期刊论文详细信息
BMC Gastroenterology
Intrahepatic cholestasis of pregnancy: observational study of the treatment with low-dose ursodeoxycholic acid
Ulla Ekblad1  Pia Suvitie1  Maria Linden1  Susanna Timonen1  Titta Joutsiniemi1 
[1] Department of Obstetrics and Gynaecology, Turku University Central Hospital, Kiinamyllynkatu 4-8, Turku, 20520, Finland
关键词: Ursodeoxycholic acid;    Intrahepatic cholestasis;    Pregnancy;   
Others  :  1224265
DOI  :  10.1186/s12876-015-0324-0
 received in 2015-04-17, accepted in 2015-07-20,  发布年份 2015
PDF
【 摘 要 】

Background

To exam the biochemical, obstetric management and pregnancy outcome in women with intrahepatic cholestasis of pregnancy (ICP) and treatment with ursodeoxycholic acid (UDCA).

Methods

Pregnancy outcome in patients with ICP (N = 307) was studied and patients treated with UDCA (N = 208) vs. no UDCA were compared. The data of the antenatal visits, deliveries and neonatal outcome of 307 pregnancies with ICP was collected from the hospital computerized delivery room log book. UDCA was used in 208 pregnancies. The diagnosis was made by maternal pruritus and elevation of total fasting bile acid (BA) (>6 μmol/l) and elevation of serum alanine aminotransferases (ALT) (>45 U/l). Maternal and neonatal data was analysed and data of the patients who used UDCA during pregnancy was analysed separately and compared with the data from patients without medication.

Results

UDCA was well tolerated. Mothers receiving UDCA had ICP diagnosed five weeks earlier than mothers without medication. At the diagnosis, levels of total BA and ALT were higher in the group using UDCA compared to the group without medication. Most deliveries were induced and perinatal outcome was good. Apgar scores at 5 min were significantly lower in UDCA group (p < 0.05), but fetal umbilical artery pH values were similar in both groups (p > 0.05). There were 30 patients with total BA > 40 μmol/l at diagnosis, 24 with UDCA and 6 without medication and those deliveries were induced soon after diagnosis. The preterm labour was also more common in these patents (p < 0.05). Women with preterm babies had significantly early onset pruritus and ICP was diagnosed earlier. Serum ALT and total BA levels were significantly higher in those pregnancies at diagnosis and also at first control.

Conclusions

Preterm labour was associated in severe ICP (total BA > 40 μmol/l), ALT levels were also significantly higher and ICP was diagnosed earlier (p < 0.05). Apgar scores were lower in preterm babies (p < 0.05), but umbilical artery pHvalues were not significantly lower. UDCA was well tolerated by pregnant women. With low-dose UDCA treatment the obstetric outcome was good. We still recommend careful obstetrical follow-up.

【 授权许可】

   
2015 Joutsiniemi et al.

【 预 览 】
附件列表
Files Size Format View
20150909051044117.pdf 608KB PDF download
Fig 4. 26KB Image download
Fig. 3. 24KB Image download
Fig. 2. 11KB Image download
Fig. 1. 11KB Image download
【 图 表 】

Fig. 1.

Fig. 2.

Fig. 3.

Fig 4.

