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-/post-prandially 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 non-fasting 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.