Generality
Pregnancy cholestasis (or intrahepatic cholestasis of pregnancy) is a complication that can develop during the second half of gestation .
This pathology is caused by an alteration of the secretion or normal flow in the duodenum of bile, a dense yellow-green substance, which is produced by the liver to allow digestion and fat absorption. This involves the pouring into the blood of bile salts and other colephyl compounds, such as bilirubin, normally secreted into bile.
The main symptom of gravidic cholestasis is the intense and persistent itching . This manifestation is usually early and is not associated with a skin rash. The itching from gravidic cholestasis can affect any part of the body, but usually starts from the palm of the hands and the soles of the feet, to then generalize to the whole body. In the presence of this characteristic itchy sensation, confirmation of the diagnosis is obtained with specific blood tests, such as the dosage of bile acids, bilirubin and transaminases.
If left untreated, pregnancy cholestasis can have serious consequences for both the mother and the fetus. These include: increased risk of fetal prematurity, death at birth and respiratory distress syndrome .
The management of gravidic cholestasis involves the taking of drugs useful to avoid the accumulation of bile acids in the bloodstream and the induction of childbirth .
What's this
What is gravidic cholestasis?
Pregnancy cholestasis is a clinical syndrome of variable severity that results from impaired normal bile flow . Usually, the pathology manifests itself in the third trimester of gestation.
Pregnancy cholestasis is characterized by an increase in bile acids in the bloodstream, which leads to generalized itching, whether or not associated with hyperchromic urine, jaundice and steatorrhea . In the presence of this disorder, it is also possible to find altered liver function parameters.
Synonyms for gravidic cholestasis
Pregnancy cholestasis is also known as hepatogestosis or intrahepatic cholestasis of pregnancy (CIG).
Causes and Risk Factors
The pregnancy cholestasis recognizes a multifactorial etiology, therefore it results from the interaction of more concause. At the base, there is an increase in biliary stasis secondary to an alteration of the secretion or normal outflow of bile in the duodenum. Pouring excess into the blood and tissues, bile salts cause irritation of the peripheral nerves, which, in turn, causes a sensation of itching, sometimes of unbearable intensity.
Several other factors contribute to the pathogenesis of gravidic cholestasis:
- Hormonal factors : gravidic cholestasis seems to depend on an increase in the normal stasis of intrahepatic bile, in combination with the greater plasma concentrations of estrogen and progesterone . The role of hormones is suggested by the fact that gravidic cholestasis occurs mainly in the terminal part of pregnancy. Furthermore, symptoms tend to resolve after childbirth, when hormone levels return to normal. Pregnancy cholestasis occurs more frequently in twin pregnancies, for the simple reason that a greater quantity of estrogen is produced which more easily overloads the liver.
- Genetic factors : pregnancy cholestasis seems to occur in genetically predisposed women, following the interaction of various environmental factors (such as diet ) and hormonal changes that occur physiologically during pregnancy. Recently, in some patients with pregnancy cholestasis, a particular genetic mutation has been detected. It should also be noted that cholestasis is more likely if the mother or sisters of the pregnant woman have already developed hepatogestosis during pregnancy.
- Environmental factors : the incidence of gravidic cholestasis varies according to different geographical areas . Furthermore, the disease appears to manifest itself more severely in the winter months . Diet can also influence the onset of gravidic cholestasis. In particular, some scientific studies argue that a selenium deficiency may play a role in the pathogenesis of the disease.
Pregnancy cholestasis can be favored by a previous liver disease at gestation; in particular, the clinical picture is frequently associated with urinary tract infections and cholelithiasis .
Cholestasis Gravidicum: how widespread is it?
The incidence of gravidic cholestasis varies according to ethnicity. More in detail, the populations in which it is found most frequently are those of Chile, Bolivia and Scandinavian countries, in which it can reach one in 50 pregnant women. In Western and Central Europe and in North America, instead, cholestasis gravidates it is observed in about 0.5-1.5% of pregnant women.
Women at risk of pregnancy cholestasis (for example, due to a positive personal or family history, twin pregnancy, etc.) must be closely monitored during gestation, especially in the third trimester when estrogen levels are highest.
