Biomarkers of Birth Asphyxia in Neonates

  • Dr. Rabindran Consultant Neonatologist, Billroth Hospital, Chennai
  • Dr D Sharad Gedam Professor of Pediatrics, L N Medical college, Bhopal, MP, India.
Keywords: Birth asphyxia, Biomarkers, Cytokines in birth asphyxia

Abstract

Birth asphyxia is a common cause of neonatal mortality. Identification of severity of asphyxia is vital for prompt management. Biomarkers can be used for timely diagnosis of asphyxia and also helps in prognosis. Serum, CSF, urine, cord blood & magnetic resonance biomarkers for asphyxia in neonates have been studied. Cytokines like IL-6 in CSF, NSE in CSF, Protein S-100b in serum, urine & cord blood, LDH in serum and saliva, CK in serum and urine, cord BDNF, Urinary UA/Cr ratio, GFAP, Glutamate in CSF, PGE2, AST, ALT, Activin A have been studied with varied diagnostic accuracy and feasibility. Research directed towards newer biomarkers like NPBI, Hypoxanthine, total hydroperoxides, AOPP, UCHL-1 & pNFH-1 for early identification of severe asphyxia have shown promising results. Cardiac biomarkers like Troponin T & I, BNP, CK-MB may aid in longterm outcome. NRBC count still remains as the oldest and best-described biomarker of asphyxia. Use of Proton & Nuclear Magnetic Resonance Spectroscopy on day 1 apart from conventional MRI have opened a new era of MR Biomarkers in neonatal asphyxia. Early identification of severity of asphyxia with judicious use of biomarkers can make a huge difference in the management and outcome of birth asphyxia.

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References

1. Gray PH, Tudehope DI, Masel JP, Burns YR, Mohay HA, O'Callaghan MJ, et al. Perinatal hypoxic-ischemic brain injury: prediction of outcome. Dev Med Child Neurol. 1993;35:965-73.

2. Thornberg E, Thiringer K, Odeback A, Milsom I. Birth asphyxia: Incidence, clinical course, and outcome in a Swedish population. Acta Paediatr 1995;84(8):927-32.DOI: 10.1111/j.1651-2227.1995.tb13794.x.

3. Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E, Thoresen M, Whitelaw A, Brocklehurst P; TOBY Study Group. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009 Oct 1;361(14):1349-58. doi: 10.1056/NEJMoa0900854.

4. Pasternak JF. Hypoxic-ischemic brain damage in the term infant. Pediatr Clin North Am 1993;40:1061-71.

5. Robertson CMT, Finer NN. Long term follow-up of term neonates with perinatal asphyxia. Clin Perinatol 1993;20:483-90.

6. Ramaswamy V, Horton J, Vandermeer B, Buscemi N, Miller S, Yager J. Systematic review of biomarkers of brain its timing, duration, and outcomes are poorly defined. injury in term neonatal encephalopathy. Pediatr Neurol 2009;40:215- 226.doi:10.1016/j.pediatrneurol.2008.09.026

7. Tekgul H, Yalaz M, Kutukculer N, Ozbek S, Kose T, Akisu M, Kultursay N, Gokben S. Value of biochemical markers for outcome in term infants with asphyxia. Pediatr Neurol 2004;31 (5) :326-332. DOI: 10.1016/j.pediatrneurol.2004.05.004.

8. Vannucci RC, Perlman JM. Intervention for perinatal hypoxic-ischemic encephalopathy. Pediatrics 1997;100:1004-14.

9. Fernandez F, Verdu A, Quero J, et al. Cerebrospinal fluid lactate levels in term infants with perinatal hypoxia. Pediatr Neurol 1986;2(1):39-42. DOI: http://dx.doi.org/10.1016/0887-8994(86)90038-X.

10. Blennow M, Hagberg H, Rosengren L. Glial fibrillary acidic protein in the cerebrospinal fluid: A possible indicator of prognosis in full-term asphyxiated newborn
infants. Pediatr Res 1995;37:260-4.

