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Glial fibrillary acidic protein as a biomarker for brain injury in neonatal CHD

Published online by Cambridge University Press:  20 January 2016

Stephanie L. McKenney
Affiliation:
Department of Pediatrics, Division of Neonatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
Fahad F. Mansouri
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America Department of Gynecology and Obstetrics, Division of Maternal-Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
Allen D. Everett
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
Ernest M. Graham
Affiliation:
Department of Gynecology and Obstetrics, Division of Maternal-Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
Irina Burd
Affiliation:
Department of Gynecology and Obstetrics, Division of Maternal-Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America Integrated Research Center for Fetal Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
Priya Sekar*
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America The Helen B. Taussig Congenital Heart Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
*
Correspondence to: P. Sekar, MD, MPH, Department of Pediatrics, Division of Pediatric Cardiology, Johns Hopkins University School of Medicine, Bloomberg Children’s M2321, 1800 Orleans St., Baltimore, MD 21287-1228, United States of America. Tel: 443 287 0529; Fax: 410 955 0897; E-mail [email protected]

Abstract

Neonates with critical CHD have evidence, by imaging, of preoperative brain injury, although the timing is unknown. We used circulating postnatal serum glial fibrillary acidic protein as a measure of acute perinatal brain injury in neonates with CHD. Glial fibrillary acidic protein was measured on admission and daily for the first 4 days of life in case and control groups; we included two control groups in this study – non-brain-injured newborns and brain-injured newborns. Comparisons were performed using the Kruskal–Wallis test with Dunn’s multiple comparisons, Student’s t-test, and χ2 test of independence where appropriate. In aggregate, there were no significant differences in overall glial fibrillary acidic protein levels between CHD patients (n=56) and negative controls (n=23) at any time point. By day 4 of life, 7/56 (12.5%) CHD versus 0/23 (0%) normal controls had detectable glial fibrillary acidic protein levels. Although not statistically significant, the 5/10 (50%) left heart obstruction group versus 1/17 (6%) conoventricular, 0/13 (0%) right heart, and 1/6 (17%) septal defect patients trended towards elevated levels of glial fibrillary acidic protein at day 4 of life. Overall, glial fibrillary acidic protein reflected no evidence for significant peripartum brain injury in neonates with CHD, but there was a trend for elevation by postnatal day 4 in neonates with left heart obstruction. This pilot study suggests that methods such as monitoring glial fibrillary acidic protein levels may provide new tools to optimise preoperative care and neuroprotection in high-risk neonates with specific types of CHD.

Type
Original Articles
Copyright
© Cambridge University Press 2016 

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Footnotes

*

Both the authors contributed equally to this work.

References

1. McQuillen, PS, Miller, SP. Congenital heart disease and brain development. Ann N Y Acad Sci 2010; 1184: 6886.Google Scholar
2. Andropoulos, DB, Hunter, JV, Nelson, DP, et al. Brain immaturity is associated with brain injury before and after neonatal cardiac surgery with high-flow bypass and cerebral oxygenation monitoring. J Thorac Cardiovasc Surg 2010; 139: 543556.Google Scholar
3. Pelinka, LE, Kroepfl, A, Leixnering, M, Buchinger, W, Raabe, A, Redl, H. GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome. J Neurotrauma 2004; 21: 15531561.CrossRefGoogle ScholarPubMed
4. Kaneko, T, Kasaoka, S, Miyauchi, T, et al. Serum glial fibrillary acidic protein as a predictive biomarker of neurological outcome after cardiac arrest. Resuscitation 2009; 80: 790794.Google Scholar
5. Lumpkins, KM, Bochicchio, GV, Keledjian, K, Simard, JM, McCunn, M, Scalea, T. Glial fibrillary acidic protein is highly correlated with brain injury. J Trauma 2008; 65: 778782; discussion 782–784.Google Scholar
6. Vos, PE, Lamers, KJ, Hendriks, JC, et al. Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury. Neurology 2004; 62: 13031310.Google Scholar
7. Pelinka, LE, Kroepfl, A, Schmidhammer, R, et al. Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma. J Trauma 2004; 57: 10061012.Google Scholar
8. Bembea, MM, Savage, W, Strouse, JJ, et al. Glial fibrillary acidic protein as a brain injury biomarker in children undergoing extracorporeal membrane oxygenation. Pediatr Crit Care Med 2011; 12: 572579.Google Scholar
9. Ennen, CS, Huisman, TA, Savage, WJ, et al. Glial fibrillary acidic protein as a biomarker for neonatal hypoxic-ischemic encephalopathy treated with whole-body cooling. Am J Obstet Gynecol 2011; 205: 251.e1-7.Google Scholar
10. Brunetti, MA, Jennings, JM, Easley, RB, et al. Glial fibrillary acidic protein in children with congenital heart disease undergoing cardiopulmonary bypass. Cardiol Young 2014; 24: 623631.Google Scholar
11. Sarnat, HB, Sarnat, MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976; 33: 696705.Google Scholar
12. Savage, WJ, Everett, AD, Casella, JF. Plasma glial fibrillary acidic protein levels in a child with sickle cell disease and stroke. Acta Haematol 2011; 125: 103106.Google Scholar
13. Savage, WJ, Barron‐Casella, E, Fu, Z, et al. Plasma glial fibrillary acidic protein levels in children with sickle cell disease. Am J Hematol 2011; 86: 427429.Google Scholar
14. Harel, S, Tomer, A, Barak, Y, Binderman, I, Yavin, E. The cephalization index: a screening device for brain maturity and vulnerability in normal and intrauterine growth retarded newborns. Brain Dev 1985; 7: 580584.Google Scholar
15. Leitner, Y, Fattal-Valevski, A, Geva, R, et al. Neurodevelopmental outcome of children with intrauterine growth retardation: a longitudinal, 10-year prospective study. J Child Neurol 2007; 22: 580587.Google Scholar
16. Hinton, RB, Andelfinger, G, Sekar, P, et al. Prenatal head growth and white matter injury in hypoplastic left heart syndrome. Pediatr Res 2008; 64: 364369.Google Scholar
17. Shillingford, AJ, Ittenbach, RF, Marino, BS, et al. Aortic morphometry and microcephaly in hypoplastic left heart syndrome. Cardiol Young 2007; 17: 189195.Google Scholar
18. Hoskoppal, A, Roberts, H, Kugler, J, Duncan, K, Needelman, H. Neurodevelopmental outcomes in infants after surgery for congenital heart disease: a comparison of single-ventricle vs. two-ventricle physiology. Congenit Heart Dis 2010; 5: 9095.Google Scholar
19. Davidson, J, Gringras, P, Fairhurst, C, Simpson, J. Physical and neurodevelopmental outcomes in children with single-ventricle circulation. Arch Dis Child 2015; 100: 449453.Google Scholar
20. Shedeed, SA, Elfaytouri, E. Brain maturity and brain injury in newborns with cyanotic congenital heart disease. Pediatr Cardiol 2011; 32: 4754.Google Scholar
21. Allen, MC, Cristofalo, EA, Kim, C. Outcomes of preterm infants: morbidity replaces mortality. Clin Perinatol 2011; 38: 441454.Google Scholar