Symptoms and Complications
Pregnancy cholestasis generally occurs in the second and third trimesters (in 80% of cases, it occurs after the 30th week of gestation).
The earliest symptom is an itching of the intense skin, sometimes followed by dark (hyperchromic) urine, mild jaundice (the white part of the eyes and, sometimes, the skin becomes yellowish) and light stools (hypocholic, colored greyish).
The most characteristic laboratory finding of gravidic cholestasis, on the other hand, is the elevation of serum levels of bile acids and / or increase in the level of hepatic transaminases (aspartate aminotransferase, AST, and alanine aminotransferase, ALT).
In gravidic cholestasis, less common symptoms are usually: fatigue, decreased appetite, nausea and vomiting.
Pregnancy cholestasis tends to recur in subsequent pregnancies (60-90%).
Cholestasis Gravidic: characteristics of itching
Pregnancy cholestasis is characterized by an itchy, persistent and very intense sensation, which starts in the second or third trimester. At the beginning, this symptom mainly involves the extremities (palms of the hands and soles of the feet), then it is accentuated in a progressive way, extending to the limbs, the trunk and the face.
Pruritic cholestasis itching exacerbates during the night and can be so severe that it limits the woman's quality of life. In some cases, this manifestation can be associated with scratching lesions (excoriations, bumps etc.).
How to distinguish it from the "physiological" itching in pregnancy?
During pregnancy, itching can be considered a fairly common symptom. The changes that occur in the future mother, such as, for example, increased water retention and the increase in volume of some parts of the body, can cause a stretch of the skin from which an itchy sensation could result. Unlike what happens in gravidic cholestasis, however, itching is mild and localized to areas subjected to greater tension, such as the abdomen, thighs and hips . In case of doubt, however, simply contact your doctor and undergo some laboratory tests to confirm or rule out the presence of gravidic cholestasis.
Cholestasis Pregnancy: possible risks for the pregnant woman
Generally, pregnancy cholestasis is benign for the patient, but may have a negative prognosis for the fetus. This pathology is related, in fact, to a greater risk of miscarriage and perinatal death .
Possible complication for the future mother is the increased tendency to postpartum hemorrhage . This last event depends on the malabsorption of vitamin K, associated with the disease (note: vitamin K is involved in the mechanisms of blood clotting). Therefore, in the last weeks of pregnancy, the doctor may indicate vitamin K intake to reduce the risk of bleeding complications.
Gravidic cholestasis: possible risks for the fetus
The accumulation of bile acids in the blood can be toxic to the unborn child.
If not adequately treated, pregnancy cholestasis correlates to an increased risk of fetal and neonatal complications, including:
- Preterm birth ;
- Amoniotic fluid stained with meconium (first faeces produced by the child);
- Abnormal fetal heart rhythm (eg bradycardia during childbirth);
- Neonatal respiratory distress syndrome .
These occurrences are more likely in the presence of a concentration in bile acid serum higher than 40 µmol / L (micromoles per liter) on an empty stomach. The management of complications of pregnancy cholestasis against the unborn child necessitates admission to neonatal intensive care .
In some cases, endouterine death is possible: in most cases, this event occurs after the 34th week of gestation, due to an acute onset fetal anoxia .
Cholestasis: course after pregnancy
Generally, pregnancy cholestasis undergoes a spontaneous regression after two to three weeks after delivery, but tends to recur with each pregnancy or with the use of oral contraceptives.
Diagnosis
Pregnancy cholestasis is suspected on the basis of symptoms and medical history and is confirmed by some blood tests, such as the dosage of bile acids, bilirubin, alkaline phosphatase and transaminases.
The most frequent laboratory alteration related to the disease is the increase in total serum bile acid levels, fasting, above 10 µmol / L. Furthermore, specific enzymes of biliary stasis, such as alkaline phosphatase and gamma-glutamyltransferase (gamma-GT), may be altered, although their increase is not significant in relation to the pathology in question.
To find the cause of gravidic cholestasis, the doctor may indicate an ultrasound scan.
Cholestasis Pregnancy: which blood tests are needed?
To support and confirm the diagnosis, blood tests are performed to highlight the most frequent alterations related to gravidic cholestasis. The most sensitive and specific laboratory finding is the increase in serum concentration of bile acids (> 10 mmol / L). In the presence of gravidic cholestasis, this may be the only biochemical anomaly found.
