Risks of Intrahepatic Cholestasis of Pregnancy (ICP)
What are the risks of ICP?

Overview

  • The few maternal risks of cholestasis include increased risks of developing preeclampsia or gestational diabetes. Prior studies have shown an increased risk for maternal bleeding at delivery but this risk is largely reduced by treatment of cholestasis.
  • Risks to the fetus include meconium passage, respiratory distress, preterm labor and stillbirth.
  • These risks mostly increase as bile levels become more severe (over 40) or in cases in which cholestasis is diagnosed earlier in pregnancy.

Meconium Staining

The first stool produced by a baby after birth is known as meconium. Meconium passage can occur during pregnancy. It was previously thought to be due to fetal distress but it is now recognized that it can occur as a normal part of the labor and birthing process. Usually meconium passage occurs in pregnancies that are past 40 weeks of gestation. However, cholestasis increases the risk of meconium passage earlier in pregnancy.  Recent studies have shown that meconium passage is around 16-18% in pregnancies complicated by cholestasis. 

The reason that meconium passage in cholestasis occurs earlier is thought to be due to increased motility of the fetal colon due to the bile acid elevations. Meconium passage is more common in ICP pregnancies with higher bile acids levels or where cholestasis was diagnosed early in the pregnancy (prior to 24-28 weeks). 

At the time of birth, meconium can be inhaled into the lungs and cause a respiratory distress in the infant called meconium aspiration syndrome.  This syndrome is luckily very rare.

Preterm Labor and Delivery

Preterm labor and preterm birth are common in pregnant patients with Intrahepatic Cholestasis of Pregnancy. This is due to the fact that the high levels of bile acids make the uterus more sensitive to the hormone oxytocin. Oxytocin is a natural hormone produced by our bodies that causes uterine contractions. 

Preterm labor occurs naturally in about 20-40% of ICP pregnancies. The risk also increases as bile acid levels increase. While it is considered a part of active management to induce early in most cases of cholestasis, delivering the baby too soon comes with considerable risks. Signs of preterm labor include cramping and early contractions and if these signs are present, you should call your doctor for evaluation. 

Respiratory Distress after birth

Cholestasis babies are at about a 3 times higher risk of having respiratory issues at birth than babies born to patients without cholestasis at the same gestational age. Recent studies have shown that elevated bile acid levels can affect the proper production of a chemical known as surfactant which helps babies to breathe after birth. The respiratory distress is thought to be due more to this alteration from the cholestasis rather than simply due to premature delivery. 

This risk seems to be increased more in cases in which cholestasis was diagnosed earlier in pregnancy and in cases with higher bile acid levels. There is a higher chance of needing admission to a NICU or Special Care Unit after birth and delivery should be planned at a hospital that can manage these infants. 

Maternal hemorrhage

Older studies prior to active treatment of patients diagnosed with ICP showed a high risk of maternal hemorrhage following delivery. This was speculated to be due to decreased vitamin K absorption, which is associated with cholestasis of pregnancy. Newer studies since the condition has been actively treated have not shown any increase in risk of hemorrhage. Vitamin K supplementation is no longer recommended routinely in pregnancies complicated by cholestasis without any other evidence of increased risk of bleeding (easy bruising, abnormal blood clotting testing). 

Stillbirth (Intrauterine Fetal Demise)

Many prior studies have shown that the risk of stillbirth is increased in a pregnancy that is complicated by cholestasis. Most of these stillbirths occur after 37 weeks of pregnancy. 

The exact cause of the stillbirths is unknown but it is thought to be due to either an irregular fetal heart rhythm or a constriction of blood flow in the placenta that is caused by the elevated bile acid levels. Stillbirth is usually a sudden event that cannot always be predicted by fetal monitoring. 

A recent study looked at over 5000 cholestasis pregnancies and showed that the risk of stillbirth increases as bile acid levels increase. These findings were reassuring for patients with low bile acid levels as the risks of stillbirth were the same in cholestasis pregnancies as normal pregnancies if bile acid levels remained below 100.

The risk of stillbirth was noted to be: 0.13% if bile acids are below 40; 0.28% for bile acids 40-99; and 3.44% for bile acids above 100. 

This study did have a large portion of the patients delivered by 38 weeks of gestation and it is unknown if this early delivery was part of the reason that the stillbirth risks were low in this study. Even with a proportion of the patients being delivered early, this is reassuring information that lower bile acid levels do not significantly increase the risk of stillbirth. 

Preeclampsia and Gestational Diabetes

Preeclampsia is a syndrome of pregnancy in which blood pressure becomes elevated. It is categorized by elevated blood pressure as well as elevated protein levels in the urine. Preeclampsia can lead to a condition called eclampsia which involves seizures in pregnancy and can be life threatening. 

Patients with cholestasis are at approximately a 5 times increased risk of developing preeclampsia. This risk increases with more elevated bile acid levels and is most common when bile acid levels are over 40 micromol/L. The finding of protein in the urine seems to occur prior to the elevation of blood pressures in most cases. 

Gestational Diabetes is a condition where blood sugars become elevated in pregnancy. This condition is significantly more common in patients with ICP. In studies, the severity of the cholestasis does not seem to matter as even mild cases of ICP have an increased risk of developing gestational diabetes. All pregnancies routinely have a screening test for gestational diabetes performed around 24-28 weeks of gestation.