TY - JOUR
T1 - Re-evaluating diagnostic thresholds for intrahepatic cholestasis of pregnancy
T2 - case-control and cohort study
AU - Mitchell, Alice L
AU - Ovadia, Caroline
AU - Syngelaki, Argyro
AU - Souretis, Kyriakos
AU - Martineau, Marcus
AU - Girling, Joanna
AU - Vasavan, Tharni
AU - Fan, Hei Man
AU - Seed, Paul T
AU - Chambers, Jenny
AU - Walters, Julian R F
AU - Nicolaides, Kypros
AU - Williamson, Catherine
N1 - Funding Information:
This work was funded by the Wellcome Trust (Grant Award: 092993/Z/10/Z, external peer review for scientific quality), ICP Support, Fetal Medicine Foundation, the National Institute for Health Research Biomedical Research Centre at Guy's and St Thomas' NHS Foundation (Grant Award: IS-BRC-1215-20006) and Tommy's (Registered charity no. 1060508). CW is supported by an NIHR Senior Investigator Award. PTS is partly funded by King's Health Partners Institute of Women and Children's Health, Tommy's and by ARC South London (NIHR). ICP Support was involved in participant recruitment for the timed meal study, and the Fetal Medicine Foundation provided the uncomplicated third trimester of pregnancy samples and funded the analysis of TSBA values for normal range calculation. We would like to thank the women who participated in the study, and the research midwives who collected the samples at the clinical research facilities at Queen Charlotte's Hospital, in particular Ramona Mannino, and the research midwives at West Middlesex University Hospital and St. Thomas' Hospital. We would like to thank Prof. Gary Frost for his advice on the calorie content for the meals for the standardised diet study. Infrastructure support was provided by the NIHR Imperial Biomedical Research Centre and the NIHR Imperial Clinical Research Facility and Guy's and St. Thomas' Clinical Research Facility. The views expressed are those of the authors and not necessarily those of King's Health Partners, Tommy's, the NHS, the NIHR or the Department of Health and Social Care.
Publisher Copyright:
© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - cholestasis
KW - clinical decision making
KW - liver diseases in pregnancy
UR - http://www.scopus.com/inward/record.url?scp=85103551915&partnerID=8YFLogxK
U2 - 10.1111/1471-0528.16669
DO - 10.1111/1471-0528.16669
M3 - Article
C2 - 33586324
SN - 1470-0328
VL - 128
SP - 1635
EP - 1644
JO - BJOG
JF - BJOG
IS - 10
ER -