Home About us Editorial board Search Ahead of print Current issue Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 2  |  Page : 588-594

Umbilicalcord S100B protein in neonatal hypoxic–ischemic encephalopathy


1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
3 Department of Pediatrics, El Shohadaa Central Hospital, Menoufia, Egypt

Date of Submission30-Nov-2016
Date of Acceptance01-Mar-2017
Date of Web Publication25-Sep-2017

Correspondence Address:
Amr A.H. Elsisy
Faculty of Medicine, Menoufia University, Shebin Elkoom, Menoufia Governorate, 32511
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_655_16

Rights and Permissions
  Abstract 

Objective
The aim of this study was to highlight the importance of cord blood S100B protein in the diagnosis of neonatal hypoxic–ischemic encephalopathy and determination of its severity.
Background
S100B is a calcium-binding protein and is a major component of the cytosol in various cell types. The S100B exerts significant influence on cellular metabolism, Ca2+homeostasis, cytoskeletal modification, cell proliferation, and cell differentiation. The presence of S100B in the cerebrospinal fluid, serum, and amniotic fluid above threshold levels is used for diagnostic/prognostic purposes.
Patients and methods
This study included 30 asphyxiated newborns and 23 weight and gestational age-matched healthy neonates as controls. Immediately after birth, blood samples were collected from all neonates and values of S100B protein were determined using enzyme-linked immunosorbent assay technique.
Results
The mean serum level of S100B protein was significantly higher in the asphyxiated group than in the control group with a significant correlation between increased S100B protein level and severity of hypoxic–ischemic insult among patients. We found that at the cutoff level for serum S100B protein of 0.44μg/l, the sensitivity was 97%, specificity was 91%, and accuracy of predicting neonatal asphyxia was 94%, with a positive predictive value of 94% and a negative predictive value of 95%.
Conclusion
It was concluded that S100B protein in the umbilical cord blood is a useful marker for early detection of neonatal hypoxic–ischemic encephalopathy in the full-term neonate and also in determining the grade of hypoxia.

Keywords: encephalopathy, ischemia, neonatal hypoxia, S100B protein


How to cite this article:
El-Meshad GM, El-Lahoney DM, Barseem NF, Helwa MA, Elsisy AA. Umbilicalcord S100B protein in neonatal hypoxic–ischemic encephalopathy. Menoufia Med J 2017;30:588-94

How to cite this URL:
El-Meshad GM, El-Lahoney DM, Barseem NF, Helwa MA, Elsisy AA. Umbilicalcord S100B protein in neonatal hypoxic–ischemic encephalopathy. Menoufia Med J [serial online] 2017 [cited 2019 Apr 18];30:588-94. Available from: http://www.mmj.eg.net/text.asp?2017/30/2/588/215474


  Introduction Top


Neonatal encephalopathy is the clinical phenotype characterized by a syndrome of disturbed neurologic function in the earliest days of life in term infants, manifested by difficulty with initiating and maintaining respiration, depression of tone and reflexes, subnormal level of consciousness, and often by seizures[1]. The incidence in developed countries is estimated to be 1.5 per 1000 live births[2], and estimates in developing countries range from 2.3 to 26.5 per 1000 live births[3].

Hypoxic–ischemic encephalopathy(HIE) may be due to any condition leading to decreased oxygen supply(hypoxia) and decreased blood supply(ischemia). With hypoxia and ischemia, the brain converts to anaerobic metabolism, resulting in the depletion of adenosine triphosphate and accumulation of lactic acid and free radicals[4]. In term neonates, 90% of asphyxia insults occur during the antepartum or intrapartum period as a result of placental insufficiency, and the remaining 10% occurs postpartum, usually secondary to pulmonary, cardiovascular, or neurologic disorders[5].

The pathway of cerebral injury in the term infant with HIE is not always clear. Many factors, including the etiology, extent of hypoxia or ischemia, maturational stage of the brain, regional cerebral blood flow, and general health of the infant before the injury, can all impact the pattern and extent of brain injury as well as the outcome following injury[6].

The development of brain injury after hypoxic–ischemic insult is an evolving process imitated during the acute insult and extending into a reperfusion phase. The principle pathogenic mechanism underlying neurological damage in HIE resulting from hypoxemia/ischemia or both is deprivation of glucose and oxygen supply, which causes a primary energy failure and initiates a cascade of biochemical events leading to cell dysfunction and ultimately to cell death[7].

