What is Pregnancy Intrahepatic Cholestasis?
Intrahepatic cholestasis of pregnancy (ICP) is a condition affecting the liver in the later stages of pregnancy. It’s sometimes called obstetric cholestasis (OC). It causes an itchy feeling and an increase in certain substances in your blood, including bile acids and other things that your liver usually deals with. Even though it’s not fully understood why this happens, we do know that all these symptoms and changes in your body go away quickly after giving birth. It is important to be aware that ICP can result in some complications during pregnancy, including the baby being stillborn, developing breathing issues, passing a certain type of stool while still in the womb, or experiencing a lack of oxygen. This piece will explain how this condition presents itself, how it’s diagnosed and how it’s managed.
What Causes Pregnancy Intrahepatic Cholestasis?
The exact cause of a condition called intrahepatic cholestasis of pregnancy (ICP), which affects pregnant women’s liver functions, remains unclear. Experts believe that it’s complicated and involves various factors such as genes, hormones, and the environment. There’s an idea that ICP occurs when pregnancy hormones that slow down the flow of bile (a substance produced by the liver) affect women who have particular genetic markers in a specific way.
This theory is supported by observations that ICP often runs in families and is more common in certain lineages, as well as the fact that the risk of getting ICP increases with every pregnancy a woman has. Researchers have also found changes in certain genes that make proteins responsible for moving drugs and other substances across a cell membrane in the liver. Other genetic markers have been associated with ICP, but more research is required to fully understand the role they play.
Another area of research is the role of pregnancy hormones in ICP. Many studies have linked high estrogen levels (as seen in pregnancies with multiple babies, certain ovarian conditions, and late second trimester pregnancy) with ICP. ICP usually happens when estrogen levels are the highest during pregnancy, and shows similar characteristics as seen in women taking high-estrogen contraceptive pills. There’s also some evidence suggesting that by-products of another hormone, progesterone, might interfere with the liver’s normal processes.
Scientists have also found links between environmental and seasonal factors and ICP. For example, the condition appears more frequently in women lacking selenium and vitamin D, substances that are often at low levels during winter in some countries. Finally, there are connections between ICP and other long-standing liver diseases. But it’s still unclear whether the liver diseases cause ICP or if pregnancy simply reveals these underlying conditions.
Risk Factors and Frequency for Pregnancy Intrahepatic Cholestasis
Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease related to pregnancy. The number of cases varies depending on ethnicity and location. It affects between 0.2 to 2% of pregnancies, with it being more common in South America and Northern Europe. In the USA, ICP is seen in about 0.2 to 0.3% of pregnancies.
People who have had ICP before, have chronic liver disease or hepatitis C, are carrying more than one baby, or are older, have a higher chance of developing ICP. Also, women who have had ICP in a previous pregnancy have a high chance (60 to 70%) of it recurring in another pregnancy.
- ICP is the most common liver disease related to pregnancy.
- The number of ICP cases varies between 0.2 to 2% of pregnancies depending on ethnicity and location.
- It’s more common in South America and Northern Europe.
- In the USA, ICP is seen in 0.2 to 0.3% of pregnancies.
- Those with higher risk include people who have had ICP before, have chronic liver disease or hepatitis C, are carrying more than one baby, or are older.
- Women who have had this disease in a previous pregnancy have a high chance (60 to 70%) of it recurring in another pregnancy.
A survey of former ICP patients and controls showed a higher incidence of liver dysfunction during pregnancy in mothers, sisters, and daughters of women who have had ICP. This indicates a possible genetic component to ICP.
Signs and Symptoms of Pregnancy Intrahepatic Cholestasis
Intrahepatic cholestasis of pregnancy (ICP), a liver condition, typically manifests between the late second and early third trimester of pregnancy. The primary symptom is an intense itch, which usually begins after 30 weeks of pregnancy. This itch can be more pronounced on the hands and feet and is usually worse at night. In addition to the itchiness, other symptoms associated with cholestasis like nausea, lack of appetite, tiredness, pain in the upper right part of the abdomen, darkened urine, and light-colored stool can occur. Yellowing of the skin (clinical jaundice) is rare but can affect around 14 to 25% of patients, and it usually appears 1 to 4 weeks after the itching starts. Some patients also report difficulty sleeping due to itchiness. A physical exam usually doesn’t reveal any significant findings, other than potential scratch marks from the itching. It’s important to note that itching is a key symptom of ICP and can occur even before any biochemical abnormalities are detected. Women who have had in vitro fertilization may experience temporary symptoms in the first trimester, unlike the persistent symptoms seen in the second and third trimester in ICP. Family history of liver problems during pregnancy in other female relatives is also considered due to the role of genetics in this condition.
