Protein S100B and Amplitude-Integrated EEG as Early Predictive Methods for Brain Injury and Seizures in Preterm Neonates

Hager Mohammed Elsheikh

Pediatrics Department, Faculty of Medicine, Tanta University, Egypt.

Mai Rabie El-Sheikh

Pediatrics Department, Faculty of Medicine, Tanta University, Egypt.

Tarek Mohammed Algohary

Pediatrics Department, Faculty of Medicine, Tanta University, Egypt.

Abd-Elrahman Mohammed Elmashad

Pediatrics Department, Faculty of Medicine, Tanta University, Egypt.

*Author to whom correspondence should be addressed.


Background: Neonatal brain injury (NBI) is a serious adverse outcome in premature neonates. The most common form of neonatal brain injury (NBI) are intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL). Improved survival of preterm infants leads to short- and long-term hazards of neurological, cognitive, respiratory, digestive, renal, cardiovascular, metabolic, immune, and psychosocial disturbances. We sought to determine the levels and prognostic value of serum S100B and the role of aEEG during the first three days of life in premature neonates (< 37 weeks) that later developed NBI in the form of intraventricular hemorrhage (IVH) or neonatal seizures to rule out the sensitivity and specificity of them in early detection of brain lesions in preterm neonates.

Aim of the Study: To evaluate the role of Protein S100B as an early predictor for neonatal brain injury in preterm neonates and the predictive and prognostic value of amplitude-integrated electroencephalography for neonatal brain injury susceptibility and severity.

Subject and Methods: This study was carried out on 50 preterm neonate (less than 37 weeks GA) who were divided according to presence or absence of brain injury into case and control groups. They were admitted in Neonatal Intensive Care Unit (NICU) of Tanta University Hospital during the period from March 2021 to March 2022.serum S100B at (Day 1 and Day 3), serial trans-cranial sonar and aEEG were done for all patients.

Results: Neonates with NBI, had significantly higher S100B concentration during the first three days of life, its level was higher in the third day than the first day, the cut-off value >810.4 ng/ml serum S100B performed a sensitivity of 72.7%and a specificity of 71.4% to predict adverse neonatal outcome. 60% neonates had normal aEEG and 40% had abnormal aEEG.72.7% of neonates with NBI had abnormal aEEG interpretation. There was a significant relationship between the electrografic seizures on aEEG and occurrence of clinical seizures as 96.7% of neonates who had abnormal aEEG suffered of clinical convulsion.

Conclusion: Protein S100B has a good predictive value regarding NBI in premature neonates and aEEG has a great role in monitoring neonatal brain function and early detection of neonatal seizures.

Keywords: Protein S100B, amplitude-integrated EEG, brain injury, seizures, neonates

How to Cite

Elsheikh, H. M., El-Sheikh, M. R., Algohary, T. M., & Elmashad, A.-E. M. (2023). Protein S100B and Amplitude-Integrated EEG as Early Predictive Methods for Brain Injury and Seizures in Preterm Neonates. Journal of Advances in Medicine and Medical Research, 35(14), 85–93.


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Blencowe H, Cousens S, Oestergaard MZ, et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: A systematic analysis and implications. Lancet. 2012;379:2162-2172.

Frey HA, Klebanoff MA. The epidemiology, etiology, and costs of preterm birth. In Seminars in Fetal and Neonatal Medicine. WB Saunders. 2016;21(2):68-73.

Roze E, Van Braeckel KN, van der Veere CN, et al. Functional outcome at school age of preterm infants with periventricular hemorrhagic infarction. Pediatrics. 2009; 123:1493–1500.

Pisani F, Facini C, Pelosi A, et al. Neonatal seizures in preterm newborns: a predictive model for outcome. European Journal of Paediatric Neurology 2016; 20(2):243-251.

Volpe JJ. Confusions in nomenclature: “Periventricular leukomalacia” and “white matter injury” identical, Distinct, or overlapping? Pediatric Neurology. 2017; 73:3-6.

