The research, led by Agata Majewska from the Department of Women and Children’s Health, King’s College London, and colleagues, found that the gestational age at which bile acids reach severely elevated levels (≥100 µmol/L) plays a crucial role in determining stillbirth risk.
The observational cohort study included 198 women with singleton pregnancies and severe ICP, a condition characterized by elevated bile acids and liver dysfunction during pregnancy. Among the participants, 15 pregnancies (7.6%) resulted in stillbirth.
The study revealed the following findings:
- The risk of stillbirth increased with each advancing week of gestation at which bile acid levels peaked (OR 1.28).
- Women who developed severe intrahepatic cholestasis of pregnancy (ICP) after 28 weeks faced over a threefold higher risk of stillbirth compared to those with an earlier onset (OR 3.47).
- Most stillbirths were preceded by a sudden and marked rise in bile acid levels, typically within five days before the event.
- Once bile acid concentrations reached or exceeded 100 µmol/L, the overall risk of stillbirth did not continue to increase proportionally.
- The timing of bile acid elevation—rather than the absolute level—was the key factor influencing the likelihood of stillbirth, with later onset or peak levels linked to higher risk.
To determine these associations, the researchers employed logistic regression and compared outcomes based on when bile acid levels first became severely elevated and when they reached their peak. They found that patients who experienced stillbirth generally reached their peak bile acid levels later in pregnancy than those who went on to have live births (p = 0.029).
Majewska and colleagues highlighted that their findings underscore the importance of frequent bile acid monitoring and individualized management strategies. The detection of a rapid bile acid surge late in pregnancy may prompt closer fetal surveillance and inform decisions about optimal timing of delivery.
While the study provides valuable insights, the authors acknowledged certain limitations. The sample included only 15 stillbirth cases, and recruitment was enriched through UK-wide networks and the charity ICP Support, which may have introduced selection bias. Moreover, the observational nature of the research and the lack of standardized bile acid testing intervals limited real-time clinical applicability.
"The study highlights that both the gestational age at onset and at the peak of severe bile acid elevation are key determinants of stillbirth in ICP. Regular bile acid testing and vigilant follow-up may help identify pregnancies at heightened risk, supporting more personalized decisions about the timing of delivery and improving perinatal outcomes," the authors concluded.
Reference: https://www.ejog.org/article/S0301-2115(25)01076-0/fulltext
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