title: Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in singleton and twin pregnancies.
abstract: OBJECTIVE
  Intrahepatic cholestasis of pregnancy (ICP) is known to be associated with fetal complications. It recently was suggested to be associated possibly with preeclampsia (PET) as well. The objective of this study was to investigate that possibility.
  
  
  METHODS
  The study group included 78 women (54 singleton and 24 twin pregnancies) who had been diagnosed with ICP based on clinical presentation, elevated liver enzymes, and elevated total bile acids (>10 μmol/L). Disease severity was based on total bile acids levels as being severe (>40 μmol/L), moderate (20-40 μmol/L), or mild (10-20 μmol/L). The course of disease was reviewed carefully in each case. The control groups were comprised of apparently healthy women with singleton (n = 200) and twin (n = 100) pregnancies that were drawn randomly from a computerized registry of all the deliveries in our institution during the study period.
  
  
  RESULTS
  The total incidence of PET was significantly higher for the patients with ICP who had singleton and twin pregnancies compared with the control groups (singletons: 7.4% vs 1.5%; P < .05; twins: 33.3% vs 6.2%; P < .05, respectively). The incidence of severe PET was also significantly higher in both singleton (11-fold) and twin (8-fold) pregnancies compared with control subjects. Severe ICP, but not mild ICP, was a major risk factor for PET among women with either singleton or twin pregnancies. The timing of the initial presentation of ICP had no effect on PET incidence rates. Preeclampsia occurred usually 2-4 weeks after the diagnosis of ICP, and proteinuria preceded elevated blood pressure in all cases. Moreover, the total bile acid levels among 33 women who were diagnosed as having PET, but not ICP, were within normal range.
  
  
  CONCLUSIONS
  ICP increases the incidence of PET; severe disease was a major risk factor for preeclampsia. Therefore, we strongly suggest including routine evaluation for preeclampsia in the treatment of women with moderate and severe ICP.
authors.affiliation: Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Medical Center, Tel Aviv, Israel, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Raz
authors.affiliation: Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Medical Center, Tel Aviv, Israel, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Anat
authors.initials: A
authors.lastname: Lavie
authors.affiliation: Clinical Laboratory Services, Lis Maternity Hospital, Tel Aviv Medical Center, Tel Aviv, Israel, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yaffa
authors.initials: Y
authors.lastname: Vered
authors.affiliation: Clinical Laboratory Services, Lis Maternity Hospital, Tel Aviv Medical Center, Tel Aviv, Israel, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ilana
authors.initials: I
authors.lastname: Goldiner
authors.affiliation: Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Medical Center, Tel Aviv, Israel, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Avital
authors.initials: A
authors.lastname: Skornick-Rapaport
authors.affiliation: Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Medical Center, Tel Aviv, Israel, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ysca
authors.initials: Y
authors.lastname: Landsberg Asher
authors.affiliation: Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Medical Center, Tel Aviv, Israel, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Sharon
authors.initials: S
authors.lastname: Maslovitz
authors.affiliation: Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Medical Center, Tel Aviv, Israel, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ishai
authors.initials: I
authors.lastname: Levin
authors.affiliation: Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Medical Center, Tel Aviv, Israel, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Lessing
authors.affiliation: Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Medical Center, Tel Aviv, Israel, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kuperminc
authors.affiliation: Department of Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Medical Center, Tel Aviv, Israel, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: elir@tasmc.health.gov.il.
authors.forename: Eli
authors.initials: E
authors.lastname: Rimon
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002780:Cholestasis, Intrahepatic; D015331:Cohort Studies; D005260:Female; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D011225:Pre-Eclampsia / Q000453:epidemiology / Q000209:etiology*; D011247:Pregnancy; D011248:Pregnancy Complications; D059285:Pregnancy, Twin; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index
keywords: bile acid; intrahepatic cholestasis of pregnancy; liver enzyme; preeclampsia; twins