Bersani I, Pluchinotta F, Dotta A, et al. Early predictors of perinatal brain damage: the role of neurobiomarkers. Clinical Chemistry and Laboratory Medicine (CCLM). 2020;58(4):471-486.

Serpero LD, Pluchinotta F and Gazzolo D. The clinical and diagnostic utility of S100B in preterm newborns. Clinica Chimica Acta. 2015;444:193-198.

Thelin EP, Nelson DW and Bellander BM. Secondary peaks of S100B in serum relate to subsequent radiological pathology in traumatic brain injury. Neurocritical Care. 2014;20(2):217-229.

Huang RZ, Zhang YJ, Zhang JF, et al. Relation between prognosis and changes of MBP and S100B in premature infants with periventricular leukomalacia. Genetics and Molecular Research. 2015;14(2): 4338-4343.

Hagberg H, Edwards AD, Groenendaal F. Perinatal brain damage: The term infant. Neurobiology of Disease. 2016;92: 102-112.

Rosen L, Hellstorm-Westas L, de Vries LS, et al. Amplitude-integrated EEG classification and interpretation in preterm and term infants. Neo Reviews. 2006; 7:76-87.

Olson DM. Neonatal seizures. Neoreviews 2012;13(4):e213-e223.

Metallinou D, Karampas G, Nyktari G, et al. S100B as a biomarker of brain injury in premature neonates. A prospective case–control longitudinal study. Clinica Chimica Acta. 2020;510:781-786.‏

Chiang ML, Chen YW, Yang CY, et al. Elevation of serum S100 protein concentration as a marker of ischemic brain damage in extremely preterm infants. J. Chin. Med. Assoc. 2015;78(10):610–616.

Lu H, Huang W, Chen X, et al. Chang, Relationship between premature brain injury and multiple biomarkers in cord blood and amniotic fluid, J. Matern. Fetal. Neonatal. Med. 2018;31(21):2898–2904.

Olischar M, Klebermass K, Waldhoer T, et al. Background patterns and sleep-wake cycles on amplitudeintegrated electroencephalography in preterms younger than 30 weeks gestational age with peri- / intraventricular haemorrhage. Pediatrics. 2007;1743-1750.

Yang L, Xu W, Yan CY. Background patterns and sleep-wake cycles on amplitude-integrated electroencephalography in preterm infants with periventricular-intraventricular hemorrhage. Zhongguo Dang dai er ke za zhi= Chinese Journal of Contemporary Pediatrics. 2016;18(10):965-970‏.

Hellström-Westas L, Klette H, Thorngren-Jerneck K, et al. Early prediction of outcome with aEEG in preterm infants with large intraventricular hemorrhages. Neuropediatrics. 2001;32(06):319-324.‏

Hellström-Westas L, Rosén I, de Vries LS, et al. Amplitude-integrated EEG Classification and Interpretation in Preterm and Term Infants. NeoReviews. 2006;7: 76-87.

Toso PA, González AJ, Pérez ME,et al. Clinical Utility of early amplitude integrated EEG In monitoring term newborns at risk of neurological injury. J Pediatr (Rio J). 2014; 90:143-8.

Chandrasekaran M, Chaban B, Montaldo P, et al. Predictive value of amplitude-integrated EEG (aEEG) after rescue hypothermic neuroprotection for hypoxic ischemic encephalopathy: A meta-analysis. J. Perinatol. 2017;37:684–689.

Kadivar M, Moghadam EM, Badv RS, et al. A comparison of conventional electroencephalography with amplitude-integrated EEG in detection of neonatal seizures. Medical Devices (Auckland, NZ). 2019;12:489.‏

Klebermass-Schrehof K, Czaba C, Olischar M, et al. Impact of low-grade intraventricular hemorrhage on long-term neurodevelopmental outcome in preterm infants. Childs Nerv Syst. 2012;28:2085-2092.

Osredkar D, Derganc M, Paro-Panjan D, et al. Amplitudeintegrated electro-encephalography in full-term newborns without severe hypoxic-ischemic ence-phalopathy: Case series. Croat. Med. J. 2006;47:285–291.