The value of prenatal indicators in predicting adverse fetal outcomes in patients with ICP

Abstract

Objective

Search for laboratory markers that can predict adverse fetal pregnancy outcomes in patients with cholestasis of pregnancy.

Methods

This was an observational case-control study conducted from December 2016 to December 2019. Pregnancy outcome data and maternal antenatal laboratory markers were collected in the intrahepatic cholestasis of pregnancy (ICP) (N=117) and normal pregnancy controls (N=100), laboratory indictors including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (γ-GT), total bilirubin (TB), direct bilirubin (DB), total bile acids (TBA), cholyglycine (CG), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), etc. The ICP group was divided into an adverse outcome and normal outcome group according to fetal pregnancy outcomes. Descriptive statistics and regression analysis were performed on the prenatal indicators of the two groups to evaluate the association between prenatal laboratory indicators in ICP patients and adverse neonatal outcomes.

Results

ALT, TBA, CG, PT, APTT, hemoglobin, red blood cell distribution width, hematocrit, mean platelet volume, and platelet distribution width in ICP patients differed significantly from those in the normal control group, which led to premature birth, amniotic fluid pollution, low birth weight and other adverse outcomes. In terms of fetal outcomes, TBA [(39.16±35.70) μmol/L vs. (24.17±18.76) μmol/L], CG [(22.17±19.42) μg/mL vs. ( 13.91±13.18) μg/mL], DB [(22.17±19.42) μg/mL vs. (13.91±13.18) μg/mL] were higher than those in the normal outcome group, while fibrinogen was lower [(4.16±1.30) g/L vs. (4.78±0.91) g/L]; the difference was statistically significant. Multivariate logistic regression analysis showed that CG(OR=1.06, 95%CI:1.01~1.12, P=0.02, FIB(OR=0.54, 95%CI:0.31~0.92, P=0.02) was independently associated with the occurrence ofadverse fetal outcomes in ICP.

Conclusions

Prenatal CG and FIB levels were independently associated with adverse fetal outcomes in patients with ICP.

Keywords

adverse neonatal outcome - cholyglycine - fibrinogen - intrahepatic cholestasis of pregnancy

Publication History

Received: 03 September 2024

Accepted after revision: 27 June 2025

Article published online:
01 August 2025

• References

• 1 Ekiz A, Kaya B, Avci ME. et al. Alanine aminotransferase as a predictor of adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy. Pak J Med Sci 2016; 32: 418-422
• 2 Wikstrom Shemer E, Marschall HU, Ludvigsson JF. et al. Intrahepatic cholestasis of pregnancy and associated adverse pregnancy and fetal outcomes: a 12-year population-based cohort study. BJOG 2013; 120: 717-723
• 3 Abu-Hayyeh S, Ovadia C, Lieu T. et al. Prognostic and mechanistic potential of progesterone sulfates in intrahepatic cholestasis of pregnancy and pruritus gravidarum. Hepatology 2016; 63: 1287-1298
• 4 Turro E, Astle WJ, Megy K. et al. Whole-genome sequencing of patients with rare diseases in a national health system. Nature 2020; 583: 96-102
• 5 Visentin M, Lenggenhager D, Gai Z. et al. Drug-induced bile duct injury. Biochim Biophys Acta Mol Basis Dis 2018; 1864: 1498-1506
• 6 Wijarnpreecha K, Thongprayoon C, Sanguankeo A. et al. Hepatitis C infection and intrahepatic cholestasis of pregnancy: A systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2017; 41: 39-45
• 7 Oztekin D, Aydal I, Oztekin O. et al. Predicting fetal asphyxia in intrahepatic cholestasis of pregnancy. Arch Gynecol Obstet 2009; 280: 975-979
• 8 Arthuis C, Diguisto C, Lorphelin H. et al. Perinatal outcomes of intrahepatic cholestasis during pregnancy: An 8-year case-control study. PloS One 2020; 15: e0228213
• 9 Germain AM, Kato S, Carvajal JA. et al. Bile acids increase response and expression of human myometrial oxytocin receptor. Am J Obstet Gynecol 2003; 189: 577-582
• 10 Zecca E, De Luca D, Marras M. et al. Intrahepatic cholestasis of pregnancy and neonatal respiratory distress syndrome. Pediatrics 2006; 117: 1669-1672
• 11 Di Mascio D, Quist-Nelson J, Riegel M. et al. Perinatal death by bile acid levels in intrahepatic cholestasis of pregnancy: A systematic review. J Matern Fetal Neonatal Med 2021; 34: 3614-3622
• 12 Wang L, Lu Z, Zhou X. et al. Effects of intrahepatic cholestasis of pregnancy on hepatic function, changes of inflammatory cytokines and fetal outcomes. Exp Ther Med 2019; 17: 2979-2984
• 13 Wang L, Matsunaga S, Mikami Y. et al. Pre-delivery fibrinogen predicts adverse maternal or neonatal outcomes in patients with placental abruption. J Obstet Gynaecol Res 2016; 42: 796-802
• 14 Catov JM, Bodnar LM, Hackney D. et al. Activation of the fibrinolytic cascade early in pregnancy among women with spontaneous preterm birth. Obstet Gynecol 2008; 112: 1116-1122