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Fetal complications due to intrahepatic cholestasis of pregnancy

  • Patrik Šimják , Antonín Pařízek EMAIL logo , Libor Vítek , Andrej Černý , Karolína Adamcová , Michal Koucký , Martin Hill , Michaela Dušková and L’uboslav Stárka
Published/Copyright: August 5, 2014

Abstract

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder of pregnancy. Diagnosis is based on the clinical picture, particularly the presence of pruritus with a deterioration of liver function tests, and typically elevated serum levels of total bile acids. ICP manifests in the second half of pregnancy, predominantly during the third trimester. Symptoms of the disease resolve spontaneously after delivery. Etiology is still not fully understood. Genetic defects in specific transport proteins, elevated levels of sex hormones, and various environmental factors are thought to play a role in the development of this disorder. Although practically benign for the pregnant woman, ICP represents a serious threat to the fetus. It increases the risk of preterm delivery, meconium excretion into the amniotic fluid, respiratory distress syndrome, and sudden intrauterine fetal death. Identifying fetuses at risk of ICP complications remains challenging. The ideal obstetrical management of ICP needs to be definitively determined. The aim of this review is to summarize the current knowledge on fetal complications of ICP and describe management options for their prevention.


Corresponding author: Doc. MUDr. Antonín Pařízek, CSc., First Faculty of Medicine, Department of Obstetrics and Gynaecology, Charles University in Prague and General University Hospital in Prague, Apolinářská 18, 128 51, Prague 2, Czech Republic, Tel.: +420 602 203 023, E-mail:

Conflict of interest statement

Author’s conflict of interest disclosure:

None declared.

Funding:

Supported by Internal Grant Agency of the Ministry of Health of the Czech Republic, (Grant/Award Number: ‘IGA MZCR NT 12211-5’).

References

[1] Al Inizi S, Gupta R, Gale A. Fetal tachyarrhythmia with atrial flutter in obstetric cholestasis. Int J Gynaecol Obstet. 2006;93:53–4.10.1016/j.ijgo.2005.12.030Search in Google Scholar PubMed

[2] Alokananda R, Rashne JT, Roshan B, Sangeeta S. Cholestasis of pregnancy. J Obstet Gynecol India. 2005;55:247–50.Search in Google Scholar

[3] Bacq Y, Sapey T, Brechot MC, Pierre F, Fignon A, Dubois F. Intrahepatic cholestasis of pregnancy: a French prospective study. Hepatology. 1997;26:358–64.10.1002/hep.510260216Search in Google Scholar PubMed

[4] 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;143:1492–501.10.1053/j.gastro.2012.08.004Search in Google Scholar PubMed

[5] Binder T, Salaj P, Zima T. Intrahepatic cholestasis in pregnancy – guidelines of treatment. Ceska Gynekol. 2007;72:94–8.Search in Google Scholar

[6] Binder T, Salaj P, Zima T, Vitek L. Randomized prospective comparative study of ursodeoxycholic acid and S-adenosyl-L-methionine in the treatment of intrahepatic cholestasis of pregnancy. J Perinat Med. 2006;34:383–91.10.1515/JPM.2006.077Search in Google Scholar PubMed

[7] Binder T, Salaj P, Zima T, Vitek L. Ursodeoxycholic acid, S-adenosyl-L-metionine and their combination in the treatment of gestational intrahepatic cholestasis (ICP). Ceska Gynekol. 2006;71:92–8.Search in Google Scholar

[8] Campos GA, Guerra FA, Israel EJ. Effect of cholic acid infusion in fetal lambs. Acta Obstet Gynecol Scand. 1986;65:23–6.10.3109/00016348609158224Search in Google Scholar PubMed

[9] Chappell LC, Gurung V, Seed PT, Chambers J, Williamson C, Thorton JG. Ursodeoxycholic acid versus placebo, and early term delivery versus expectant management, in women with intrahepatic cholestasis of pregnancy: semifactorial randomised clinical trial. Br Med J. 2012;344:e3799.10.1136/bmj.e3799Search in Google Scholar PubMed PubMed Central

[10] Colombo C, Roda A, Roda E, Buscaglia M, dell’Agnola CA, Filipetti P, et al. Correlation between fetal and maternal serum bile acid concentrations. Pediatr Res. 1985;19:227–31.10.1203/00006450-198502000-00018Search in Google Scholar PubMed

