Serial Protein S-100 Serum Levels in Preterm Babies with Perinatal Asphyxia and Periventricular White Matter Lesions

ABSTRACT

In the last years new diagnostic technologies were developed to assess brain development and to identify early brain injury. Some of them are very attractive methods but invasive, expensive, and time-consuming. The availability of clinically useful serum markers of risk for perinatal brain damage will easily permit the development of rational strategies for prevention of cerebral insults in neonates and more accurate prognostic counseling. In this study, protein S-100 (PS-100), a cytosolic constituent of neuroglial cells, was measured serially, during the neonatal period, in a group of preterm infants suffering perinatal asphyxia. Protein S-100 was measured at 1, 7, and 21 days of life by radioimmunoassay. Cerebral ultrasound confirmed cerebral white matter insult. The results of this study show significantly higher protein S-100 serum levels in asphyxiated preterm babies with periventricular white matter lesions, with a peak at 24 hours of life (5.7 ± 2.9 μg/L) compared with healthy preterm babies (0.6 ± 0.3 μg/L) (p <0.05) and progressively lower values at seven (3.3 ± 2.4 μg/L) and 21 days (2.2 ± 1.3 μ/L) of life (p <0.05). These data suggest that elevated protein S-100 serum levels can be considered an indicator of regional brain damage in preterm infants, allowing noninvasive, superior scrutiny of perinatal asphyxia and potential early preventive strategies.

