Serum S100β protein reference values in a paediatric population

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Los resultados se muestran también desglosados por sexos (gris oscuro para varones y gris claro para mujeres). Los grupos de edad entre los que se observan diferencias significativas vienen representados por las letras «a» (< 12 meses) y «b» (12-24 meses y > 24 meses)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Arroyo Hernández, J. Rodríguez Suárez, F. Álvarez Menéndez" "autores" => array:3 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Arroyo Hernández" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Rodríguez Suárez" ] 2 => array:2 [ "nombre" => "F." 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Iriondo, M. Izquierdo, E. Salguero, J. Aguayo, M. Vento, M. Thió" "autores" => array:7 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Iriondo" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Izquierdo" ] 2 => array:2 [ "nombre" => "E." "apellidos" => "Salguero" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Aguayo" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Vento" ] 5 => array:2 [ "nombre" => "M." 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(B) Chest radiograph of the newborn at the time of discharge. (C) Longitudinal lung ultrasound in the same patient, showing a diffuse and compact pattern of lines. The arrow points at the thickened and irregular pleura. Once the patient was intubated, lung sliding was observed bilaterally. (D) Longitudinal lung ultrasound of the patient with a normal hyperechoic pleural line. A lines are thin and parallel to one another, with discernible rib shadows confirming normal appearance without B lines or comet tail artefacts." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J. Rodríguez-Fanjul, C. Balcells Esponera, J. Moreno Hernando, G. Sarquella-Brugada" "autores" => array:4 [ 0 => array:2 [ "nombre" => "J." "apellidos" => "Rodríguez-Fanjul" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Balcells Esponera" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Moreno Hernando" ] 3 => array:2 [ "nombre" => "G." 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Arroyo Hernández, J. Rodríguez Suárez, F. Álvarez Menéndez" "autores" => array:3 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Arroyo Hernández" "email" => array:1 [ 0 => "mireiaah@yahoo.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J." "apellidos" => "Rodríguez Suárez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "F." "apellidos" => "Álvarez Menéndez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Pediatría, Hospital San Agustín, Avilés, Asturias, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Área de Gestión Clínica de Pediatría, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Bioquímica Clínica, Área de Gestión Clínica Laboratorio de Medicina, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Valores de referencia de la proteína S100β en población pediátrica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1271 "Ancho" => 1621 "Tamanyo" => 74429 ] ] "descripcion" => array:1 [ "en" => "Serum S100β protein levels by age. The results are also disaggregated by sex (dark grey for males and light grey for females). The age groups between which significant differences were found are represented by the letters ‘a’ (<12 months) and ‘b’ (12–24 months and >24 months)." ] ] ] "textoCompleto" => "IntroductionThe use of biomarkers has proven helpful in the management of different diseases. Data for the paediatric population are usually scarce due to the restrictions placed on research studies. Thus, the concentration patterns of different markers, initially studied in adults, are usually extrapolated to children, as has been the case of protein S100β. This protein, which is predominantly found in astroglial and Schwann cells,<a class="elsevierStyleCrossRef" href="#bib0135">1</a> is secreted by astrocytes as a cytokine with neurotrophic and gliotrophic effects.<a class="elsevierStyleCrossRefs" href="#bib0140">2–4</a> Under normal conditions, it is detected in minimal concentrations in peripheral blood. Its mean half-life ranges between 25min and 2h.<a class="elsevierStyleCrossRefs" href="#bib0155">5–8</a> This protein may be of interest in cases of acute neurologic pathology, such as brain injury or neonatal hypoxic-ischaemic encephalopathy. Diagnostic strategies based on biomarkers have been proposed as an alternative to computed tomography in the management of brain injury.<a class="elsevierStyleCrossRefs" href="#bib0175">9,10</a>The serum concentrations of S100β reported in healthy adults range between 0.02 and 0.05μg/dL.<a class="elsevierStyleCrossRefs" href="#bib0185">11–14</a> These values cannot be extrapolated to children, as serum levels of S100β seem to change with age,<a class="elsevierStyleCrossRefs" href="#bib0135">1,3,15</a> with higher levels found in the first three years of life.<a class="elsevierStyleCrossRef" href="#bib0210">16</a> Furthermore, serum concentrations of S100β vary depending on the method used for its determination.