Other parameters that may be high (but not always) in the case of gravidic cholestasis are:
- aminotransferase;
- Bilirubin (direct hyperbilirubinemia);
- Alkaline phosphatase;
- GT range.
Prenatal tests and postpartum follow up
Once diagnosed with cholestasis, a careful monitoring of the pregnant woman and the unborn child is foreseen, by:
- Prenatal tests, such as umbilical artery doppler and non-stress test;
- Control of bile acid levels .
These examinations must be performed weekly or every 15 days to guide the therapy and have an indication for the timing of the delivery induction.
After delivery, patients with pregnancy cholestasis should measure bile acid levels and liver parameters every 3-6 months: if the values remain high, the doctor will indicate the appropriate diagnostic investigations.
Treatment
Therapy of pregnancy cholestasis should be started as soon as the diagnosis is made.
The objectives are to prevent accumulation in the blood circulation of bile acids, correct biochemical abnormalities, relieve itching and complete pregnancy.
The therapy of first choice for this pathology consists in the oral intake of ursodeoxycholic acid (UDCA) .
It should be noted that, as in other cholestatic syndromes, no treatment is always completely effective and the solution is represented by childbirth.
Pharmacological therapy
Ursodeoxycholic acid is a hydrophilic bile acid, non-toxic and well tolerated, which can improve bile flow.
This medicine helps to avoid the potential cytotoxicity of bile acids accumulated in the blood, reduces itching and normalizes biochemical markers of liver function; however, ursodeoxycholic acid does not decrease the incidence of fetal complications. For this reason, constant monitoring of the conditions of the future mother and the unborn child is suggested.
In addition to ursodeoxycholic acid, in the event of cholestasis, the doctor may also prescribe the intake of:
- S-Adenosyl-Methionine : essential amino acid associated with folic acid appears to have a preventive effect of NTDs (neural tube defects); in combination with ursodeoxycholic acid, S-adenosyl-methionine can help reduce the severity of pruritus and normalize serum levels of bile acids;
- Cholestyramine : it is an ionic exchange resin that represents the therapeutic alternative to ursodeoxycholic acid. This binds to the bile acids in the intestine and prevents its reabsorption, forming a complex later excreted in the feces. As a rule, the use of this drug is not recommended during pregnancy, as it interferes with the absorption of fat-soluble vitamins and can worsen any maternal and fetal coagulopathies. If prescribed to manage gravidic cholestasis, therefore, the doctor will indicate an appropriate vitamin supplementation (vitamins A, D, E, K);
- Oral antihistamines (eg cetirizine and loratadine): may decrease the intensity of itching.
In addition to giving birth, in order to reduce the risk of bleeding following a malabsorption deficit, vitamin K is also indicated, in the form of:
- Phytomenadione (Vitamin K1);
- Menadione (Vitamin K3).
Supply
From the point of view of nutrition, in the presence of gravidic cholestasis, it is important to adopt a diet with a low fat content . In this sense, elaborate cooking and fries should be limited, while lean meats and fish, extra virgin olive oil (3 tablespoons per day) and fresh cheeses (not more than 2-3 times a week) can be chosen.
In general, cooking foods should be simple (steamed, boiled, grilled). Finally, it is a good habit, even to promote a regular intestinal function, to take at least 2-3 portions of vegetables and fruit a day daily.
Induction of childbirth
In the presence of gravidic cholestasis, the birth can be induced at the 36th-37th week of gestation, when lung development is now complete. At the moment, induction seems to be the best approach to reduce the risk of fetal death.
On the instructions of the gynecologist, the birth can be performed vaginally or by caesarean section.
Cholestasis Gravidicum: after childbirth
- The pregnancy cholestasis resolves in the puerperium, indicatively within 4-6 weeks from the birth of the child. Usually, the values of bile acids and transaminases undergo a rapid decrease immediately after the birth with resolution of the symptoms in the following months.
- After delivery, the women who developed the disease during pregnancy are not advised to take the estrogen-progestin contraceptive pill, as it could induce the same symptoms as gravid cholestasis.
