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Fruit of the Womb
Fruit of the Womb

Intrahepatic Cholestasis of Pregnancy - A Bitch of an Itch

Recently, we had a woman diagnosed late in pregnancy with intrahepatic cholestasis of pregnancy, or obstetric cholestasis (OC). Despite reassuring fetal heart rate testing, the baby died in utero awaiting induction of labor that had been scheduled within 48 hours of diagnosis. As is usually the case in OC, no specific fetal or placental abnormalities were noted at the delivery. The baby had no evidence of growth restriction or infection, but had passed meconium (had a bowel movement) prior to delivery and was found to have aspirated that material into its lungs.

OC is an enigmatic, relatively common, and potentially serious complication of pregnancy, as the aforementioned case illustrates. Most women with this condition present in third trimester with intense itching (pruritus) without a rash. Generally, the itching is localized to the abdomen, legs, palms, and soles, but can be generalized. The itching can be so intense that these women develop excoriations, secondary infections, and even scarring as a result of their scratching.

Although specific criteria for the diagnosis are not agreed upon, the condition is characterized by some degree of hepatic dysfunction, as manifested by elevated levels of serum bile acids and, often, modest elevations of serum transaminases (ALT and AST). Generally, these abnormalities are not more than two- to three-fold normal levels, but more than 90%, if not all, patients with OC will have both bile acid and transaminase abnormalities. Itching is not uncommon in ‘normal’ pregnancy with complaints of the same occurring in about 50% of all gestations (particularly in first trimester and localized to the abdomen), but this is not accompanied by hepatic involvement to the extent that laboratory abnormalities are found early and only about 3% of these women will go on to develop true OC. Cases of OC have been described wherein the laboratory abnormalities did not develop until 15 weeks or more after the “itching” began.

There appears to be a genetic predisposition to the condition. About 0.5-1.0% of Caucasians develop OC, but these figures are doubled in women from Southeast Asia, and certain ethnic subgroups can have even much higher rates. For example, Reyes and colleagues (Ann Intern Med 1978;88:487-93) showed OC affects 5.5% of pregnancies in Chilean Araucanians. Others have also shown that sisters have a 17% coincidence of OC (Eloranta ML, et al., Clin Genet 2001;60:42-5). Recent studies have shown mutations in specific genes, MDR3 (ABCB4) and BSEP (ABCB11), that affect hepatic phospholipid and bile acid transport, respectively, and the presence of these mutations have been correlated with cases of poor fetal outcomes (Schneider G, et al., Hepatology 2007;45:150-8). As a consequence, women with OC seem to have an increased sensitivity to the cholestatic effects of pregnancy hormones, especially estrogens, but how this translates to fetal complications remains unknown. Women with true OC may have a history of “itching” while taking estrogen-containing oral contraceptives.

In the next post, we will go on to discuss maternal and fetal risks of OC, as well as management options…
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