Effect of Fasting on Total Bile Acid Levels in Pregnancy

Abstract

OBJECTIVE: To evaluate differences between fasting and nonfasting bile acid levels in asymptomatic and symptomatic pregnant women. METHODS: This is a report of two prospective cohort studies describing bile acid levels in the fasting and nonfasting state in pregnancy. The first cohort included asymptomatic women with singleton pregnancies. Women with a diagnosis of cholestasis, symptoms of cholestasis, or intolerance to components of a standardized meal were excluded. Bile acid levels were measured during the second and third trimesters after fasting and again 2 hours after a standardized meal. The second cohort included symptomatic women with singleton pregnancies in whom fasting and nonfasting bile acid levels were measured at the time of symptom evaluation. A cutoff of 10 micromoles/L was used for diagnosis. RESULTS: A total of 27 women were included in the asymptomatic cohort. Median [interquartile range] fasting bile acid levels were significantly lower than nonfasting levels in both the second trimester (4.65 micromoles/L [1.02–29.57] vs 13.62 micromoles/L [2.03–40.26]; P<.001) and third trimester (8.31 micromoles/L [1.14–51.26] vs 17.35 micromoles/L [1.77–62.93]; P<.001). Bile acid levels exceeded 10 micromoles/L in 21% of the fasting samples and in 58% of the nonfasting samples in the third trimester. A total of 26 women were included in the symptomatic cohort. Median [interquartile range] fasting bile acid levels were significantly lower than nonfasting values (11.5 micromoles/L [7–56] vs 13.5 micromoles/L [9–142]; P<.001). Six patients in the symptomatic cohort (23%) had nonfasting bile acid levels greater than 10 micromoles/L that dropped below 10 micromoles/L when fasting. CONCLUSION: Fasting bile acid levels are significantly lower when compared with nonfasting values in both asymptomatic and symptomatic pregnant women. In asymptomatic women, nonfasting bile acid levels often exceeded 10 micromoles/L whereas fasting values did not. In symptomatic women, fasting bile acid levels resulted in 23% fewer diagnoses of cholestasis when compared with nonfasting values. These findings suggest that fasting evaluation of bile acid levels or a higher threshold for diagnosis of cholestasis should be considered.

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

“…Our study confirms that TSBA levels increase in response to food intake and that differences between fasting and postprandial measurements are clinically and statistically significant 11,29 .…”

“…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 .…”

“…Even though widely used in clinical laboratories, the most important limitation of the enzymatic method is low sensitivity, as the lowest concentration of TSBA measurable is around 1.5 μmol/L 18,29 . Nevertheless, 100% of the measured values resulted above the evaluation limit.…”

“…The Royal College of Obstetricians and Gynaecologists (RCOG) guideline recommends that the upper limit of pregnancy-specific ranges of TSBA should be used for diagnosis 25 . Nevertheless, reference ranges used in clinical laboratories are most often fasting values measured in nonpregnant subjects, a result of extremely limited data for pregnancy-specific reference ranges 4,11,17,29 . Consequently, there is a wide range of diagnostic criteria for ICP.…”

“…Most guidelines recommend the use of TSBA values of 10 to 15 μmol/L as a diagnostic threshold, but this may be reduced to 6-10 μmol/L in fasting women 1,9,10 . In clinical practice, the most widely used threshold is non-fasting 10 μmol/L, despite not being supported by strong evidence 9,29 .…”