Objective: To determine the optimal total serum bile acid (TSBA) threshold and sampling time for accurate intrahepatic cholestasis of pregnancy (ICP) diagnosis. Design: Case–control, retrospective cohort studies. Setting: Antenatal clinics, clinical research facilities. Population: Women with ICP or uncomplicated pregnancies. Methods: Serial TSBA measurements were performed pre-/postprandially in 42 women with ICP or uncomplicated pregnancy. Third-trimester non-fasting TSBA reference ranges were calculated from 561 women of black, south Asian and white ethnicity. Rates of adverse perinatal outcomes for women with ICP but peak non-fasting TSBA below the upper reference range limit were compared with those in healthy populations. Main outcome measures: Sensitivity and specificity of common TSBA thresholds for ICP diagnosis, using fasting and postprandial TSBA. Calculation of normal reference ranges of non-fasting TSBA. Results: Concentrations of TSBA increased markedly postprandially in all groups, with overlap between healthy pregnancy and mild ICP (TSBA <40 μmol/l). The specificity of ICP diagnosis was higher when fasting, but corresponded to <30% sensitivity for diagnosis of mild disease. Using TSBA ≥40 μmol/l to define severe ICP, fasting measurements identified 9% (1/11), whereas non-fasting measurements detected over 91% with severe ICP. The highest upper limit of the non-fasting TSBA reference range was 18.3 µmol/l (95% confidence interval: 15.0–35.6 μmol/l). A re-evaluation of published ICP meta-analysis data demonstrated no increase in spontaneous preterm birth or stillbirth in women with TSBA <19 µmol/l. Conclusions: Postprandial TSBA levels are required to identify high-risk ICP pregnancies (TSBA ≥40 μmol/l). The postprandial rise in TSBA in normal pregnancy indicates that a non-fasting threshold of ≥19 µmol/l would improve diagnostic accuracy. Tweetable abstract: Non-fasting bile acids improve the diagnostic accuracy of intrahepatic cholestasis of pregnancy diagnosis.

Original languageEnglish
Pages (from-to)1635-1644
Number of pages10
Issue number10
Early online date6 Apr 2021
Publication statusPublished - Sept 2021


  • cholestasis
  • clinical decision making
  • liver diseases in pregnancy


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