11. Thornberg E, Thiringer K, Hagberg H, Kjellmer I. Neuron specific enolase in asphyxiated newborns: Association with encephalopathy and cerebral function
monitor trace. Arch Dis Child Fetal Neonatal 1995 Jan;72(1):F39-42.

12. Huang CC, Wang ST, Chang YC, Lin KP, Wu PL. Measurement of the urinary lactate:creatinine ratio for the early identification of newborn infants at risk for hypoxicischemic encephalopathy. N Engl J Med 1999 Jul 29;341(5):328-35.

13. Bader D, Gozal D, Weinger-Abend M, Berger A, Lanir A. Neonatal urinary uric acid/creatinine ratio as an additional marker of perinatal asphyxia. Eur J Pediatr 1995;154:747-9.

14. Akisu M, Kultursay N. Value of the urinary uric acid to creatinine ratio in term infants with perinatal asphyxia. Acta Paediatr Jpn 1998 Feb;40(1):78-81. DOI: 10.1111/j.1442-200X.1998.tb01408.x

15. Nagdyman N, Komen W, Ko HK, Muller C, Obladen M. Early biochemical indicators of hypoxic-ischemic encephalopathy after birth asphyxia. Pediatr Res 2001;49:502-6.

16. Karunatilaka DH, Amaratunga GWDS, Perera KDNI, Caldera V. Serum creatine kinase and lactic dehydrogenase levels as useful markers of immediate and long-term outcome of perinatal asphyxia. Sri Lanka Journal of Child Health, 2000; 29: 49-52.

17. Martha Douglas-Escobar, Michael D. Weiss. Neonatal Biomarkers of Brain Injury. NeoReviews Vol.14 No.10 October 2013 e501. doi:10.3389/fneur.2012.00144.

18. Martin-Ancel A, Garcia-Alix A, Pascual-Salcedo D, Cabanas F, Valcarce M, Quero J. Interleukin-6 in the cerebrospinal fluid after perinatal asphyxia is related to
early and late neurological manifestations.Pediatrics 1997 Nov;100(5):789-94. doi: 10.1542/peds.100.5.789.

19. Savman K, Blennow M, Gustafson K, Tarkowski E, Hagberg H. Cytokine response in cerebrospinal fluid after birth asphyxia. Pediatr Res 1998 Jun;43(6):746-51.

20. Oygur N, Sonmez O, Saka O, Yegin O. Predictive value of plasma and cerebrospinal fluid tumor necrosis factor-alpha and interleukin 1 beta concentration on
outcome of full term infants with hypoxic ischemic encephalopathy. Arch Dis Child Fetal Neonatal 1998 Nov;79(3):F190-3.

21. Shalak LF, Laptook AR, Jafri HS, Ramilo O, Perlman JM.Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants. Pediatrics 2002 Oct;110(4):673-80.

22. Ramaswamy V, Horton J, Vandermeer B, Buscemi N, Miller S,Yager J. Systematic review of biomarkers of brain injury in term neonatal encephalopathy. Pediatr
Neurol 2009 Mar; 40(3): 215–26.doi: 10.1016/j.pediatrneurol.2008.09.026.

23. H. Aly, M.T. Khashaba, M. El-Ayouty, O. El-Sayed and B.M. Hasanein, IL-1beta, IL-6 and TNF-alpha and outcomes of neonatal hypoxic ischemic encephalopathy, Brain Dev 2006, Apr;28(3):178-82.

24. Minami M, Kuraishi Y, Yabuuchi K, Yamazaki A, Satoh M. Induction of interleukin-1beta mRNA in rat brain after transient forebrain ischemia. J Neurochem. 1992;58:390 –392.

25. Hagberg H, Gilland E, Bona E, Hanson LA, HahinZoric M, Blennow M, Holst M, McRae A, Söder O. Enhanced expression of interleukin (IL)-1 and IL-6 messenger RNA and bioactive protein after hypoxiaischemia in neonatal rats. Pediatr Res. 1996 Oct;40(4):603-609.

26. Liu T, Clark RK, McDonnell PC, Young PR, White RF, Barone FC, Feuerstein GZ. Tumor necrosis factoralpha expression in ischemic neurons. Stroke. 1994 Jul;25(7):1481-8.

