Intrahepatic cholestasis of pregnancy - Time to redefine the reference range of total serum bile acids: A cross-sectional study

Objective To establish pregnancy-specific reference ranges for fasting and postprandial total serum bile acid (TSBA) concentrations. Design Cross-sectional study. Setting Tertiary-care university hospital. Population Healthy pregnant women at term admitted to the Obstetrics Department over a period of 1 year. Exclusion criteria were an established diagnosis of intrahepatic cholestasis of pregnancy (ICP) or any coexisting condition of increased risk for ICP. Methods Both fasting (after 8-14 h of fasting) and postprandial (2 h after meal) TSBA concentrations were measured in 612 women (with 528 fasting samples and 377 postprandial samples) by automated enzymatic spectrophotometric assay. Main outcome measures Fasting and postprandial TSBA concentrations in 612 women. Results Reference intervals of 4.4-14.1 mu mol/L for fasting TSBA and 4.7-20.2 mu mol/L for postprandial TSBA were established. The postprandial values were significantly higher than the fasting values, with a median increase of 1.0 mu mol/L (p < 0.0001). A correlation between fasting TSBA concentrations and postprandial concentrations was found, as well as correlations with fetal sex, parity and assisted reproductive technologies. A seasonal pattern was noticed for both fasting and postprandial TSBA, with the highest values measured in the winter season (p < 0.01 and 0.02, respectively) Conclusions Normal pregnancy is associated with mild hypercholanaemia, and therefore a higher threshold should be considered for the diagnosis of ICP. We suggest using the upper reference limits observed in our healthy pregnant population (14 mu mol/L for fasting TSBA and 20 mu mol/L for postprandial TSBA). As the fasting measurement is more specific for the diagnosis, and the postprandial measurement is essential for the assessment of severity, it is recommended to measure both values rather than use random sampling.