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The risk of infant and fetal death by each additional week of expectant management in intrahepatic cholestasis of pregnancy by gestational age

Published:February 13, 2015DOI:https://doi.org/10.1016/j.ajog.2015.02.012

      Objective

      The objective of the study was to characterize the risk of infant and fetal death by each additional week of expectant management vs immediate delivery in pregnancies complicated by cholestasis.

      Study Design

      This was a retrospective cohort study of 1,604,386 singleton, nonanomalous pregnancies of women between 34 and 40 weeks’ gestation with and without intrahepatic cholestasis of pregnancy (ICP) in the state of California during the years of 2005-2008. International Classification of Diseases, 9th version, codes and linked hospital discharge and vital statistics data were utilized. For each week of gestation, the following outcomes were assessed: the risk of stillbirth, the risk of delivery (represented by the risk of infant death at a given week of gestation), and the composite risk of expectant management for 1 additional week. Composite risk combines the risk of stillbirth at this gestational age week plus the risk of infant death if delivered at the subsequent week of gestation.

      Results

      Among women with ICP, the mortality risk of delivery is lower than the risk of expectant management at 36 weeks’ gestation (4.7 vs 19.2 per 10,000). The risk of expectant management remains higher than delivery and continues to rise by week of gestation beyond 36 weeks. The risk of expectant management in women with ICP reaches a nadir at 35 weeks (9.1 per 10,000; 95% confidence interval, 1.4–16.9) and rises at 36 weeks (19.2 per 10,000; 95% confidence interval, 7.6–30.8).

      Conclusion

      Among women with ICP, delivery at 36 weeks’ gestation would reduce the perinatal mortality risk as compared with expectant management. For later diagnoses, this would also be true at gestational ages beyond 36 weeks. Timing of delivery must take into account both the reduction in stillbirth risk balanced with the morbidities associated with preterm delivery.

      Key words

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      Linked Article

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          The recent publication by Puljic et al1 on the management of intrahepatic cholestasis of pregnancy (ICP), while stimulating, has various major issues that invalidate the results and conclusions.
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          We read with great interest the article by Puljic et al.1 The authors demonstrated that intervention at 37 weeks reduced the risk of either neonatal or intrauterine fetal deaths. Unfortunately the authors did not distinguish between mild and severe intrahepatic cholestasis of pregnancy. Severe form (bile acids >40) has been shown to have an increased risk of adverse perinatal outcome, which is difficult to prevent with antenatal fetal surveillance.2,3,4 Meconium has been shown to be an independent risk factor for adverse fetal outcomes (odds ratio 7.3) in these patients.
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          We thank Professor Wensink for his letter to the editor regarding our article investigating the risk of stillbirth in patients with intrahepatic cholestasis of pregnancy (ICP).1 Based on our retrospective cohort study, we concluded that ICP was associated with an increased risk of stillbirth as compared to pregnancies without ICP. Furthermore, we found that delivery at 36 weeks’ gestation would minimize overall perinatal mortality. Professor Wensink’s main objections to our study were in regards to the validity of our composite mortality calculation, the fact that we claim that there is a lack of evidence regarding specific bile acid levels and correspondent fetal outcomes, and lastly, the turnaround time of bile acid results.
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