Eric M Graham1, Renee' H Martin2, Andrew M Atz3, Kasey Hamlin-Smith4, Minoo N Kavarana5, Scott M Bradley5, Bahaaldin Alsoufi6, William T Mahle7, Allen D Everett8. 1. Division of Pediatric Cardiology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC. Electronic address: grahamem@musc.edu. 2. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC. 3. Division of Pediatric Cardiology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC. 4. Department of Pediatrics, Medical University of South Carolina, Charleston, SC. 5. Department of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, SC. 6. Department of Cardiothoracic Surgery, Children's Healthcare of Atlanta and Emory University, Atlanta, Ga. 7. Division of Pediatric Cardiology, Department of Pediatrics, Children's Healthcare of Atlanta and Emory University, Atlanta, Ga. 8. Division of Cardiology, Department of Pediatrics, Johns Hopkins University, Baltimore, Md.
Abstract
BACKGROUND:Neurodevelopmental disability is the most significant complication for survivors of infant surgery for congenital heart disease. In this study we sought to determine if perioperative circulating brain injury biomarker levels are associated with neurodevelopmental outcomes at 12 months. METHODS: A secondary analysis of a randomized controlled trial of neonates who underwentcardiac surgery was performed. Glial fibrillary acidic protein (GFAP) was measured: (1) before skin incision; (2) immediately after bypass; (3) 4 and (4) 24 hours postoperatively. Linear regression models were used to determine an association with the highest levels of GFAP and Bayley Scales of Infant and Toddler Development third edition (BSID) composite scores. RESULTS: There were 97 subjects who had cardiac surgery at a mean age of 9 ± 6 days and completed a BSID at 12.5 ± 0.6 months of age. Median (25th-75th percentile) levels of GFAP were 0.01 (0.01-0.02), 0.85 (0.40-1.55), 0.07 (0.05-0.11), and 0.03 (0.02-0.04) ng/mL at the 4 time points, respectively. In univariate analysis GFAP was negatively associated with cognitive, language, and motor composite scores. GFAP levels immediately after bypass differed between institutions; 1.57 (0.92-2.48) versus 0.77 (0.36-1.21) ng/mL (P = .01). After adjusting for center and potential confounders, GFAP was independently associated with BSID motor score (P = .04). CONCLUSIONS:Higher GFAP levels at the time of neonatal cardiac operations were independently associated with decreased BSID motor scores at 12 months. GFAP might serve as a diagnostic means to acutely identify perioperative brain-specific injury and serve as a benchmark of therapeutic efficacy for investigational treatments, discriminate center-specific effects, and provide early prognostic information for intervention.
RCT Entities:
BACKGROUND:Neurodevelopmental disability is the most significant complication for survivors of infant surgery for congenital heart disease. In this study we sought to determine if perioperative circulating brain injury biomarker levels are associated with neurodevelopmental outcomes at 12 months. METHODS: A secondary analysis of a randomized controlled trial of neonates who underwent cardiac surgery was performed. Glial fibrillary acidic protein (GFAP) was measured: (1) before skin incision; (2) immediately after bypass; (3) 4 and (4) 24 hours postoperatively. Linear regression models were used to determine an association with the highest levels of GFAP and Bayley Scales of Infant and Toddler Development third edition (BSID) composite scores. RESULTS: There were 97 subjects who had cardiac surgery at a mean age of 9 ± 6 days and completed a BSID at 12.5 ± 0.6 months of age. Median (25th-75th percentile) levels of GFAP were 0.01 (0.01-0.02), 0.85 (0.40-1.55), 0.07 (0.05-0.11), and 0.03 (0.02-0.04) ng/mL at the 4 time points, respectively. In univariate analysis GFAP was negatively associated with cognitive, language, and motor composite scores. GFAP levels immediately after bypass differed between institutions; 1.57 (0.92-2.48) versus 0.77 (0.36-1.21) ng/mL (P = .01). After adjusting for center and potential confounders, GFAP was independently associated with BSID motor score (P = .04). CONCLUSIONS: Higher GFAP levels at the time of neonatal cardiac operations were independently associated with decreased BSID motor scores at 12 months. GFAP might serve as a diagnostic means to acutely identify perioperative brain-specific injury and serve as a benchmark of therapeutic efficacy for investigational treatments, discriminate center-specific effects, and provide early prognostic information for intervention.
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