Vol 91, No 5 (2020)
Research paper
Published online: 2020-05-29

open access

Page views 1481
Article views/downloads 1086
Get Citation

Connect on Social Media

Connect on Social Media

Evaluation of predictive value of biochemical markers for adverse obstetrics outcomes in pregnancies complicated by cholestasis

Milena Guszczynska-Losy1, Przemyslaw K. Wirstlein2, Ewa Wender-Ozegowska2, Malgorzata Kedzia2
Pubmed: 32495933
Ginekol Pol 2020;91(5):269-276.

Abstract

Objectives: Intrahepatic cholestasis of pregnancy (ICP) is significantly more often associated with an abnormal perinatal
outcome compared to a group of healthy pregnant women.
The aim of the study was to analyse the correlation between the adverse perinatal outcome and the biochemical parameters
in pregnancy complicated by cholestasis, and to assess their predictive value for neonatal complications.
Material and methods: Eighty-six patients with ICP were divided into 3 groups according to their fasting serum bile acid
level [group I n = 60, 10–39.90 μmol/L; group II n = 20, 40–99.90 μmol /L; group III n = 6, TBA (total bile acids) ≥ 100.00 μmol/L].
Linear regression models were created to determine the relation of serum TBA, ALT, and AST concentration with total adverse
perinatal outcome, defined as an occurrence of at least one perinatal outcome: stillbirth, preterm birth, spontaneous and
iatrogenic preterm birth, presence of meconium in amniotic fluid, Apgar score (< 7 in 5th min), pH from umbilical artery
(< 7.1), necessity for NICU admission, the presence of breathing disorders, and the need to perform phototherapy.
Results: TBA ≥ 40.00 μmol/L is connected to an elevated risk of the occurrence of total adverse perinatal outcome (OR = 4.17,
p = 0.0037, AUC = 0.62, p = 0.046). TBA ≥ 40.00 μmol/L is a predictor of preterm birth (OR 2.3, p = 0.0117), iatrogenic preterm
birth (OR 2.5, p = 0.006), admission to NICU (OR 2.38, p = 0.0094), intubation or assisted ventilation (OR 2.16, p = 0.0301), and
phototherapy (OR 2.0, p = 0.0438). The threshold value of TBA for the need for phototherapy was 52.7 μmol/L (AUC = 0.67,
p = 0.0089) and for preterm birth, 32.1 μmol/L (AUC = 0.62, p = 0.0251).
Conclusions: Pregnant women with ICP and TBA serum level over 40.00 μmol/L have a worse prognosis regarding obstetric
outcomes. The concentration of bile acids is a predictor of the occurrence of adverse perinatal outcomes, although the
concentration of ALT and AST failed to show such a connection.

Article available in PDF format

View PDF Download PDF file

References

  1. McIlvride S, Dixon PH, Williamson C. Bile acids and gestation. Mol Aspects Med. 2017; 56: 90–100.
  2. Yeap SP, Harley H, Thompson R, et al. Biliary transporter gene mutations in severe intrahepatic cholestasis of pregnancy: Diagnostic and management implications. J Gastroenterol Hepatol. 2019; 34(2): 425–435.
  3. Geenes V, Williamson C. Intrahepatic cholestasis of pregnancy. World J Gastroenterol. 2009; 15(17): 2049–2066.
  4. Kenyon AP, Piercy CN, Girling J, et al. Obstetric cholestasis, outcome with active management: a series of 70 cases. BJOG. 2002; 109(3): 282–288.
  5. Ovadia C, Seed PT, Sklavounos A, et al. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet. 2019; 393(10174): 899–909.
  6. Cui D, Zhong Y, Zhang L, et al. 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.
  7. Geenes VL, Lim YH, Bowman N, et al. A placental phenotype for intrahepatic cholestasis of pregnancy. Placenta. 2011; 32(12): 1026–1032.
  8. Ibrahim E, Diakonov I, Arunthavarajah D, et al. Bile acids and their respective conjugates elicit different responses in neonatal cardiomyocytes: role of Gi protein, muscarinic receptors and TGR5. Sci Rep. 2018; 8(1): 7110.
  9. Güven D, Altunkaynak BZ, Altun G, et al. Histomorphometric changes in the placenta and umbilical cord during complications of pregnancy. Biotech Histochem. 2018; 93(3): 198–210.
  10. Diken Z, Usta IM, Nassar AH. A clinical approach to intrahepatic cholestasis of pregnancy. Am J Perinatol. 2014; 31(1): 1–8.
  11. Kawakita T, Parikh LI, Ramsey PS, et al. Predictors of adverse neonatal outcomes in intrahepatic cholestasis of pregnancy. Am J Obstet Gynecol. 2015; 213(4): 570.e1–570.e8.
  12. Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates. Hepatology. 2004; 40(2): 467–474.
  13. Chen H, Zhou Y, Deng DR, et al. Intrahepatic cholestasis of pregnancy: biochemical predictors of adverse perinatal outcomes. J Huazhong Univ Sci Technolog Med Sci. 2013; 33(3): 412–417.
  14. Morton A, Laurie J. The biochemical diagnosis of intrahepatic cholestasis of pregnancy. Obstet Med. 2019; 12(2): 76–78.
  15. Bomba-Opoń D, Drews K, Huras H, et al. Polish Gynecological Society Recommendations for Labor Induction. Ginekol Pol. 2017; 88(4): 224–234.
  16. Pata O, Vardarelı E, Ozcan A, et al. Intrahepatic cholestasis of pregnancy: correlation of preterm delivery with bile acids. Turk J Gastroenterol. 2011; 22(6): 602–605.
  17. Garcia-Flores J, Cañamares M, Cruceyra M, et al. Clinical value of maternal bile Acid quantification in intrahepatic cholestasis of pregnancy as an adverse perinatal outcome predictor. Gynecol Obstet Invest. 2015; 79(4): 222–228.
  18. Çelik S, Çalışkan CS, Çelik H, et al. Predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy. Ginekol Pol. 2019; 90(4): 217–222.
  19. Oztas E, Erkenekli K, Ozler S, et al. Can routine laboratory parameters predict adverse pregnancy outcomes in intrahepatic cholestasis of pregnancy? J Perinat Med. 2015; 43(6): 667–674.
  20. Grymowicz M, Czajkowski K, Smolarczyk R. Pregnancy course in patients with intrahepatic cholestasis of pregnancy treated with very low doses of ursodeoxycholic acid. Scand J Gastroenterol. 2016; 51(1): 78–85.
  21. Chappell LC, Bell JL, Smith A, et al. PITCHES study group. Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial. Lancet. 2019; 394(10201): 849–860.