Research Article| Volume 63, ISSUE 2, P456-461, August 2015

Intrahepatic cholestasis of pregnancy and cancer, immune-mediated and cardiovascular diseases: A population-based cohort study

Published:March 14, 2015DOI:

      Background & Aims

      Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease in pregnancy. It is associated with hepatobiliary diseases that might predispose to cancer and also with gestational diabetes and preeclampsia. In this study, we examined associations between ICP and cancer, and immune-mediated and cardiovascular diseases.


      By linking the Swedish Medical Birth Register and the Swedish Patient Register, we identified 11,388 women with ICP and 113,893 matched women without ICP who gave birth between 1973 and 2009. Diagnoses of cancer and immune-mediated and cardiovascular diseases both before and after delivery were obtained from the Patient Register. The main outcome measures were hazard ratios (HRs), calculated through Cox regression, for the indicated diseases after delivery.


      ICP was not associated with later overall cancer (HR 1.07, 95% confidence interval [CI] 0.94–1.21), but it was associated with later liver and biliary tree cancer (HR 3.61, 95% CI 1.68–7.77, and 2.62, 95% CI 1.26–5.46, respectively). ICP was also associated with later immune-mediated diseases (HR 1.28, 95% CI 1.19–1.38), and specifically diabetes mellitus (HR 1.47, 95% CI 1.26–1.72), thyroid disease (HR 1.30, 95% CI 1.14–1.47), psoriasis (HR 1.27, 95% CI 1.07–1.51), inflammatory polyarthropathies (HR 1.32, 95% CI 1.11–1.58) and Crohn’s disease (HR 1.55, 95% CI 1.14–2.10), but not ulcerative colitis (HR 1.21, 95% CI 0.93–1.58). Women with ICP also had a small increased risk of later cardiovascular disease (HR 1.12, 95% CI 1.06–1.19).


      Women with ICP have increased risk of later hepatobiliary cancer and immune-mediated and cardiovascular diseases.

      Graphical abstract


      ICP (intrahepatic cholestasis of pregnancy), HR (hazard ratio), CI (confidence interval), ICD (International Classification of Disease)


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        • Joshi D.
        • James A.
        • Quaglia A.
        • Westbrook R.H.
        • Heneghan M.A.
        Liver disease in pregnancy.
        Lancet. 2010; 375: 594-605
        • Lammert F.
        • Marschall H.U.
        • Glantz A.
        • Matern S.
        Intrahepatic cholestasis of pregnancy: molecular pathogenesis, diagnosis and management.
        J Hepatol. 2000; 33: 1012-1021
        • Geenes V.
        • Williamson C.
        Intrahepatic cholestasis of pregnancy.
        World J Gastroenterol. 2009; 15: 2049-2066
        • Glantz A.
        • Marschall H.U.
        • Mattsson L.A.
        Intrahepatic cholestasis of pregnancy: relationships between bile acid levels and fetal complication rates.
        Hepatology. 2004; 40: 467-474
        • Wikstrom Shemer E.
        • Marschall H.U.
        • Ludvigsson J.F.
        • Stephansson O.
        Intrahepatic cholestasis of pregnancy and associated adverse pregnancy and fetal outcomes: a 12-year population-based cohort study.
        BJOG. 2013; 120: 717-723
        • Geenes V.
        • Chappell L.C.
        • Seed P.T.
        • Steer P.J.
        • 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: 1482-1491
        • 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: 723-728
        • Marschall H.U.
        • Wikstrom Shemer E.
        • Ludvigsson J.F.
        • Stephansson O.
        Intrahepatic cholestasis of pregnancy and associated hepatobiliary disease: a population-based cohort study.
        Hepatology. 2013; 58: 1385-1391
        • Martineau M.
        • Raker C.
        • Powrie R.
        • Williamson C.
        Intrahepatic cholestasis of pregnancy is associated with an increased risk of gestational diabetes.
        Eur J Obstet Gynecol Reprod Biol. 2014; 176: 80-85
        • Charlton F.
        • Tooher J.
        • Rye K.A.
        • Hennessy A.
        Cardiovascular risk, lipids and pregnancy: preeclampsia and the risk of later life cardiovascular disease.
        Heart Lung Circ. 2014; 23: 203-212
        • Bellamy L.
        • Casas J.P.
        • Hingorani A.D.
        • Williams D.
        Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis.
        Lancet. 2009; 373: 1773-1779
        • Lauenborg J.
        • Mathiesen E.
        • Hansen T.
        • Glumer C.
        • Jorgensen T.
        • Borch-Johnsen K.
        • et al.
        The prevalence of the metabolic syndrome in a danish population of women with previous gestational diabetes mellitus is three-fold higher than in the general population.
        J Clin Endocrinol Metab. 2005; 90: 4004-4010
        • Rich-Edwards J.W.
        • Fraser A.
        • Lawlor D.A.
        • Catov J.M.
        Pregnancy characteristics and women’s future cardiovascular health: an underused opportunity to improve women’s health?.
        Epidemiol Rev. 2014; 36: 57-70
        • Turunen K.
        • Molsa A.
        • Helander K.
        • Sumanen M.
        • Mattila K.J.
        Health history after intrahepatic cholestasis of pregnancy.
        Acta Obstet Gynecol Scand. 2012; 91: 679-685
        • Papacleovoulou G.
        • Abu-Hayyeh S.
        • Nikolopoulou E.
        • Briz O.
        • Owen B.M.
        • Nikolova V.
        • et al.
        Maternal cholestasis during pregnancy programs metabolic disease in offspring.
        J Clin Invest. 2013; 123: 3172-3181
        • Dixon P.H.
        • Wadsworth C.A.
        • 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: 76-84
        • Dann A.T.
        • Kenyon A.P.
        • Wierzbicki A.S.
        • Seed P.T.
        • Shennan A.H.
        • Tribe R.M.
        Plasma lipid profiles of women with intrahepatic cholestasis of pregnancy.
        Obstet Gynecol. 2006; 107: 106-114