Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates

Abstract

Intrahepatic cholestasis of pregnancy (ICP), characterized by pruritus in the second half of pregnancy, entails an increased risk to the fetus. This study was designed to determine the incidence and fetal complication rates in ICP, and to define groups at increased risk. In an prospective cohort study conducted between February 1, 1999, and January 31, 2002, all 45,485 pregnancies in a defined region of Sweden (Västra Götaland) were screened for ICP, defined as otherwise unexplained pruritus of pregnancy in combination with fasting serum bile acid levels >10 mol/L. Pruritus was reported by 937 (2.1%) women, and ICP was diagnosed in 693 (1.5%). Simple logistic regression analyses showed that the probability of fetal complications (spontaneous preterm deliveries, asphyxial events, and meconium staining of amniotic fluid, placenta, and membranes) increased by 1%-2% per additional mol/L of serum bile acids. Complementary analyses showed that fetal complications did not arise until bile acid levels were >40 mol/L. Gallstone disease and a family history of ICP were significantly (P < .001) more prevalent in the group of ICP patients with higher bile acid levels. In conclusion, we found an incidence of ICP in our population of 1.5%. From complication rates recorded prospectively, we could define a mild (81%) and a severe (19%) form of ICP, the latter with bile acid levels >40 mol/L. No increase in fetal risk was detected in ICP patients with bile acid levels < 40 mol/L, and we propose that these women be managed expectantly, which would significantly reduce the costs of medical care. I ntrahepatic cholestasis of pregnancy (ICP) is a condition characterized by pruritus in the second half of pregnancy. It persists until delivery, after which it ceases promptly. A genetic background is suggested by family clustering and demographic variations, with the highest incidences reported from Chile-Bolivia (6%-27%) and Sweden (1-1.5%). 1 ICP is associated with an increased risk of preterm delivery in 19%-60%, 2-5 intrapartum fetal distress in 22%-41%, and intrauterine fetal death (IUFD) in 0.75%-1.6% of the affected pregnancies. [3][4][5][6] The diagnostic criteria for ICP have varied over time in different reports, making complication rates difficult to compare. When, in addition to pruritus, clinical jaundice was used to define ICP, higher fetal complication rates were reported than when diagnosis was based only on elevated bile acid and transaminase levels. 2,3,6 -8 The Swedish ICP incidence figure is taken from a study using only pruritus in pregnancy as the inclusion criterion, and that study did not report increased fetal risk associated with ICP. 9 Nowadays, elevation of serum bile acids is considered to be the most appropriate laboratory parameter for diagnosis of the condition. 8,10 -12 It is reasonable to believe that ICP constitutes a continuum, ranging from light to severe forms, but there has been an absence of algorithms to identify pregnancies entailing increased fetal risk. The aims of this prospective cohort stu...

The prevalence of intrahepatic cholestasis of pregnancy in a primarily Latina Los Angeles population

“…Current literature has not uniformly agreed upon the criteria for ICP. Most studies use the combination of pruritus and elevated serum bile acid concentration 4,25 as the defining criteria for ICP; however, the lower threshold for serum bile acid concentration and criteria for pruritus differ. In addition, other studies require the use of additional biochemical markers such as elevated transaminases as inclusion criteria for ICP.…”

“…Authors from Scandinavian countries report a prevalence of approximately 2%. 4,9 Rates from France and the United Kingdom are less than 1%. 10 The prevalence of ICP in the United States has been reported from two studies to be between 0.001 and 0.32%.…”

“…The most commonly accepted laboratory criterion for ICP is an elevated total serum bile acid concentration. 4 The exact pathophysiologic mechanisms leading to poor obstetric and fetal outcomes seen in ICP are unknown; however, dysfunctional serum bile acid metabolism may play a central role. Higher total serum bile acid levels are associated with higher rates of fetal complications, although adverse outcomes have been reported in patients receiving treatment that effectively lowered total serum bile acids to normal.…”

Cholestasis of Pregnancy : A Prospective Study

“…Persistent abnormalities should prompt reconsideration of other underlying chronic liver diseases like primary biliary cirrhosis, primary sclerosing cholangitis or chronic hepatitis C. ICP recurs during subsequent pregnancies in 45-70% cases with varying severity of recurrent episodes. ICP increases the risk of preterm delivery (up to 19-60%), meconium staining of amniotic fluid (up to 27%), fetal bradycardia (up to 14%), fetal distress (22-41%) and fetal loss (0.4-4.1%), particularly when associated with fasting serum bile acid levels > 40 μmol/L [5]. The pathogenesis of fetal complications is still poorly understood, although a role for bile acids or toxic metabolites of bile acids has been suggested.…”

Intrahepatic cholestasis of pregnancy — A heterogeneous group of pregnancy‐related disorders?†‡

“…1 ICP was responsible for 21% of cases of jaundice evolving during pregnancy in a series from Switzerland in which viral hepatitis (42%) and bile duct obstruction by gallstones (6%) represented the major causes of jaundice not specific to pregnancy. 2 ICP increases the risk of preterm delivery (19%-60%), fetal distress (22%-41%) [3][4][5][6][7] and fetal loss (0.4%-1.6%), [3][4][5][6][7][8] particularly when associated with fasting serum bile acid levels Ͼ40 mol/L. 8 ICP is observed in Ͻ0.2% of pregnancies in most areas of Central and Western Europe and North America.…”