Inflammation markers may predict fetal risk in ICP: Study
Blood levels could provide 'accessible, cost-effective' measures
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Blood levels of certain pro-inflammatory proteins are elevated in people with intrahepatic cholestasis of pregnancy (ICP), and these inflammatory markers may help predict the risk of adverse fetal outcomes, according to a study.
Combining these inflammatory markers with blood levels of bile acids, a commonly used predictor of ICP-related outcomes, improved the predictive accuracy for preterm birth (before 37 weeks of gestation) and abnormally low birth weight.
“Based on these findings, blood inflammatory parameters may serve as accessible and cost-effective indicators for understanding the inflammatory microenvironment in ICP and predicting fetal outcomes,” the researchers wrote.
The study, “The Potential Value of Blood Inflammatory Parameters in Diagnosing the Inflammatory Microenvironment and Predicting Fetal Outcomes in Patients With Intrahepatic Cholestasis of Pregnancy,” was published in Mediators of Inflammation by a team of researchers in China.
Bile is a digestive substance that’s produced in the liver then shipped out to the intestines through a series of tubes called bile ducts. ICP, the most common pregnancy-related liver disease, is marked by cholestasis, or stalled bile flow, where bile builds up to toxic levels in the liver and spills into the bloodstream. The condition increases the risk of complications for both the mother and the baby, including preterm birth, low birth weight, and stillbirth.
Inflammation and ICP
“Although the severity of ICP and related fetal risks can be evaluated using [blood bile acid] levels, this method remains limited by insufficient sensitivity and specificity,” the researchers wrote. A test’s sensitivity refers to its ability to accurately identify people with a given condition, while specificity refers to its ability to accurately rule out cases without the condition.
“A growing body of research has revealed that both [body-wide] and localized inflammation are key contributors to the [development] of ICP, potentially exacerbating the condition and increasing the likelihood of adverse pregnancy outcomes,” the team wrote.
The scientists analyzed blood levels of immune signaling molecules related to inflammation, along with several inflammatory scoring indicators, in 67 pregnant women with ICP and an equal number without ICP.
The researchers zeroed in on four signaling molecules — interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) — levels of which were significantly elevated among ICP patients. IL-6, TNF-alpha, and INF-gamma are key pro-inflammatory molecules, while IL-10 is an anti-inflammatory molecule that can be elevated as a response to excess inflammation.
All but one of the four inflammatory scoring indicators evaluated, derived from immune and blood cells, were also significantly higher in the ICP group relative to the control group.
“The results combined with [blood] inflammatory factors showed that the blood inflammatory parameters of ICP patients increased to varying degrees, indicating that there may be an inflammatory microenvironment in ICP patients,” the team wrote.
Higher levels of many of these inflammation markers were also significantly associated with higher blood levels of liver damage markers, including bile acids, and with lower birth weight and a lower 1-minute Apgar score, suggesting a baby may need immediate medical assistance.
The researchers then evaluated the predictive potential of these inflammation markers in terms of adverse fetal outcomes. Statistical analyses showed that while blood bile acid levels alone could predict the risk of preterm birth or low birth weight with reasonable accuracy, combining them with levels of inflammation markers markedly improved the predictive potential.
Specifically, blood bile acid levels could distinguish preterm birth cases from non-preterm cases with 78.3% accuracy. This was increased to 86.5% when these were combined with both inflammation-related molecules and inflammatory scoring indicators. For low birth weight, blood bile acid level alone had a predictive ability of 77.4%, which was raised to 91.6% when all indicators were combined.
The team then looked at potential links between genetic variants associated with different levels of inflammation markers and ICP to identify possible risk factors. They found that variants linked to higher blood levels of TNF-alpha and interleukin-2, another potent pro-inflammatory molecule, were potential risk factors for ICP.
“Our findings highlight the significant contribution of blood inflammatory parameters to ICP, offering valuable insights to guide future diagnostic and therapeutic research,” the researchers wrote. “Patients with markedly altered inflammatory parameters may therefore require closer fetal surveillance and earlier clinical intervention.”
