Association of intraoperative circulating-brain injury biomarker and neurodevelopmental outcomes at 1 year among neonates who have undergone cardiac surgery

• Type of Material: Article
• Authors: Eric M. Graham, Medical University of South Carolina; Renee H. Martin, Medical University of South Carolina; Andrew M. Atz, Medical University of South Carolina; Kasey Hamlin-Smith, Medical University of South Carolina; Minoo N. Kavarana, Medical University of South Carolina; Scott M. Bradley, Medical University of South Carolina; Bahaaldin Alsoufi, Emory University; William Mahle, Emory University; Allen D. Everett, Johns Hopkins University
• Language: English
• Date: 2019-05-01
• Publisher: Mosby-Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 by The American Association for Thoracic Surgery.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jtcvs.2019.01.040
• Title of Journal or Parent Work: Journal of Thoracic and Cardiovascular Surgery
• Volume: 157
• Issue: 5
• Start Page: 1996
• End Page: 2002
• Grant/Funding Information: This work was supported in part by grant HL112968 from the National Heart, Lung, and Blood Institute (NHLBI).
• Keywords: Life Sciences & Biomedicine; Behavior; Cardiopulmonary bypass; Cardiovascular System & Cardiology; congenital heart disease; Congenital heart disease; Respiratory System; Surgery; Fibrillary acidic protein; Science & Technology; cardiopulmonary bypass; glial fibrillary acidic protein; Cardiac & Cardiovascular Systems; Transposition; Children
• Research Categories: Biology, Neuroscience; Health Sciences, Public Health; Health Sciences, Medicine and Surgery; Health Sciences, Health Care Management

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 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.