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Abstract

We appreciate the comments made by Rezai et al concerning our publication, Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated with elevated bile acid levels.1Brouwers L. Koster M.P.H. Page-Christiaens G.C.M.L. et al.Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated with elevated bile acid levels.Am J Obstet Gynecol. 2015; 212: 100.e1-100.e7Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar The aim of this study was to investigate the association between bile acid (BA) levels and adverse pregnancy outcomes. The most severe adverse pregnancy outcome was sudden fetal death in 2 cases, both of which occurred in the severe intrahepatic cholestasis of pregnancy (ICP) group, defined as BA of 100 mmol/L or greater. Although we did not specifically report on the presence of risk factors that may have contributed to these deaths, we state and can confirm here that in addition to the ICP, no risk factors or predictive findings for perinatal mortality in these women were present, and despite intensive monitoring in these patients, both fetal deaths occurred unexpectedly. We therefore concluded that in these cases, the only factor present that is potentially predictive of fetal death was a marked increase in BA levels (119 mmol/L and 199 mmol/L). We acknowledge the fact that late preterm delivery has its downsides and have stated in the Comment section that “the possible iatrogenic consequences of late preterm induced labor must be balanced against the probability of the prevention of intrauterine deaths.” In fact, our center actively participated in several multicenter randomized controlled trials within the Dutch Consortium, resulting in a conservative approach between 34 and 37 weeks of gestation in women with preterm premature rupture of membranes2van der Ham D.P. Vijgen S.M. Nijhuis J.G. et al.Induction of labor versus expectant management in women with preterm prelabor rupture of membranes between 34 and 37 weeks: a randomized controlled trial.PloS Med. 2012; 9: e1001208Crossref PubMed Scopus (89) Google Scholar and in women with hypertensive disorders,3Broekuijsen, et al. Delivery versus expectant monitoring for late preterm hypertensive disorders of pregnancy (HYPITAT-II): a multicenter, open label, randomized controlled trial. Am J Obstet Gynecol 210(Suppl, Abstract 2).Google Scholar preventing unnecessary iatrogenic late preterm births. However, in the absence of methods for fetal monitoring in ICP and given its devastating consequences, we propose earlier intervention in a small subset of cases with BA of 100 mmol/L or greater, in line with a recent presentation at the Society for Maternal-Fetal Medicine meeting in San Diego, CA.4Puljic et al. The risk of infant and fetal death by each additional week of expectant management in intrahepatic cholestasis of pregnancy by gestational age. Am J Obstet Gynecol 212(Suppl, Abstract 77).Google Scholar The statement of Rezai et al that spontaneous preterm birth occurred most frequently in the mild ICP group is not correct. We refer to Table 2, in which the spontaneous preterm birth rate is presented in the lower section under the heading, Adverse neonatal outcome, being 2.8% (3 of 108), 3.5% (3 of 86), and 19% (4 of 21) in the mild, moderate, and severe ICP groups, respectively. In the regression analysis, the highest BA levels were associated with spontaneous preterm birth. We hope we have clarified the comments raised by Rezai et al. Intrahepatic cholestasis of pregnancy: maternal and fetal outcomes associated with elevated bile acid levelsAmerican Journal of Obstetrics & GynecologyVol. 213Issue 1PreviewWe read with interest the retrospective review of intrahepatic cholestasis of pregnancy (ICP) by Brouwers et al.1 During the study period, to avoid unexplained term stillbirth, the standard of care for ICP-affected pregnancies included active management to deliver infants as early as 37 weeks of gestational age (GA). However, despite routine implementation of active management, 2 fetal deaths occurred in the group affected by severe ICP. Regrettably, the reader is not provided with any information to consider confounders that may have contributed to the perinatal mortality such as fetal gestational age, maternal cardiovascular disease, or prior cases of intrauterine death or growth restriction. Full-Text PDF