27. Szaflarski J, Burtrum D, Silverstein FS. Cerebral hypoxia-ischemia stimulates cytokine gene expression in perinatal rats. Stroke. 1995 Jun;26(6):1093-100.

28. Mohamed T. Khashabaa, Basma O. Shoumana, Bothina M. Hasaneina, Ali A. Shaltouta , Hala M. AlMarsafawya , Mohamed M. Abdel-Azizb , Tahmina Ahmadc, Hany Alyc. Interleukin-1β , interleukin-6, and tumor necrosis factor-α in the cerebrospinal fluid of term infants with hypoxic-ischemic encephalopathy after postnatal treatment with magnesium sulfate. Journal of Pediatric Neurology 2011;9(3):299–304 .DOI 10.3233/JPN-2011-0501.

29. Ozdemir A, Oygür N, Gültekin M, Copkun M, Yegin O. Neonatal tumor necrosis factor, interleukin-1alpha, interleukin-1B and interleukin-6 response to Infection. Am J Perinatol 1994;11:282-4

30. Selmaj KW, Farooq M, Norton WT, Raine CS, Brosnan CF. Proliferation of astrocytes in vitro in response to cytokines: A primary role for tumor necrosis factor. J Immunol 1990 Jan 1;144(1):129-35.

31. Hama T, Miyamoto M, Tsukui H, Nishio C, Hatanaka H.Interleukin 6 as a neurotrophic factor for promoting the survival of cultured basal forebrain cholinergic neurons
from postnatal rats. Neurosci Lett. 1989 Oct 9;104(3):340-4.

32. Maeda Y, Matsumoto M, Hori O, et al. Hypoxia/reoxygenation-mediated induction of astrocyte interleukin-6: A paracrine mechanism potentially enhancing neuron survival. J Exp Med 1994;180:2297- 308.

33. Ancel AM, Alix-AG, Salcedo DP, Cabanas F, Valcarce M, Quero J. Interleukin-6 in the cerebral fluid after perinatal asphyxia is related to early and late neurologic manifestations. Pediatrics 1997;100:789-94.

34. Chiesa C, Pellegrini G, Panero A, T. De Luca, M. Assumma, F. Signore, L. Pacifico. Umbilical cord interleukin-6 levels are elevated in term neonates with perinatal asphyxia. Eur J Clin Invest. 2003 Mar;33(4):352–358.DOI: 10.1046/j.1365-2362.2003.01136.x.

35. Ana Martın-Ancel, Alfredo Garcıa-Alix, Dora Pascual-Salcedo, Fernando Cabanas, Manuel Valcarce, Jose Quero.Interleukin-6 in the Cerebrospinal Fluid After Perinatal Asphyxia Is Related to Early and Late Neurological Manifestations. Pediatrics 1997;100:789 –794.

36. De Praeter C, Vanhaesebrouck P, Govaert P, et al.Creatine Kinase Isoenzyme BB concentrations in the cerebrospinal fluid of newborns. Pediatrics 1991;
88:1204-10.
37. Fernandez F, Verdu A, Quero J. A serum CPK-BB Isoenzyme in the assessment of brain damage in asphyctic term infants. Acta Paediatr Scand. 1987 Nov;76(6):914-8.

38. Celtik C, Acunas B, Oner N, Pala O. Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemicbencephalopathy. Brain Dev 2004 Sep;26(6):398-402.

39. Garcia-Alix A, Cabanas F, Pellicer A, Hernanz A, Stiris TA, Quero J. Neuron-specific enolase and myelin basic protein: relationship of cerebrospinal fluid concentrations to the neurologic condition of asphyxiated full-term infants. Pediatrics. 1994 Feb;93(2):234-40.

40. Persson L, Hardemark HG, Gustafsson J, Rundstrom G, Mendel-Hartvig I, Esscher T, Pahlman S. S-100 protein and neuron-specific enolase on cerebrospinal fluid
and serum: Markers of cell damage in human central nervous system. Stroke 1987 Sep-Oct;18(5):911-8.

