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.