Urobilinogen, Maternal Weight Loss and Impending Parturition at Term
Urobilinogen, Maternal Weight Loss and Impending Parturition at Term
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?
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.
Inclusion 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.

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 Exclusion Criteria: 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).

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