S100 Protein in Serum as a Prognostic Marker for Cerebral Injury in Term Newborn Infants with Hypoxic Ischemic Encephalopathy

Abstract

The astroglial protein S100 is an established biochemical marker for CNS injury in the adult. The aim was to investigate whether S100 in serum is a prognostic marker of cerebral injury in term newborn infants with hypoxic ischemic encephalopathy (HIE) after perinatal asphyxia. Serum S100 was measured on postnatal days 1-4 in 62 term infants with birth asphyxia. The infants were classified for HIE and had follow-up for at least 18 mo. Infants with moderate and severe HIE had significantly higher S100 levels on postnatal day 1 (p ϭ 0.031) and day 2 (p ϭ 0.008) than infants with mild or no HIE. The levels of S100 decreased on days 2 and 3 in all infants with HIE. The median S100 level on postnatal day 1 was higher in nine infants who died neonatally and in 10 infants who developed cerebral palsy (CP), compared with 43 infants with no signs of impairment at follow up, 14.0 (0.5-60.0) g/L, 20.7 (0.2-64.0) g/L and 5.5 (0.7-120.0) g/L, respectively. A level of S100 above 12 g/L the first day of life was significantly more frequent in infants who died or developed CP than in infants with no impairment at follow up (p ϭ 0.02). Increased S100 levels were significantly inversely correlated with perinatal pH in the infants and associated with abnormal CTG at admission to the labor ward. Early determination of serum S100 may reflect the extent of brain damage in infants with HIE after asphyxia. Abbreviations CP, cerebral palsy CSF, cerebrospinal fluid CTG, cardiotocography FHR, fetal heart rate HIE, hypoxic ischemic encephalopathy S100, S100 protein including the subunits ␣␤ and ␤␤ aEEG, amplitude integrated EEG GFAP, glial fibrillary acidic protein Birth asphyxia remains a considerable problem in perinatal medicine with an incidence around 0.6 -0.8% of births (1-3). About half of these infants develop hypoxic ischemic encephalopathy (HIE) (2, 4). Those with moderate and severe HIE are at high risk of developing cerebral palsy (CP) (5-8). Prognostic assessment of brain injury after perinatal asphyxia will become essential for proper selection concerning early cerebroprotective treatment, which might be a likely option in the near future (9, 10). Several biochemical markers in cerebrospinal fluid (CSF) have been associated with cerebral complications in infants after perinatal asphyxia (11-14) and recently also S100 in CSF (15). A prognostic marker in serum would be of great value. S100 is a calcium binding protein present in the CNS. The dimers ␣␤ and ␤␤ of S100 are mainly specific for the nervous system and present chiefly in the astroglial cells of the CNS (16,17). S100 ␣␣ is present in many organs outside the CNS and will not be discussed in this report, where S100 will be used for the brain-specific S100 with subunits ␣␤ and ␤␤.The astroglial protein S100 is an established biochemical marker for CNS injury in the adult, in whom increased levels of S100 in CSF have been reported after cerebral insults (18,19). S100 in blood has been shown to be a marker of brain damage in adult stroke (20, 21) and a potential marker for c...

Does Serum Osmolarity Change as a Result of the Reflex Neuroprotective Mechanism of Cerebral Osmo-Regulation after Minor Head Trauma?

“…Only two markers seem to have a diagnostic adjunct in adults : neuron-specific enolase (NSE) and S100B protein 5,7,10,13,14,17,28,[34][35][36] . An S100B has been found in astrocytes, bone marrow, fat and skeletal muscle, while NSE has been detected in neurons, platelets and red blood cells 5) .…”

S100B protein related neonatal hypoxia

“…These authors collected blood samples from the 1 s t to the 4 t h day of life and the concentrations in newborn infants with HIE were decre a sing, but above average values found for the contro l s . The authors found a significant correlation between S100B concentrations on the 1 st day and acidosis 18 .…”

“…Significant contributions in the a rea of perinatology, such as in the administration of nitric oxide, brain hemorrhage studies and analysis of amniotic fluid in twins have shown that S100B p rotein is useful as a brain injury marker 1 2 , 1 6 , 1 7 . Addit i o n a l l y, its prognostic role was shown when it was associated with HIE in term newborn infants and a relation with moderate and severe stages could be found 12,18 . The goal of this study was to check if S100B protein could be used as a brain injury marker in term n e w b o rninfants who developed HIE, if its variations show different degrees of involvement and if there is any correlation with other substances, among them, lactate.…”

Cannabinoid as a neuroprotective strategy in perinatal hypoxic-ischemic injury

“…Moreover, the beneficial effect induced by WIN administration was also extended to glial cells, with the maintenance of S100 protein levels (Fig. 1, unpublished data), an early and sensitive biochemical marker of cerebral injury in term newborn infants with hypoxic-ischemic encephalopathy [136][137][138][139][140] . Another group reported that WIN also had a neuroprotective effect on 7-d- old rat forebrain slices exposed to oxygen-glucose deprivation, based on the reductions of glutamate release, TNF-α release and iNOS expression [133] .…”