KEYWORDS

Protein S-100 - perinatal asphyxia - white matter lesion - preterm infant

REFERENCES

• 1 Amato M, Donati F. Update on perinatal hypoxic insult: mechanism, diagnosis and interventions.  Eur J Ped Neurol . 2000;  4 203-209
• 2 Huppi P, Amato M. Advanced magnetic resonance imaging techniques in perinatal brain injury.  Biol Neonate . 2001;  80 7-14
• 3 Vannucci R C, Perlman J M. Interventions for perinatal hypoxic-ischemic encephalopathy.  Pediatrics . 1997;  100 1004-1014
• 4 Gunn A J, Gunn T R, Gunning M I. Neuroprotection with prolonged head cooling started before postischemic seizures in fetal sheep.  Pediatrics . 1998;  102 1098-1106
• 5 Nagdyman N, Komen W, Ko H K. Early biochemical indicators of hypoxic-ischemic encephalopathy after birth asphyxia.  Pediatr Res . 2001;  49 502-506
• 6 Missler U, Wiesmann M, Friedrich C. S-100 protein and neuron-specific enolase concentrations in blood as indicators of infarction volume and prognosis in acute ischemic stroke.  Stroke . 1997;  28 1956-1960
• 7 Persson I, Hardemark H G, Gustaffson J. S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: markers of cell damage in human central nervous system.  Stroke . 1987;  18 911-918
• 8 Volpe J J. Neurology of the Newborn.  3rd ed. Philadelphia: W.B. Saunders 1995: 314-368
• 9 Matus A, Mughal S. Immunohistochemical localization of S-100 protein in brain.  Nature . 1975;  258 746-748
• 10 Volpe J J. Brain injury in the premature infant: neuropathology, clinical aspects and pathogenesis.  MRDD Res Rev . 1997;  3 3-312
• 11 Jonsson H, Johnsson P, Alling C. Significance of serum S100 release after coronary artery bypass grafting.  Ann Thorac Surg . 1998;  65 1639-1644
• 12 Westaby S, Johnsson P, Parry A. Serum S100 protein: a potential marker for cerebral events during cardiopulmonary bypass.  Ann Thorac Surg . 1996;  61 88-92
• 13 Ballard J, Khoury J, Wedig K. New Ballard score, expanded to include extremely premature infants.  J Pediatr . 1991;  119 417-423
• 14 Amato M, Straume B. Iridopupillarmembran zur Bestimmung des Gestationsalters des Fruhgeborenen.  Gynaekol Rundsch . 1981;  21 55-78
• 15 Distefano G, Curreri R, Betta P. Influence of gestational age and perinatal hypoxic insult on protein S-100 serum levels.  Neonatologica . 2000;  1 5-9
• 16 Gluckman P, Pinal C, Gunn A. Hypoxic-ischemic brain injury in the newborn: pathophysiology and potential strategies for intervention.  Semin Neonatal . 2001;  6 109-120
• 17 Huppi P S, Warfield S, Kikinis R. Quantitative magnetic resonance imaging of brain development in premature and mature newborns.  Ann Neurol . 1998;  43 224-235
• 18 Wilson-Costello D, Borawski E, Friedman H. Perinatal correlates of cerebral palsy and other neurologic impairment among very low birth weight children.  Pediatrics . 1998;  102 315-322
• 19 Saliba E, Marret S. Cerebral white matter damage in the preterm infant: pathophysiology and risk factors.  Semin Neonatol . 2001;  6 121-133
• 20 Volpe J J. Brain injury in the premature infant: from pathogenesis to prevention.  Brain Dev . 1997;  19 519-534
• 21 Amato M, Gambon R, Howald H, Von Muralt G. Correlation of raised cord-blood CK-BB and the development of peri-intraventricular hemorrhage in preterm infants.  Neuropediatrics . 1986;  17 173-174
• 22 Amato M, Huppi P, Gambon R. Serum Creatine-kinase-BB concentration in very low birth weight babies with posthemorrhagic ventricular dilatation.  Brain Dev . 1992;  14 226-229
• 23 Walsh P, Jedeikin R, Ellis G. Assessment of neurologic outcome in asphyxiated term infants by use of serial CK-BB isoenzyme measurement.  J Pediatr . 1982;  6 988-992
• 24 Becker M, Menzel K. Brain-typical creatinkinase in the serum of newborn infants with brain damage.  Acta Paediatr Scand . 1978;  67 177-180
• 25 Von Menzel K, Schambach K, Topke B. Bedeutung von Serum CPK Aktivitaet and CPH Isoenzyme fur die Entwicklungsdiagnose asphyktischer Neugeborener.  Kinderaerztl Prax . 1974;  242 413-417
• 26 Meberg A, Hetland O, Sommer F. Creatine kinase in cerebrospinal fluid in newborn infants.  Clin Chim Acta . 1978;  85 95-97
• 27 Amato M, Gambon R, Von Muralt G. Accuracy of Apgar score and arterial cord blood pH in diagnosis of perinatal brain damage assessed by CK-BB isoenzyme measurement.  J Perinat Med . 1986;  14 335-338
• 28 Fellman V, Raivio K O. Reperfusion injury as the mechanism of brain damage after perinatal asphyxia.  Pediatr Res . 1997;  41 599-606
• 29 Williams C E, Gunn A J, Gluckmann P D. Delayed seizures occurring with hypoxic-ischemic encephalopathy in the fetal sheep.  Pediatr Res . 1990;  27 561-565
• 30 Zimmer D B, Cornwall E H, Landar H. The S100 protein family: history, function and expression.  Brain Res Bull . 1995;  37 417-429
• 31 Hardenmark H G, Ericsson N, Kotwica Z. S-100 Protein and neuron-specific enolase in CSF after experimental traumatic or focal ischemic brain damage.  J Neurosurg . 1989;  71 727-731
• 32 Oka A, Belliveau M J, Rosenberg P A, Volpe J J. Vulnerability of oligodendroglia to glutamate: pharmacology, mechanisms and prevention.  J Neurosci . 1993;  13 1441-1453
• 33 Shashoua V E, Hesse G W, Moore B W. Proteins of the brain extracellular fluid: evidence for release of S-100 protein.  J Neurochem . 1994;  42 1536-1541
• 34 Gunn A J, Gluckman P D, Gunn T R. Selective head cooling in newborn infants after perinatal asphyxia: a safety study.  Pediatrics . 1998;  102 885-891
• 35 Thoresen M, Penrice J, Lorek A. Mild hypothermia after severe transient hypoxia-ischemia ameliorates delayed cerebral energy failure in the newborn piglet.  Pediatr Res . 1995;  37 667-670