The diagnosis of perinatal asphyxia is primarily based on assessment of the general health of the infant(Apgar score), confirmation of the presence of a metabolic acidosis(cord blood pH and base deficit), and the need for resuscitation. If an episode of asphyxia results in central nervous system dysfunction, this neuronal injury is called neonatal encephalopathy[8].

In 1976, Sarnat and Sarnat designed a score, the Sarnat score, which was a combination of neurological symptoms, as described above, and the accompanying electroencephalographic features. This score was in fact a grading of the severity of the encephalopathy caused by the perinatal hypoxia–ischemia. It contains three stages, HIE stage 1, HIE stage 2, and HIE stage 3, the last stage being the most severe stage of encephalopathy. The most severely affected infants typically progress from stage 1 to stage 3[9].

Asphyxia can lead to multiorgan dysfunction and a redistribution of cardiac output to maintain cerebral, cardiac, and adrenal perfusion while potentially compromising renal, gastrointestinal, and skin perfusion[10].

The aim of this study was to highlight the importance of cord blood S100B protein in the diagnosis of neonatal HIE and determination of its severity.


  Patients and Methods Top


This cross-sectional study was conducted on 30 asphyxiated full-term neonates delivered in Shebin El-Kom Teaching Hospital during a period of 6months from January 2016 to June 2016. These were compared with 23 age-matched apparently healthy term neonates as a control group with no obstetrical problems.

Inclusion criteria

Inclusion criteria were as follows: profound metabolic or mixed acidosis in an umbilical artery blood sample; persistence of an Apgar score of 0–3 for longer than 5min; neonatal neurologic complications(e.g.,seizures and coma); and multiple organ involvement(e.g.,the kidney, lung, liver, heart, and intestines)[11].

Exclusion criteria

Exclusion criteria were as follows: prematurity, traumatic brain injuries, maternal drug addiction, major congenital malformation, Down's syndrome, intrauterine infection, and general anesthesia during birth process.

All cases and controls were subjected to the following: full maternal history with special emphasis on medical and obstetric data at delivery, including the mode of delivery; Apgar score at 1 and 5min and resuscitation data; assessment of gestational age using the Ballard scoring system; anthropometric measurements(head circumference, weight, and length), evaluation of vital signs and socioeconomic status; full systemic examination; and neurological examination with the assessment of severity of HIE using Sarnat's staging.

Serum sampling and determination of S100B protein level

Cord blood samples were collected as early as possible immediately after birth and analyzed for arterial blood gases. Blood film was prepared to measure the level of nucleated red blood cells(RBCs). Avolume of 1ml of cord blood sample was collected from all neonates included in the study, and it was centrifuged at 2500rpm. for 5min and frozen at–80°C for a maximum of 6months. S100B protein level was measured in these samples.

The kit was based on standard sandwich enzyme-linked immunosorbent assay technology. The purified anti-S100B antibody was precoated onto 96-well plates, and the horseradish peroxidase-conjugated anti-S100B antibody was used as detection antibodies. The standards, test samples, and HRP-conjugated detection antibody were added to the wells, and mixed and incubated; thereafter, unbound conjugates were washed away with wash buffer. tetramethylbenzidine (TMB) substrates (A and B) were used to visualize HRP enzymatic reaction. TMB was catalyzed by HRP to produce a blue color product that changed to yellow color after adding acidic stop solution. The density of the yellow product is proportional to the S100B amount of sample captured in plate. The optical density absorbance was read at 450nm in a microplate reader, and then the concentration of S100B was calculated(Chongqing Biospes Co. Ltd Chongqing, China).

This study has been approved by the ethical committee of Faculty of Medicine, Menoufia University. Moreover, informed consent from parents of each studied neonate was obtained.


