Background. The objectives of this study were to assess the preoperative and postoperative serum brain- derived neurotrophic factor (BDNF) levels in neonates undergoing surgery for congenital heart defects (CHD). Also to explore the relationship between changes in BDNF levels and the impact of perioperative factors including intraoperative body temperature, aortic cross-clamp time, perfusion time, operation time, inotropic score, vasoactive inotropic score and lactate levels.

Methods. Forty-four patients with CHD and 36 healthy neonates were included in the study. Blood samples for serum BDNF levels were collected three times: preoperatively, and at 24 and 72 hours postoperatively from each patient in the operated group. Additionally, samples were collected once from each individual in the non-operated case group and the control group. Serum BDNF levels were analyzed using the Elabscience ELISA (Enzyme-Linked Immunosorbent Assay) commercial kit. Cranial ultrasonography (USG) was performed on all infants with CHD. Following cardiac surgery, patients underwent second and third cranial USG examinations at 24 and 72 hours postoperatively, respectively.

Results. Forty-four consecutive patients with CHD were divided into two groups as follows: the operated group (n=30) and the non-operated group (n=14). Although there were no differences in the baseline serum BDNF levels between the case and control groups, the preoperative serum BDNF levels were significantly lower in the patients operated compared to the non-operated patients. The serum BDNF levels at the 24th hour postoperatively were higher than the preoperative levels. However, no significant correlation was found between the serum BDNF levels at 24 and 72 hours postoperatively as well as the cranial USG findings at corresponding times.

Conclusions. Serum BDNF levels were initially lower in neonates with CHD who underwent surgery, but increased during the early postoperative period. These results suggest that serum BDNF levels are influenced by CHD and the postoperative period. 

Keywords: brain derived neurotrophic factor, cardiac surgery, congenital heart defects, neonates

How to cite

Fatalov K, Turan Ö, Özkan M, et al. Pre- and postoperative levels of serum brain-derived neurotrophic factor in neonates with congenital heart defects. Turk J Pediatr 2024; 66: 151-160. https://doi.org/10.24953/turkjpediatr.2024.4562


