Correlation of maternal serum bile acid induced placental inflammation by Gpbar-1 and NF-κB pathway with fetal outcome in intrahepatic cholestasis of pregnancy: a case control study

Alpana Singh; Shivani Sharma; Prerna Batra; B. D. Banerjee

doi:10.18203/2320-1770.ijrcog20260895

Authors

Alpana Singh Department of Obstetrics and Gynaecology, University College of Medical Sciences, GTB Hospital, Delhi, India
Shivani Sharma Department of Obstetrics and Gynaecology, University College of Medical Sciences, GTB Hospital, Delhi, India
Prerna Batra Department of Paediatrics, University College of Medical Sciences, GTB Hospital, Delhi, India
B. D. Banerjee Department of Biochemistry, University College of Medical Sciences, GTB Hospital, Delhi, India

DOI:

https://doi.org/10.18203/2320-1770.ijrcog20260895

Keywords:

Bile acid, Ursodeoxycholic acid, Intrahepatic cholestasis of pregnancy, NF-κB, Placental inflammation, Gpbar-1, Gene expression, Fetal outcome, Maternal and neonatal complications

Abstract

Background: Intrahepatic cholestasis of pregnancy (IHCP) is a pregnancy-specific liver disorder associated with adverse fetal outcomes. Elevated maternal serum bile acids (BAs) trigger placental inflammation through the G-protein-coupled bile acid receptor 1 (Gpbar-1) and nuclear factor Kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway. This study investigates Gpbar-1 and NF-κB gene expression in placental tissue of IHCP patients and its correlation with fetal outcomes.

Methods: This prospective case-control study, conducted between November 2019 and October 2021 at a tertiary care hospital, included 30 diagnosed IHCP cases and 30 gestational age-matched healthy controls. Serum bile acid levels were measured (using Elisa), and placental tissue was analyzed post-delivery using quantitative reverse transcription PCR (RT-qPCR) for Gpbar-1 and NF-κB gene expression. Maternal and fetal outcomes such as preterm delivery, fetal distress, low APGAR score, meconium-stained liquor, and NICU admission were recorded.

Results: Serum bile acid levels were significantly higher in IHCP cases (p<0.001). Gene expression analysis showed a 2.192-fold upregulation of Gpbar-1 (p=0.019) and a 2.396 -fold upregulation of NF-κB in IHCP placentas (p=0.029). Adverse fetal outcomes were not significantly correlated with higher gene expression.

Conclusions: Elevated bile acid levels in IHCP activate the Gpbar-1/NF-κB pathway, leading to placental inflammation and adverse fetal outcomes. Targeting this pathway may improve pregnancy outcomes in IHCP. Further research on anti-inflammatory therapies is recommended.

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