Intrahepatic cholestasis of pregnancy

A disorder in which bile acids are not completely released by the liver of pregnant women during the second and third trimester of pregnancy, increasing their concentration in blood and amniotic fluid. It occurs in about 0.2-2% of pregnant women, and although it is not serious for the woman and reverses after delivery, it increases the risk of severe consequences for the fetus.

The exact causes of this disturbance in the digestive functioning of pregnant women are unknown. Pregnancy hormones seem to be involved, since they may slow down the normal flow of bile. Other factors that may favor intrahepatic cholestasis during gestation are:

  • History of intrahepatic cholestasis in previous pregnancies. About 60%-70% of women present this condition recurrently in subsequent pregnancies, and it can reach 90% in severe cases.
  • Previous personal history of liver damage or disease including cholelithiasis or Hepatitis C or B infections.
  • Twin or multiple pregnancies.
  • Assisted reproduction techniques.

In order to decipher the genetic contribution to this condition, and to avoid or minimize adverse outcomes, especially fetal outcomes, the FinnGen project has recently undertaken, through GWAS analysis, the study of maternal genetic predisposing factors in 1200 cases and 122,000 controls. As a result, 10 loci significantly related to the predisposition to develop this disorder have now been identified.

Symptoms

Intense itching usually at night without rash is the main symptom, in most women on the palms of the hands or soles of the feet, or even in some pregnant women on all parts of the body, however, after delivery, it usually disappears within a few days.

  • Other less common signs and symptoms include.
  • Jaundice (yellowing of the skin and whites of the eyes).
  • Nausea.
  • Loss of appetite.

The consequences on the pregnant mother would be limited to fat malabsorption which could trigger blood clotting problems, but this is a very rare complication. However, on the developing fetus, more serious complications such as fetal distress, meconium inhalation, premature delivery or intrauterine fetal death could occur.

Prevention

At present the available knowledge about intrahepatic cholestasis of pregnancy does not allow its early prevention. However, as with other pathologies, following a healthy and balanced diet with plenty of fresh fruits and vegetables can help reduce the risk of cholestasis or its severity, as well as other problems during pregnancy.

Number of observed variants

13.5 million variants

Number of risk loci analyzed in the study

9 loci

Bibliography

Pillarisetty LS et al. Pregnancy Intrahepatic Cholestasis.

Mayo Clinic [March 2022]

Hagenbeck C et al. Management of Intrahepatic Cholestasis of Pregnancy: Recommendations of the Working Group on Obstetrics and Prenatal Medicine - Section on Maternal Disorders. Geburtshilfe Frauenheilkd. 2021;81(8):922-939

FinnGen. FinnGen Documentation of R5 release 2021 [2022/02]

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