Cord blood troponin I levels: biomarker evidence of fetal cardiac injury in intrahepatic cholestasis of pregnancy

Abstract

BackgroundIntrahepatic cholestasis of pregnancy (ICP) has been linked to sudden stillbirth. The suddenness of the stillbirths in these cases have led clinicians to suspect that the pathogenesis of stillbirth in women with ICP is not related to asphyxia but rather to an undefined etiology. One leading hypothesis relates certain bile acid metabolites to myocardial injury. ObjectiveThe purpose of this study is to determine whether cord blood troponin I levels are increased in fetuses born to mothers with the diagnosis of ICP. Study DesignA prospective case-control study was performed at a single institution between 2017-2019 which enrolled 87 pregnant patients with the diagnosis of ICP (total bile acids (TBA) ≥10μmol/L) as cases and 122 randomly selected pregnant patients (asymptomatic with intrapartum total bile acids <10μmol/L) as controls. Cord blood troponin I collection was performed at delivery in both groups using a commercially available chemiluminescent immunoassay. Values ≤0.04ng/ml were considered as negative. Values >0.04ng/ml were considered positive. The primary outcome was the presence of elevated troponin levels in both cases and controls as a surrogate marker for cardiac status. Our secondary outcomes included. NICU stay, low APGAR scores, neonatal acidosis and hypoxia represented by cord blood pH and base excess levels at time of birth. Chi square and t-tests were performed to compare social and obstetrical variables. A p value of <0.05 was considered significant. A stratification by TBA range of <40μmol/L, 40-100μmol/L, and >100μmol/L was performed to assess the relationship between the different severities of ICP (by risk of fetal demise, with TBA of >100μmol/L considered most at risk) and the likelihood of a positive troponin I result. Finally, a logistic regression analysis was performed in order to determine if levels of ≥10μmol/L were associated with elevated troponin levels. ResultsThe mean gestational age of at delivery was 38.96±1.47 and 37.71±1.59 weeks of gestation in the controls and cases respectively (p value <0.001). The mean TBA value for was 5.2±1.28ng/ml and 43.2±40.62ng/ml in the controls and cases respectively (p value <0.001). Cord blood troponin I was positive in 15 of 122 (12.30%) controls and in 20 of 87 (22.99%) cases. (p<0.001). When further stratified by TBA levels of <40, 40-100, and >100, we found a positive correlation between higher TBA levels and a positive troponin I test (p=0.002). When controlling for gestational age at delivery, maternal age and BMI, higher TBA levels were associated with a positive troponin I level (aOR 1.015 95% CI 1.004,1.026). ConclusionElevated troponin I was more likely to be found in patients with ICP than those without ICP. When stratified by TBA levels, a positive troponin I level was more likely to be found with higher levels of TBA. Additionally, as TBA levels increased, they were more likely to be associated with a positive troponin I level. Though there were no stillbirths in our cohort, our findings suggest a potential relationship between cardiac injury and high levels of TBA demonstrated by the presence of elevated troponin I levels in cord blood at the time of birth.