<a class="elsevierStyleCrossRef" href="#bib0215">17</a> All these are barriers to establishing reference values for children, which nevertheless are essential in order to be able to use this protein in different diagnostic and prognostic scenarios.Thus, the aim of our study was to determine the serum concentrations of S100β in healthy children from birth to 14 years of age in our setting (Hospital Universitario Central de Asturias).Patients and methodsWe conducted a descriptive prospective study at the Hospital Universitario Central de Asturias (HUCA) between June 2008 and May 2010, following approval by the Regional Clinical Research Ethics Committee. We obtained the signed informed consent of the parents or guardians of all children included in the study.We collected blood samples from healthy children aged 0–14 years as part of the preoperative evaluation for minor surgeries. In addition to these samples, we included blood samples from children seen at the paediatric emergency department that were collected for a variety of processes. We excluded samples obtained from children with diseases that could lead to elevated S100β serum concentrations, such as acute or chronic diseases of the central nervous system (CNS), bone fractures, Down syndrome, kidney failure, or developmental delay, and samples from children that had experienced a febrile seizure in the week preceding the blood being drawn.We divided the sample into three age groups: age less than 12 months, age between 12 and 24 months, and age more than 24 months.All samples were collected in bottles without an anticoagulant and submitted to the department of clinical biochemistry (Medicine Laboratory) of the HUCA. They were centrifuged at 3000rpm for 10min (Labofuge 400R; Heraeus, Boadilla, Spain). The serum was then collected and stored at −80°C until testing. The determination of S100β protein in serum samples was performed by electrochemiluminescence using a Cobas e-601 analyser (Roche Diagnostics, Mannheim, Germany), which performs a sandwich protocol with two incubation periods and a total testing time of 18min. Each determination was performed twice, following manufacturer's recommendations. The lower detection limit for the method was 0.005μg/L, and the variability coefficient less than 2%.Data analysisWe performed the statistical analysis with the software SPSS version 18 (SPSS Inc, Chicago, USA). We have expressed the data as means±standard deviations (SDs), medians, and 95% confidence intervals (CIs). After checking the normality of the distributions by interpretation of Q–Q plots, we analysed the differences between groups with Student's t test (two groups) and multifactorial ANOVA with the Tukey HSD post hoc test (more than two groups). We set the level of statistical significance at P<.05.ResultsWe included 257 patients in the study, of whom 179 were male (69.7%) and 78 female (30.4%). More than half of the blood samples (67.3%) were obtained from preoperative evaluations.The mean age and standard deviation of the boys were 5.5±3.75 years, with a median of 4.76 years. In girls, the mean age was 4.61±4.19 years and the median 3.40 years. We did not find statistically significant differences in age between the sexes (Student's t, P=.096), and 26.8% of the children were aged less than 2 years.The mean serum concentration of the S100β protein in the overall sample was 0.156 (0.140–0.172)μg/L. The means in each age group were 0.350 (0.280–0.421)μg/L in children aged less than 12 months, 0.165 (0.139–0.190)μg/L in children aged 12–24 months, and 0.121 (0.109–0.133)μg/L in children aged more than 24 months.When we considered the sex of the patients, the concentration was significantly higher in girls (0.191 [0.153–0.230]μg/L) than in boys (0.141 [0.126–1.156]μg/L) (Student's t, P=.018). The analysis by age group did not show significant differences between the sexes (P=.137, P=.690 and P=.129, respectively).The multifactorial ANOVA showed that the mean serum concentrations of S100β differed significantly between age groups (P<.001), while a significant difference in mean concentrations was not found between the sexes (P=.141). There was a significant interaction effect between both factors (P=.017), which indicates that the observed protein concentration differences between age groups are not the same in both sexes. The serum levels of S100β were higher in females than in males (although these differences were not statistically significant), especially in the youngest age group. As for the differences observed between age groups, the post hoc analysis showed that the protein concentration was significantly higher in the group of individuals aged less than 12 months compared to the other two groups (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>We calculated percentiles and 95% CIs for the three age groups (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). We were unable to calculate the 95% CI for every percentile for the group aged 1–2 years due to the small sample size.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>The regression analysis showed an inverse correlation between age and serum concentrations of the protein, which decreased as aged increased, with the decrease being most pronounced in the early years of life. The separate analysis of protein concentrations in patients aged 2 years and less showed a linear relationship between concentration and age, and the regression model obtained was statistically significant (ANOVA, P<.001) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).