Challenging the safety of progesterone supplementation: is it associated with early-onset intrahepatic cholestasis of pregnancy

Progesterone & early‑onset ICP

Abstract

BACKGROUND & OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is a gestational problem causing liver dysfunction characterized by itching, biochemical evidence of raised bile acids, and altered liver enzymes (LFTs). It is associated with serious perinatal outcomes. The objective of the study is to evaluate whether exogenous progesterone use during pregnancy is associated with ICP and adverse perinatal outcomes.

METHODOLOGY: This retrospective case-control study was carried out at Sadiq Abbasi Hospital, Bahawalpur, from February 2021 to December 2023. The cases were pregnant women diagnosed with ICP, and the controls were pregnant women who did not have ICP. Data included demographics, progesterone supplementation, obstetric outcomes, and biochemical markers. Associations were interpreted using Chi-square/Fisher’s exact tests and multivariable logistic regression adjusted for maternal age, BMI, parity, and prior ICP.

 RESULTS: Women with ICP have received more progesterone than controls (52% vs 20%, p < 0.001). Progesterone support in the first trimester was related to an increased risk of ICP (aOR 2.8, 95% CI: 1.9–4.1, p < 0.001). The ICP group also delivered a higher incidence of preterm delivery (35% vs 12%, p < 0.001), lower birth weight neonates, and increased NICU admissions.

CONCLUSION: Progesterone supplementation, specifically in early pregnancy, is a risk factor for the development of ICP. This emphasizes the need for regular and careful checking of bile acid levels in women using exogenous progesterone, as it may elevate the odds of getting an early-onset ICP leading to obstetric complications.