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Am J Perinatol 2021; 38(09): 889-996
DOI: 10.1055/s-0041-1729160
SMFM Fellowship Series Article

From Pruritus to Cholestasis: Building a Statistical Model and Online Application to Predict a Diagnosis Prior to Bile Acid Determination

Andres F. Ramirez Zamudio 
1   Department of Obstetrics, Gynecology, and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York
,
Erica Monrose
2   Icahn School of Medicine at Mount Sinai, New York, New York
,
Stephanie Pan
3   Department of Population Health Science and Policy, The Blavatnik Family Women's Health Research Institute, Icahn School of Medicine at Mount Sinai, New York, New York
,
Lauren Ferrara
4   Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York
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Abstract

Objective This study aimed to create a statistical model using clinical and laboratory parameters to predict which patients presenting with pruritus in pregnancy will have elevated total bile acids (TBA) and thus, have a high risk of intrahepatic cholestasis of pregnancy (ICP).

Study Design Retrospective cohort study of patients presenting with pruritus in pregnancy and had TBA sent from a single public hospital from January 1, 2017, to December 31, 2017. Primary outcome is TBA ≥ 10 µmol/L. Multivariate logistic regression with stepwise and backward variable selection were used to create predictive models. Four models were compared using Akaike information criterion (AIC), C-statistic, and the DeLong nonparametric approach to test for differences between area under the curve (AUC) of receiver operating characteristic (ROC) curves. Internal validation was performed via fivefold cross-validation technique on the best-fitting, most parsimonious model.

Results Of the 320 patients with pruritus, 153 (47.8%) had elevated bile acid levels ≥10 µmol/L. Sixty-nine variables were assessed for association with the primary outcome. Five variables were significantly associated with elevated TBA: pruritus of palms and soles (adjusted odds ratio [aOR]: 2.35 [95% confidence interval, CI: 1.22, 4.54]), gestational hypertension (aOR: 0.10 [95% CI: 0.02, 0.60]), log of total bilirubin (aOR: 4.71 [95% CI: 2.28, 9.75]), systolic blood pressure (aOR: 0.97 [95% CI: 0.94, 0.99]), and alanine aminotransferase (aOR: 1.05 [95% CI: 1.02, 1.07]). The final model was chosen for being parsimonious while having the lowest AIC with highest AUC (0.85; 95% CI: 0.81, 0.89). Internal validation using a probability threshold of 50% demonstrated a sensitivity of 65.5%, specificity of 83.5%, and accuracy of 75.1%.

Conclusion We provide a predictive model using five simple variables to determine the probability that a patient presenting with pruritus in pregnancy carries the diagnosis of ICP. This tool, available via a web app, is designed to aid providers and enhance clinical judgment in difficult triage situations.

Key Points

  • Currently, no standard method to triage pruritus in pregnancy exists.

  • We present a predictive statistical model using five readily available clinical variables.

  • Final calculator yields probability of having intrahepatic cholestasis of pregnancy.

