Levels of Neuron-Specific Enolase and S-100B in the Serum of Neonates in Early Diagnosis of Possible Neurotoxic Effects of Hyperbilirubinemia/ Hiperbilirubineminin Olası Erken Nörotoksik Etkilerini Belirlemede, Yenidoğanların Serumunda Neuron-Spesifik Eno

Yıl 2015, Cilt: 22 Sayı: 1, 3 - 7, 10.04.2015

Fatih Kışlal Dilek Sarıcı Nilgün Altuntaş Aydın Çelik Okhan Akın Mesut Koçak Aslı Çelebi Tayfur

Öz

Abstract

Aim: The laboratory and imaging methods are not sufficiently sensitive to determine precisely the neurotoxic effects of bilirubin in neonates. The neuron-specific enolase and calcium binding protein B, which are sensitive biomarkers of cellular damage in the central nerve system, were used in the present study to demonstrate possible neurotoxic effects of bilirubin below 20 mg/dL. We hypothesized that neuron-specific enolase and calcium binding protein B might be helpful for our purposes.

Material and Methods: The present study included 33 full-term infants hospitalized for phototherapy treatment (patient group) along with 29 healthy full-term infants (control group). The serum bilirubin levels of the patient group were all below 20 mg/dl. Two serum samples were obtained from all 62 infants at an interval of at least 48hrs which were used for the measurement of bilirubin, calcium binding protein B, and neuron-specific enolase levels.

Results: There was no significant difference in terms of the serum levels of calcium binding protein B between the patient and control groups but there was a significant difference of the serum levels of neuron-specific enolase between the groups. In addition, there were no significant changes in the levels of calcium binding protein B and neuron-specific enolase among the patient group before and after the phototherapy.

Conclusion: We conclude that, considering the serum levels of calcium binding protein B and neuron-specific enolase, a serum bilirubin level of <20mg/dL had no neurotoxic effect on the central nerve system. The results of the present study are consistent with the accepted safe level of bilirubin, <20mg/dL, in a full-term newborn.

Key Words: Bilirubin Encephalopathy; Neonatal Hyperbilirubinemia; Neuron-Specific Enolase; Calcium Binding Protein B.

 Özet

Amaç: Yenidoğanlarda bilirubinin nörotoksik etkisini tam olarak göstermede, kullanılan laboratuvar ve görüntüleme metodları yeterince hassas değildir. Çalışmamızda 20mg/dl’in altındaki bilirubinin muhtemel nörotoksik etkisini gösterebilmek için, santral sinir sistemindeki hücresel hasarı gösteren hassas belirteçler olan nöron-spesifik enolaz ve kalsiyum bağlayıcı protein B kullanıldı. Çalışmamız nöron-spesifik enolaz ve kalsiyum bağlayıcı protein B düzeylerini ölçmenin, bu amaç için uygun olabileceği hipotezi üzerine kurgulandı.

Gereç ve Yöntemler: Çalışmada fototerapi tedavisi için hastaneye yatışı yapılan 33 term bebek (hasta gurubu) ve 29 sağlıklı term bebek (kontrol grubu) yer aldı. Fototerapi alması gereken bebeklerin serum bilirubin düzeyleri 20mg/dl’nin altında idi. Bütün bebeklerden, bilirubin, nöron-spesifik enolaz ve kalsiyum bağlayıcı protein B seviyelerini ölçmek için, en az 48 saat arayla iki serum örneği alındı.

Bulgular: Hasta ve kontrol gruplarının kalsiyum bağlayıcı protein B seviyeleri arasında anlamlı bir fark bulunmadı fakat nöron-spesifik enolaz değerleri arasında anlamlı bir fark bulundu. Hasta grubunda fototerapi öncesi ve sonrası nöron-spesifik enolaz ve kalsiyum bağlayıcı protein B değerleri arasında anlamlı bir değişim gözlenmedi.

Sonuç: Kalsiyum bağlayıcı protein B ve nöron-spesifik enolaz serum düzeyleri referans alındığında, 20mg/dl’in altındaki serum bilirubin değerlerinin nörotoksik etkisi olmadığı sonucuna vardık. Bu çalışmanın sonuçları, term bebeklerde kabul edilen güvenli bilirubin seviyesi olan 20mg/dl ile uyumludur.

Anahtar Kelimeler: Bilirubin Ensefalopati; Neonatal Hiperbilirubinemi; Nöron-Spesifik Enolaz; Kalsiyum Bağlayıcı Protein B.

