Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: Semifactorial randomised clinical trial

BMJ (Online)

Volumn 344, Issue 7862, 2012, Pages

  Chappell, Lucy C ^a   Gurung, Vinita ^b   Seed, Paul T ^a   Chambers, Jenny ^c   Williamson, Catherine ^c   Thornton, James G ^d  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b CITY HOSPITAL   (United Kingdom)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

^d QUEEN S MEDICAL CENTRE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; BILE ACID; PLACEBO; URSODEOXYCHOLIC ACID; CHOLAGOGUE;

ADULT; ARTICLE; BILE ACID BLOOD LEVEL; CESAREAN SECTION; CLINICAL FEATURE; CONTROLLED STUDY; DOSE RESPONSE; DOWN REGULATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG WITHDRAWAL; EXPECTANT MOTHER; FEASIBILITY STUDY; FEMALE; FOLLOW UP; GASTROINTESTINAL SYMPTOM; GESTATIONAL AGE; HUMAN; INTRAHEPATIC CHOLESTASIS; INTRAHEPATIC CHOLESTASIS OF PREGNANCY; LABOR MANAGEMENT; LOOSE FECES; MAJOR CLINICAL STUDY; MULTICENTER STUDY; NAUSEA; OUTCOME ASSESSMENT; PATIENT COMPLIANCE; PREGNANCY OUTCOME; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; VISUAL ANALOG SCALE; VOMITING; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; LABOR INDUCTION; PREGNANCY; PREGNANCY COMPLICATION; STATISTICS; WATCHFUL WAITING;

ADULT; CESAREAN SECTION; CHOLAGOGUES AND CHOLERETICS; CHOLESTASIS, INTRAHEPATIC; FEASIBILITY STUDIES; FEMALE; HUMANS; LABOR, INDUCED; PREGNANCY; PREGNANCY COMPLICATIONS; PREGNANCY OUTCOME; PRURITUS; URSODEOXYCHOLIC ACID; WATCHFUL WAITING; YOUNG ADULT;

EID: 84862665365     PISSN: 17561833     EISSN: None     Source Type: Journal    
DOI: 10.1136/bmj.e3799     Document Type: Article

References (46)

1. Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol 2009;15:2049-66.
2. Fisk NM, Bye WB, Storey GN. Maternal features of obstetric cholestasis: 20 years experience at King George V Hospital. Aust N Z J Obstet Gynaecol 1988;28:172-6.
3. Saleh MM, Abdo KR. Intrahepatic cholestasis of pregnancy: review of the literature and evaluation of current evidence. J Womens Health (Larchmt) 2007;16:833-41. (Pubitemid 47264832)
4. Brites D, Rodrigues CM, Cardoso Mda C, Graca LM. Unusual case of severe cholestasis of pregnancy with early onset, improved by ursodeoxycholic acid administration. Eur J Obstet Gynecol Reprod Biol 1998;76:165-8. (Pubitemid 28031906)
5. Abedin P, Weaver JB, Egginton E. Intrahepatic cholestasis of pregnancy: prevalence and ethnic distribution. Ethn Health 1999;4:35-7. (Pubitemid 29488195)
6. Saleh MM, Abdo KR. Consensus on the management of obstetric cholestasis: National UK survey. BJOG 2007;114:99-103. (Pubitemid 44923939)
7. Zapata R, Sandoval L, Palma J, Hernandez I, Ribalta J, Reyes H, et al. Ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy. A 12-year experience. Liver Int 2005;25:548-54. (Pubitemid 40861904)
8. Royal College of Obstetricians and Gynaecologists. Obstetric cholestasis (Greentop guideline 43). RCOG, 2006.
9. Roncaglia N, Arreghini A, Locatelli A, Bellini P, Andreotti C, Ghidini A. Obstetric cholestasis: outcome with active management. Eur J Obstet Gynecol Reprod Biol 2002;100:167-70. (Pubitemid 34028135)
10. Williamson C, Hems LM, Goulis DG, Walker I, Chambers J, Donaldson O, et al. Clinical outcome in a series of cases of obstetric cholestasis identified via a patient support group. BJOG 2004;111:676-81. (Pubitemid 38869755)
11. Thornton JG, Hornbuckle J, Vail A, Spiegelhalter DJ, Levene M. Infant wellbeing at 2 years of age in the Growth Restriction Intervention Trial (GRIT): multicentred randomised controlled trial. Lancet 2004;364:513-20.
12. Boers KE, Vijgen SM, Bijlenga D, van der Post JA, Bekedam DJ, Kwee A, et al. Induction versus expectant monitoring for intrauterine growth restriction at term: randomised equivalence trial (DIGITAT). BMJ 2010;341:c7087.
13. Koopmans CM, Bijlenga D, Groen H, Vijgen SM, Aarnoudse JG, Bekedam DJ, et al. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks' gestation (HYPITAT): a multicentre, open-label randomised controlled trial. Lancet 2009;374:979-88.
14. Buchanan SL, Crowther CA, Levett KM, Middleton P, Morris J. Planned early birth versus expectant management for women with preterm prelabour rupture of membranes prior to 37 weeks' gestation for improving pregnancy outcome. Cochrane Database Syst Rev 2010;(3):CD004735.
15. Dare MR, Middleton P, Crowther CA, Flenady VJ, Varatharaju B. Planned early birth versus expectant management (waiting) for prelabour rupture of membranes at term (37 weeks or more). Cochrane Database Syst Rev 2006;(1):CD005302.
16. Clark SL, Miller DD, Belfort MA, Dildy GA, Frye DK, Meyers JA. Neonatal and maternal outcomes associated with elective term delivery. Am J Obstet Gynecol 2009;200:156 e1-4.
17. MacKay DF, Smith GC, Dobbie R, Pell JP. Gestational age at delivery and special educational need: retrospective cohort study of 407,503 schoolchildren. PLoS Med 2010;7:e1000289.
18. Boyle EM, Poulsen G, Field DJ, Kurinczuk JJ, Wolke D, Alfirevic Z, et al. Effects of gestational age at birth on health outcomes at 3 and 5 years of age: population based cohort study. BMJ 2012;344:e896.
19. Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. BMJ 1990;300:230-5. (Pubitemid 20045528)
20. Rogers W. Regression standard errors in clustered samples. Stata Tech Bull 1993;13:19-23.
21. Frison L, Pocock SJ. Repeated measures in clinical trials: analysis using mean summary statistics and its implications for design. Stat Med 1992;11:1685-704.
22. Gurung V, Williamson C, Chappell L, Chambers J, Briley A, Broughton Pipkin F, et al. Pilot study for a trial of ursodeoxycholic acid and/or early delivery for obstetric cholestasis. BMC Pregnancy Childbirth 2009;9:19.
23. Burrows RF, Clavisi O, Burrows E. Interventions for treating cholestasis in pregnancy. Cochrane Database Syst Rev 2001;(4):CD000493.
24. Diaferia A, Nicastri PL, Tartagni M, Loizzi P, Iacovizzi C, Di Leo A. Ursodeoxycholic acid therapy in pregnant women with cholestasis. Int J Gynaecol Obstet 1996;52:133-40. (Pubitemid 26039234)
