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A diagnosis of cholestasis is established in the presence of raised (above 14) bile acids and itching. There may also be a two to four fold increase in transaminases and a small rise in bilirubin levels. Alkaline phosphatase is raised in normal pregnancy (normal values 133-418 iu/l in the third trimester (Reference1) as it is produced by the placenta. Therefore at present its contribution to the diagnosis is debatable. A careful history may reveal cyclical itching or itching whilst on the oral contraceptive pill or during a previous pregnancy.

Differential diagnosis

Care must be taken to exclude other underlying liver disorders especially in the presence of markedly raised liver function or jaundice. A past or family history of liver disease should be sought and risk factors for hepatitis and liver disease in general, such as drugs and alcohol, should be identified. A full hepatitis screen should include cytomegalovirus and Epstein Barr virus as well as serology for types A B and C. An upper abdominal ultrasound may be useful although the presence of gallstones may be incidental. Autoimmune liver disease may present with similar biochemistry or itching and may be diagnosed by testing for anti-smooth muscle antibodies (chronic active hepatitis) and anti-mitochondrial antibodies (primary biliary cirrhosis).

The mainstay of current management is early delivery, which may help to reduce the stillbirth rate (Reference2). The majority of stillbirths occur at term, and the current recommendation is to induce delivery by 37-38 weeks.


Unfortunately the situation is analogous to diabetic pregnancies in that sudden stillbirth may occur without evidence of prior fetal compromise. There is usually no evidence of placental insufficiency. Doppler umbilical artery velocimetry has not been shown to correlate with bile acid or alanine aminotransferase levels (Reference3). However in the absence of an agreed protocol for fetal surveillance, a suggested regime would include fortnightly growth scans with weekly liquor and Doppler estimations and cardiotocography two or three times a week (Reference4). In some cases inpatient monitoring may be appropriate although no studies to date examine the outcome with inpatient versus outpatient care. Maternal liver function, bile acids and clotting (PT/APTT) should be checked at least weekly.

Ursodeoxycholic acid (Urso)

This improves maternal itching and normalises biochemistry (Reference5). Only one randomised controlled trial of its usage in cholestasis exists in the literature (Reference6). This was stopped prematurely because of one stillbirth, which was found to be in the control group. Of the 15 patients who completed the trial there were no adverse effects in the mothers or their babies. There were 5 premature deliveries and one stillbirth in the control group but none in the trial group.

Urso works by normalising the bile acid pool (Reference7), stimulating bile flow and competing for bile acid receptors. Clinically it improves maternal pruritis, lowers maternal bile acids and corrects the abnormal ratio of progesterone metabolites (Reference8). It also lowers bile acids in cord blood and amniotic fluid (Reference9) although bile acids in meconium remain unchanged (Reference10). Although unlicensed in pregnancy it is increasingly being used (8-12mg/kg in two daily divided doses).

Other drugs

One small trial looked at dexamethasone usage (Reference11). There is certainly a role for dexamethasone for fetal lung maturity in those cases where delivery is anticipated before 36 weeks. S-adnosylmethionine has also been used (Reference12,Reference13) and compared to ursodeoxycholic acid (Reference14).

Vitamin K should be given to women with deranged clotting as a result of cholestasis, and in addition should be considered for all women with cholestasis to help prevent primary post partum haemorrhage and haemorrhagic disease of the newborn.


Symptoms and biochemistry should resolve within one to two weeks postpartum. All women should be followed up and in the absence of normalisation of biochemistry, they should be investigated for an alternative cause of their raised liver function.

All women with cholestasis should avoid the oral contraceptive pill as this can cause a similar condition. They should also be warned that the recurrence rate in subsequent pregnancies is high. There is no evidence to date that hormone replacement therapy is harmful


1.Girling JC, Dow E, Smith JH. Liver function tests in pre-eclampsia: importance of comparison with a reference range derived from a normal pregnancy. Br J Obstet Gynaecol 1997; 104: 246-50, Abstract

2. Rioseco AJ. Ivankovic MB. Manzur A. Hamed F. Kato SR. Parer JT. Germain AM. Intrahepatic cholestasis of pregnancy: a retrospective case-control study of perinatal outcome. American Journal of Obstetrics & Gynecology. 1994;170(3):890-5, Abstract

3. Zimmermann P, Koskinen J, Vaalamo P, Ranta T. Doppler umbilical artery velocimetry in pregnancies complicated by intrahepatic cholestasis. Journal of Perinatal Medicine 1991; 19(5):351-5, Abstract

4.Kelly A, Nelson-Piercy C. Obstetric cholestasis:PACE review. The Obstetrician and Gynaecologist 2000;2(3) 29-31

5. Palma J, Reyes H, Ribalta J et al. Effects of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy. Hepatology 1992; 15:1043-7, Abstract

6.Palma J. Reyes H. Ribalta J. Hernandez I. Sandoval L. Almuna R. Liepins J. Lira F. Sedano M. Silva O. Toha D. Silva JJ. Ursodeoxycholic acid in the treatment of cholestasis of pregnancy: a randomized, double-blind study controlled with placebo. Journal of Hepatology. 1997; 27(6): 1022-8, Abstract

7.Brites D, Rodrigues CMP, Oliveira N, Da Conceicao Cardoso M, Graca LM. Correction of maternal serum bile acid profile during ursodeoxycholic acid therapy in cholestasis of pregnancy. Journal of Hepatology. 1998; 28(1): 91-98, Abstract

8. Meng LJ. Reyes H. Axelson M. Palma J. Hernandez I. Ribalta J. Sjovall J. Progesterone metabolites and bile acids in serum of patients with intrahepatic cholestasis of pregnancy: effect of ursodeoxycholic acid therapy. Hepatology. 1997;26(6):1573-9, Abstract

9.Mazzella G, Nichola R, Francesco A et al Ursodeoxycholic acid administration in patients with cholestasis of pregnancy: Effects on primary bile acids in babies and mothers. Hepatology. 2001;33(3):504-508, Abstract

10. Rodrigues CMP, Marin JJG, Brites D. Bile acid patterns in meconium are influenced by cholestasis of pregnancy and not altered by ursodeoxycholic acid.Gut 1999;45(3):446-452., Abstract

11.Hirvioja M-L, Tuimala R, Vuori J. The treatment of intrahepatic cholestasis of pregnancy by dexamethasone. Br J Obstet Gynaecol 1992; 99:109-11, Abstract

12. Frezza M, Centini G, Caareri G et al. S-Adenosylmethionine for the treatment of intrahepatic cholestasis of pregnancy. Results of a controlled clinical trial. Hepatogastroenterology. 1990; 37(12):122-5, Abstract

13. Ribalta J. Reyes H. Gonzalez MC. Iglesias J. Arrese M. Poniachik J. Molina C. Segovia N. 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;13(6):1084-9, Abstract

14. Floreani A. Paternoster D. Melis A. Grella PV. S-adenosylmethionine versus ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy: preliminary results of a controlled trial. European Journal of Obstetrics, Gynecology, & Reproductive Biology.1996; 67(2):109-13, Abstract

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