Re-Evaluating Diagnostic Thresholds For Intrahepatic Cholestasis Of Pregnancy: Case-Control And Cohort Study

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 mu mol/l). The specificity of ICP diagnosis was higher when fasting, but corresponded to <30% sensitivity for diagnosis of mild disease. Using TSBA >= 40 mu mol/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 mu mol/l (95% confidence interval: 15.0-35.6 mu mol/l). A re-evaluation of published ICP meta-analysis data demonstrated no increase in spontaneous preterm birth or stillbirth in women with TSBA Postprandial TSBA levels are required to identify high-risk ICP pregnancies (TSBA >= 40 mu mol/l). The postprandial rise in TSBA in normal pregnancy indicates that a non-fasting threshold of >= 19 mu mol/l would improve diagnostic accuracy.Tweetable abstract Non-fasting bile acids improve the diagnostic accuracy of intrahepatic cholestasis of pregnancy diagnosis.