  1. Varrica A, Satriano A, Gavilanes ADW, et al. S100B increases in cyanotic versus noncyanotic infants undergoing heart surgery and cardiopulmonary bypass (CPB). J Matern Fetal Neonatal Med 2019; 32: 1117-1123. https://doi.org/10.1080/14767058.2017.1401604
  2. Jufar AH, Lankadeva YR, May CN, et al. Renal and cerebral hypoxia and inflammation during cardiopulmonary bypass. Compr Physiol 2021; 12: 2799-2834. https://doi.org/10.1002/cphy.c210019
  3. Chen J, Zimmerman RA, Jarvik GP, et al. Perioperative stroke in infants undergoing open heart operations for congenital heart disease. Ann Thorac Surg 2009; 88: 823-829. https://doi.org/10.1016/j.athoracsur.2009.03.030
  4. Meyer DB, Jacobs JP, Hill K, Wallace AS, Bateson B, Jacobs ML. Variation in perfusion strategies for neonatal and infant aortic arch repair: contemporary practice in the sts congenital heart surgery database. World J Pediatr Congenit Heart Surg 2016; 7: 638-644. https://doi.org/10.1177/2150135116658458
  5. Barkhuizen M, Abella R, Vles JSH, Zimmermann LJI, Gazzolo D, Gavilanes AWD. Antenatal and perioperative mechanisms of global neurological injury in congenital heart disease. Pediatr Cardiol 2021; 42: 1-18. https://doi.org/10.1007/s00246-020-02440-w
  6. Graham EM, Martin RH, Atz AM, et al. Association of intraoperative circulating-brain injury biomarker and neurodevelopmental outcomes at 1 year among neonates who have undergone cardiac surgery. J Thorac Cardiovasc Surg 2019; 157: 1996-2002. https://doi.org/10.1016/j.jtcvs.2019.01.040
  7. Sanchez-de-Toledo J, Chrysostomou C, Munoz R, et al. Cerebral regional oxygen saturation and serum neuromarkers for the prediction of adverse neurologic outcome in pediatric cardiac surgery. Neurocrit Care 2014; 21: 133-139. https://doi.org/10.1007/s12028-013-9934-y
  8. Trakas E, Domnina Y, Panigrahy A, et al. Serum neuronal biomarkers in neonates with congenital heart disease undergoing cardiac surgery. Pediatr Neurol 2017; 72: 56-61. https://doi.org/10.1016/j.pediatrneurol.2017.04.011
  9. Vedovelli L, Padalino M, Suppiej A, et al. Cardiopulmonary-bypass glial fibrillary acidic protein correlates with neurocognitive skills. Ann Thorac Surg 2018; 106: 792-798. https://doi.org/10.1016/j.athoracsur.2018.03.083
  10. Vergine M, Vedovelli L, Simonato M, et al. Perioperative glial fibrillary acidic protein is associated with long-term neurodevelopment outcome of infants with congenital heart disease. Children (Basel) 2021; 8: 655. https://doi.org/10.3390/children8080655
  11. Bar-Yosef O, Greidinger D, Iskilova M, Hemi R, Tirosh T, Vardi A. Neurological deficit is predicted by S100B in children after cardiac surgery. Clin Chim Acta. 2018 ;481: 56-60. https://doi.org/10.1016/j.cca.2018.02.032
  12. Chiperi LE, Tecar C, Toganel R. Neuromarkers which can predict neurodevelopmental impairment among children with congenital heart defects after cardiac surgery: a systematic literature review. Dev Neurorehabil 2023; 26: 206-215. https://doi.org/10.1080/17518423.2023.2166618
  13. Deinhardt K, Chao MV. Shaping neurons: Long and short range effects of mature and proBDNF signalling upon neuronal structure. Neuropharmacology 2014; 76: 603-609. https://doi.org/10.1016/j.neuropharm.2013.04.054
  14. Chouthai NS, Sampers J, Desai N, Smith GM. Changes in neurotrophin levels in umbilical cord blood from infants with different gestational ages and clinical conditions. Pediatr Res 2003; 53: 965-969. https://doi.org/10.1203/01.PDR.0000061588.39652.26
  15. Rao R, Mashburn CB, Mao J, Wadhwa N, Smith GM, Desai NS. Brain-derived neurotrophic factor in infants <32 weeks gestational age: correlation with antenatal factors and postnatal outcomes. Pediatr Res 2009; 65: 548-552. https://doi.org/10.1203/PDR.0b013e31819d9ea5
  16. Ahn SY, Chang YS, Sung DK, Sung SI, Ahn JY, Park WS. Pivotal role of brain-derived neurotrophic factor secreted by mesenchymal stem cells in severe intraventricular hemorrhage in newborn rats. Cell Transplant 2017; 26: 145-156. https://doi.org/10.3727/096368916X692861
  17. Korhonen L, Riikonen R, Nawa H, Lindholm D. Brain derived neurotrophic factor is increased in cerebrospinal fluid of children suffering from asphyxia. Neurosci Lett 1998; 240: 151-154. https://doi.org/10.1016/s0304-3940(97)00937-3
  18. Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr 2013; 13: 59. https://doi.org/10.1186/1471-2431-13-59
  19. Inder TE, Perlman JM, Volpe JJ. Preterm intraventricular hemorrhage/posthemorrhagic hydrocephalus. In: Volpe JJ, editor. Volpe’s Neurology of the Newborn. 6th ed. Elsevier; 2018: 637-698. https://doi.org/10.1016/B978-0-323-42876-7.00024-7
  20. Amoureux S, Sicard P, Korandji C, et al. Increase in levels of BDNF is associated with inflammation and oxidative stress during cardiopulmonary bypass. Int J Biomed Sci 2008; 4: 204-211.
  21. Chiperi LE, Huţanu A, Tecar C, Muntean I. Serum markers of brain injury in pediatric patients with congenital heart defects undergoing cardiac surgery: diagnostic and prognostic role. Clin Pract 2023; 13: 1253-1265. https://doi.org/10.3390/clinpract13050113
  22. Sukhanova IA, Sebentsova EA, Khukhareva DD, et al. Gender-dependent changes in physical development, BDNF content and GSH redox system in a model of acute neonatal hypoxia in rats. Behav Brain Res 2018; 350: 87-98. https://doi.org/10.1016/j.bbr.2018.05.008
  23. Xie H, Leung KL, Chen L, et al. Brain-derived neurotrophic factor rescues and prevents chronic intermittent hypoxia-induced impairment of hippocampal long-term synaptic plasticity. Neurobiol Dis 2010; 40: 155-162. https://doi.org/10.1016/j.nbd.2010.05.020
  24. Ferrer I, Krupinski J, Goutan E, Martí E, Ambrosio S, Arenas E. Brain-derived neurotrophic factor reduces cortical cell death by ischemia after middle cerebral artery occlusion in the rat. Acta Neuropathol 2001; 101: 229-238. https://doi.org/10.1007/s004010000268
  25. Liu F, Yang S, Du Z, Guo Z. Dynamic changes of cerebral-specific proteins in full-term newborns with hypoxic-ischemic encephalopathy. Cell Biochem Biophys 2013; 66: 389-396. https://doi.org/10.1007/s12013-012-9478-3
  26. Basaran M, Sever K, Kafali E, et al. Serum lactate level has prognostic significance after pediatric cardiac surgery. J Cardiothorac Vasc Anesth 2006; 20: 43-47. https://doi.org/10.1053/j.jvca.2004.10.010
  27. Brossard-Racine M, du Plessis AJ, Vezina G, et al. Prevalence and spectrum of in utero structural brain abnormalities in fetuses with complex congenital heart disease. AJNR Am J Neuroradiol 2014; 35: 1593-1599. https://doi.org/10.3174/ajnr.A3903
  28. Miller SP, McQuillen PS, Hamrick S, et al. Abnormal brain development in newborns with congenital heart disease. N Engl J Med 2007; 357: 1928-1938. https://doi.org/10.1056/NEJMoa067393
  29. Howell HB, Zaccario M, Kazmi SH, Desai P, Sklamberg FE, Mally P. Neurodevelopmental outcomes of children with congenital heart disease: A review. Curr Probl Pediatr Adolesc Health Care 2019; 49: 100685. https://doi.org/10.1016/j.cppeds.2019.100685