal yes/no)

        7. Date and time of admission

        8. Admission Diagnosis

        9. Date and time of delivery

       10. Co-morbidities, pregnancy complications

       11. Delivery Mode

       12. Indication for Cesarean Section if applicable Note that it is not possible to determine
           the time of onset of active labor, only the time of hospital admission. We are assuming
           that most women who go into active, natural labor present to the hospital within 12-18
           hours. The day of hospital admission, then, serves as a rough, best estimate for onset
           of natural, active labor.

      The following data will be collected from the patients' clinic record.

        1. Patient's Name

        2. Birthdate

        3. Age

        4. MRN (megawest number)

        5. Date of delivery (from hospital record)

        6. Date of first clinic visit

        7. Number of clinic visits

        8. Weight on first clinic visit

        9. Total pregnancy weight gain

       10. Date of last clinic visit

       11. Weight at that visit

       12. Urine dipstick result at that visit

       13. Sterile vaginal exam (SVE) (dilation, effacement, station) at that visit

       14. Date of Visit prior to last clinic visit

       15. Weight at that visit

       16. Urine dipstick result at that visit

       17. SVE at that visit

       18. Pregnancy Complications

      Note that after 36 weeks gestation, prenatal visits are scheduled weekly at OSU Clinics.
      Therefore, unless the patient is not compliant with routine visits, natural labor for a term
      pregnancy will take place no longer than seven days from last clinic visit. No other data
      will be collected from any patient charts.

      Analysis:

      Data will be analyzed using PC SAS Version 9.1 (SAS Institute, Cary, NC). The two components
      of the study will be analyzed separately. The weight loss leg of the study will utilize an
      independent t-test in an effort to determine the relationship of weight loss (yes/no) to time
      to delivery. For the urobilinogen component of the study, we will utilize correlation
      techniques to assess the relationship of time to delivery and urobilinogen level.
      Significance will be determined at the 0.05 level.

      Confidentiality:

      All records and lab results will be maintained at Oklahoma State University Medical Center,
      department of medical records and laboratory storage on the hospital's Meditech system. All
      of the documents linking patient names to these numbers and charts will be destroyed after
      data collection is complete.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Population is mothers between the ages of 18 and 34 years of age with a single intrauterine
        pregnancy between 37 weeks and 41 weeks gestational age. (Both very young mothers and women
        35 and older have increased risk of premature delivery.) The patients will have an
        admission diagnosis of either active labor or spontaneous rupture of membranes. Active
        labor is defined as uterine contractions resulting in changes either in the cervical
        dilatation, the effacement of the cervix and/or descent of the fetal head in the pelvis.
      
Keywords: Weight loss, urobilinogen