Intrahepatic Cholestasis of Pregnancy (ICP)

What is ICP?

Intrahepatic cholestasis of pregnancy (ICP) refers to a liver condition that usually develops during the second and third trimester. ICP is characterized by pruritus and also an elevation in serum bile acid concentrations and may result a risk for stillbirth and prematurity. The puritus normally starts on the palms and the soles of the feet and is worse at night.

What causes ICP?

The cause of ICP is unknown, but current research suggests genetic, hormonal, and environmental factors.

In some ICP patients, a particular gene mutation has been detected. However, the genetic basis of ICP is complex.

From some research, the disease is seen more commonly in the colder months in Chile and Scandinavia for unknown reasons. In Europe, about 0.2-2.4% of pregnant women will get the condition; in South America ICP is more common. In China, Sichuan and Shanghai have higher rates of ICP than in other cities.

Estrogen is one of the reasons known to cause cholestasis. ICP therefore typically develops in late pregnancy and in women carrying twins or triplets because the serum concentrations of estrogen is higher in these situations.

The administration of progesterone may also be a risk factor for ICP. It is recommended that progesterone treatment be avoided in pregnant women with a previous history of ICP.

What are the symptoms of ICP and how can it be diagnosed?

Symptoms include:

  • Intolerable itching start from Palm and soles of feet(result Loss of sleep & Loss of appetite)
  • Dark urine or pale stools (less common)
  • Abdominal pain (uncommon)
  • In same cases, jaundice occurs after the onset of itching
  • Nausea

A diagnosis of ICP is based on the presence of pruritus associated with elevated bile acid levels above the normal range. As bile acids are not part of a routine liver function test (LFT), this test must be specifically requested by your doctor. Your doctor may also need you to undergo a routine live function test (LFT). If the LFT test is normal, it doesn’t mean you don’t have ICP, because serum bile acid levels typically rise before liver enzymes increase.

What are the risks associated with ICP?

ICP heightens the risk of infant stillbirth (intrauterine death of the baby), meconium-stained amniotic fluid, premature (early) labor, fetal distress (being unwell), and an increased risk for neonatal respiratory distress syndrome (which appears to be associated with bile acids entering the lungs).

The most concerning issue is the risk of spontaneous fetal death which appears to increase with higher bile acid levels and with advancing gestational age. Except for other causes for stillbirth (like preeclampsia, diabetes, IUGI etc.), the rate of stillbirth after 37 weeks of pregnancy caused by ICP is approximately 1.2%. The pathophysiology of fetal death in ICP is poorly understood, but may be related to the sudden development of a fetal arrhythmia or vasospasm of the placental chorionic surface vessels induced by high levels of bile acids. Coexistent pregnancy complications (such as gestational diabetes, preeclampsia) may also play a role. The risk for bleeding (hemorrhage) is increased in both mother and child, because vitamin K, which is essential for blood clotting, is not absorbed properly.

What’s the treatment of ICP?

ICP cannot be cured. However, treatment for ICP is available and helpful for both mother and baby.

Treatment for ICP focuses on reducing pruritus and preventing maternal and fetal complications. UDCA (ursodeoxycholic acid) is considered as the first-line treatment for ICP which is safe both for mother and baby.

This treatment can help improve pruritus, serum bilirubin, aminotransferase and bile salt levels, higher birth weight, and a greater proportion of deliveries at term. And the treatment can usually be stopped until delivery. The only adverse effect may be mild diarrhea in the mother. Several other treatments for ICP may be beneficial in individual patients, which include hydroxyzine, cholestyramine, and S-adenosyl-methionine (SAMe). Discuss with your physicians on use and which treatment is right for you.

The best approach is early delivery, so your doctor may prefer to deliver the baby early (between weeks 37 and 38 of your pregnancy) in order to keep the risk for your baby as low as possible. But the timing should be guided by balancing the risk of fetal death against the potential risks of prematurity. Usually delivery may be after the baby’s lungs are fully developed. It is important to monitor of the baby regularly and closely.

If the total serum bile acid is based on limited data, or concentrations ≥100 micromol/L, your doctor may discuss delivery prior to 36 weeks of gestation. But this early delivery should carefully consider how maternal and fetal benefits of ending the pregnancy outweigh the potential morbidity of prematurity. Discuss this with your doctors.

What does follow-up for ICP after delivery include?

The maternal prognosis in ICP is good. Pruritus usually disappears in the first few days following delivery, accompanied by normalization of serum bile acid concentrations and other liver tests. The patient should be referred to a liver specialist to assess for underlying hepatobiliary diseases if laboratory abnormalities do not return to normal. Liver function and bile acid concentration levels should be checked six to eight weeks after delivery. ICP also tends to recur in subsequent / following pregnancies in 60 to 70 percent. Affected women may be at increased risk for the development of gallstones (60-90%).

ICP has no contraindications in breastfeeding.