You are a helpful, respectful, and honest assistant. Always answer as helpfully as possible, while being safe. Your answers should not include any harmful, unethical, racist, sexist, toxic, dangerous, or illegal content. Please ensure that your responses are socially unbiased and positive in nature. If a question does not make any sense or is not factually coherent, explain why instead of answering something not correct. If you don't know the answer to a question, please don't share false information.
What is Intrahepatic cholestasis of pregnancy and explain in detail?
Intrahepatic cholestasis of pregnancy (ICP), also known as obstetric cholestasis, cholestasis of pregnancy, jaundice of pregnancy, and prurigo gravidarum, is a medical condition in which cholestasis occurs during pregnancy. It typically presents with itching and can lead to complications for both mother and baby.
Pruritus (itching) is a common symptom of pregnancy, affecting around 23% of women. The majority of times, itching is a minor annoyance caused by changes to the skin, especially that of the abdomen. However, there are instances when itching may be a symptom of ICP. Although typically noticed on the palms of the hands and the soles of the feet, the itching can occur anywhere on the body.
ICP occurs most commonly in the third trimester, but can begin at any time during the pregnancy.

Signs and symptoms
Most women with this condition present in the third trimester (although it can present as early as seven weeks) with itching without a rash. Typically, the itching is localized to the palms of the hands and soles of the feet, but can be anywhere on the body.
Hallmarks of ICP include the following symptoms:Most common:

Itching, in particular but not limited to that of the palms of the hands and soles of the feet, without presence of a rash
Itching that is more noticeable in the evening
Darker urineLess common:

Lighter stools
Increased clotting time (due to possibly associated vitamin K deficiency)
Fatigue
Increased nausea
Decrease in appetite
Jaundice (less than 10% of women)
Upper right quadrant painNot all ICP sufferers have all of the above symptoms.

Mechanism
The causes of intrahepatic cholestasis of pregnancy are still not fully understood, but are thought to be caused through a combination of genetics, hormones and environment. Hormones, environmental and genetic factors are all thought to contribute to the condition.
ICP commonly occurs in the third trimester at the time when hormone levels are at their highest.
Twin and triplet pregnancies, which are associated with higher hormone levels, show a higher incidence of ICP.
ICP resolves quickly after delivery, when placental hormone production ceases.
Older high-dose estrogen oral contraceptive pills could cause features of ICP.

Estrogens
Estrogens, and particularly glucuronides such as estradiol-17β-D-glucuronide, have been shown to cause cholestasis in animal studies, by reducing bile acid uptake by hepatocytes.

Progesterone
Treatment with progesterone in the third trimester of pregnancy has been shown to be associated with the development of ICP, and levels of metabolites of progesterone, particularly sulfated progesterone, are higher in patients with ICP than unaffected women, suggesting that progesterone may have a bigger role than estrogen in ICP.

Genetic factors
Clustering of cases of ICP in families, geographic variation in rates of ICP, and recurrence of ICP in 45-70% of subsequent pregnancies all suggest a genetic component to the disease. Genetic mutations in the hepatocellular transport protein ABCB4 (MDR3), which controls secretion of phosphatidylcholine into bile, have been found in cases of ICP.Genetic mutations affecting hepatic bile salt transport molecules have also been found in patients with progressive familial intrahepatic cholestasis. It has been found that mothers of patients with this disease have a higher incidence of ICP, suggesting that heterozygote carriers of these mutations are also predisposed to ICP.In addition to genetic changes to bile salt transport molecules, high levels of estrogen glucuronides have been shown to inhibit the bile salt export pump (BSEP) ABCB11, and high levels of progesterone to inhibit the ABCB4 (MDR3) phospholipid transporter.Consequently, both genetic mutations in hepatocyte proteins involved in bile secretion together with inhibition of those proteins by high levels of hormone metabolites in pregnancy may have roles in the pathogenesis of ICP.

Environmental factors
A number of features of ICP suggest that environmental factors also have a role in the disease:

It has been reported that the incidence of ICP is higher in winter than summer.
The incidence of ICP in Chile has dropped from 14% of pregnancies before 1975 to 4% in 2016.
ICP recurs in between 60% and 90% of subsequent pregnancies.
Low serum selenium levels have been linked to ICP, although the role of selenium in bile secretion is not known.

Diagnosis
ICP is diagnosed by blood tests including a serum bile acid test and liver function test. While most pregnant women experience some itch from time to time, itching without a visible rash, or persistent or extensive itch symptoms should be reported to the midwife or obstetrician. It is important to note that as the level of itch does not correlate with bile acid levels (shown to be the most likely cause of stillbirth in ICP), the itch in ICP can range from being mild to severe.To obtain a diagnosis of ICP, a liver function test and a serum bile acid test should be requested. Although the ALT level may be raised, 20% of women with ICP will always have a normal LFT test result