41. Aniko Roka, Dorottya Kelen, Jozsef Halasz, Gabriella Beko, Denis Azzopardi, Miklos Szabo. Serum S100B and neuron-specific enolase levels in normothermic and
hypothermic infants after perinatal asphyxia. Acta Pædiatrica. DOI:10.1111/j.1651-2227.2011.02480.x

42. Heizmann CW. Calcium binding S100 proteins in the central nervous system. Neurochem Res 1999 Sep;24(9):1097-100.

43. Gazzolo D, Vinesi P, Marinoni E, Di Iorio R, Marras M, Lituania M, Pierluigi Bruschettini, Fabrizio Michetti. S100B protein concentrations in cord blood: correlations
with gestational age in term and preterm deliveries. Clin Chem 2000 Jul; 46(7): 998–1000.

44. Gazzolo D, Di Iorio R, Marinoni E, Masetti P, Serra G, Giovannini L, et al. S100B protein is increased in asphyxiated term infants developing intraventricular
haemorrhage. Crit Care Med 2002; 30: 1356–60.

45. Qian J, Zhou D, Wang YW. Umbilical artery blood S100 beta protein: a tool for the early identification of neonatal hypoxic-ischemic encephalopathy. Eur J Pediatr.
2009 Jan;168(1):71-7. doi: 10.1007/s00431-008-0711-4.

46. Murabayashi M, Minato M, Okuhata Y, Makimoto M, Hosono S, Masaoka N, et al. Kinetics of serum S100B in newborns with intracranial lesions. Pediatr Int 2008; 50:
17–22.

47. Giuseppe D, Sergio C, Pasqua B, Giovanni LV, Salvatore C, Frigiola A, Petra H, Maurizio A. Perinatal asphyxia in preterm neonates leads to serum changes in protein S-100 and neuron specific enolase. Curr Neurovasc Res 2009 May;6(2):110-6.

48. Gazzolo D, Frigiola A, Bashir M, Iskander I, Mufeed H, Aboulgar H, Venturini P, Marras M, Serra G, Frulio R, Michetti F, Petraglia F, Abella R, Florio P. Diagnostic accuracy of S100B urinary testing at birth in full-term asphyxiated newborns to predict neonatal death. PLoS One. 2009;4(2):e4298. doi: 10.1371/journal.pone.0004298.

49. Michetti F, Gazzolo D. S100B protein in biological fluids: a tool for perinatal medicine. Clin Chem 2002 Dec;48(12):2097-104.

50. Michetti F, Corvino V, Geloso MC, Lattanzi W, Bernardini C, Serpero L, Diego Gazzolo. The S100B protein in biological fluids: more than a lifelong biomarker of brain distress. J Neurochem 2012; 120: 644– 59.DOI: 10.1111/j.1471-4159.2011.07612.x.

51. Florio P, Abella R, Marinoni E, Di Iorio R, Li Volti G, Galvano F, Pongiglione G, Frigiola A, Pinzauti S, Petraglia F, Gazzolo D. Biochemical markers of perinatal brain damage. Front Biosci (Schol Ed) 2010 Jan 1;2:47-72. doi: 10.2741/s45.

52. Gazzolo D, Abella R, Marinoni E, di Iorio R, Li Volti G, Galvano F, et al. New markers of neonatal neurology. J Matern Fetal Neonatal Med 2009; 22: 09/2009; 22 Suppl
3:57-61. DOI: 10.1080/14767050903181468

53. Gazzolo D, Bruschettini M, Lituania M, Serra G, Bonacci W, Michetti F. Increased urinary S100B protein as an early indicator of intraventricular hemorrhage in preterm infants: correlation with the grade of hemorrhage. Clin Chem. 2001 Oct;47(10):1836-8.

54. Gazzolo D, Marinoni E, Di Iorio R, Bruschettini M, Kornacka M, Lituania M, et al. Measurement of urinary S100B protein concentrations for the early identification
of brain damage in asphyxiated full-term infants. Arch Pediatr Adolesc Med. 2003;157(12):1163-1168. doi:10.1001/archpedi.157.12.1163.

