Re-evaluating diagnostic thresholds for intrahepatic cholestasis of pregnancy: case-control and cohort study

Alice Mitchell, Caroline Ovadia, Argyro Syngelaki, Kyriakos Souretis, Marcus G Martineau, Joanna Girling, Tharni Vasavan, Cyrus Fan, Paul Townsend Seed, Jenny Chambers, Julian R F Walters, Kypros H. Nicolaides, Catherine Williamson

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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 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: TSBA concentrations increased markedly postprandially in all
groups, with overlap between healthy pregnancy and mild ICP
(TSBA<40μmol/L). The specificity of ICP diagnosis was higher when
fasting, however, corresponded to <30% sensitivity for diagnosis of mild
disease. Using TSBA ≥40μmol/L to define severe ICP, fasting
measurements identified 9% (1/11), while non-fasting measurements
detected over 91% with severe ICP. The highest upper limit of the nonfasting
TSBA reference range was 18.3μmol/L (95% confidence interval
15.0 to 35.6μmol/L). A re-evaluation of published ICP meta-analysis
data demonstrated no increase in spontaneous preterm birth or stillbirth
in women with TSBA <19μmol/L.
Conclusions: Postprandial TSBA levels are required to identify high-risk
ICP pregnancies (TSBA≥40μmol/L). The postprandial TSBA rise in normal
pregnancy indicates that a non-fasting threshold of ≥19μmol/L would
improve diagnostic accuracy.
Original languageEnglish
JournalBritish Journal of Obstetrics and Gynaecology
Publication statusAccepted/In press - 12 Feb 2021


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