Serum biomarkers, quality of life, and family functioning following pediatric neurocritical illness

LEARNING OBJECTIVES: Pediatric critical illness impacts child and family functioning and quality of life. We hypothesized that serum biomarkers of brain injury (neuron specific enolase [NSE], S100b), recovery (vascular endothelial growth factor [VEGF]), and inflammation (C‐reactive protein [CRP]) are associated with quality of life and family function following neurocritical illness. METHODS: Secondary analysis of a randomized controlled trial evaluating a rehabilitation intervention in pediatric neurocritical illness. Serum biomarkers from hospital discharge were analyzed with a Luminex assay. Primary outcomes were the PedsQL and McMaster Family Assessment (MFAD) at 6 months. Linear regression (β = coefficient) was performed for discharge biomarker fluorescence index and total and subdomain scores of PedsQL and MFAD. Multivariable analysis included age, sex, and admission Pediatric Index of Mortality score. RESULTS: Of 19 subjects studied, 11 were male (58%) with a median age of 11 (interquartile range 8‐13 years). Higher MFAD was associated with elevated CRP in multivariable regression (β = 0.000033, p=0.007) indicating poor family function when greater inflammation present. Higher MFAD subdomain scores including affective involvement (β = 0.000028, p=0.032), behavioral control (β = 0.00003, p=0.038), general functioning (β = 0.00003, p=0.014), communication (β = 0.000041, p=0.006), and roles (β = 0.000031, p=0.014) were also associated with elevated CRP. Higher MFAD (β = ‐0.008, p=0.028) and subdomains problem solving (β = ‐0.011, p=0.014) and roles (β = ‐0.012, p=0.005) were associated with lower S100b on univariate regression suggesting poor family function in subjects with less brain injury. Similarly, higher MFAD subdomain roles (β ‐0.000022, p=0.031) was associated with lower NSE. Higher PedsQL subdomains of physical functioning (β = ‐0.025 p=0.031) and social functioning (β = ‐0.024 p=0.032) were associated with lower VEGF on multivariable regression indicating better quality of life in patients with less recovery at discharge. CONCLUSIONS: Increased inflammatory biomarkers at discharge are associated with family dysfunction following pediatric neurocritical illness. Poor family function and lower quality of life would be anticipated with worse brain injury and less recovery at discharge, making this an unexpected finding which may limit the screening utility of these biomarkers.