  Results Top


In the present study, there was no significant difference between the asphyxiated and the nonasphyxiated groups with regard to gestational age, birth weight, sex consanguinity, socioeconomic status, and mode of delivery[Table1]. Accordingto our results, the maternal history included premature rupture of membranes, antepartum hemorrhage, pre-eclampsia, and history of previous pregnancies, delivery, or abortion, but they were not significant risk factors for the increased incidence of HIE[Table2]. In our study, there was a highly significant difference between the two studied groups with regard to clinical manifestations: cyanosis, 21cases in the asphyxiated group; abnormal resting posture (distal flexion and frog leg position), 16cases in the asphyxiated group; abnormal consciousness (stupor, lethargy, and comatose), 19cases in the asphyxiated group; abnormal muscle tone(hypotonia and flaccidity), 18cases in the asphyxiated group; poor or absent suckling reflex, 24cases in the asphyxiated group; absent Moro reflex, 19cases in the asphyxiated group; and convulsions, 18cases in the asphyxiated group(P<0.001). Other clinical manifestations showed a significant difference between the two groups: abnormal respiratory pattern(rapid deep, rapid shallow, and apnea), 16cases in the asphyxiated group, and grunting with respiration, nine cases in the asphyxiated group(P=0.001). Other clinical manifestations showed no significant difference between the two groups, such as pallor or birth injuries(P>0.05)[Table3]. In the present study, Apgar scores at 1 and 5min were significantly lower in cases(with mean values of 2.07±0.83 and 3.97±0.89, respectively) when compared with controls. As regards arterial blood gases, our results showed that the mean pH(7.11±0.11), PaO2(55.71±9.41mmHg), PaCO2(37.29±5.32mmHg), HCO3(13.51±2.38 mmol/l), and base excess (BE) (14.17±2.13 mmol/l) were significantly lower in hypoxic newborns when compared with the control group. The present study showed that the mean serum level of S100B protein was significantly higher in the HIE group(0.72±0.17μg/l) compared with the control group(0.24±0.14μg/l), and the percentage of cases that had nucleated RBCs in the blood was 70.6% in comparison with controls(29.4%)[Table4]. In addition, there was a strong correlation between increased concentrations of S100B protein in serum and the severity of HIE in the patient group[Table5]. This study demonstrated a highly significant negative correlation between serum S100B protein level and Apgar score at 1 and 5min. Moreover, there was a highly significant negative correlation between serum S100B protein level and arterial pH and PaO2, whereas a highly significant positive correlation was found between serum S100B protein and base excess[Table6]. According to our results, the best cutoff value of serum S100B protein in predicting HIE was 0.44μg/l(P<0.001), with a sensitivity of 97%, specificity of 91%, positive predictive value(PPV) of 94%, negative predictive value(NPV) of 95%, and diagnostic accuracy of 94%[Figure 1]. Moreover, our results showed that the best cutoff value for nucleated red blood cells(NRBCs) was 5 NRBCs/100 white blood cells(WBC) to detect hypoxia with a sensitivity of 80%, specificity of 78%, PPV of 83%, NPV of 75%, and diagnostic accuracy of 79%[Figure 2].
Figure 1: Receiver operating characteristic (ROC) curve to determine the sensitivity and specificity of serum S100B protein with a cutoff point of 0.44 μg/l to diagnose hypoxic–ischemic encephalopathy. Area under curve: 0.967.

Click here to view
Figure 2: Receiver operating characteristic (ROC) curve to determine the sensitivity and specificity of nucleated red blood cells (normoblasts) with cutoff point of 5 nucleated red blood cells/100 white blood cells to diagnose hypoxic–ischemic encephalopathy. Area under curve: 0.806.

Click here to view
Table 1: Sociodemographic data, anthropometric measures, and mode of delivery of the studied groups

Click here to view
Table 2: Comparison between the studied groups as regards their maternal history

Click here to view
Table 3: Comparison between the studied groups as regards their clinical picture

Click here to view
Table 4: Comparison between the two groups as regards Apgar score and laboratory investigations

Click here to view
Table 5: Comparison between the Sarnat stages as regards serum level of S100B protein (n=30)

Click here to view
Table 6: Correlation between S100B protein level and arterial blood gas and Apgar score at 1 and 5 min among cases

Click here to view



  Discussion Top


HIE remains a serious condition, causing significant mortality and long-term morbidity. Despite major advances in monitoring technology and knowledge of fetal and neonatal pathologies, perinatal asphyxia remains a major concern[12].

The mechanism of damage from hypoxic–ischemic insult involves a series of events such as a decrease in intracellular energy, a decrease in membrane Na +and K +-ATPase activity, an increase in intracellular Ca 2+, and membrane lipid peroxidation[13].

There are some studies on S100B protein level as a marker for HIE and evaluation of S100B protein level in different HIE clinical stages caused by perinatal asphyxia.

The aim of the present study was to highlight the importance of cord blood S100B protein in the diagnosis of neonatal HIE in full-term neonates and thus could be marker in these cases.

In our results there was no statistically significant difference between the HIE and control groups as regards sex, mode of delivery, weight, and gestational age.