[11] EASL. Clinical practice guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51:237–67.10.1016/j.jhep.2009.04.009Search in Google Scholar PubMed

[12] Floreani A, Cardeli I, Paternoster D, Soardo G, Azzaroli F, Esposito W, et al. Hepatobiliary phospholipid transporter ABCB4, MDR3 gene variants in a large cohort of Italian women with intrahepatic cholestasis of pregnancy. Dig Liver Dis. 2008;40:366–70.10.1016/j.dld.2007.10.016Search in Google Scholar PubMed

[13] Geenes V, Chappell LC, Seed PT, Steer PJ, Knight M, Williamson C. Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: a prospective population-based case-control study. Hepatology. 2014;59:1482–91.10.1002/hep.26617Search in Google Scholar PubMed PubMed Central

[14] Germain AM, Kato S, Carvajal JA, Valenzuela GJ, Valdes GL, Glasinovic JC. Bile acids increase response and expression of human myometrial oxytocin receptor. Am J Obstet Gynecol. 2003;189:577–82.10.1067/S0002-9378(03)00545-3Search in Google Scholar

[15] Glantz A, Marschall HU, Mattson LA. Intrahepatic cholestasis of pregnancy: relationship between bile acid levels and fetal complication rates. Hepatology. 2004;40:467–74.10.1002/hep.20336Search in Google Scholar

[16] Gurung V, Middleton P, Milan SJ, Hague W, Thorton JG. Interventions for treating cholestasis in pregnancy. Cochrane Database Syst Rev. 2013;6:CD000493.10.1002/14651858.CD000493.pub2Search in Google Scholar

[17] Jain R, Suri V, Chopra S, Chawla YK, Kohli KK. Obstetric cholestasis: outcome with active management. J Obstet Gynaecol Res. 2013;39:953–9.10.1111/jog.12005Search in Google Scholar

[18] Kauppila A, Korpela H, Makila UM, Yrjanheikki E. Low serum selenium concentration and glutathione peroxidase activity in intrahepatic cholestasis of pregnancy. Br Med J (Clin Res Ed). 1987;294:150–2.10.1136/bmj.294.6565.150Search in Google Scholar

[19] Kirwan WO, Smith AN, Mitchel WD, Falconer JD, Eastwood MA. Bile acids and colonic motility in the rabbit and the human. Q J Exp Physiol Cogn Med Sci. 1980;65:135–44.Search in Google Scholar

[20] Lammert F, Marschall HU, Glantz A, Matern S. Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management. J Hepatol. 2000;33:1012–21.10.1016/S0168-8278(00)80139-7Search in Google Scholar

[21] Lee RH, Goodwin TM, Greenspoon J, Incerpi M. The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population. J Perinatol. 2006;26:527–32.10.1038/sj.jp.7211545Search in Google Scholar PubMed

[22] Lee RH, Incerpi MH, Miller DA, Pathak B, Goodwin TM. Sudden death in intrahepatic cholestasis of pregnancy. Obstet Gynecol. 2009;113:528–31.10.1097/AOG.0b013e31818db1c9Search in Google Scholar PubMed

[23] Lee RH, Kwok KM, Ingles S, Wilson ML, Mullin P, Incerpi M, et al. Pregnancy outcomes during an era of aggressive management for intrahepatic cholestasis of pregnancy. Am J Perinatol. 2008;25:341–5.10.1055/s-2008-1078756Search in Google Scholar PubMed

[24] Mazzela G, Rizzo N, Azzaroli F, Simoni P, Bovicelli L, Miracolo A, et al. Ursodeoxycholic administration in patients with cholestasis of pregnancy: effects of primary bile acids in babies and mothers. Hepatology. 2001;33:504–8.10.1053/jhep.2001.22647Search in Google Scholar PubMed

[25] Miragoli M, Gaudesius G, Rohr S. Electronic modulation of cardiac impulse conduction by myofibroblasts. Circ Res. 2006;98:421–8.10.1161/01.RES.0000214537.44195.a3Search in Google Scholar

[26] Miragoli M, Sheikh Abdul 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;54:1282–92.10.1002/hep.24492Search in Google Scholar

[27] Oelberg DG, Downey SA, Flynn MM. Bile salt-induced intracellular Ca++ accumulation in type II pneumocytes. Lung. 1990;168:297–308.10.1007/BF02719707Search in Google Scholar

