부산대학교 도서관

Introduction: Neurodevelopmental delay is hallmark for children with congenital heart defects. Risk factors include industrial contaminants in medical devices, such as cyclohexanone.Hypothesis: To evaluate associations between perioperative cyclohexanone and cyclohexanone metabolites with perioperative biomarkers of brain injury.Methods: From 75 neonates who underwent congenital heart surgery involving cardiopulmonary bypass (CPB), we assayed perioperative serum samples (preoperation, post-CPB, 24 hours postoperation) for cyclohexanone, two cyclohexanone metabolites (trans-1,2- and trans-1,4-cyclohexanediol), and biomarkers of brain injury: glial fibrillary acidic protein (GFAP), neurofilament light (NF-L), and Tau. We calculated the molar sum of cyclohexanone metabolites (Σmetabolites), and at each timepoint we used quantile regression to evaluate differences in median brain injury biomarker concentrations (pg/mL) per doubling in concentration of cyclohexanone or Σmetabolites (ng/mL). We adjusted associations for cyclohexanone assay batch, postnatal age at surgery (days), weight at surgery (kg), The Society of Thoracic Surgeons and The European Association for Cardio-Thoracic Surgery (STAT) mortality risk category, and total duration of CPB (min).Results: In adjusted analyses, a doubling in preoperation cyclohexanone concentration was associated with a 19 pg/mL (95% CI: 3, 35) greater median Tau concentration. Similarly, a doubling in post CPB cyclohexanone was associated with an 88 pg/mL (95% CI: 20, 156) greater median concentration of Tau and 137 pg/mL (95% CI: 54, 220) greater median concentration of NF-L. Associations with Σmetabolites were generally null, though a doubling in post-CPB concentration was associated with a 34.7 pg/mL (95% CI: -0.8, 70) greater NF-L and 54.1 pg/mL (95% CI: 15, 94) greater Tau concentration. Associations with GFAP at all timepoints were null.Conclusions: Perioperative cyclohexanone exposure is associated with worse neurodevelopmental outcomes and in this study, cyclohexanone levels were associated with NF-L and Tau which are measures of axonal damage. Interventions to reduce cyclohexanone exposure may improve long term neurodevelopment.