Intrahepatic cholestasis of pregnancy and bile acid levels

We read with great interest the study reported by Glantz et al.1 Although the authors should be congratulated on the data collected, we would nevertheless like to comment on their conclusions. Because these researchers had prospectively detected no increase of fetal risk in intrahepatic cholestasis of pregnancy (ICP) patients with bile acid levels less than 40 μmol/L, they proposed to manage these women expectantly to reduce the costs of medical care.1 We offer two reasons why this approach should be treated with caution. First, the pathogenesis of intrauterine fetal death (IUFD) in ICP remains unclear.2 It has only been speculated, and never demonstrated, that bile acids may be the cause of IUFD in ICP. Moreover, it has never been demonstrated that they are solely responsible for IUFD in ICP and that other parameters do not play a role.3 Second, among the three IUFDs that were reported by Glantz et al. during the observation period, one occurred while bile acid levels were less than 40 μmol/L (27 μmol/L).1 Moreover, there was a slight increase in meconium staining of amniotic fluid, placenta, and membranes when bile acid levels were between 10 and 39 μmol/L compared with normal controls. Although not statistically significant, these facts may be clinically significant. As the authors themselves report, "the low incidence of IUFD (0.4%) was due to increased attention devoted to ICP and its symptoms during the study which had led to high rates of induction of labor and planned cesarean section" (25% distributed as follows: 21% when bile acid levels were less than 10 μmol/L, 24% when bile acid levels were between 10 and 39 μmol/L, and 32% when bile acid levels were greater than 40 μmol/L).1 Therefore, why should obstetricians abandon active management, which is currently the only method that could reduce IUFD?4 The policy of active management usefulness has been reinforced recently by the findings of Williamson et al.5 These authors assessed the clinical outcome of 227 ICP patients. Among singleton pregnancies, 20 IUFDs were found. The median gestation at which IUFD occurred was 38 weeks, and only two IUFDs occurred before 37 weeks.5 As compared with the risk of required ventilation for respiratory distress syndrome at an earlier gestation (i.e., 1:557 (0.2%) at 37 weeks and 1:1692 at 38 weeks),6 the arguments weigh in favor of active management. We believe that in the absence of a randomized study, it is not a viable approach to propose to ICP patients with bile acid levels less than 40 μmol/L an expectant management based solely on bile acid levels.7 Loïc Sentilhes M.D.*, Eric Verspyck M.D., Ph.D.*, Horace Roman M.D.*, Loïc Marpeau M.D., Ph.D.*, * Department of Obstetrics and Gynecology, Rouen University Hospital–Charles Nicolle, Rouen, France.