The Mechanical PR Interval in Fetuses of Women With Intrahepatic Cholestasis of Pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is associated with several adverse obstetric outcomes; the risk for fetal death is the most notable, affecting 2% to 4% of ICP pregnancies. Evidence from both animal and human studies suggests that fetal death in ICP results from an acute cardiac event that could be a bile acid effect on cardiomyocyte contractility or electrical conduction. Previous studies in adult populations suggest that prolongation of the PR interval may increase the risk of tachyarrhythmias.This pilot study was designed to determine whether the fetal mechanical PR interval is altered in ICP. Fetal echocardiographic studies were performed for 14 women with ICP and 7 control subjects. Blood samples were taken from all patients and control subjects for liver function tests (measurement of aspartate aminotransferase, alanine aminotransferase, and serum total bile acids). Multivariable linear regression analysis was used to determine the relationship between ICP and the mechanical PR interval, while adjusting for potential confounders.The PR interval was significantly longer in the ICP group compared with the control group (124 vs. 110 milliseconds; P = 0.006). The liver function tests were significantly higher in women with ICP compared with the controls (aspartate aminotransferase [53 vs. 23 IU/L; P = 0.002], alanine aminotransferase [63 vs. 19 IU/L; P = 0.002], and total bile acids [28.3 vs. 6.2 fmol/L; P < 0.001]). Multivariable linear regression showed that patients with ICP had a significant increase in the PR interval of 14 milliseconds (95% confidence interval, 4–24 milliseconds; P = 0.01).These findings demonstrate a significant alteration in the conduction system in fetuses of pregnancies complicated by ICP compared with normal controls. Future studies are needed to investigate the possibility that measurement of the PR interval may help predict the risk of fetal death and other adverse fetal outcomes in ICP.