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.

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 membranes and in women with hypertensive disorders, 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.

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.