Certain fatty molecules may help diagnose liver disease in pregnancy
Some short-chain fatty acids may protect against disease progression: Study
Blood levels of certain fatty molecules, called short-chain fatty acids (SCFAs), in pregnant women may help diagnose intrahepatic cholestasis of pregnancy (ICP), according to a study in China.
SCFAs are a family of by-products, or metabolites, produced when friendly bacteria in the gut break down indigestible foods, such as dietary fiber.
“Certain maternal [blood] SCFAs, specifically caproic and acetic acids, demonstrated excellent diagnostic efficiency for ICP,” researchers wrote.
The study, “Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy,” was published in the World Journal of Hepatology.
ICP is a form of cholestasis, which is a slowed or stalled flow of the digestive fluid bile out of the liver to the intestines. It normally appears during the middle and late stages of pregnancy.
ICP may lead to liver damage, adverse fetal outcomes
The condition may lead to damage in the liver, resulting in acid bile leakage to the blood, and to symptoms such as itching, fatigue, and jaundice, or yellowing of the skin and the whites of the eyes. While symptoms usually disappear after delivery, ICP is associated with an increased risk of adverse fetal outcomes.
“Recent research has shed light on the role of gut [microbes] and their metabolites in the progression of ICP,” the researchers wrote.
Prior studies have linked SCFAs to several pregnancy-related complications, with other research showing some may help treat such complications.
“However, the metabolic profile of SCFAs in patients with ICP remains unclear,” the researchers wrote.
With this in mind, a team of researchers in China analyzed the SCFA profiles in maternal and umbilical cord blood of 34 pregnant women with ICP and 30 pregnant women without ICP (who served as controls). None of the women had other pregnancy-related complications.
The two groups had similar ages, education levels, and number of pregnancies and births. However, women with ICP had a significantly shorter uterine height and smaller abdominal circumference, indicative of baby growth restriction or low levels of the fluid that surrounds the baby during pregnancy.
In addition, the ICP group had significantly lower levels of hemoglobin, which is the protein that carries oxygen in red blood cells, while bile acids and other markers of liver damage were found at higher levels in the blood.
Babies from mothers with ICP were born earlier, weighing less
Babies from ICP mothers were born significantly earlier (37.8 vs. 39.4 gestational weeks) and weighing less (3.1 vs 3.5 kg, or 6.8 vs 7.7 pounds). Also, most ICP patients gave birth by cesarean section (67.6% vs. 23.3% who gave birth vaginally), compared with women who had normal pregnancies.
Moreover, maternal blood levels of all but one SCFA were significantly reduced in women with ICP relative to healthy controls, particularly acetic and caproic acid. The exception was isobutyric acid, which was found at significantly higher levels in the ICP group.
In blood samples from the umbilical cord, most SCFAs showed a decreasing trend in the ICP group, with acetic acid and isovaleric acid being significantly lower than in controls. Isobutyric acid levels were also significantly reduced in women with ICP, therefore displaying an opposite trend than what was observed in maternal blood.
In both groups, higher total SCFAs levels in umbilical cord blood were significantly associated with higher levels in maternal blood. In terms of individual SCFAs, only acetic and caproic acids showed such a link.
The researchers then calculated the area under the curve (AUC), a statistical measure that assesses how well a given test can distinguish between two groups. AUC values can range from 0.5 (meaning no discrimination) to 1 (perfect discrimination).
Results showed “multiple SCFAs in maternal serum possessed excellent diagnostic capabilities for ICP,” the researchers wrote, with caproic acid showing the highest diagnostic efficacy (AUC of 0.97). It was followed by isobutyric acid (AUC of 0.86), and acetic acid (AUC of 0.82).
Certain maternal [blood] SCFAs, specifically caproic and acetic acids, demonstrated excellent diagnostic efficiency for ICP.
Higher levels of acetic, caproic acids linked to less severe liver damage
When correlating SCFA levels with clinical indicators, the team found higher levels of acetic and caproic acids in maternal and cord blood were significantly associated with lower bile acid levels, indicating less severe liver damage.
Acetic acid has been shown to regulate intestinal inflammation and reduce liver fat, suggesting that it may play a protective role in ICP progression.
Higher caproic acid levels were also significantly linked to a higher newborn birth weight, which might be related to a metabolic adaptation. “However, further exploration is necessary to determine whether it exerts … protective effects on patients with ICP and their fetuses,” the researcher wrote.
Higher blood levels of isobutyric acid were significantly associated with higher bile acid levels in maternal blood, while an opposite association was observed in the cord blood. Of note, this SCFA has been associated with pregnancy-related complications.
“The results of this study imply that elevated isobutyric acid levels in maternal blood circulation not only lead to [disease-causing] changes in the mother but also impact the growth and development of the fetus in the uterus,” the researchers wrote.
More studies “are required to elucidate [SCFAs] mechanisms of action, providing a solid theoretical foundation for SCFAs as diagnostic and therapeutic targets for ICP,” the team concluded.
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