55. Bashir M, Frigiola A, Iskander I, Said HM, Aboulgar H, Frulio R, Bruschettini P, Michetti F, Florio P, Pinzauti S, Abella R, Mussap M, Gazzolo D. Urinary S100A1B and S100BB to predict hypoxic ischemic encephalopathy at term. Front Biosci (Elite Ed). 2009 Jun 1;1:560-7.

56. K. Thorngren-Jerneck, C. Alling, A. Herbst, I. AmerWahlin, K. Marsal. S100 protein in serum as a prognostic marker for cerebral injury in term newborn infants with
hypoxic ischemic encephalopathy;Pediatr Res (2004) 55, 406–412; doi:10.1203/01.PDR.0000106806.75086.D3.

57. Heba S. Elmahdy, Abed Elrahman Elmashad, Adel A. Hagaga, Sahar Hamouda. Serum protein S100B and nucleated red blood cell counts as early markers of cerebral damage in neonates with hypoxic ischemic encephalopathy. Journal of Pediatric Neurology 7 (2009) 337–343. DOI 10.3233/JPN-2009-0332.

58. Francesco M Risso, Laura D Serpero, Luc JI Zimmermann, Antonio WD Gavilanes, Rosanna Frulio, Fabrizio Michetti, Pasquale Florio, Moataza Bashir, Iman Iskander, Hala Mufeed, Hanna Aboulgar, Diego Gazzolo. Urine S100 BB and A1B dimers are valuable predictors of adverse outcome in full-term asphyxiated infants. Acta Pædiatrica .DOI:10.1111/apa.12343.

59. Risso FM, Serpero LD, Zimmermann LJ, Gavilanes AW, Frulio R, Michetti F, Florio P, Bashir M, Iskander I, Mufeed H, Aboulgar H, Gazzolo D. Perinatal asphyxia: kidney failure does not affect S100b urine concentrations. Clin Chim Acta. 2012 Jan 18;413(1-2):150-3. doi: 10.1016/j.cca.2011.09.011.

60. Barberi I, Calabro MP, Cordaro S, Gitto E, Sottile A, Prudente D, Bertuccio G, Consolo S. Myocardial ischaemia in neonates with perinatal asphyxia. Electrocardiographic, echocardiographic and enzymatic correlations. Eur J Pediatr. 1999 Sep;158(9):742-7.

61. Gunes T, Ozturk MA, Koklu SM, Narin N, Koklu E. Troponin- T levels in perinatally asphyxiated infants during the first 15 days of life. Acta Paediatr. 2005 Nov;94(11):1638-43.

62. Roka A, Vasarhelyi B, Bodrogi E, Machay T, Szabo M. Changes in laboratory parameters indicating cell necrosis and organ dysfunction in asphyxiated neonates on moderate systemic hypothermia. Acta Paediatr. 2007 Aug;96(8):1118-21.

63. Reddy S, Dutta S, Narang A. Evaluation of lactate dehydrogenase, creatine kinase and hepatic enzymes for the retrospective diagnosis of perinatal asphyxia among
sick neonates. Indian Pediatr. 2008 Feb;45(2):144-7.

64. Karlsson M, Wiberg-Itzel E, Chakkarapani E, Blennow M, Winbladh B, Thoresen M. Lactate dehydrogenase predicts hypoxic ischaemic encephalopathy in newborn infants: a preliminary study. Acta Paediatr. 2010 Aug;99(8):1139-44. doi: 10.1111/j.1651-2227.2010.01802.x.

65. Fernandez F, Quero J, Verdii A, Ferreiros MC, Daimiel E, Roche MC. LDH isoenzymes in CSF in the diagnosis of neonatal brain damage. Acta Neurol Scand. 1986 Jul;74(1):30-3.

66. Akshay Mehta, Deepak Chawla, Jasbinder Kaur, Vidushi Mahajan, Vishal Guglani. Salivary lactate dehydrogenase levels can provide early diagnosis of hypoxic– ischaemic encephalopathy in neonates with birth asphyxia. Acta Pædiatrica. 2015 104(6): e236–e240. DOI:10.1111/apa.12964.