There was no sex difference as regards hypoxic insult. This is in accordance with that reported by other authors(Tekgul etal. [14] and Kirimi etal.[15]. However, Futrakual etal. [16] found a significant relation between HIE and male sex in their study as risk factors for HIE.

There was no statistically significant difference between the HIE and the control group as regards the mode of delivery, and this is in accordance with other authors[14],[15],[17],[18]. However, Kaye [19] and Zhang etal. [20] stated that cesarean section was highly associated with HIE, and Butt etal. [21] found that HIE developed in 76.5% of vaginal delivered cases, whereas cesarean section occurred in 23.5% of cases. The variation in different studies concerning mode of delivery may be attributed to the fact that neonatal encephalopathy may originate early in the antepartum period in some cases of HIE.

There was no statistically significant difference between the HIE and the control group as regards gestational age. This is in accordance with the findings of Vasiljevic etal.[22]. Futrakual etal. [16] stated that gestational age, particularly post-term gestation, is significantly associated with HIE; this might be related to the uteroplacental insufficiency.

The current study showed no statistically significant difference between the HIE and control groups as regards birth weight. This is in accordance with the findings of Ghotbi and Najibi[23], but Aired [24] reported that infants with intrauterine growth retardation play a significant role in the occurrence of severe asphyxia due to placental insufficiency. This conflict may be attributed to deprivation of our sample from cases with intrauterine growth retardation.

In the present study, the median of Apgar score at 1 and 5min was 2 and 4, respectively, and it was significantly lower than that in the control group, which had a normal Apgar score(6–10 at 1 and 5min). Cases showed a statistically significantly low Apgar score compared with controls, and this is in agreement with the findings of Karlsson etal.[25].

In the present study, we found that nucleated RBCs can be a reliable marker to detect hypoxia, but there are many markers superior to it as its sensitivity was 80%, specificity was 78%, PPV was 83%, NPV was 75%, and diagnostic accuracy was 79% with a cutoff point of 5 NRBCs/100 WBC. This is in accordance with the findings of Boskabadi etal.[26], who showed a sensitivity of 83.4% and a specificity of 73.5% for nucleated RBCs. Moreover, Lailah etal. [27] found that nucleated RBC count was reliable in detecting HIE as area under the curve was 84% and the best cutoff for nucleated RBC in diagnosing hypoxia was greater than 4.5/100 WBCs with a sensitivity of 77%, specificity of 83%, PPV of 82%, and NPV 78% with a diagnostic accuracy of 80%.

In the present study, S100B protein levels were significantly higher in hypoxic than in healthy newborns. This is in accordance with the findings of Beharier etal. [28] and Douglas-Escobar and Weiss[29].

The mean S100B protein in the asphyxiated group was 0.72μg/l, whereas the mean S100B protein in the control group was 0.24μg/l. This is in agreement with the findings of Sofijanova etal.[30], who found that the mean S100B protein in asphyxiated newborn was 0.642μg/l, and in the control group the mean S100B was 0.119μg/l. In addition, S100B protein cutoff point was 0.12μg/l for predicting HIE. This is in agreement with the present study, in which S100B protein cutoff point was 0.44μg/l. Qian etal. [31] found that umbilical cord arterial blood concentration of S100B more than 2.20 μg/l has a sensitivity of 87% and a specificity of 88% in predicting moderate-to-severe HIE. Thelack of agreement between the study by Qian etal. [31] and the present study may be attributed to the following: first, the two umbilical arteries transport metabolites from the fetus back to the placenta, and hence the biochemical markers in them can reflect the condition of the fetus more accurately; second, it can be attributed to environmental factors and individual variations between western and middle east people.

In the present study serum S100B protein level showed a sensitivity of 97% and specificity of 91%, PPV of 94%, and NPV of 95% with a diagnostic accuracy of 94%, which is superior to other markers such as lactate, which showed a sensitivity of 94% and specificity of 87%[32].

Moreover, S100B protein is superior to other markers such as NRBCs, which showed a sensitivity of 83.4% and specificity of 73.5%[26].

High S100B protein sensitivity and specificity values were observed in the present study for identifying HIE in full-term neonates with low Apgar score or the need for cardiopulmonary resuscitation at birth. These data are important for supporting early diagnosis and being able to opportunely initiate therapeutic measures for preventing mortality and long-term neurological consequences.

The present study compared S100B protein results with the different clinical stages of the Sarnat clinical classification for HIE diagnosis and showed that there was a positive correlation between HIE stage and S100B protein level. This is in accordance with the findings of Qian etal.[31]. However, Nagdyman etal. [33] found that asphyxiated term infants had elevated S100B protein levels in their umbilical vein blood, but no difference was observed between mild and moderate or severe HIE.