25. Palma J, Reyes H, Ribalta J, Hernandez I, Sandoval L, Almuna R, et al. Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo. J Hepatol 1997;27:1022-8. (Pubitemid 27523961)
26. Nicastri PL, Diaferia A, Tartagni M, Loizzi P, Fanelli M. A randomised placebo-controlled trial of ursodeoxycholic acid and S-adenosylmethionine in the treatment of intrahepatic cholestasis of pregnancy. Br J Obstet Gynaecol 1998;105:1205-7. (Pubitemid 28526205)
27. Glantz A, Marschall HU, Lammert F, Mattsson LA. Intrahepatic cholestasis of pregnancy: a randomized controlled trial comparing dexamethasone and ursodeoxycholic acid. Hepatology 2005;42:1399-405. (Pubitemid 43260043)
28. Liu Y, Qiao F, Liu H, Liu D. Ursodeoxycholic acid in the treatment of intraheptic cholestasis of pregnancy. J Huazhong Univ Sci Technolog Med Sci 2006;26:350-2.
29. Gurung V, Stokes M, Middleton P, Milan SJ, Hague, Thornton JG . Interventions for treating cholestasis in pregnancy. Cochrane Database Syst Rev 2011 (submitted).
30. Webster J, Chappell L, Cheng F, Breeze A, Lucas N, Plaat F, et al. Operative delivery rates following induction of labour for obstetric cholestasis. Obstetr Med 2011;4:66-9.
31. Reid R, Ivey KJ, Rencoret RH, Storey B. Fetal complications of obstetric cholestasis. BMJ 1976;1:870-2.
32. Costoya AL, Leontic EA, Rosenberg HG, Delgado MA. Morphological study of placental terminal villi in intrahepatic cholestasis of pregnancy: histochemistry, light and electron microscopy. Placenta 1980;1:361-8. (Pubitemid 11253242)
33. Liebhart M, Wojcicka J. Microscopic patterns of placenta in cases of pregnancy complicated by intrahepatic cholestasis (idiopathic jaundice). Pol Med J 1970;9:1589-600.
34. Laatikainen T, Ikonen E. Serum bile acids in cholestasis of pregnancy. Obstet Gynecol 1977;50:313-8. (Pubitemid 8181620)
35. Perez MJ, Macias RI, Marin JJ. Maternal cholestasis induces placental oxidative stress and apoptosis. Protective effect of ursodeoxycholic acid. Placenta 2006;27:34-41. (Pubitemid 41662877)
36. Geenes V, Lim Y, Bowman N, Tailor H, Dixon P, Chambers J, et al. A placental phenotype for intrahepatic cholestasis of pregnancy. Placenta 2011 Oct 18. [Epub ahead of print].
37. Williamson C, Gorelik J, Eaton BM, Lab M, de Swiet M, Korchev Y. The bile acid taurocholate impairs rat cardiomyocyte function: a proposed mechanism for intra-uterine fetal death in obstetric cholestasis. Clin Sci (Lond) 2001;100:363-9. (Pubitemid 32324333)
38. Abdul Kadir SH, Ali NN, Mioulane M, Brito-Martins M, Abu-Hayyeh S, Foldes G, et al. Embryonic stem cell-derived cardiomyocytes as a model to study fetal arrhythmia related to maternal disease. J Cell Mol Med 2009;13:3730-41.
39. Sheikh Abdul Kadir SH, Miragoli M, Abu-Hayyeh S, Moshkov AV, Xie Q, Keitel V, et al. Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes. PLoS One 2010;5:e9689.
40. Miragoli M, Kadir SH, Sheppard MN, Salvarani N, Virta M, Wells S, et al. A protective antiarrhythmic role of ursodeoxycholic acid in an in vitro rat model of the cholestatic fetal heart. Hepatology 2011;54:1282-92.
41. Al Inizi S, Gupta R, Gale A. Fetal tachyarrhythmia with atrial flutter in obstetric cholestasis. Int J Gynaecol Obstet 2006;93:53-4. (Pubitemid 46137878)
42. Gorelik J, Shevchuk AI, Diakonov I, de Swiet M, Lab M, Korchev Y, et al. Dexamethasone and ursodeoxycholic acid protect against the arrhythmogenic effect of taurocholate in an in vitro study of rat cardiomyocytes. BJOG 2003;110:467-74. (Pubitemid 36556129)
43. Campos GA, Castillo RJ, Toro FG. [Effect of bile acids on the myometral contractility of the isolated pregnant uterus]. Rev Chil Obstet Ginecol 1988;53:229-33.
44. Campos GA, Guerra FA, Israel EJ. Effects of cholic acid infusion in fetal lambs. Acta Obstet Gynecol Scand 1986;65:23-6. (Pubitemid 16105515)
45. Zecca E, De Luca D, Marras M, Caruso A, Bernardini T, Romagnoli C. Intrahepatic cholestasis of pregnancy and neonatal respiratory distress syndrome. Pediatrics 2006;117:1669-72. (Pubitemid 46071395)
46. Zecca E, Costa S, Lauriola V, Vento G, Papacci P, Romagnoli C. Bile acid pneumonia: a "new" form of neonatal respiratory distress syndrome? Pediatrics 2004;114:269-72. (Pubitemid 38857601)