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      Bile Acid Determination after Standardized Glucose Load in Pregnant Women

      case-report

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          Abstract

          Objective Intrahepatic cholestasis of pregnancy (ICP) is a rare liver disorder, usually manifesting in the third trimester and associated with increased perinatal morbidity and mortality. The hallmark laboratory abnormality in ICP is elevated fasting serum bile acids; however, there are limited data on whether a nonfasting state affects a pregnant woman's total bile acids. This study assesses fasting and nonfasting bile acid levels in 10 healthy pregnant women after a standardized glucose load to provide insight into the effects of a glucose load on bile acid profiles.

          Study Design Pilot prospective cohort analysis of serum bile acids in pregnant women. A total of 10 healthy pregnant women from 28 to 32 weeks' gestation were recruited for the study before undergoing a glucose tolerance test. Total serum bile acids were collected for each subject in the overnight fasting state, and 1 and 3 hours after the 100-g glucose load.

          Results There was a statistically significant difference between fasting versus 3-hour values. There was no statistically significant difference between fasting versus 1-hour and 1-hour versus 3-hour values.

          Conclusion There is a difference between fasting and nonfasting total serum bile acids after a 100-g glucose load in healthy pregnant women.

          Most cited references29

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          Pregnancy and laboratory studies: a reference table for clinicians.

          To establish normal reference ranges during pregnancy for common laboratory analytes. We conducted a comprehensive electronic database review using PUBMED and MEDLINE databases. We also reviewed textbooks of maternal laboratory studies during uncomplicated pregnancy. We searched the databases for studies investigating various laboratory analytes at various times during pregnancy. All abstracts were examined by two investigators and, if they were found relevant, the full text of the article was reviewed. Articles were included if the analyte studied was measured in pregnant women without major medical problems or confounding conditions and if the laboratory marker was measured and reported for a specified gestational age. For each laboratory marker, data were extracted from as many references as possible, and these data were combined to establish normal reference ranges in pregnancy. When possible, the 2.5 and 97.5 percentiles were reported as the normal range. In some of the reference articles, however, the reported range was based on the minimum and maximum value of the laboratory constituent. In those cases, the minimum to maximum range was used and combined with the 2.5 and 97.5 percentile range. We found that there is a substantial difference in normal values in some laboratory markers in the pregnant state when compared with the nonpregnant state. It is important to consider normal reference ranges specific to pregnancy when interpreting some laboratory results that may be altered by the normal changes of pregnancy.
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            Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo.

            Intense pruritus and the risk of stillbirths and premature deliveries justify the search for an effective pharmacologic treatment of intrahepatic cholestasis of pregnancy. This study was designed to test the efficacy of ursodeoxycholic acid in maternal pruritus, the biochemical abnormalities and the outcome of pregnancy, in patients with intrahepatic cholestasis of pregnancy of early onset. Pregnant patients hospitalized in a secondary case-referral center with intense pruritus and abnormal serum levels of bile salts and aminotransferases, detected before week 33 of pregnancy, were randomly assigned to receive ursodeoxycholic acid, 1 g per day orally, or an identical placebo, until delivery, in a double-blind study. A 3-week trial period was chosen to compare drug and placebo effects. The follow-up was extended for 3 months after delivery. Twenty-four patients entered the trial; eight had deliveries before 2 weeks of treatment and one dropped out. The study was then completed in 15 patients: eight received ursodeoxycholic acid and seven placebo. No adverse effects were detected in the mothers or in their babies. After 3 weeks of treatment, patients receiving ursodeoxycholic acid (mean daily dose 16 mg/kg body weight) had a significant improvement in pruritus (p<0.02), in serum bilirubin (0.36+/-0.19 mg/dl (mean+/-SD) versus 0.95+/-0.48 in patients receiving placebo, p<0.01), in aspartate aminotransferase (52+/-42 IU/l vs 98+/-44, p<0.05) and in alanine aminotransferase (54+/-50 IU/l vs 229+/-154, p<0.01); serum total bile salts also tended to be lower in patients receiving ursodeoxycholic acid (26.3+/-33.7 micromol/l vs 55.0+/-44.8, p N.S.). Deliveries occurred at or near term in all mothers who received ursodeoxycholic acid (mean week of pregnancy: 38), while they occurred before week 36 of pregnancy in five patients who received placebo, including one stillbirth. All babies born alive had birth weights adequate for gestational age and they were thriving normally 3 months after delivery. Ursodeoxycholic acid is effective and safe in patients with intrahepatic cholestasis of pregnancy of early onset, attenuating pruritus and correcting some biochemical abnormalities in the mothers. Relevant aspects of fetal outcome were also improved in patients receiving ursodeoxycholic acid compared to placebo.
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              Longitudinal profiles of 15 serum bile acids in patients with intrahepatic cholestasis of pregnancy.

              Increased maternal serum bile acids are implicated in intrahepatic cholestasis of pregnancy. Individual bile acid profiles and their relationship with disease progression, however, remain unknown. The purpose of this prospective study was to determine the temporal changes in bile acids in normal pregnancy and in pregnancies complicated with intrahepatic cholestasis of pregnancy and pruritus gravidarum. A validated method for the evaluation of 15 bile acids (conjugated and unconjugated) in a single serum sample was developed using high-performance liquid chromatography/mass spectrometry (HPLC-MS) with an electrospray interface. Bile acid concentrations were assessed in samples (16 weeks of gestation to 4 weeks postpartum) from women with, or who later developed, intrahepatic cholestasis of pregnancy (n=63) and were compared with those from normal pregnant women (n=26) and from women with pruritus gravidarum (n=43). Intrahepatic cholestasis of pregnancy was associated with a predominant increase in cholic acid conjugated with taurine and glycine, from 24 weeks of pregnancy. Ursodeoxycholic acid (UDCA) treatment (> or =21 days, n=15) significantly reduced serum taurocholic and taurodeoxycholic acid concentrations (P<0.01). Bile acid profiles were similar in normal pregnancy and pregnancy associated with pruritus gravidarum. The bile acid profiles and effects of treatment by UDCA implicate a role for taurine-conjugated bile acids in the syndrome of intrahepatic cholestasis of pregnancy. [corrected] With regard to individual bile acid profiles, pruritus gravidarum is a disorder quite distinct from intrahepatic cholestasis of pregnancy.
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                Author and article information

                Journal
                AJP Rep
                AJP Rep
                10.1055/s-00000169
                AJP Reports
                Thieme Medical Publishers (333 Seventh Avenue, New York, NY 10001, USA. )
                2157-6998
                2157-7005
                19 June 2015
                October 2015
                : 5
                : 2
                : e168-e171
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, University of Minnesota, Minneapolis, Minnesota
                [2 ]Biostatistics and Bioinformatics Core, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota
                [3 ]Department of Obstetrics and Gynecology, Hennepin County Medical Center, Minneapolis, Minnesota
                Author notes
                Address for correspondence April Adams, MD Department of Obstetrics and Gynecology University of Minnesota, Minneapolis, MN adam0780@ 123456umn.edu
                Article
                150010
                10.1055/s-0035-1555128
                4603848
                a433c5bf-4773-48cb-972b-8468517354cb
                © Thieme Medical Publishers
                History
                : 02 February 2015
                : 14 May 2015
                Categories
                Article

                bile acids,cholestasis,pregnancy,liver disease
                bile acids, cholestasis, pregnancy, liver disease

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