Intrahepatic cholestasis of pregnancy, also known as Intrahepatic cholestasis of pregnancy, cholestasis gravidarum or obstetric cholestasis, is a complication that can arise in the third trimester of pregnancy and affects about 1% of pregnant women. Cholestasis is characterized by elevated levels of bilirubin in the blood and is caused by obstruction of the bile ducts within the liver.
→ Symptoms: The main symptom of cholestasis of pregnancy is an intense itching, especially in the palms and soles of the feet, which usually occurs from the 30th week of pregnancy. There may also be jaundice, nausea and loss of appetite.
Complications: cholestasis is associated with an increased risk of premature birth, respiratory failure of the newborn and intrauterine death.
→ Treatment: the treatment with ursodeoxycholic acid and the induction of pregnancy from the 37th week of gestation.
To define intrahepatic cholestasis of pregnancy, it is necessary to first know what is cholestasis and what is the role of the liver and bile ducts in this disease.
Our red blood cells have a lifespan of 4 months on average. When they age, they are transported to the spleen for destruction. One of the products released in this destruction process is bilirubin, a yellow-green pigment.
Every day, millions of red blood cells are destroyed and all the bilirubin released is carried by the bloodstream to the liver, where it will be metabolized.
In the liver, the bilirubin coming from the blood, called indirect bilirubin. It is transformed into direct bilirubin, which is a water-soluble form easier to excrete.
When the liver functions normally, direct bilirubin is drained by intrahepatic ducts into the common bile duct and then into the intestines, where it mixes with the stool and is eliminated from the body
We call cholestasis any situation where there is reduction or blockage of this bilirubin drainage. We say that cholestasis is intrahepatic when the obstruction is in the non-internal ducts of the liver, or extrahepatic when the problem is in the bile ducts outside the liver.
The obstruction of the bilirubin drainage causes this pigment to accumulate in the blood and later in the skin.
The intrahepatic cholestasis of pregnancy is, as the name says, a incidence of cholestasis that originates in the liver and occurs during pregnancy.
The mechanism by which the cholestasis of pregnancy develops has not yet been fully clarified. The disease probably involves a combination of genetic, hormonal and environmental factors.
It is speculated that the pregnancy hormones act directly on the bile transport in the intrahepatic ducts, causing a considerable delay of their exits.
The reasons why we think that estrogen and progesterone play a vital role in the appearance of intrahepatic cholestasis of pregnancy are the following:
- Cholestasis occurs almost exclusively in the third trimester of pregnancy, the stage when these hormones are at their peak.
- Twin pregnancies, which have higher levels of estrogen and progesterone, have a higher incidence of cholestasis than non-twin pregnancies.
- The picture of cholestasis usually improves rapidly after the end of pregnancy, together with the abrupt fall of hormone levels.
- Cholestasis usually occurs in the first trimester of pregnancy in women who, when trying to get pregnant, experienced ovarian stimulation with hormones.
- Outside of pregnancy, cholestasis is more common in women who take birth control pills based on estrogen and progesterone.
But only high levels of hormones are not enough to justify the onset of cholestasis, which affects only 1 in 100 pregnant women.
A genetic predisposition also seems to be necessary and explains why the disease has a strong family and ethnic component. In some populations, the incidence of cholestasis is quite low, around 1 case per 1000 pregnancies (0.1%). In some countries, however, as in Chile, the rate is 2% and becomes 27% if we only consider Araucanian women (Amerindians).
For reasons not yet clear, cholestasis gravidarum is more common in the winter, especially in countries with cold climates, such as Sweden, Finland and Chile itself.
The main signs and symptoms of obstetric cholestasis occur from the third trimester of pregnancy and are caused by the increased concentration of bilirubin in the blood and its subsequent deposition in the skin.
The most characteristic symptom is itching on the palms of the hands and soles of the feet, which comes without any visible lesion on the skin and can spread through the rest of the body, such as belly, torso and face. Although there are no injuries initially, over time, from being so scratched, the skin may begin to present abrasions.
This itching is more common at night and its intensity varies from moderate to severe and can interrupt the already problematic sleep of pregnant women.
It is important to note that it is very common for pregnant women to have some degree of pruritus at the end of pregnancy, especially in the womb, without having any clinical significance. Only when the itching is very intense and persistent is that we have to worry about the possibility of being cholestasis gravidarum.
In about 25% of pregnant women, one to four weeks after the onset of itching, other signs and symptoms may occur, such as jaundice (yellow skin), loss of appetite, nausea, abdominal pain , mainly in the quadrant upper right abdomen, very pale stools, steatorrhea (fat in the stool), dark urine, fatigue and delay in blood clotting.
Most pregnant women with itching in the final stage of pregnancy have cholestasis. But if the itching is intense and affects the palms of the hands and soles of the feet, the obstetrician should be informed.
On the part of the mother, the main problem is usually the increased risk of bleeding during delivery, which arises from steatorrhea and the consequent malabsorption of vitamin K, an essential factor for normal blood clotting. Fortunately, this complication is unusual.
Cholestasis gravidarum is a much more serious problem for the fetus than for the mother. As bilirubin crosses the placental barrier, it easily accumulates in the amniotic fluid and in the baby’s body.
Among the possible fetal complications of intrahepatic cholestasis of pregnancy, the three most important are:
- Premature delivery.
- Respiratory distress syndrome of the newborn (caused by the presence of bilirubin in the lungs).
- Intrauterine fetal death.
Intrahepatic cholestasis is diagnosed when the pregnant woman has the following changes:
- Intense pruritus (itching) and persistent, especially in the hands and feet, started in the third trimester of pregnancy.
- High blood levels of bilirubin.
- High blood levels of transaminases (GOT and GPT) .
The treatment of cholestasis of pregnancy has two objectives: to alleviate the symptoms of the mother and reduce the risk of complications for the fetus.
For such purposes, a drug called ursodeoxycholic acid is currently the most widely used.
The dose of 300 mg of ursodeoxycholic acid, 2 or 3 times a day, is able to achieve the following results:
- Reduction of pruritus in more than 60% of cases.
- Reduction in the levels of GOT and GPT.
- Reduction in blood levels of bilirubin.
- 67% reduction in the risk of respiratory distress syndrome of the newborn
- Reduction of 44% in the risk of premature birth
To reduce the exposure of the fetus to bilirubin, induction of labor is now recommended when the pregnancy reaches 37 weeks. Some doctors wait until 38 or 39 weeks, if the treatment with ursodeoxycholic acid has been very effective with resolution of maternal pruritus and great drop in bilirubin values.
On the other hand, interruption of pregnancy with less than 36 weeks should be considered in severe cases that do not respond to treatment.