[28] Oztekin D, Aydal I, Oztekin O, Okcu S, Borecki R, Tinar S. Predicting fetal asphyxia in intrahepatic cholestasis of pregnancy. Arch Gynecol Obstet. 2009;280:975–9.10.1007/s00404-009-1052-xSearch in Google Scholar

[29] 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;100:167–70.10.1016/S0301-2115(01)00463-8Search in Google Scholar

[30] Ropponen A, Sund R, Riikonen S, Ylikorkala O, Aittomaki K. Intrahepatic cholestasis of pregnancy as an indicator of liver and biliary diseases: a population-based study. Hepatology. 2006;43:723–8.10.1002/hep.21111Search in Google Scholar

[31] Sentilhes L, Verspyck E, Pia P, Marpleau L. Fetal death in a patient with intrahepatic cholestasis of pregnancy. Obstet Gynecol. 2006;107:458–60.10.1097/01.AOG.0000187951.98401.f7Search in Google Scholar

[32] Sepulveda WH, Gonzales C, Cruz MA, Rudolph MI. Vasoconstrictive effect of bile acids on isolated human placental chorionic veins. Eur J Obstet Gynecol Reprod Biol. 1991;42:211–15.10.1016/0028-2243(91)90222-7Search in Google Scholar

[33] Shand AW, Dickinson JE, D’Orsogna L. Refractory fetal supraventricular tachycardia and obstetric cholestasis. Fetal Diagn Ther. 2008;24:277–81.10.1159/000151676Search in Google Scholar PubMed

[34] 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:e9689.10.1371/journal.pone.0009689Search in Google Scholar PubMed PubMed Central

[35] Strehlow SL, Pathak B, Goodwin TM, Perez BM, Ebrahimi M, Lee RH. The mechanical PR interval in fetuses of women with intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol. 2010;203:455.el–5.10.1016/j.ajog.2010.05.035Search in Google Scholar PubMed

[36] Sun Y, Kiani MF, Postlethwaite AE, Weber KT. Infarct scar as living tissue. Basic Res Cardiol. 2002;97:343–7.10.1007/s00395-002-0365-8Search in Google Scholar PubMed

[37] Wang CH, Chen X, Zhou SF, Li X. Impaired fetal adrenal function in intrahepatic cholestasis of pregnancy. Med Sci Monit. 2011;17:265–71.10.12659/MSM.881766Search in Google Scholar PubMed PubMed Central

[38] Wikstrom Shemer E, Thorsell M, Östlund E, Blomberg B, Marschall HU. Stereological assessment of placental morphology in intrahepatic cholestasis of pregnancy. Placenta. 2012;11:914–18.10.1016/j.placenta.2012.08.005Search in Google Scholar PubMed

[39] Williamson C, Gorelik J, Eaton BM, Lab M, de Swiet M, Korchev Y. The bile acid taurocholate impairs rat cardiomyocyte function: a proposed mechanism of intrauterine fetal death in obstetric cholestasis. Clin Sci. 2001;100:363–9.10.1042/CS20000164Search in Google Scholar

[40] 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;114:269–72.10.1542/peds.114.1.269Search in Google Scholar PubMed

[41] Zecca E, De Luca D, Babbato G, Marras M, Tiberi E, Romagnoli C. Predicting respiratory distress syndrome in neonates from mothers with intrahepatic cholestasis of pregnancy. Early Hum Dev. 2008;84:337–41.10.1016/j.earlhumdev.2007.09.012Search in Google Scholar PubMed

[42] Zecca E, De Luca D, Marras M, Caruso A, Bernardini T, Romagnoli C. Intrahepatic cholestasis of pregnancy and neonatal respiratory distress syndrome. Pediatrics. 2006;117:1669–72.10.1542/peds.2005-1801Search in Google Scholar PubMed

[43] Zhou F, He MM, Liu ZF, Zhang L, Gao BX, Wang XD. Expression of corticotrophin-releasing hormone and its receptor in patients with intrahepatic cholestasis of pregnancy. Placenta. 2013;34:401–6.10.1016/j.placenta.2013.02.006Search in Google Scholar PubMed

The authors stated that there are no conflicts of interest regarding the publication of this article.

Received: 2014-3-12
Accepted: 2014-7-7
Published Online: 2014-8-5
Published in Print: 2015-3-1

©2015 by De Gruyter

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