Keywords

calculator - cholestasis - pruritus - pregnancy - transaminitis


Publication History

Received: 06 July 2020

Accepted: 02 March 2021

Article published online:
02 May 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Geenes V, Chappell LC, Seed PT, Steer PJ, Knight M, Williamson C. Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: a prospective population-based case-control study. Hepatology 2014; 59 (04) 1482-1491
    CrossrefPubMedSearch in Google Scholar
  • 2 Williamson C, Hems LM, Goulis DG. et al. Clinical outcome in a series of cases of obstetric cholestasis identified via a patient support group. BJOG 2004; 111 (07) 676-681
    CrossrefPubMedSearch in Google Scholar
  • 3 Rook M, Vargas J, Caughey A, Bacchetti P, Rosenthal P, Bull L. Fetal outcomes in pregnancies complicated by intrahepatic cholestasis of pregnancy in a Northern California cohort. PLoS One 2012; 7 (03) e28343
    CrossrefPubMedSearch in Google Scholar
  • 4 Reid R, Ivey KJ, Rencoret RH, Storey B. Fetal complications of obstetric cholestasis. BMJ 1976; 1 (6014): 870-872
    CrossrefPubMedSearch in Google Scholar
  • 5 Pata O, Vardarelı E, Ozcan A. et al. Intrahepatic cholestasis of pregnancy: correlation of preterm delivery with bile acids. Turk J Gastroenterol 2011; 22 (06) 602-605
    CrossrefPubMedSearch in Google Scholar
  • 6 Oztekin D, Aydal I, Oztekin O, Okcu S, Borekci R, Tinar S. Predicting fetal asphyxia in intrahepatic cholestasis of pregnancy. Arch Gynecol Obstet 2009; 280 (06) 975-979
    CrossrefPubMedSearch in Google Scholar
  • 7 Lo TK, Lau WL, Lam HSW, Leung WC, Chin RKH. Obstetric cholestasis in Hong Kong--local experience with eight consecutive cases. Hong Kong Med J 2007; 13 (05) 387-391
    PubMedSearch in Google Scholar
  • 8 Lee RH, Kwok KM, Ingles S. et al. Pregnancy outcomes during an era of aggressive management for intrahepatic cholestasis of pregnancy. Am J Perinatol 2008; 25 (06) 341-345
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Laatikainen T, Ikonen E. Fetal prognosis in obstetric hepatosis. Ann Chir Gynaecol Fenn 1975; 64 (03) 155-164
    PubMedSearch in Google Scholar
  • 10 Kenyon AP, Piercy CN, Girling J, Williamson C, Tribe RM, Shennan AH. Obstetric cholestasis, outcome with active management: a series of 70 cases. BJOG 2002; 109 (03) 282-288
    CrossrefPubMedSearch in Google Scholar
  • 11 Glantz A, Marschall H-U, Mattsson L-A. Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates. Hepatology 2004; 40 (02) 467-474
    CrossrefPubMedSearch in Google Scholar
  • 12 Fisk NM, Storey GN. Fetal outcome in obstetric cholestasis. Br J Obstet Gynaecol 1988; 95 (11) 1137-1143
    CrossrefPubMedSearch in Google Scholar
  • 13 Bull LN, Hu D, Shah S. et al. Intrahepatic cholestasis of pregnancy (ICP) in U.S. Latinas and Chileans: clinical features, ancestry analysis, and admixture mapping. PLoS One 2015; 10 (06) e0131211
    CrossrefPubMedSearch in Google Scholar
  • 14 Abedin P, Weaver JB, Egginton E. Intrahepatic cholestasis of pregnancy: prevalence and ethnic distribution. Ethn Health 1999; 4 (1-2): 35-37
    CrossrefPubMedSearch in Google Scholar
  • 15 Reyes H, Gonzalez MC, Ribalta J. et al. Prevalence of intrahepatic cholestasis of pregnancy in Chile. Ann Intern Med 1978; 88 (04) 487-493
    CrossrefPubMedSearch in Google Scholar
  • 16 Kohari KS, Carroll R, Capogna S, Ditchik A, Fox NS, Ferrara LA. Outcome after implementation of a modern management strategy for intrahepatic cholestasis of pregnancy. J Matern Fetal Neonatal Med 2017; 30 (11) 1342-1346
    CrossrefPubMedSearch in Google Scholar
  • 17 Marschall H-U, Wikström Shemer E, Ludvigsson JF, Stephansson O. Intrahepatic cholestasis of pregnancy and associated hepatobiliary disease: a population-based cohort study. Hepatology 2013; 58 (04) 1385-1391
    CrossrefPubMedSearch in Google Scholar
  • 18 Kenyon AP, Piercy CN, Girling J, Williamson C, Tribe RM, Shennan AH. Pruritus may precede abnormal liver function tests in pregnant women with obstetric cholestasis: a longitudinal analysis. BJOG 2001; 108 (11) 1190-1192
    PubMedSearch in Google Scholar
  • 19 Fisk NM, Bye WB, Storey GN. Maternal features of obstetric cholestasis: 20 years experience at King George V Hospital. Aust N Z J Obstet Gynaecol 1988; 28 (03) 172-176
    CrossrefPubMedSearch in Google Scholar
  • 20 DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988; 44 (03) 837-845
    CrossrefPubMedSearch in Google Scholar
  • 21 Hastie T, Tibshirani R, Friedman J. The Elements of Statistical Learning: Data Mining, Inference, and Prediction. 2nd ed.. New York, NY: Springer-Verlag; 2009
    CrossrefSearch in Google Scholar
  • 22 Elfituri A, Ali A, Shehata H. Managing recurring obstetric cholestasis with metformin. Obstet Gynecol 2016; 128 (06) 1320-1323
    CrossrefPubMedSearch in Google Scholar