A new international study has found that intrahepatic cholestasis of pregnancy, or ICP, is tied to broader disruptions in how the body handles bile acids, fats, and cholesterol. The investigation, published in Nature Communications, combined genetic data from more than 4,700 women who had the condition and a control group of over 436,000 women from Finland, Iceland, Estonia, and Denmark. The disorder affects roughly 0.2% to 2% of pregnant women, usually appearing after the 30th week of gestation. The most common symptom is severe itching on the palms and soles, which can be caught during routine prenatal visits. Confirmation comes from raised liver enzymes and higher bile acid levels in the blood. The condition normally goes away after delivery, but it carries an increased risk of preterm birth and stillbirth. Earlier work had pointed to genetic factors playing a role in susceptibility to the disorder, but many of the underlying biological pathways stayed unclear. The analysis identified 26 genetic regions linked to the disorder, including ten that had not been reported before.
“The genes located in these regions influence how the liver processes bile acids, fats and cholesterol,” said Jaakko Tyrmi, a postdoctoral research fellow at Tampere University and the University of Oulu. “This supports the idea that the underlying cause of ICP is a disruption in liver metabolism, triggered by hormonal changes during pregnancy.” Women who experienced the disorder were found to have a higher chance later in life of developing liver and bile duct diseases — including fatty liver disease, gallstones, and bile duct inflammation. They also faced raised risks for some autoimmune conditions, such as Crohn’s disease, along with thyroid disorders and type 2 diabetes.
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One surprising finding involved pancreatitis.
“Our analyses also suggested a possible shared genetic basis between ICP and pancreatitis, which is inflammation of the pancreas,” Tyrmi said. “This is a new discovery that, to our knowledge, has not been reported previously. However, further studies are needed to better understand this connection.”
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The results could help doctors identify women at higher risk for ICP, improve how the condition is diagnosed and treated, and catch related diseases earlier. The work was published as a peer-reviewed early access article and draws on some of the largest DNA datasets available for pregnancy-related liver disease.
Not every detail is fully mapped yet.
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The exact mechanisms that trigger the metabolic disruption during pregnancy remain an open question. But the study provides a clearer genetic framework, one that shifts the focus from symptom management toward understanding the root cause.