Intrahepatic Cholestasis of Pregnancy and Associated Adverse Pregnancy and Fetal Outcomes

Abstract

Intrahepatic cholestasis of pregnancy (ICP) is a common liver disease, with incidence rates of 0.4% to 15%. Intrahepatic cholestasis of pregnancy is characterized by unexplained pruritus, classically of the palms and soles, with elevated bile acids or transaminases in the late second or third trimester of pregnancy. Adverse fetal outcomes include spontaneous preterm birth, antenatal passage of meconium, and stillbirth. In a nationwide cohort of singleton births in Sweden, between 1997 and 2009, the prevalence of ICP and association with adverse pregnancy and fetal outcomes were assessed. The Swedish Medical Birth Register listed 1,213,668 singleton deliveries occurring in 1997 to 2009. Covariate data were maternal age at delivery, patient’s antenatal body mass index, parity, cigarette smoking, coexisting diseases, preeclampsia, and gestational diabetes. Infant data included small for gestational age, large for gestational age (LGA), macrosomia, postterm pregnancy, moderate and very preterm birth, stillbirth, low Apgar score, and neonatal death. The main outcome measure was stillbirth. Secondary outcomes were gestational diabetes, preeclampsia, preterm birth, neonatal death, low Apgar score, meconium aspiration, LGA, macrosomia, small for gestational age, and mode of labor onset. The risk of adverse pregnancy outcomes was determined in relation to ICP by crude odds ratios (ORs) and adjusted ORs (aORs) with 95% confidence intervals (CIs). Data were analyzed using SAS 9.2. A total of 5477 singleton births were to mothers with ICP. Essential hypertension was present in 1.1% and 0.6% of women with and without ICP, respectively; rates for diabetes mellitus were 1.3% and 0.4%, respectively. Women with ICP had an increased risk of gestational diabetes (aOR, 2.81; 95% CI, 2.32–3.41) and preeclampsia (aOR, 2.62; 95% CI, 2.32–2.78) compared with women without ICP. No increased risks of antepartum bleeding or placental complications (aOR, 0.78; 95% CI, 0.56–1.07) were found. A strong association was apparent between ICP and moderate preterm birth (aOR, 3.30; 95% CI, 3.00–3.63); the risk of very preterm birth was decreased (aOR, 0.47; 95% CI, 0.27–0.81). Women with ICP had a higher risk of undergoing cesarean section (CS; aOR 1.26; 95% CI, 1.13–1.33), specifically emergency CS; no associated risk was seen for elective CS (aOR, 1.04; 95% CI, 0.93–1.16). A strong association was noted between ICP and labor induction (aOR, 11.76; 95% CI, 11.04–12.52). When analysis was restricted to women with spontaneous labor onset, the aOR for emergency CS among women with ICP was 1.25 (95% CI, 1.05–1.50). The highest risk for preterm birth in women with ICP was for iatrogenic preterm birth (aOR, 5.95; 95% CI, 5.23–6.60); the risk for spontaneous preterm birth was only marginally increased (aOR, 1.60; 95% CI, 1.47–1.93). Women with ICP had a significantly reduced risk for postterm delivery (aOR, 0.21; 95% CI, 0.17–0.21). No significant increases were noted in risk of neonatal death (aOR, 0.45; 95% CI, 0.15–1.40) or meconium aspiration (aOR, 1.41; 95% CI, 0.72–2.72). Infants of women with ICP were significantly more likely to have an Apgar score of less than 7 at 5 minutes (aOR, 1.45; 95% CI, 1.14–1.85) and were more often LGA (aOR, 2.27; 95% CI, 2.02–2.55). For deliveries with spontaneous labor, the aOR for Apgar score of less than 7 at 5 minutes for women with ICP was 1.78 (95% CI, 1.19–2.64). Women with ICP who were actively managed were not at an increased risk for stillbirth compared with women without ICP. The association of ICP with gestational diabetes and preeclampsia is important to consider in the diagnostic process for women with ICP to improve clinical management. Further studies of ICP-related morbidity should focus on the shared pathologic mechanisms leading to preeclampsia and gestational diabetes.