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.
Keywords: Cholestasis; clinical decision-making; liver diseases in pregnancy.
© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.