- Intense itchiness, often concentrated on the hands and feet, usually starting after 30 weeks of pregnancy
- Other cholestasis symptoms such as nausea, loss of appetite, fatigue, upper right abdominal pain, dark urine, and pale stool
- Rarely, clinical jaundice (skin yellowing), affecting around 14-25% of patients, typically appearing 1 to 4 weeks after the start of itchiness
- Insomnia due to itching for some patients
- Potential scratch marks on the skin from itching
- Transient symptoms in the first trimester for women who have had in vitro fertilization
- Family history of liver problems during pregnancy
Testing for Pregnancy Intrahepatic Cholestasis
Intrahepatic cholestasis of pregnancy (ICP), a liver condition that affects pregnant women, can be identified through a common symptom of itchy skin, particularly in the last three months of pregnancy. It also involves elevated levels of bile acids in the mother’s blood. Other diseases that can cause similar symptoms and lab results should also be ruled out.
If your liver function tests are abnormal but you haven’t experienced itchy skin, you might need further investigation to find another cause. The most reliable test for ICP measures total serum bile acid, which refers to the total amount of bile acids in your blood. This test can correctly identify ICP in 91 to 93 percent of cases, where the cut-off value is 10 micromol/L. Most studies diagnose ICP when bile acids are between 10 and 14 micromoles/L.
In severe cases of ICP, where bile acid levels are usually over 40 micromol/L, there is an increased risk of complications for the baby. Other tests that measure liver function, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), may show slightly elevated levels but usually won’t be more than double the normal value during pregnancy.
Sometimes an enzyme called serum alkaline phosphatase may be elevated, sometimes up to four times the usual value, but this generally doesn’t help in diagnosing ICP. Around a quarter of ICP cases may show raised bilirubin levels, but it rarely exceeds 6 mg/dL. If prothrombin time, a measure of how quickly your blood clots, is high it could be due to a lack of vitamin K (which aids in blood clotting) but it is rare for this to cause a high risk of bleeding after childbirth.
Interestingly, a study found that an enzyme called autotaxin, which converts a certain substance into LPA (an itch-causing agent), was greatly increased in ICP patients compared to pregnant women without the condition and patients with a different kind of liver disease who did or did not have itchy skin. The same researchers also reported that high serum autotaxin activity could be a very reliable marker of ICP, helping to distinguish it from other conditions that cause itchy skin in pregnancy and other liver diseases that can occur during pregnancy. This enzyme is increased to a much lesser extent in normal pregnancy or in those taking birth control pills when compared to ICP. Therefore, measuring serum autotaxin can be a useful test in identifying causes of itchy skin and elevated bile acid levels.
Treatment Options for Pregnancy Intrahepatic Cholestasis
Once a diagnosis of intrahepatic cholestasis of pregnancy (ICP) is established, immediate treatment is required. The goal of this treatment is to lower the risk of health issues for the newborn and the mother, and to provide relief from the mother’s symptoms.
Ursodeoxycholic acid (UDCA) is the preferred drug for treating ICP. This medication is generally well tolerated and commonly prescribed. Side effects such as nausea, vomiting, and diarrhea can occur but are relatively rare. UDCA does not harm the baby and can effectively reduce levels of harmful bile acids in the mother’s blood. Studies indicate that patients with ICP who were treated with UDCA had better outcomes compared to those treated with other drugs.
In some cases where symptoms don’t improve with UDCA, other drugs like rifampin, cholestyramine, and S-adenosyl-L-methionine may be considered. Rifampin promotes the detoxification and elimination of bile acid, and cholestyramine reduces bile acid absorption in the intestines. In some situations, antihistamines may also be used to provide relief from itching.
Regular antenatal (before birth) testing for women with ICP is generally recommended even though there is no solid proof that it identifies babies at risk. However, many professionals find it reassuring to conduct regular testing to look for any signs of complications.
When it comes to timing of delivery, some professionals advocate for the early elective birth of the baby in an attempt to reduce the risk of sudden fetal death. This decision should take into account the balance between the risk of fetal death and the potential risks of early birth. In some cases, if the mother’s total bile acid concentration is very high, it’s recommended to consider delivery by 35 to 36 weeks of pregnancy.
Delivery before 37 weeks of pregnancy may be considered in women with ICP in certain situations such as worsening of maternal symptoms including jaundice not improving with medications, a history of intrauterine fetal death due to ICP, or extremely high total serum bile acid concentration. However, having ICP is not a condition that necessitates cesarean delivery. After the baby’s birth, the mother’s itching typically disappears within a few days and her bile acid levels should normalize.
