Anamnestic and biochemical predictors of obstetric and perinatal complications in intrahepatic cholestasis of pregnancy

Objective. To determine the anamnestic and biochemical predictors of obstetric and perinatal complications in women with intrahepatic cholestasis of pregnancy (ICP).
Materials and methods. 59 women with ICP and 30 pregnant women included into the comparison group were examined. The characteristics of the reproductive history, anamnesis of the disease, complaints, biochemical parameters of liver function (syndromes of cholestasis and hepatocyte cytolysis, function of protein synthesis), features of the course and treatment of ICP were studied.
Results. The main predictors of preterm birth in the women with ICP were: age (P(U)=0.027), multiple pregnancy (OR=17.5, p=0.033); alkaline phosphatase (ALP) blood level > 499 U/l (AUC=0.801; p=0.008); De Ritis Ratio value ≤ 0.49 (AUC=0.757; p=0.005). The main prognostic markers for meconium staining of amniotic fluid (MSAF) in the patients with ICP were: ICP in previous pregnancies (OR=7.1; p=0.029); serum bile acid concentration > 14 μmol/l (AUC=0.718; p=0.043); total bilirubin blood level > 13 μmol/l (AUC=0.773; p=0.007); ALP activity > 484 U/l (AUC=0.728; p=0.033); blood creatinine concentration ≤ 60 μmol/l (AUC=0.930; p=0.0001) in asymptomatic course. The development of respiratory disorders in children born to women with asymptomatic ICP was associated with a total protein concentration in the blood of 78 g/l or less (AUC=0.852; p=0.0001).
Conclusion. The anamnesis of the disease and the determination of the levels of the biochemical parameters of liver function allows predicting obstetric and perinatal complications in ICP.

1. Полунина ТЕ, Тазитдинов РХ. Внутрипеченочный холестаз беременных. Терапия. 2020;1:85-95. DOI: https://dx.doi.org/10.18565/therapy.2020.1.85-95

2. Бик-Мухаметова ЯИ, Захаренкова ТН. Факторы риска внутрипеченочного холестаза беременных. В: Актуальные проблемы медицины: сб. науч. ст. Респ. науч.-практ. конф. и 26-й итоговой науч. сессии ГомГМУ, Гомель, 3–4 ноября 2016 года. 2017:85-88.

3. Успенская ЮБ, Шептулин АА. Клиника, диагностика и лечение внутрипеченочного холестаза беременных. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2017;27(4):96-101.

4. Успенская ЮБ. Современное состояние проблемы холестаза беременных. Проблемы женского здоровья. 2013;8(3):70-76. [дата обращения 2022 март 18]. Режим доступа: http://gzrf.ru/com_publish/file/journal260.pdf

5. Geenes V, Williamson С. Intrahepatic cholestasis of pregnancy. World Journal of Gastroenterology. 2009;15(17):2049-2066. DOI: https://doi.org/10.3748/wjg.15.2049

6. Zhang Y, Li F, Wang Y, Pitre A, Fang Zh, Frank MW, Calabrese C, Krausz KW, Neale G, Frase Sh, Vogel P, Rock ChO, Gonzalez FJ, Schuetza JD. Maternal bile acid transporter deficiency promotes neonatal demise. Nat Commun. 2015;6:81-86. DOI: https://doi.org/10.1038/ncomms9186

7. Ozkan S, Ceylan Y, Veli Ozkan O, Yildirim S. Review of a challenging clinical issue: Intrahepatic cholestasis of pregnancy. World J Gastroenterol. 2015;21(23):7134-7141. DOI: https://doi.org/10.3748/wjg.v21.i23.7134

8. Turunen K, Sumanen M, Haukilahti R-L, Kirkinen P, Mattila K. Good pregnancy outcome despite intrahepatic cholestasis. Scand J Prim Health Care. 2010;28(2):102-107. DOI: https://dx.doi.org/10.3109/02813431003784001

9. Herraez E, Lozano E, Poli E, Keitel V, De Luca D, Williamson C, Marin J, Macias RI. Role of macrophages in bile acid-induced inflammatory response of fetal lung during maternal cholestasis. Journal of Molecular Medicine. 2014;4:359-372. DOI: https://dx.doi.org/10.1007/s00109-013-1106-1

10. Rodríguez M, Moreno J, Márquez R, Eltit R, Martinez F, Sepúlveda-Martínez A, Parra-Cordero M. Increased PR Interval in Fetuses of Patients with Intrahepatic Cholestasis of Pregnancy. Fetal Diagn Ther. 2016;4:298-302. DOI: https://doi.org/10.1159/000444297

11. Laura N, Vargas J. Bull Serum Bile Acids in Intrahepatic Cholestasis of Pregnancy: Not just a Diagnostic test. Hepatology. 2014;59(4):1220-1202.

12. Козлов ПВ, Самсонова ИВ. Внутрипеченочный холестаз беременных. РМЖ. Мать и дитя. 2019;2(4):274-279.

13. Cui D, Zhong Y, Zhang L, Du H. Bile acid levels and risk of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy: A meta-analysis. J Obstet Gynaecol Res. 2017;43(9):1411-1420. DOI: https://doi.org/10.1111/jog.13399

14. Marschall H-U. Management of intrahepatic cholestasis of pregnancy. Expert Rev Gastroenterol Hepatol. 2015;9(10):1273-1279. DOI: https://doi.org/10.1586/17474124.2015.1083857

15. Zhang Y, Lu L, Victor DW, Xin Y, Xuan S. Ursodeoxycholic Acid and S-adenosylmethionine for the Treatment of Intrahepatic Cholestasis of Pregnancy: A Meta-analysis. Hepat Mon. 2016;16(8):e38558. DOI: https://doi.org/10.5812/hepatmon.38558