Obstetric cholestasis
Piotr Milkiewicz, Elwyn Elias, Catherine Williamson, and Judith Weaver

Obstetric cholestasis (or intrahepatic cholestasis of pregnancy) remains widely disregarded as an important clinical problem, with many obstetricians still considering its main symptom, pruritus, a natural association of pregnancy. Obstetric cholestasis is associated with cholesterol gallstones. It may be extremely stressful for the mother but also carries risks for the baby.

Clinical studies clearly show that when obstetric cholestasis complicates pregnancies it may lead to premature births in up to 60%, fetal distress in up to 33%, and intrauterine death in up to 2% of patients.1 The cause of fetal death is acute anoxia.2 The incidence of obstetric cholestasis varies from 0.1% to 1.5% of pregnancies in Europe and 9.2%-15.6% in South American countries such as Bolivia or Chile. It is particularly high in the native Araucanian population in Chile, where the proportion of affected pregnancies reaches nearly 28%.3 The low quoted incidence of obstetric cholestasis in Europe may reflect an underestimation of the problem, and growing awareness of the condition will probably increase the numbers. For example, early studies from North America, published in 1962, showed its incidence to be less than 0.1%, whereas a study published 17 years later estimated the incidence to be around 0.7%.1

The aetiology of obstetric cholestasis is undoubtedly multifactorial, with genetic, environmental, and hormonal factors having important roles. Historically obstetric cholestasis has been associated with the cholestatic effect of oestradiol metabolites, in particular 17- oestradiol glucuronide. Progesterone metabolites, however, play an even more important part in its pathogenesis. Patients with obstetric cholestasis have a significantly increased ratio of 3  to 3  hydroxysteroids and large amounts of mono or disulphated progesterone metabolites excreted in their urine.4 Excess of these metabolites in the urine in obstetric cholestasis may be related to malfunction of biliary canalicular transporters normally responsible for their secretion from hepatocytes into bile. Several of these transporters have recently been characterised. These include proteins responsible for bile canalicular secretion of bile acids (bile salt export pump), organic anions (multidrug resistant protein 2) or phospholipids (multidrug resistance protein 3).

BMJ 2002; 324: 123-124.