67. Thoresen M, Liu X, Jary S, Brown E, Sabir H, Stone J, Cowan F, Karlsson M. Lactate dehydrogenase in hypothermia-treated newborn infants with hypoxicischaemic encephalopathy. Acta Paediatr. 2012 Oct;101(10):1038-44. doi: 10.1111/j.1651- 2227.2012.02778.x.

68. Aps JK, Martens LC. Review: the physiology of saliva and transfer of drugs into saliva. Forensic Sci Int.2005 Jun 10;150(2-3):119-31.

69. Miller CS, King CP Jr, Langub MC, Kryscio RJ, Thomas MV. Salivary biomarkers of existing periodontal disease: a cross-sectional study. J Am Dent Assoc. 2006 Mar;137(3):322-9.

70. Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD,Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005 Feb 19-25;365(9460):663-70.

71. De Praeter C, Vanhaesebrouck P, Govaert P, Delanghe J, Leroy J. Creatine kinase isoenzyme BB concentrations in the cerebrospinal fluid of newborns: relationship to short term outcome. Pediatrics. 1991 Dec;88(6):1204-10.

72. S Atef, G Gad, S Imam, M Shawky. Cord Blood Brain Derived Neurotrophic Factor: Diagnostic and Prognostic Marker in Fullterm Newborns with Perinatal Asphyxia ;
Arch Dis Child 2012;97: A314 doi:10.1136/archdischild- 2012-302724.1094.

73. Imam SS, Gad GI, Atef SH, Shawky MA. Cord blood brain derived neurotrophic factor: diagnostic and prognostic marker in full-term newborns with perinatal asphyxia. Pak J Biol Sci. 2009 Dec 1;12(23):1498-504.

74. Bembea MM, Savage W, Strouse JJ, Schwartz JM, Graham E, Thompson CB, Everett A.. Glial fibrillary acidic protein as a brain injury biomarker in children undergoing extracorporeal membrane oxygenation.Pediatr Crit Care Med. 2011 Sep;12(5):572-9. doi: 10.1097/PCC.0b013e3181fe3ec7.

75. Ennen CS, Huisman TA, Savage WJ, Northington FJ, Jennings JM, Everett AD, Graham EM. Glial fibrillary acidic protein as a biomarker for neonatal hypoxicischemic encephalopathy treated with whole-body cooling. Am J Obstet Gynecol. 2011 Sep;205(3):251.e1-7. doi: 10.1016/j.ajog.2011.06.025.

76. Riikonen R, Kero P, Simell 0. Excitatory amino acids in cerebrospinal fluid in neonatal asphyxia. Pediatr Neurol. 1992 Jan-Feb;8(1):37-40. doi: 10.1016/0887- 8994(92)90050-9.

77. Hagberg H, Thornberg E, Blennow M, Kjellmer I, Lagercrantz H, Thiringer K, et al. Excitatory amino acids in the cerebrospinal fluid of asphyxiated infants: Relationship to hypoxic-ischemic encephalopathy. ActaPaediatr., 1993; 82: 925-9.

78. Ek M, Engblom D, Saha S, Blomqvist A, Jakobsson PJ, Ericsson-Dahlstrand A. Inflammatory response: pathway across the blood-brain barrier. Nature. 2001 Mar 22;410(6827):430-1.

79. Herlenius E. An inflammatory pathway to apnea and autonomic dysregulation. Respir Physiol Neurobiol. 2011 Sep 30;178(3):449-57. doi: 10.1016/j.resp.2011.06.026.

80. Hofstetter AO, Saha S, Siljehav V, Jakobsson PJ, Herlenius E. The induced prostaglandin E2 pathway is a key regulator of the respiratory response to infection and
hypoxia in neonates. Proc Natl Acad Sci U S A. 2007. Jun 5;104(23):9894-9.

81. Lars Bjerk, Kristin Leifsdottir, Sipra Saha, Eric Herlenius. PGE2 – metabolite levels in CSF correlate to HIE score and outcome after perinatal asphyxia. Acta Pædiatrica 2013 Nov 102(11); 1041–1047. DOI:10.1111/apa.12361.

