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Published:August 08, 2015DOI:https://doi.org/10.1016/j.ajog.2015.08.006
      We thank Henderson et al for the interest shown in our study and would like to offer our comments in reply.
      In our study, we had 1 case of intrauterine fetal death (IUFD) in a woman with dichorionic diamniotic twins’ pregnancy and severe intrahepatic cholestasis of pregnancy (ICP) at 30 weeks of gestation. The patient had been under observation, which included routine fetal monitoring 3 times per a day, in our Department for 1 week before this event. Importantly, a pathologic fetal heart rate monitoring of the dead fetus was documented several hours after a normal heart monitoring of both twins.
      In their letter, Henderson et al suggest that this case of IUFD may be related to the 18% difference in fetal growth between the fetuses. Being that the accepted definition for growth discrepancy is 20% of the larger twin’s weight (in this case 1675 g) and that the dead fetus weighted 1369 g, which is compatible with the 56th weight percentile for gestational age, both intrauterine growth restriction (IUGR) and discrepancy do not exist in this case. Moreover, although IUGR is associated with increased perinatal death in twins in all gestational ages, growth discordance alone is not.
      • Garite T.J.
      • Clark R.H.
      • Elliott J.P.
      • Thorp J.A.
      Twins and triplets: the effect of plurality and growth on neonatal outcome compared with singleton infants.
      Indeed, as Henderson et al rightfully stated, whether or not ICP is associated with increased risk of fetal death is debatable, but the evidence that supports the true existence of such a connection is accumulating, mostly for singleton pregnancies. Geenes et al
      • Geenes V.
      • Chappell L.C.
      • Seed P.T.
      • Steer P.J.
      • Knight M.
      • Williamson C.
      Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: a prospective population-based case-control study.
      recently showed in their prospective case-control study that women with severe ICP were at increased risk for stillbirth.
      The unpredictable nature of IUFD in pregnancies that are complicated by ICP and reports of abnormal heart tracing in ICP-affected pregnancies led investigators to hypothesize that these cases of IUFD are caused by impaired fetal cardiomyocyte function that resulted in fetal cardiac arrest. Indeed, the bile acid taurocholate was shown to impair the rate of contraction, the synchronicity, and the calcium dynamics of rat cardiomyocytes in a dose dependent manner,
      • Gorelik J.
      • Harding S.E.
      • Shevchuk A.I.
      • et al.
      Taurocholate induces changes in rat cardiomyocyte contraction and calcium dynamics.
      which could result in fetal dysrhythmia and in sudden IUFD.
      In summary, the data in this case of IUFD that included the facts that the woman had severe ICP, that the dead fetus’s monitoring suddenly became pathologic, that there was no evidence of IUGR, and that the autopsy was normal support the occurrence of a cardiac event attributed to ICP.

      References

        • Garite T.J.
        • Clark R.H.
        • Elliott J.P.
        • Thorp J.A.
        Twins and triplets: the effect of plurality and growth on neonatal outcome compared with singleton infants.
        Am J Obstet Gynecol. 2004; 191: 700-707
        • Geenes V.
        • Chappell L.C.
        • Seed P.T.
        • Steer P.J.
        • Knight M.
        • Williamson C.
        Association of severe intrahepatic cholestasis of pregnancy with adverse pregnancy outcomes: a prospective population-based case-control study.
        Hepatology. 2014; 59: 1482-1491
        • Gorelik J.
        • Harding S.E.
        • Shevchuk A.I.
        • et al.
        Taurocholate induces changes in rat cardiomyocyte contraction and calcium dynamics.
        Clin Sci (Lond). 2002; 103: 191-200

      Linked Article

      • Severe intrahepatic cholestasis of pregnancy is a risk factor for preeclampsia in singleton and twin pregnancies
        American Journal of Obstetrics & GynecologyVol. 213Issue 6
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          We welcomed the evidence-based report by Raz et al1 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.2,3 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.
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