Importantly, having ICP does not prevent a mother from breastfeeding and is in fact encouraged. Follow-up testing of liver function and bile acids should be done a month or two after birth to make sure everything has returned to normal. In cases where abnormalities persist, further investigation would be necessary to determine any other underlying conditions.
What else can Pregnancy Intrahepatic Cholestasis be?
When a pregnant woman experiences cholestasis, a condition characterized by impaired bile flow, the possible causes can fall into two groups. The first group includes conditions that cause itchiness or “pruritis”, while the second group includes conditions that result in abnormal liver function.
The conditions that could lead to itchiness during pregnancy include:
- Pemphigoid gestationis
- Pruritis gravidarum (itchiness during pregnancy)
- Prurigo of pregnancy (skin rash)
- Atopic dermatitis (a type of eczema)
- Allergic reactions
The following conditions could lead to impaired liver function during pregnancy:
- HELLP syndrome, characterized by hemolysis (breaking down of red blood cells), elevated liver enzymes, and low platelet count
- Acute fatty liver of pregnancy
- Viral hepatitis
- Primary biliary cirrhosis (a liver disease)
- Drug-induced liver damage
What to expect with Pregnancy Intrahepatic Cholestasis
The pregnancy condition known as intrahepatic cholestasis (ICP) usually has a harmless outcome for the mother. In this condition, symptoms and abnormal liver activity typically disappear quickly after childbirth. However, in some women, these abnormal liver function test results might not go away and might need further check-up to find out if there’s another underlying cause.
Research showed that women who experienced ICP had a higher chance of developing liver and bile duct disorders later in life. Conditions such as hepatitis C, long-term hepatitis, liver scarring or cirrhosis, and gallstones or inflammation of the bile duct were found more commonly in these women compared to women who didn’t have ICP during pregnancy.
When it comes to their children, kids born from mothers with ICP may have a higher likelihood to develop obesity and unhealthy levels of fat in their blood when they turn 16. Lastly, it’s also important to know that if a woman had ICP in her previous pregnancy, there’s a high chance (60 to 70 percent) that it may happen again in her future pregnancies.
Possible Complications When Diagnosed with Pregnancy Intrahepatic Cholestasis
Intrahepatic cholestasis of pregnancy, or ICP, is a condition that poses significant risks to the fetus, and is known to be one of the dangerous factors for sudden fetal demise. ICP is also linked to an increased risk of problematic pregnancy outcomes. This happens because the mother’s bile acids can cross the placenta, accumulate in the fetus and the amniotic fluid, and cause harmful complications.
A comprehensive analysis carried out by Ovadia and his colleagues, which included 23 different studies and compared the results of pregnant women with ICP with healthy pregnant women, revealed that ICP is associated with increased fetal complications. The complications include:
- Sudden fetal death inside the uterus
- Amniotic fluid stained with meconium, a newborn baby’s first feces
- Spontaneous preterm birth
- Iatrogenic preterm birth, or birth prematurely triggered by medical treatment
- Admission of the newborn into an ICU
In women experiencing ICP, bile acids from the mother can pass through the placenta into the fetus and amniotic fluid, causing these complications. The exact reason is not known, but it may be due to bile acid accumulation in the uterine muscle tissue, resulting in increased activity of the uterus. This can lead to preterm labor, which is more common in women with ICP.
Of all the complications, sudden fetal death caused by ICP is the most worrisome. The reason for fetal death is not clearly understood, but it could be due to the harmful effects of bile acids on the fetal heart, causing irregular heartbeat and spasms in the placental blood vessels. This could result in the fetus being deprived of oxygen-rich blood from the mother, thereby causing asphyxia. The risk of fetal death escalates with high levels of bile acids, especially when bile acid levels exceed 100 micromol/L.
Preventing Pregnancy Intrahepatic Cholestasis
In simple terms, intrahepatic cholestasis of pregnancy (ICP) is a condition that slows or stops the normal flow of bile in the liver during pregnancy, which can lead to itching and potentially complications for mother and baby. Women who have had ICP in the past may experience a flare-up if they take medications that contain estrogen, like some birth control pills. Therefore, if it’s possible, these women should avoid taking birth control pills that contain estrogen or use the lowest dose available.
Because these women are more likely to have ICP again in future pregnancies, it’s very important for them to be closely monitored by their healthcare professionals when they are pregnant. This helps in early detection and management of this condition, reducing any potential risks to both mother and baby.