Anahtar Kelimeler

Bilirubin Ensefalopati; Neonatal Hiperbilirubinemi; Nöron-Spesifik Enolaz; Kalsiyum Bağlayıcı Protein B

Kaynakça

• Stoll BJ, Kliegman RM. Jaundice and hyperbilirubinemia in the newborn. In: Behrman RE, Kliegman RM, Jenson HB. (eds) Nelson Textbook of Pediatrics. Saunders Comp. (19th edition) 2011:608-12.
• Provisional Committee for Quality Improvement and Sub-committee on Hyperbilirubinemia, American Academy of Pediatrics. Practice parameter: Management of hyperbilirubinemia in the healthy term newborn. Pediatrics 1994;94:558-65.
• Shapiro SM, Popelka GR. Auditory impairment in infants at risk for bilirubin-induced neurologic dysfunction. Semin Perinatol 2011;35:162-70.
• Gürses D, Kiliç I, Sahiner T. Effects of hyperbilirubinemia on cerebrocortical electrical activity in newborns. Pediatr Res 2002;52:125-30.
• Haimoto H, Hosoda S, Kato K. Differential distribution of immunoreactive S100α and S100B proteins in normal non-nervous human tissues. Lab Invest 1987;57:489-98.
• Yang Q, Hamberger A, Hyden H, Wang S, Stigbrand T, Haglig KG. S100B has a neuronal localization in the hindbrain revealed by an antigen retrieval method. Brain Res 1995;696:49-61.
• Gazzolo D, Marinomi E, Iorio RD, Bruschettini M, Kornacka M, Lituania M et al. Urinary S100 B protein measurements: A tool for early identification of hypoxic ischemic encephalopathy in asphyxiated full-term infants. Crit Care Med 2004;32:131-6.
• Berger RP, Beers SR, Richichi R, Wiesman D, Adelson PD. Serum biomarker concentrations and outcome after pediatric traumatic brain injury. J Neurotrauma 2007;24:1793-801.
• Akelma AZ, Celik A, Ozdemir O, Kavak Akelma F, Abaci A, Razi CH et al. Neuron-specific enolase and S100B protein in children with carbon monoxide poisoning: children are not just small adults. Am J Emerg Med 2013;31:524-8.
• 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 Ed.1995;72:39-42.
• Celtik C, Acunaş B, Oner N, Pala O. Neuron-specific enolase as a marker of the severity and outcome of hypoxic ischemic encephalopathy. Brain Dev 2004;26:398-402.
• Shiihara T, Miyake T, Izumi S, Watanabe M, Kamayachi K, Kodama K et al. Serum and cerebrospinal fluid S100B, neuron-specific enolase, and total tau protein ain acute encephalopathy with biphasic seizures and late reduced diffusion: a diagnostic validity. Pediatr Int 2012;54:52-5.
• Thorngren-Jerneck K, Alling C, Herbst A, Amer-Wahlin I, Marsal K. S100 protein in serum as a prognostic marker for cerebral injury in term newborn infants with hypoxic ischemic encephalopathy. Pediatr Res 2004;55:406-12.
• 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.
• Kristina TJ, Christer A, Andreas H, Isisi AW, Karel M. S-100 protein in serum as a prognostic marker for cerebral injury in term newborn infants with hypoxic encephal encephalopathy. Pediatr Res 2004;55:406-12.
• Gazzolo D, Marinomi E, Iorio RD, Bruschettini M, Kornacka M, Lituania M et al. Measurement of urinary S100 B protein concentration for the early identification of brain damage in asphyxiated full-term infants. Arch Pediatr Adolesc Med 2003;157:1163-8.
• Gazzolo D, Di lorio R, Marinomi E, Marinoni E, Lituania M, Marras M et al. S100B protein is increased in asphyxiated term infant developing intraventriculer hemorrhage. Crit Care Med 2002;30:1356-60.
• Gazzolo D, Vinesi P, Bartocci M, Geloso MC, Bonacci W, Serra G et al. Elavetad S100 blood level as early indicators of intraventriculer hemorrhage in preterm infants. Correlation with cerebral Doppler Velocimetry. J Neurol Sci 1999;170:32-5.
• Garcia-Alix A, Cabanas F, Pellicer A, Stinis TA, Quero J, Hernans A. Neuron specific enolase and myelin basic protein: relationship of cerebrospinal fluid concentration to the neurological of asphyxiated full-term infants. Pediatrics 1994;93:234-40.
• Massaro AN, Chang T, Kadom N, Tsuchida T, Scafidi J, Glass P et al. Biomarkers of brain injury in neonatal encephalopathy treated with hypothermia. J Pediatr 2012;16:434-40.
• AAP Subcommittee on Neonatal Hyperbilirubinemia. Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation. Pediatrics 2004;114:297-316.
• Grimmer I, Berger-Jones K, Bührer C, Brandl U, Obladen M. Late neurological sequela of non-hemolytic hyperbilirubinemia of healthy term neonates. Acta Paediatr Scand 1999;88:661-3.
• Ozmert E, Erdem G, Topcu M, Yurdakök M, Tekinalp G, Genç D et al. Long-term follow-up of indirect hyperbilirubinemia in full-term Turkish infants. Acta Paediatr Scand 1996;85:1440-4.
• Semba R, Kato K. Increased nervous system-specific enolases in rat plasma and cerebrospinal fluid in bilirubin encephalopathy detected by an enzyme immunoassay. J Neurochem 1982;39:360-5.
• Akman I, Özek E, Kulekçi S, Türkdoğan D, Cebeci D, Akdaş F. Auditory neuropathy in hyperbilirubinemia: is there a correlation between serum bilirubin, neuron specific enolase and auditory neuropathy? Int J Audiol 2004;43:516-22.
• Okumus N, Turkyilmaz C, Onal EE, Atalay Y, Serdaroğlu A, Elbeg S et al. Tau and S100B proteins as biochemical markers of bilurubin-ınduced neurotoxity in term neonates. Pediatr Neurol 2008;39:245-52.