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Bile acid reference intervals for evidence-based practice

Research output: Contribution to journalArticlepeer-review

Caroline Ovadia, Alice L. Mitchell, Corey Markus, William M. Hague, Catherine Williamson

Original languageEnglish
Pages (from-to)1897-1898
Number of pages2
JournalBJOG: An International Journal of Obstetrics and Gynaecology
Issue number11
Early online date15 Apr 2022
Accepted/In press24 Mar 2022
E-pub ahead of print15 Apr 2022
PublishedOct 2022

Bibliographical note

Funding Information: Funding for new data analyses was provided by ICP Support and the Fetal Medicine Foundation. CO consults for Mirum Pharmaceuticals. CW consults for GSK and Mirum Pharmaceuticals, and is supported by an NIHR Senior Investigator Grant. ALM receives funding from the JP Moulton Charitable Foundation. Completed disclosure of interests form available to view online as supporting information.

King's Authors


In this edition, Huri et al. (BJOG 2022) have added to the growing literature defining pregnancy-specific reference ranges for total serum bile acid (TSBA) concentrations.

Reference intervals in clinical pathology are typically calculated using an ‘indirect resource’, such as stored laboratory samples. Results are partitioned into biologically relevant groups (typically age and sex), outliers are excluded to remove anomalous results due to disease, and the central 95% of the population is calculated for each group. Two large studies, that of Huri et al. and our own (Mitchell et al. BJOG 2021;128:1635–44), have recently calculated reference intervals for non-fasting TSBA concentrations in the third trimester of pregnancy, finding strikingly similar results for the upper limit (20.2 and 18.3 μmol/l, respectively). Both studies excluded samples with cholestatic pathology before analysis, treating the cohorts as a ‘direct resource’ and obviating exclusion of outliers.

However, the results demonstrate outliers within each dataset. In the study by Huri et al. this may have been the result of the selected participants having other gestational diseases (for example, gestational diabetes) and originating from samples taken during hospital admission; the reason for women being inpatients may have influenced serum bile acid concentrations and therefore confounded the findings. To assess the impact of excluding outliers, we used the block D/R (Zellner et al. arXiv preprint; 1907.09637.) procedure to identify outliers in our dataset (from outpatient samples routinely taken and limited to uncomplicated pregnancies), and reanalysis revealed a slight reduction in the upper limit of the reference interval and narrowing of the confidence interval (Table 1).

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