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

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.

Intrahepatic Cholestasis of Pregnancy - time to redefine the reference range of total serum bile acids: a cross-sectional study

“…In our analysis, we found that TSBA concentrations for both groups of samples were not normally distributed, but rather had a positive skewness distribution, in accordance with other studies 26,28 (figure 1-2). We found a median of 7.6 μmol/L for the fasting TSBA with an upper reference limit (97.5 th percentile) of 14.1 μmol/L (95% CI 12.7-15.5 μmol/L).…”

“…We believe the strengths also include the prospective design, the accurate selection of eligible patients, the generalizability, and the clinical relevance of the results. Since no correlation has been reported between TSBA levels and gestational age within the third trimester 26 , our results could be applicable to the third trimester of pregnancy. The duration of the study over one year allowed us to evaluate the seasonality of TSBA levels.…”

“…It has recently been suggested that higher thresholds should be used for the diagnosis of ICP, also given the low risk of stillbirth demonstrated recently for TSBA levels < 100 μmol/L 26,29 .…”

Intrahepatic Cholestasis of Pregnancy

“…1 is based on the RCOG Green-top Guideline No. 43 from 2011 which is continually updated according to the most recent findings (see also Mitchell et al, 2021 78 and Ovadia et al 2021 79 ). When this article went to press, the RCOG had not yet updated its recommendations.…”

“…1 basiert auf der RCOG Green-top Guideline No. 43. aus dem Jahr 2011 und wird fortlaufend entsprechend den aktuellen Erkenntnissen angepasst, siehe auch dazu Mitchell et al, 2021 78 und Ovadia et al 2021 79 . Bei Drucklegung dieses Artikels hat die RCOG die Empfehlungen überarbeitet.…”