Perioperative Brain Damage Biomarkers Predict Neurodevelopmental Delay After Infant Cardiac Surgery: A Multicenter Study.

BACKGROUND: Infants with congenital heart disease are at high risk for neurodevelopmental impairment following cardiac surgery. Brain damage biomarkers may provide insight into perioperative brain injury and neurodevelopmental outcomes. METHODS: Prospective observational study conducted in two pediatric/neonatal cardiac intensive care units in North America and Europe in children undergoing cardiac surgery. Blood samples were obtained preoperatively and at 0, 24, 48, and 72 hours postoperatively to measure glial fibrillary acidic protein, ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), neurofilament light (NFL), and microtubule-associated protein tau (TAU). Neurodevelopment was assessed at 2-years using the Bayley Scales of Infant and Toddler Development, Third Edition, and a postoperative brain magnetic resonance imaging (MRI) was performed. RESULTS: A total of 105 patients were evaluated by at least one study outcome modality (neurodevelopmental follow-up and/or brain MRI), including 61 patients with neurodevelopmental assessment. Despite differences in surgical complexity between centers, neurodevelopmental outcomes and MRI brain injury rates did not differ. All brain damage biomarkers showed dynamic perioperative changes. Brain injury was detected on MRI in 47.8% of patients but was not associated with outcomes. Higher perioperative NFL levels were associated with adverse neurodevelopmental outcomes. NFL concentrations were increased in patients with cognitive delay (P = 0.01) and predicted cognitive and language delay (area under the curve = 0.65; 0.76, respectively). Patients with language and motor delay showed higher NFL levels (P = 0.04). UCH-L1 was associated with cognitive delay, whereas glial fibrillary acidic protein and total TAU were not associated with outcomes. CONCLUSIONS: Elevated perioperative NFL levels were associated with and predictive of adverse neurodevelopmental outcomes, whereas UCH-L1 showed a weaker association with cognitive delay. Although MRI-detected brain injury was frequent, it was not associated with neurodevelopmental outcome.