<elsevierMultimedia ident="fig0010"></elsevierMultimedia>DiscussionIn recent years, there has been a growing interest in the use of biomarkers in the management of different pathologies and biological processes—which requires their determination to be easy, quick and economical—and in learning the normal concentration patterns of these proteins in the populations of interest and the concentration patterns in the pathologies in which they are meant to be applied. When it comes to CNS pathologies, biomarkers with an adequate sensitivity and specificity are not yet available. In the paediatric field, protein S100β could be a potentially useful biomarker in different biological fluids, such as peripheral blood, cord blood, urine, cerebrospinal fluid, etc.There are often ethical and legal obstacles to performing clinical research in children, which limits the number of patients included in studies. This frequently leads to the extrapolation of values found in adults to paediatric patients. However, the influence of age, which is associated with different degrees of organ and system development and maturation, periods of rapid growth, and differences in hepatic and renal metabolism, may preclude the possibility of making such extrapolations.To our knowledge, our study is the first conducted in Spain to analyse S100β concentrations in healthy paediatric patients, which is why we had a keen interest in obtaining data on the concentration patterns of this protein in our setting using the method available to us (electrochemiluminescence).Most of the samples we used were obtained from preoperative evaluations for minor surgical interventions, to which we added samples from children with other conditions (the largest number corresponded to children with fever without source) and observed that this circumstance did not influence serum S100β levels or the presence of bilirubin in blood, which was consistent with what Kleindienst et al. had reported in adults.<a class="elsevierStyleCrossRef" href="#bib0220">18</a>The first studies in paediatric patients did not address the potential effects of age, but observed that concentrations were higher than in adults. The study by Gazzolo et al. was the first to provide data on paediatric patients broken down by age group.<a class="elsevierStyleCrossRef" href="#bib0140">2</a> The highest serum levels of S100β have been reported in healthy infants, decreasing in later ages.<a class="elsevierStyleCrossRefs" href="#bib0145">3,19</a> Higher concentrations of S100β in newborns with lower gestational ages have been found in other biological fluids.<a class="elsevierStyleCrossRefs" href="#bib0230">20,21</a> The variation in the serum concentration of this protein between the early months of life and later ages may be due to differences in the blood–brain barrier and brain circulation, as well as to the function of the protein, with evidence of a gradual decrease in the serum concentration of S100β. This reduction could reflect a reduced release of this trophic factor at more advanced stages of brain maturation. Other evidence has described a possible increase in serum S100β from age 7 years on, which may be related to height growth and nerve elongation,<a class="elsevierStyleCrossRefs" href="#bib0140">2,15</a> a fact that we did not observe in our sample. This hypothesis is supported by the presence of S100β in peripheral nerves and by its stimulating action on neurite outgrowth.<a class="elsevierStyleCrossRef" href="#bib0140">2</a>Previous studies on serum S100β concentrations in children have provided few data for the first years of life, and it is common for the youngest age group to be the least represented<a class="elsevierStyleCrossRef" href="#bib0145">3</a> or for the age distribution of the children to not be reported,<a class="elsevierStyleCrossRef" href="#bib0135">1</a> with the exception of the study conducted by Bouvier.<a class="elsevierStyleCrossRef" href="#bib0210">16</a> This may be related to the difficulty of obtaining samples in this age group. Thus, we considered that including 69 children in this age range in the study would provide highly relevant data for elucidating concentration patterns of S100β in this age group.We also observed an inverse correlation between serum S100β concentrations and age, consistent with previous evidence,<a class="elsevierStyleCrossRef" href="#bib0140">2</a> with concentrations being significantly higher in the first 2 years of life and essentially starting to decrease from age 1 year until reaching a stable mean value for all subsequent age groups.Different age intervals have been suggested for analysis, and reference values for serum S100β concentrations in children aged more and less than 3 years proposed in recent years, with mean S100β values similar to the mean for our sample.<a class="elsevierStyleCrossRefs" href="#bib0175">9,16,22</a> The differences observed between the various studies that use electrochemiluminescence methods are probably due to differences in the age distributions of their samples. Our findings suggest that serum S100β concentrations are stable from age 2 years with levels similar to those described in adults,<a class="elsevierStyleCrossRefs" href="#bib0175">9,22,23</a> which makes it possible to establish reference values for children aged more than 2 years, in whom the mean serum concentration of S100β is 0.120μg/L (0.083) with a 50th percentile of 0.100μg/L. In a study of a sample of 186 children, Bouvier proposed calculating reference values for different age subgroups in children aged less than 3 years (0–3 months, 4–9 months, 10–24 months, 25–36 months) and found no significant differences between the groups.