Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Sep;128(10):1635-1644.
doi: 10.1111/1471-0528.16669. Epub 2021 Apr 6.

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

A L Mitchell  1 , C Ovadia  1 , A Syngelaki  2 , K Souretis  2 , M Martineau  3 , J Girling  4 , T Vasavan  1 , H M Fan  1 , P T Seed  5 , J Chambers  6 , Jrf Walters  3 , K Nicolaides  2 , C Williamson  1
Affiliations

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

A L Mitchell et al. BJOG. 2021 Sep.

Abstract

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.

PubMed Disclaimer

References

    1. Wood AM, Livingston EG, Hughes BL, Kuller JA. Intrahepatic cholestasis of pregnancy. Obstet Gynecol Surv 2018;73:103-9.
    1. Lee RH, Goodwin TM, Greenspoon J, Incerpi M. The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population. J Perinatol 2006;26:527-32.
    1. Abedin P, Weaver JB, Egginton E. Intrahepatic cholestasis of pregnancy: prevalence and ethnic distribution. Ethn Heal 1999;4:35-7.
    1. Wong LFA, Shallow H, O'Connell MP. Comparative study on the outcome of obstetric cholestasis. J Matern Neonatal Med 2008;21:327-30.
    1. Bicocca MJ, Sperling JD, Chauhan SP. Intrahepatic cholestasis of pregnancy: review of six national and regional guidelines. Eur J Obstet Gynecol Reprod Biol 2018;231:180-7.

Publication types

Supplementary concepts

LinkOut - more resources