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

Published:August 08, 2015DOI:https://doi.org/10.1016/j.ajog.2015.08.007
      To the Editors:
      We welcomed the evidence-based report by Raz et al
      • Raz Y.
      • Lavie A.
      • Vered Y.
      • Goldiner I.
      • Skornick-Rapaport A.
      • Landesber Asher Y.
      • Maslovitz S.
      • Levin I.
      • Lessing J.B.
      • Kupermic M.J.
      • Rimon E.
      Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in singleton and twin pregnancies.
      describing a relationship between intrahepatic cholestasis of pregnancy (ICP) and preeclampsia. They tested a plausible hypothesis that elevated serum bile acids (the hallmark of ICP) are a risk for preeclampsia. Common inflammatory processes may link these 2 obstetric conditions.
      • Staff A.C.
      • Redman C.W.G.
      Preeclampsia, the decidual battle ground and future maternal cardiovascular disease.
      • Allen K.
      • Jaeschke H.
      • Copple B.L.
      Bile acids induce inflammatory genes in hepatocytes.
      The authors used 2 study groups: (1) gravid women with uncomplicated and ICP-affected pregnancies whose information was culled from a retrospective cohort to identify the targeted association and (2) an important smaller prospective group to confirm that bile acids are not elevated in pregnancies that are affected by preeclampsia. In contrast to the authors’ evidence-based primary conclusion, in the absence of data, the death of 1 twin in their study group was ascribed to ICP-related adverse perinatal outcome. As an alternate explanation, we suggest that the fetal death in this study may be related to the 18% discrepant growth between the female twins. To support the assertion that the stillbirth was associated with ICP, the authors cite a report of alleged similar unexplained stillbirths.
      • Lee R.H.
      • Incerpt M.H.
      • Miller D.A.
      • Pathk B.
      • Goodwin B.
      Sudden fetal death in intrahepatic cholestasis of pregnancy.
      However, rather than identify ICP as a cause for unexplained stillbirth, this cited report describes 32- and 34-week gestations with abnormal intrapartum fetal heart tracings that continued for >30 minutes before fetal death occurred. It is certainly possible that elevated bile acids were directly related to the fetal heart rate abnormalities that were documented in the article referenced by the authors. However, we would contend that these intrapartum deaths should not be described as unexplained stillbirths attributed to ICP.

      References

        • Raz Y.
        • Lavie A.
        • Vered Y.
        • Goldiner I.
        • Skornick-Rapaport A.
        • Landesber Asher Y.
        • Maslovitz S.
        • Levin I.
        • Lessing J.B.
        • Kupermic M.J.
        • Rimon E.
        Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in singleton and twin pregnancies.
        Am J Obstet Gynecol. 2015; 213: 395.e1-395.e8
        • Staff A.C.
        • Redman C.W.G.
        Preeclampsia, the decidual battle ground and future maternal cardiovascular disease.
        Placenta. 2014; : S26-S41
        • Allen K.
        • Jaeschke H.
        • Copple B.L.
        Bile acids induce inflammatory genes in hepatocytes.
        Am J Pathol. 2011; 178: 175-186
        • Lee R.H.
        • Incerpt M.H.
        • Miller D.A.
        • Pathk B.
        • Goodwin B.
        Sudden fetal death in intrahepatic cholestasis of pregnancy.
        Obstet Gynecol. 2009; 113: 528-531

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