Moreover, we found that there were significant correlations between umbilical cord blood S100B protein and PH, BE, and Apgar score at 1 and 5min. This is in agreement with the findings of Qian etal.[30], who stated that there was a close correlation between the S100B protein in arterial cord blood and pH(r=−0.74, P <0.001), and the correlation was even stronger between S100B protein and BE(r=−0.79, P <0.001). As expected, S100B protein also correlated significantly to the Apgar score at 1min(r=−0.65, P <0.001) and the Apgar score at 5min(r=−0.72, P <0.001).


  Conclusion Top


The measurement of S100B protein in the umbilical cord blood is rapid, noninvasive, inexpensive, and simple to perform, and could possibly become a useful marker for early detection of HIE in the full-term neonate and also in determining the severity of the disease and subsequently the short-term outcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
RamaswamyV, HortonJ, VandermeerB, BuscemiN, MillerS, YagerJ. Systematic review of biomarkers of brain injury in term neonatal encephalopathy. Pediatr Neurol 2009; 40:215–226.  Back to cited text no. 1
    
2.
KurinczukJJ, White-KoningM, BadawiN. Epidemiology of neonatal encephalopathy and hypoxic–ischemic encephalopathy. Early Hum Dev 2010; 86:329–338.  Back to cited text no. 2
    
3.
HornAR, SwinglerGH, MyerL, HarrisonMC, LinleyLL, NelsonC, etal. Defining hypoxic ischemic encephalopathy in newborn infants: benchmarking in a South African population. JPerinat Med 2013; 41:211–217.  Back to cited text no. 3
    
4.
PerlmanJM. Intervention strategies for neonatal hypoxic ischemic cerebral injury. Clin Ther 2006; 28:1353–1365.  Back to cited text no. 4
    
5.
HigginsRD, ShankaranS. Hypothermia for hypoxic ischemic encephalopathy in infants. Early Hum Dev 2009; 85:49–52.  Back to cited text no. 5
    
6.
GunnAJ, BennetL. Fetal hypoxia and patterns of brain injury. Insights from animal models. Clin Perinatol 2009; 36:579–593.  Back to cited text no. 6
    
7.
VolpeJJ. Neurology of the newborn. 5thed. Philadelphia: Saunders Elsevier; 2008.  Back to cited text no. 7
    
8.
DammannO, FerrieroD, GressensP. Neonatal encephalopathy or hypoxic-ischemic encephalopathy? Appropriate terminology matters. Pediatr Res 2011; 70:1–2.  Back to cited text no. 8
    
9.
SarnatHB, SarnatMS. Neonatal encephalopathy following fetal distress. Aclinical and electroencephalographic study. Arch Neurol 1976; 83:696–705.  Back to cited text no. 9
    
10.
DurkanAM, AlexanderRT. Acute kidney injury post neonatal asphyxia. JPediatr 2011; 158:29–33.  Back to cited text no. 10
    
11.
American Academy of Pediatrics and American College of Obstetrics and Gynecology. Neonatal encephalopathy and cerebral palsy: defining the pathogenesis and pathophysiology. Pedia 2003; 111:316–322.  Back to cited text no. 11
    
12.
ObaidKA. Outcome significance of perinatal versus postnatal fetal depression. Diyala J Med 2011; 1:11–16.  Back to cited text no. 12
    
13.
VannucciRC. Experimental biology of cerebral hypoxia-ischemia: relation to perinatal brain damage. Pediatr Res 1990; 27:317–326.  Back to cited text no. 13
    
14.
TekgulH, YalazM, KutukcherN, GokbenS. Value of biochemical markers for outcome in term infants with asphyxia. Pediatr Neurol 2006; 3:326–332.  Back to cited text no. 14
    
15.
KirimiE, PekerE, TuncerO, YapiciogluH, NarliN, SatarM. Increased serum malondialdehyde level in neonates with hypoxic-ischemic encephalopathy: prediction of disease severity. JInt Med Res 2010; 38:220–226.  Back to cited text no. 15
    
16.
FutrakualS, PraisuwannaP, ThaitumyanonP. Risk factors for hypoxic. Ischemic encephalopathy in asphyxiated newborn infants. JMed Assoc Thai 2006; 89:322–328.  Back to cited text no. 16
    