【 参考文献 】
  • [1]Lammert F, Marschall H-U, Glantz A, Matern S: Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management. J Hepatol 2000, 33:1012-21.
  • [2]Reyes H: Review: intrahepatic cholestasis. A puzzling disorder of pregnancy. J Gastroenterol Hepatol 1997, 12:211-6.
  • [3]Dixon PH, Wadsworth CA, Chambers J, Donnelly J, Cooley S, Buckley R, et al.: A comprehensive analysis of common genetic variation around six candidate loci for intrahepatic cholestasis of pregnancy. Am J Gastroenterol 2014, 109(1):76-84.
  • [4]Simják P, Pařízek A, Vítek L, Cerný A, Adamcová K, Koucký M, et al. J Perinat Med. 2014. doi:10.1515/jpm-2014-0089.
  • [5]Glantz A, Marchall H-U, Mattsson L-Å: Intrahepatic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates. Hepatology 2004, 40:467-74.
  • [6]Beuers U, Pusl T: Intrahepatic cholestasis of pregnancy- a heterogenous group of pregnancy-related disorders. Hepatology 2006, 43:647-9.
  • [7]European Association for the Study of the Liver: Clinical practice guidelines: management of cholestatic liver diseases J Hepatol 2009, 51(2):237-67.
  • [8]Chappell LC, Gurung V, Seed PT, Chambers J, Williamson C, Thornton JG: Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial. BMJ 2012, 344:e3799.
  • [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(2):167-70.
  • [10]Heikkinen J, Mäentausta O, Ylöstalo P, Janne O: Serum bile acid levels in intrahepatic cholestasis of pregnancy during treatment with phenobarbital or cholestyramine. Eur J Obstet Reprod Biol 1982, 14:153-62.
  • [11]Ribalta J, Reyes H, Gonzales M, Iglesias J, Arrese M, Poniachic J: S-Adenosyl-L-methionine in the treatment of patients with intrahepatic cholestasis of pregnancy: a randomized, double-blind placebo controlled study with negative results. Hepatology 1991, 18:1084-9.
  • [12]Roncaglia N, Locatelli A, Arreghini A, Assi F, Cameroni I: A randomised controlled trial of ursodeoxycholic acid and S-adenosyl-l-methionine in the treatment of gestational cholestasis. BJOG 2004, 111:17-21.
  • [13]Glantz A, Marschall H-U, Lammert F, Mattsson L-Å: Intrahepatic cholestasis of pregnancy: a randomized controlled trial comparing dexametasone and ursodeoxycholic acid. Hepatology 2005, 42:1399-405.
  • [14]Diaferia A, Nicastri P, Tartagni M, Loizzi P, Iacovizzi C, Di Leo A: Ursodeoxycholic acid therapy in pregnant women with cholestasis. Int J Gynecol Obstet 1996, 52:133-40.
  • [15]Gurung V, Middleton P, Milan S, Hague W, Thornton J. Interventions for treating cholestasis in pregnancy. Cochrane Database Syst Rev. 2013;24:6
  • [16]Bacq Y, Sentilhes L, Reyes HB, Glantz A, Kondrackiene J, Binder T et al. Efficacy of ursodeoxycholic acid in treating intrahepatic cholestasis of pregnancy: a meta-analysis. Gastroenterology. 2012;143:1492–501.
  • [17]Palma J, Reyes H, Ribalta J, Iglesias J, Gonzalez M, Hernandez I et al. Effects of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy. Hepatology. 1992;15:1043–7.
  • [18]Nicastri P, Diaferia A, Tartagni M, Loizzi P, Fanelli M: A randomised placebo-controlled trial of ursodeoxycholic acid and S-adenosylmethione in the treatment of intrahepatic cholestasis of pregnancy. Br J Obstet Gynaecol 1998, 105:1205-7.
  • [19]Palma J, Reyes H, Ribalta J, Hernandez I, Sandoval L, Almura R et al. Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomised, double-blind study controlled with placebo. J Hepatol. 1997;27:1022–8.
  • [20]Grand’Maison S, Durand M, Mahone M: The effects of ursodeoxycholic acid treatment for intrahepatic cholestasis of pregnancy on maternal and fetal outcomes: a meta-analysis including non-randomized studies. J Obstet Gynaecol Can 2014, 36:632-41.
  • [21]Mazzella G, Rizzo N, Azzaroli F, Simoni P, Bovicelli L, Miracolo A et al. Ursodeoxycholic acid administration in patients with cholestasis of pregnancy: effects on primary bile acids in babies and mothers. Hepatology. 2001;33:504–8.
  • [22]Zapata R, Sandoval L, Palma J, Hernandez I, Ribalta J, Rayes H et al. Ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy. A 12-year experience. Liver Int. 2005;25:548–54.
  • [23]Puljic A, Kim E, Page J, Esakoff T, Shaffer B, LaCoursiere D, et al. The risk of infant and fetal death by each additional week of expectant management in intrahepatic cholestasis of pregnancy by gestational age. Am J Obstet Gyn. 2015;212:667.
  • [24]Mozurkewich E, Chilimigras J, Koepke E, Keeton K, King V: Indications for induction of labour: a best-evidence review. BJOG 2009, 116:626-36.
  • [25]Curet L, Zachman R, Rao A, Poole W, Morrison J, Burkett G: Effect of mode of delivery on incidence of respiratory distress syndrome. Int J Gynaecol Obstet 1988, 27:165-70.
  • [26]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.
  • [27]Geenes V, Chappell L, Seed P, Steer P, Knight M, Williamson C: Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: a prospective population-based case–control study. Hepatology 2013.
  文献评价指标  
  下载次数:46次 浏览次数:5次