Early Biochemical Indicators of Hypoxic-Ischemic Encephalopathy after Birth Asphyxia

Hypoxic-ischemic encephalopathy (HIE) after perinatal asphyxia is a condition in which serum concentrations of brain-specific biochemical markers may be elevated. Neuroprotective interventions in asphyxiated newborns require early indicators of brain damage to initiate therapy. We examined brain-specific creatine kinase (CK-BB), protein S-100, and neuron-specific enolase in cord blood and 2, 6, 12, and 24 h after birth in 29 asphyxiated and 20 control infants. At 2 h after birth, median (quartiles) serum CK-BB concentration was 10.0 U/L (6.0–13.0 U/L) in control infants, 16.0 U/L (13.0–23.5 U/L) in infants with no or mild HIE, and 46.5 U/L (21.4–83.0 U/L) in infants with moderate or severe HIE. Serum protein S-100 was 1.6 μg/L (1.4–2.5 μg/L) in control infants, 2.9 μg/L (1.8–4.7 μg/L) in asphyxiated infants with no or mild HIE, and 17.0 μg/L (3.2–34.1 μg/L) in infants with moderate or severe HIE 2 h after birth. No significant difference was detectable in serum neuron-specific enolase between infants with no or mild and moderate or severe HIE 2 and 6 h after birth. A combination of serum protein S-100 (cutoff value, 8.5 μg/L) and CK-BB (cutoff value, 18.8 U/L) 2 h after birth had the highest predictive value (83%) and specificity (95%) of predicting moderate and severe HIE. Cord blood pH (cutoff value, <6.9) and cord blood base deficit (cutoff value, >17 mM) increase the predictive values of protein S-100 and CK-BB. We conclude that elevated serum concentrations of protein S-100 and CK-BB reliably indicate moderate and severe HIE as early as 2 h after birth.

[1]  A. David Edwards,et al.  Assessment of Neonatal Encephalopathy by Amplitude-integrated Electroencephalography , 1999, Pediatrics.

[2]  A. Raabe,et al.  Serum S-100 and neuron-specific enolase for prediction of regaining consciousness after global cerebral ischemia. , 1998, Stroke.

[3]  H. Sarnat,et al.  Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. , 1976, Archives of neurology.

[4]  D. Warner Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia. , 1993 .

[5]  J. R. Moore,et al.  COMPARISON OF TWO METHODS OF PREDICTING OUTCOME IN PERINATAL ASPHYXIA , 1986, The Lancet.

[6]  M. Blennow,et al.  Glial Fibrillary Acidic Protein in the Cerebrospinal Fluid: A Possible Indicator of Prognosis in Full-Term Asphyxiated Newborn Infants? , 1995, Pediatric Research.

[7]  P. Halligan,et al.  Is there a relationship between serum S-100β protein and neuropsychologic dysfunction after cardiopulmonary bypass? , 2000 .

[8]  A. Martín-Ancel,et al.  Interleukin-6 in the cerebrospinal fluid after perinatal asphyxia is related to early and late neurological manifestations. , 1997, Pediatrics.

[9]  P. Eken,et al.  Prognostic value of early somatosensory evoked potentials for adverse outcome in full-term infants with birth asphyxia , 1991, Brain and Development.

[10]  R. Cuestas Creatine Kinase Isoenzymes in High-Risk Infants , 1980, Pediatric Research.

[11]  MartinWiesmann,et al.  S-100 Protein and Neuron-Specific Enolase Concentrations in Blood as Indicators of Infarction Volume and Prognosis in Acute Ischemic Stroke , 1997 .

[12]  G. Ellis,et al.  Assessment of neurologic outcome in asphyxiated term infants by use of serial CK-BB isoenzyme measurement. , 1982, The Journal of pediatrics.

[13]  M. Wiesmann,et al.  S-100 protein and neuron-specific enolase concentrations in blood as indicators of infarction volume and prognosis in acute ischemic stroke. , 1997, Stroke.

[14]  J. Quero,et al.  Serum CPK–BB Isoenzyme in the Assessment of Brain Damage in Asphyctic Term Infants , 1987, Acta paediatrica Scandinavica.

[15]  L. Lindberg,et al.  Serum S-100 protein levels after pediatric cardiac operations: a possible new marker for postperfusion cerebral injury. , 1998, The Journal of thoracic and cardiovascular surgery.