17.
UzodimmaCC, OkoromahCAN, EkureE, EzeakaCV, NjokanmaFO. Correlation of cardiac troponin T level, clinical parameters and myocardial ischemia in perinatal asphyxia. Niger J Paediatr 2013; 40:165–168.  Back to cited text no. 17
    
18.
MahaAT, SohierSA, HanyME. Study of DNA damage in asphyxiated newborns. Menoufia Med J 2013; 27:50–54.  Back to cited text no. 18
    
19.
KayeD. Antenatal and intra-partum risk factors for birth asphyxia among emergency obstetric referrals in Mulago Hospital, Kampala, Uganda. East Afr Med J 2003; 80:PP30–PP32.  Back to cited text no. 19
    
20.
ZhangH, HaoS, FanX, YangLU, RuopengS. The combined detection of umbilical cord nucleated red blood cells and lactate: early prediction of neonatal hypoxic ischemic encephalopathy. JPerinat Med 2008; 36:240–247.  Back to cited text no. 20
    
21.
ButtTK, FarooquiR, KhanMA. Risk factors for hypoxic ischemic encephalopathy in children. JColl Physicians Surg Pak 2008; 18:428–432.  Back to cited text no. 21
    
22.
VasiljevicB, Maglajlic-DjukicS, GojnicM, StankovicS, IgnjatovicS, LutovacD. New insights into the pathogenesis of perinatal hypoxic-ischemic brain injury. Pediatr Int 2011; 53:454–462.  Back to cited text no. 22
    
23.
GhotbiN, NajibiB. Measurement of the urinary lactate/creatinine ratio for early diagnosis of the hypoxic–ischemic encephalopathy in newborns. Iran J Ped 2010; 20:35–40.  Back to cited text no. 23
    
24.
AiredAI. Birth asphyxia and hypoxic-ischemic encephalopathy: incidence and severity. Ann Trop Paediatr J 1991; 11:331–335.  Back to cited text no. 24
    
25.
KarlssonM, Wiberg-ItzelE, ChakkarapaniE, BlennowM, WinbladhB, ThoresenM. Lactate dehydrogenase predicts hypoxic ischemic encephalopathy in newborn infants. Acta Paediatr 2010; 99:1139–1144.  Back to cited text no. 25
    
26.
BoskabadiH, MaamouriG, SadeghianMH, Ghayour-MobarhanM, HeidarzadeM, ShakeriMT, etal. Early diagnosis of perinatal asphyxia by nucleated red blood cell count. Arch Iran Med 2010; 13:275–281.  Back to cited text no. 26
    
27.
LailahM, NerminR, NagyA, SamiaHR. Early predictions of hypoxic-ischemic encephalopathy by umbilical cord nucleated red blood cells and lactate. Med J Cairo Univ 2011; 79:625–631.  Back to cited text no. 27
    
28.
BeharierO, KahnJ, ShustermanE, SheinerE. S100B–a potential biomarker for early detection of neonatal brain damage following asphyxia. JMatern Fetal Neonatal Med 2012; 25:1523–1528.  Back to cited text no. 28
    
29.
Douglas-EscobarM, WeissMD. Biomarkers of hypoxic-ischemic encephalopathy in newborns. Front Neurol 2012; 3:144.  Back to cited text no. 29
    
30.
SofijanovaA, PiperkovaK, Al KhaliliD. Predicting outcome after sever brain injury in risk neonates using the serum s100b biomarker: results using single(24h) time point*. Contributions Sec Biol Med Sci 2012; XXXIII:147–156.  Back to cited text no. 30
    
31.
QianJ, ZhouD, WangYW. Umbilical artery blood S100 beta protein: a tool for the early identification of neonatal hypoxic-ischemic encephalopathy. Eur J Pediatr 2009; 168:71–77.  Back to cited text no. 31
    
32.
BekenS, Aydın B, DilliD, ErolS, Zenciroğlu A, Okumuş N. Can biochemical markers predict the severity of hypoxic-ischemic encephalopathy? Turk J Pediatr 2014; 56:62–68.  Back to cited text no. 32
    
33.
NagdymanN, KomenW, KoHK, Müller C, ObladenM. Early biochemical indicators of hypoxic–ischemic encephalopathy after birth asphyxia. Pediatr Res 2001; 49:502–506.  Back to cited text no. 33
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table1], [Table2], [Table3], [Table4], [Table5], [Table6]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Patients and Methods
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed357    
    Printed0    
    Emailed0    
    PDF Downloaded62    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]