82. Gunes T, Ozturk MA, Koklu SM, Narin N, Koklu E. Troponin-T levels in perinatally asphyxiated infants during the first 15 days of life. Acta Paediatr. 2005 Nov;94(11):1638-43.

83. Perrone S, Bracci R, Buonocore G. New biomarkers of fetal-neonatal hypoxic stress. Acta. Paediatr Suppl 2002;438:135-138.

84. S Perrone et al.post asphyxial reperfusion injury of the newborns. Pediatrics 1996; 98: 883–9

85. Buonocore G, Zani S, Sargentini I, Gioia D, Signorini C, Bracci R. Hypoxia-induced free iron release in the red cells of newborn infants. Acta Paediatr. 1998 Jan;87(1):77-81.

86. Buonocore G, Perrone S, Longini M, Terzuoli L, Bracci R. Total hydroperoxide and advanced oxidation protein products in preterm hypoxic babies. Pediatr Res. 2000 Feb;47(2):221-4.

87. Buonocore G, Perrone S, Carlini M, Bagnoli F, Gatti MG,Paffetti P, et al. Non protein bound iron plasma levels in critically ill newborn. Biol Neonate 2001; 80: 93-4.

88. Bracci R, Perrone S, Buonocore G. Red blood cell involvement in fetal/neonatal hypoxia. Biol Neonate 2001; 79: 210–12.DOI:10.1159/000047093.

89. Douglas-Escobar M1, Yang C, Bennett J, Shuster J, Theriaque D, Leibovici A, Kays D, Zheng T, Rossignol C, Shaw G, Weiss MD. A pilot study of novel biomarkers in neonates with hypoxic-ischemic encephalopathy. Pediatr Res. 2010 Dec;68(6):531-6. doi: 10.1203/PDR.0b013e3181f85a03.

90. D Sweetman, K Armstrong, JFA Murphy, EJ Molloy .Cardiac biomarkers in neonatal hypoxic ischaemia. Acta Pædiatrica. 2012 101, pp. 338–343. DOI:10.1111/j.1651-
2227.2011.02539.x

91. Costa S, Zecca E, De Rosa G, De Luca D, Barbato G, Pardeo M, Romagnoli C. Is serum troponin T a useful marker of myocardialdamage in newborn infants with
perinatal asphyxia? Acta Paediatr. 2007 Feb;96(2):181-4.

92. Boo NY, Hafidz H, Nawawi HM, Cheah FC, Fadzil YJ, Abdul Aziz BB, Ismail Z. Comparison of serum cardiac troponin T and creatine kinase MB isoenzyme mass concentrations in asphyxiated term infants during the first 48 hours of life. J Paediatr Child Health. 2005 Jul;41(7):331-7.

93. Turker G, Babaoglu K, Duman C, Gokalp A, Zengin E, Arisoy AE. The effect of blood gas and Apgar score on cord blood cardiac Troponin I. J Matern Fetal Neonatal
Med. 2004 Nov;16(5):315-9

94. Turker G, Babaoglu K, Gokalp AS, Sarper N, Zengin E, Arisoy AE. Cord blood cardiac Troponin I as an early predictor of short-term outcome in perinatal hypoxia. Biol
Neonate. 2004;86(2):131-7.

95. Trevisanuto D, Picco G, Golin R, Doglioni N, Altinier S, Zaninotto M, Zanardo V. Cardiac Troponin I in asphyxiated neonates. Biol Neonate. 2006;89(3):190-3.

96. Kanik E, Ozer EA, Bakiler AR, Aydinlioglu H, Dorak C, Dogrusoz B, Kanik A, Yaprak I. Assessment of myocardial dysfunction in neonates with hypoxicischemic encephalopathy: is it a significant predictor of mortality? J Matern Fetal Neonatal Med. 2009 Mar;22(3):239-42. doi: 10.1080/14767050802430834.

