Obstetric cholestasis: outcome with active management

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Abstract

Objective: Conservative management of intrahepatic obstetric cholestasis is associated with a high stillbirth rate despite monitoring of fetal well-being with non-stress test and amniotic fluid volume assessment. Most cases of stillbirth are associated with meconium passage. We prospectively evaluated the effect of a management protocol inclusive of surveillance for presence of meconium and induction of labor at 37 weeks. Study Design: Between January 1989 and December 1997, all women with obstetric cholestasis underwent transcervical amnioscopy after 36 weeks for assessment of amniotic fluid color, in addition to standard monitoring of fetal well-being (semi-weekly non-stress test and amniotic fluid volume determinations). Amniocentesis for fetal lung maturity and amniotic fluid color assessment was performed before 36 weeks in severe cases. Labor was induced at 37 weeks or earlier in the presence of non-reassuring fetal testing, meconium, or severe maternal symptoms unresponsive to therapy with mature fetal lungs. The obstetric outcome of the group with cholestasis was compared with that of the general obstetric population at our Institution during the study period. The rate of fetal death in the study group was compared with that of series published within the last 20 years, which used expectancy and conventional monitoring of fetal well-being. Statistical analysis utilized Fisher’s exact test, Chi-square, and Student’s t-test with P value <0.05 or an odds ratio (OR) with 95% confidence interval (CI) not inclusive of the unity considered significant. Results: Obstetric cholestasis was diagnosed in 206/20,815 pregnant women (1%) at a median gestational age of 34 weeks (range 20–40). Delivery was prompted by non-reassuring fetal testing in four cases (2%). Meconium passage was documented in 33 cases (16%), in 11 of which before onset of labor and in 10 before 37 weeks. The rate of meconium passage before 37 weeks (17.9 versus 2.9%, OR=7.3; 95% CI 3.3, 16.0) was significantly higher in obstetric cholestasis than in the general obstetric population, whereas the cesarean section rate was similar in the two groups (15.1 versus 16.0%, OR=0.9; 95% CI 0.6, 1.4). The fetal death rate was significantly lower in the group managed with the current strategy than in the published series of obstetric cholestasis (0/218 versus 14/888, P=0.045). Conclusion: In pregnancies complicated by obstetric cholestasis, a protocol inclusive of search for meconium and elective delivery at 37 weeks, in addition to standard monitoring of fetal well-being, can significantly reduce the stillbirth rate without increasing the cesarean delivery rate.

Introduction

Obstetric cholestasis is the most common liver disease of pregnancy, and is characterized by intrahepatic cholestasis triggered by environmental, infectious and hormonal factors in genetically predisposed women. This disorder is associated with increased risk of stillbirth and perinatal death [1]. The mechanism underlying cholestasis-associated stillbirths is unknown and conventional monitoring of fetal well-being does not predict most cases of fetal death, which may occur within 24 h of a reactive non-stress test [2], [3], [4], [5]. Indeed, most stillbirths are not preceded by signs of chronic hypoxia, such as oligohydramnios or fetal growth restriction, or by acute fetal hypoxemia, as manifested by fetal heart rate changes. Interestingly, meconium passage has been reported in 86% of cholestasis-associated fetal deaths [3], [6], [7], [8], [9]. The mechanism underlying such association has not been elucidated. Most fetal deaths occur towards the end of pregnancy, and some series suggest an association between severity of maternal symptoms and poor fetal outcome [2].

The aim of this study was to evaluate whether a management strategy inclusive of search for presence of meconium and elective delivery at 37 weeks, in addition to standard monitoring of fetal well-being, could decrease the stillbirth rate in obstetric cholestasis compared with that of series published in the last 20 years.

Section snippets

Materials and methods

During the period January 1989 to December 1997 all pregnant women with a diagnosis of obstetric cholestasis at our Department of Obstetrics and Gynecology were prospectively followed with a consistent protocol. The diagnosis of obstetric cholestasis was made in the presence of severe generalized pruritus with onset during the second or third trimester of pregnancy, persisting up to the time of delivery and disappearing after delivery, without skin or medical conditions known to be associated

Results

During the study period, obstetric cholestasis was diagnosed in 206/20,815 pregnant women (1%), including 194 singleton and 12 twin pregnancies. Table 1 displays the demographic and obstetric characteristics of the study population. The median (range) highest serum aspartate aminotransferase after diagnosis was 87 mg/dl (11–1127, n.v. 8–41 mg/dl), serum alanine aminotransferase was 159 mg/dl (8–1734, n.v. 8–41 mg/dl), and bile acids level 16.5 μmol/l (0.6–200, n.v. <6 μmol/l). In 26 cases the serum

Comment

The risk of fetal mortality associated with gestational cholestasis is considerable [1] and traditional monitoring of fetal well-being has not been shown to prevent cholestasis-associated stillbirths. Even series in which patients with gestational cholestasis were hospitalized and underwent daily fetal monitoring reported cases of stillbirth with reassuring fetal testing as recently as 7 h before fetal death [4], [9]. Our experience represents one of the largest series ever published, and it

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