New Blood Biomarkers Help Diagnose Pregnancy-Linked Liver Complication

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder linked to pregnancy and can pose serious risks for both mother and baby, including premature delivery and stillbirth. Diagnosis currently relies on measuring bile acids in the blood, but this marker alone is not always accurate, especially when it comes to identifying disease severity. As a result, many cases may be detected late or not fully stratified, limiting timely clinical decision-making. New blood-based indicators have now been shown to reliably detect the condition and distinguish mild from severe disease while also reflecting risks to newborn outcomes.

Researchers at Jiangnan University (Wuxi, China) have demonstrated that blood levels of the metabolite palmitic acid and the protein ACSL1 can accurately identify intrahepatic cholestasis of pregnancy and assess its severity. The study, published in Molecular and Cell Biology of Lipids, demonstrates that measuring these molecules, particularly when combined with bile acid levels, significantly improves diagnostic accuracy and provides insight into disease progression and pregnancy outcomes.

ICP occurs when the normal flow of bile from the liver is disrupted during pregnancy, a process closely linked to placental function. Although symptoms often resolve after delivery, the condition increases the risk of maternal complications such as bleeding and gestational diabetes, as well as fetal complications, including low birth weight, preterm birth, and stillbirth. Because bile acids remain the only routinely used laboratory marker, researchers have been searching for more sensitive and specific biomarkers.

To identify new candidates, the researchers first analyzed protein and metabolite changes in placental tissue from a rat model of induced cholestasis and compared them with healthy controls. These findings were then validated using placental and blood samples from pregnant women with and without the condition. More than 1,500 proteins and over 200 metabolites were identified as altered in the disease model, with integrated analyses indicating that disrupted fatty acid metabolism is a central feature.

Palmitic acid and ACSL1 emerged as key molecules involved in both fatty acid degradation and biosynthesis pathways. Levels of both were significantly elevated in placental tissue and blood samples from women with intrahepatic cholestasis of pregnancy compared with healthy pregnant women. Higher levels were also strongly associated with increased bile acids, earlier delivery, and lower newborn birth weight.

Importantly, blood concentrations of palmitic acid and ACSL1 rose with disease severity. Diagnostic performance analysis showed that combining these two markers with bile acids achieved excellent accuracy in distinguishing affected pregnancies from healthy ones and in separating mild from severe cases, outperforming bile acids alone.

Further experiments also uncovered a link between disrupted fatty acid metabolism and ferroptosis, an iron-dependent form of cell death driven by lipid peroxidation. This suggests that altered fat metabolism and ferroptosis may work together to damage placental tissue in intrahepatic cholestasis of pregnancy, offering new insight into disease mechanisms and potential therapeutic targets.

The researchers concluded that using palmitic acid and ACSL1 alongside bile acids could substantially improve early diagnosis and risk stratification for ICP. Larger clinical studies are planned to confirm these findings and support their translation into routine prenatal care.