97. Kecskes Z, Dunster KR, Colditz PB. NSE and S100 after hypoxia in the newborn pig. Pediatr Res. 2005 Nov;58(5):953-7.

98. Fujii EY, Kozuki M, Mu J, Ino Y, Ushioda N, Tomimatsu T, Fukuda H, Kanzaki T, Nakayama M, Murata Y. Correlation of neuron-specific enolase and S100B with histological cerebral damage in fetal sheep after severe asphyxia. Brain Res. 2004 Aug 20;1018(1):136-40.

99. Anderson GW. Studies on the nucleated red cell count in the chorionic capillaries and the cord blood of various ages of pregnancy. Am J Obstet Gynecol 1942; 42: 1–14.

100. Ghosh B, Mittal S, Kumar S, Dadhwal V. Prediction of perinatal asphyxia with nucleated red blood cells in cord blood of newborns. Int J Gynaecol Obstet. 2003 Jun;81(3):267-71.

101. J.P. Phelan, M.O. Ahn, L.M. Korst and G.I. Martin, Nucleated red blood cells: a marker for fetal asphyxia? Am J Obstet Gynecol. 1995 Nov;173(5):1380-4.

102. U. Vatansever, B. Acunaş B, Demir M, Karasalihoglu S, Ekuklu G, Ener S, Pala O. Nucleated red blood cell counts and erythropoietin levels in high-risk neonates, Pediatr Int. 2002 Dec;44(6):590-5.

103. L.M. Korst, J.P. Phelan, M.O. Ahn and G.I. Martin, Nucleated red blood cells: an update on the marker for fetal asphyxia. Am J Obstet Gynecol. 1996 Oct;175(4 Pt
1):843-6.

104. Walsh BH1, Boylan GB, Dempsey EM, Murray DM. Association of nucleated red blood cells and severity of encephalopathy in normothermic and hypothermic infants. Acta Paediatr. 2013 Feb;102(2):e64-7. doi: 10.1111/apa.12086.

105. Walsh BH, Boylan GB, Murray DM. Nucleated red blood cells and early EEG: predicting Sarnat stage and two year outcome. Early Hum Dev. 2011 May;87(5):335-9. doi: 10.1016/j.earlhumdev.2011.01.041.

106. Haiju Z, Suyuan H, Xiufang F, Lu Y, Sun R. The combined detection of umbilical cord nucleated red blood cells and lactate: early prediction of neonatal hypoxic ischemic encephalopathy. J Perinat Med. 2008;36(3):240-7. doi: 10.1515/JPM.2008.035.

107. Ferber A, Fridel Z, Weissmann-Brenner A, Minior VK, Divon MY.Are elevated fetal nucleated red blood cell counts an indirect reflection of enhanced erythropoietin activity? Am J Obstet Gynecol. 2004 May;190(5):1473-5.

108. G. Buonocore, S. Perrone, D. Gioia , Gatti MG, Massafra C, Agosta R, Bracci R. Nucleated red blood cell count at birth as an index of perinatal brain damage; Am J
Obstet Gynecol. 1999 Dec;181(6):1500-5..

109. Sudhin Thayyil, Manigandan Chandrasekaran, Andrew Taylor, Alan Bainbridge, Ernest B. Cady, FInstP, W. K. Kling Chong, Shahed Murad, Rumana Z. Omar, Nicola J. Robertson. Cerebral Magnetic Resonance Biomarkers in Neonatal Encephalopathy: A Metaanalysis.Pediatrics 2010 Jan;125:e382–e395. doi: 10.1542/peds.2009-1046

110. H Barta, A Jermendy, M Kolossvary, G Rudas, M Szabo. Prognostic Performance of Proton of life in asphyxiated neonates. 10.1136/archdischild-2014-307384.408

111. Gluckman P D, Williams C E. When and why do brain cells die? Dev Med Child Neurol. 1992 Nov;34(11):1010-4.
Published
2015-09-30
How to Cite
1.
Dr. Rabindran, Dr D Sharad Gedam. Biomarkers of Birth Asphyxia in Neonates. Biomed Rev: J Basic Appl Med Sci [Internet]. 2015Sep.30 [cited 2021May18];2(3):63-1. Available from: https://biomedicalreview.in/jbams/article/view/18
Section
Review Article