A Novel Brain Injury Biomarker Correlates with Cyanosis in Infants with Congenital Heart Disease

Abstract

Cyanotic heart lesions are a complex subset of congenital heart disease (CHD) in which patients are desaturated until surgical repair or palliation. We hypothesized that a direct relationship would exist between degree of desaturation and presence of systemic inflammation and brain injury in unrepaired patients less than 1 year of age. The pre-operative desaturation with augmented systemic inflammation would predict a more complex post-operative course. Fifty patients with CHD were enrolled in this study and classified as cyanotic (O₂ ≤ 90%) or acyanotic (O₂ > 90%) based on SpO₂. Serum inflammatory mediators measured included interleukins (IL)-6, IL-8, IL-12p70, IL-10, IL-1β, tumor necrosis factor (TNF)-α, interferon (INF)-γ; macrophage inhibitory factor (MIF) and a novel brain biomarker, phosphorylated neurofilament heavy subunit (pNF-H). Twenty-two cyanotic and 28 acyanotic subjects were enrolled with SpO₂ of 78 ± 18% and 98 ± 2% (p < 0.001), respectively, and mean age of 72 days (range 2-303) and 102 days (range 1-274), respectively. Cyanotic vs acyanotic subjects had elevated serum IL-6 (6.6 ± 7.6 vs 2.9 ± 2.9 pg/ml, p = 0.019) and pNF-H (222 ± 637 vs 57 ± 121 pg/ml, p = 0.046), and both biomarkers correlated with degree of desaturation (Spearman rank-order correlation ρ = - 0.30, p = 0.037 and ρ = - 0.29 p = 0.049, respectively). Post-operative inotrope scores at 24 h and duration of mechanical ventilation correlated inversely with pre-operative oxygen saturation (ρ = - 0.380, p = 0.014 and ρ = - 0.362, p = 0.020, respectively). The degree of pre-operative desaturation correlated with a more complicated post-operative course supporting the need for advanced peri-operative therapy in this population.

Keywords: Brain injury; Bypass surgery; Congenital heart disease; Cytokines; Neurofilament; Systemic inflammation.