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Obstetrics
Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in singleton and twin pregnancies

Preliminary data were presented at the 61st Annual Scientific Meeting of the Society for Gynecologic Investigation, Florence, Italy, March 26-29, 2014.
https://doi.org/10.1016/j.ajog.2015.05.011Get rights and content

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.

Study Design

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.

Conclusion

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.

Section snippets

Setting

This study was conducted at the Tel Aviv Sourasky Medical Center, which is a tertiary referral center with >11,000 deliveries per year. The study was approved by the Institutional Review Board, which waived informed consent.

Study population

In our institution, pregnant women with elevated liver enzymes and/or pruritus are tested routinely for serum TBA levels. In addition, we perform an investigation to rule out preeclampsia, TORCH infection (Toxoplasmosis, Rubella, Cytomegalovirus, Parvo virus, Herpes virus,

Results

The incidence of ICP in our population, (overall –0.1%; 9 per 10,000 deliveries and 121 per 10,000 deliveries for singleton and twins, respectively) is similar to that reported from Canada.5

A total of 78 women with ICP (54 singleton and 24 twin pregnancies) were included in the study group. The obstetric and demographic characteristics of the women in the study and control groups are presented in Table 1. The maternal age of women with singleton pregnancies and ICP was significantly higher than

Comment

We have demonstrated an increased incidence of preeclampsia and of severe preeclampsia among women with ICP in both singleton and twin pregnancies, compared with control subjects, and a correlation with disease severity. The incidence of preeclampsia in our control groups is similar to that reported by Sibai et al.33, 34 Our results are further supported by a recent study in which women with ICP were more likely to experience preeclampsia than were control subjects (adjusted odds ratio, 2.62).7

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    • Trends in gestational age at delivery for intrahepatic cholestasis of pregnancy and adoption of society guidelines

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      In our adjusted analysis, neonatal outcomes were no worse with advancing GA to 37 weeks in patients with ICP. All patients delivered preterm were significantly more likely than those delivered at term to have another indication prompting delivery, including hypertension, diabetes mellitus, and multiple pregnancy, consistent with data regarding the frequent overlap of ICP with these diagnoses, which may preclude prolonging pregnancy.22 Importantly, the demonstrated effect on NICU admission and adverse neonatal outcomes were observed independently of these comorbid conditions in patients with ICP according to the adjusted analyses performed.

    • Changes in serum total bile acid concentrations are associated with the risk of developing adverse maternal and perinatal outcomes in pregnant Chinese women

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      A prospective population-based case-control study showed that women with severe ICP and singleton pregnancies were at an increased risk of having a preterm delivery (OR = 5.39, 95% CI: 4.17, 6.98) [35]. Raz et al. demonstrated that severe ICP could significantly increase the risk of developing preeclampsia in both singleton and twin pregnancies [36]. However, previous studies on the association between the TBA concentration and the risk of developing AMPO have only been performed in women with ICP.

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    The authors report no conflict of interest.

    Cite this article as: Raz Y, Lavie A, Vered Y, et al. Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in singleton and twin pregnancies. Am J Obstet Gynecol 2015;213:395.e1-8.

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