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

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 1year 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 (O(2)90%) or acyanotic (O-2>90%) based on SpO(2). Serum inflammatory mediators measured included interleukins (IL)-6, IL-8, IL-12p70, IL-10, IL-1, tumor necrosis factor (TNF)-, interferon (INF)-; 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 SpO(2) of 78 +/- 18% and 98 +/- 2% (p<0.001), respectively, and mean age of 72days (range 2-303) and 102days (range 1-274), respectively. Cyanotic vs acyanotic subjects had elevated serum IL-6 (6.6 +/- 7.6 vs 2.9 +/- 2.9pg/ml, p=0.019) and pNF-H (222 +/- 637 vs 57 +/- 121pg/ml, p=0.046), and both biomarkers correlated with degree of desaturation (Spearman rank-order correlation =-0.30, p=0.037 and =-0.29 p=0.049, respectively). Post-operative inotrope scores at 24h and duration of mechanical ventilation correlated inversely with pre-operative oxygen saturation (=-0.380, p=0.014 and =-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.