[16]  D. Hilt,et al.  The S100 protein family. , 1988, Trends in biochemical sciences.

[17]  D. Hilt,et al.  The S 100 protein family , 1988 .

[18]  Peggy Wu,et al.  Measurement of the urinary lactate:creatinine ratio for the early identification of newborn infants at risk for hypoxic-ischemic encephalopathy. , 1999, The New England journal of medicine.

[19]  C. Fitz,et al.  The prognostic value of computed tomography as an adjunct to assessment of the term infant with postasphyxial encephalopathy. , 1981, The Journal of pediatrics.

[20]  H. Hagberg,et al.  Neuron specific enolase in asphyxiated newborns: association with encephalopathy and cerebral function monitor trace. , 1995, Archives of disease in childhood. Fetal and neonatal edition.

[21]  H. Lassmann,et al.  Induction of experimental autoimmune encephalomyelitis by CD4+ T cells specific for an astrocyte protein, Sl00ß , 1997 .

[22]  C. Rider,et al.  Evidence for a new form of enolase in rat brain. , 1975, Biochemical and biophysical research communications.

[23]  A. Hamberger,et al.  Excitatory amino acids in the cerebrospinal fluid of asphyxiated infants: relationship to hypoxic‐ischemic encephalopathy , 1993, Acta paediatrica.

[24]  I. Rosén,et al.  Predictive value of early continuous amplitude integrated EEG recordings on outcome after severe birth asphyxia in full term infants. , 1995, Archives of disease in childhood. Fetal and neonatal edition.

[25]  M. Levene,et al.  The Use Of A Calcium‐Channel Blocker, Nicardipine, For Severely Asphyxiated Newborn Infants , 1990, Developmental medicine and child neurology.

[26]  M. Sherman,et al.  Interventions for perinatal hypoxic-ischemic encephalopathy. , 1998, Pediatrics.

[27]  F. Suzuki,et al.  Induction of adipose S-100 protein release by free fatty acids in adipocytes. , 1986, Biochimica et biophysica acta.

[28]  H. Przuntek,et al.  Serum levels of neuron-specific enolase and s-100 protein after single tonic-clonic seizures , 1999, Journal of Neurology.

[29]  M. Hennerici,et al.  Leakage of brain-originated proteins in peripheral blood: temporal profile and diagnostic value in early ischemic stroke , 1997, Journal of the Neurological Sciences.

[30]  Richard H. Paul,et al.  Asphyxial complications in the term newborn with severe umbilical acidemia. , 1992 .

[31]  J. Brown,et al.  An international network for evaluating neuroprotective therapy after severe birth asphyxia. , 1999, Seminars in perinatology.

[32]  C. Alling,et al.  Serum S100 protein: a potential marker for cerebral events during cardiopulmonary bypass. , 1996, The Annals of thoracic surgery.

[33]  A. Edwards,et al.  Mild Hypothermia after Severe Transient Hypoxia-Ischemia Ameliorates Delayed Cerebral Energy Failure in the Newborn Piglet , 1995, Pediatric Research.

[34]  N. Finer,et al.  Hypoxic-ischemic encephalopathy in term neonates: perinatal factors and outcome. , 1981, The Journal of pediatrics.

[35]  J. Perlman,et al.  Renal injury in the asphyxiated newborn infant: relationship to neurologic outcome. , 1988, The Journal of pediatrics.

[36]  A. García-Alix,et al.  Neuron-specific enolase and myelin basic protein: relationship of cerebrospinal fluid concentrations to the neurologic condition of asphyxiated full-term infants. , 1994, Pediatrics.

[37]  V. J. Britton,et al.  Creatine kinase isoenzyme activity in human placenta and in serum of women in labor. , 1977, Clinical chemistry.

[38]  Marzena Wylezinska,et al.  Delayed (“Secondary”) Cerebral Energy Failure after Acute Hypoxia-Ischemia in the Newborn Piglet: Continuous 48-Hour Studies by Phosphorus Magnetic Resonance Spectroscopy , 1994, Pediatric Research.

[39]  Y. Kim,et al.  Serial measurement of interleukin-6, transforming growth factor-beta, and S-100 protein in patients with acute stroke. , 1996, Stroke.