Introduction
Intrahepatic cholestasis of pregnancy (ICP) is characterised by maternal pruritus and elevated serum bile acids. It affects around 0.7% of pregnancies in the UK1 and typically presents in the third trimester. It is associated with adverse perinatal outcomes including stillbirth, preterm labour and neonatal unit admission. An increase in preterm birth is seen with serum bile acid concentrations above 40 µmol/L, and the risk of stillbirth is increased in women when peak serum bile acid concentrations are 100 µmol/L or more.2
The mainstay of treatment has been ursodeoxycholic acid (UDCA), a bile acid produced in small amounts by the gut microbiota in humans.3Surveys across the UK found that 97% of obstetricians used UDCA to treat ICP4 and it is recommended in six national guidelines, but evidence for its efficacy is limited. A 2013 Cochrane review5of 21 trials with a total of 1197 women concluded that UDCA improved maternal pruritus, albeit by a small amount. In women treated with UDCA there was no difference in adverse perinatal outcomes, but the number of events overall was small. The largest trial analysed in that meta-analysis included only 111 women, and the majority of the trials were assessed as being at moderate-to-high risk of bias.
The PITCHES trial was published in August 2019 and was the largest trial to date investigating the efficacy of UDCA in 605 women with ICP.6 It was a parallel-group, double-blind, multicentre, randomised placebo-controlled trial with individual randomisation to UDCA or placebo using a 1:1 allocation ratio. The primary outcome of the trial was a composite measure of adverse perinatal outcomes. Secondary maternal data, including biochemical measurements and itch severity, were collected at antenatal visits from randomisation to delivery. The trial found that there was no evidence that treatment with UDCA significantly reduced adverse perinatal outcomes.
It is nevertheless possible that there is a group of women with ICP who do respond to treatment with UDCA, either in terms of a reduction in bile acid concentrations or in itch severity, possibly leading to better perinatal outcomes. These women would need to be identified from their presenting characteristics in order for them to receive targeted treatment. This secondary analysis of the PITCHES trial aims to investigate whether a particular group of women, identified by their characteristics at presentation, might benefit from targeted treatment with UDCA.