The mind-liver connection: Exploring psychological stress and its association with the risk of developing intrahepatic cholestasis of pregnancy

Abstract

Objective: To determine the relationship between intrahepatic cholestasis of pregnancy (ICP) and psychological stress (by the DASS-21 questionnaire) in Pakistani pregnant women in the second and third trimesters.

Methodology: A prospective observational study was conducted from August 2024 to August 2025 at the Department of Physiology, Islamic International Medical College (IIMC), jointly with Holy Family Hospital, Rawalpindi and Prime Lab Diagnostics. 140 pregnant women who aged between 20-40 years, were enrolled after taking informed consent. The DASS-21 questionnaire was used in the second trimester and repeated in the third trimester to measure depression, anxiety and stress levels. ICP symptoms such as nocturnal itching were observed throughout pregnancy. Liver function and serum bile acids tests were performed in both the trimesters to ascertain the diagnosis. Later, the participants were divided into ICP and non-ICP groups. DASS-21 scores were compared between the two groups.

Results: Depression, anxiety, and stress scores were significantly higher in the ICP group during the third trimester (p < 0.01). Wilcoxon signed-rank tests revealed a prominent rise in depression and stress from the second to third trimester within the ICP group. Logistic regression identified third-trimester depression (OR: 1.34, p = 0.005) and stress (OR: 1.17, p = 0.026) as significant predictors of ICP. Model fit was acceptable (Hosmer-Lemeshow p = 0.174; AUC = 0.796).

Conclusion: Third-trimester psychological stress, particularly depression and stress symptoms, is associated with ICP. Routine antenatal screening may help identify women at risk for timely intervention.