<a class="elsevierStyleCrossRef" href="#bib0210">16</a> While it is possible that such differences in the serum concentrations of S100β do exist in the early months of life, we consider that these divisions are not too practical. In our sample, we identified two age subgroups in children younger than 2 years with significantly different values (P<.001). Thus, we propose reference values for children aged less than 1 year, children aged 1–2 years, and children aged more than 2 years. Since one of the potential clinical applications of the determination of protein S100β levels would be its use in the management of children with traumatic brain injury, the age groups we propose would fit those proposed for the management of this pathology.<a class="elsevierStyleCrossRefs" href="#bib0250">24,25</a>Gazzolo et al. reported higher concentrations of S100β in females,<a class="elsevierStyleCrossRef" href="#bib0235">21</a> which they attributed to sex differences in the pattern of cerebral maturation, both in the intrauterine period and in adulthood,<a class="elsevierStyleCrossRef" href="#bib0140">2</a> while the potential interaction of sex hormones with S100β cannot be ruled out. However, subsequent studies have not observed these differences in healthy children.<a class="elsevierStyleCrossRefs" href="#bib0145">3,26</a> When we compared S100β levels in males and females in our sample for each age group (because variations in the sex distribution of different age groups could be a source of bias), we found no significant differences in the serum concentrations of this protein. However, the serum S100β levels seemed higher in females in the youngest age group.We think it is worth noting that the reference values for S100β protein serum concentrations described in this study are the first proposed for the paediatric population of Spain.Limitations of the study<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">1.The study was conducted in a single centre, so the data may not be representative of other paediatric populations.</li><li class="elsevierStyleListItem" id="lsti0010">2.The study included few children aged less than 2 years.</li></ul>ConclusionsWhen we analysed serum S100β values in a sample of healthy children, we observed the following:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">1.The concentration of S100β remains stable after age 2 years, so that reference values for S100β can be established for individuals aged more than 2 years.</li><li class="elsevierStyleListItem" id="lsti0020">2.In the first two years of life, the serum concentration of S100β is higher, the younger the child.</li><li class="elsevierStyleListItem" id="lsti0025">3.There were no differences in the serum levels of S100β between the sexes.</li></ul>FundingXI Grants for Clinical Research and Epidemiology in Paediatrics of the Fundación Ernesto Sánchez-Villares (2008). Funds received: 2500 euro.Conflicts of interestThe authors have no conflicts of interest to declare" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres631239" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec644089" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres631240" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec644088" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Patients and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Data analysis" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Limitations of the study" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Conclusions" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Funding" ] 12 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflicts of interest" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-04-01" "fechaAceptado" => "2015-07-15" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec644089" "palabras" => array:3 [ 0 => "Protein S100β" 1 => "Reference values" 2 => "Children" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec644088" "palabras" => array:3 [ 0 => "Proteína S100β" 1 => "Valores de referencia" 2 => "Niños" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionS100β protein has been proposed as a potential biomarker for both chronic and acute neurological disorders. Reference values of this protein are well defined in adults but not in children, in whom serum levels appear to vary with age. Reference values for serum S100β in children from 0 to 14 years are presented. Materials and methodsA prospective study was conducted on 257 healthy children, who were divided into three age groups (under 12 months, 12–24 months and over 24 months). ResultsThe study included 179 boys and 78 girls, with a mean age of 5.5 (3.75) years. The mean serum concentration of protein S100β was 0.156 (0.140–0.172)μg/L. In children under 12 months, serum S100β concentration was 0.350 (0.280–0.421)μg/L; 0.165 (0.139–0.190)μg/L in the group between 12 and 24 months and 0.121 (0.109–0.133)μg/L in children older than 24 months. An inverse relationship was observed between age and serum S100β, which declines as age increases. No differences were observed between sexes. ConclusionsThe concentration of S100β remains stable after two years of age, being possible to establish a baseline of S100β for over two years. During the first two years of life, S100β serum concentration is higher, the lower the age of the child. No differences in serum S100β levels between sexes are observed." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónLa proteína S100β se ha propuesto como posible biomarcador en patología neurológica, tanto crónica como aguda. Los valores normales de esta proteína están bien definidos en adultos, no así en niños, en los que los valores séricos parecen variar con la edad. Nuestro objetivo es describir valores de referencia de S100β sérica en niños de 0 a 14 años. Material y métodosEstudio prospectivo en 257 niños sanos. Se establecieron 3 grupos por edad (menores de 12 meses, de 12 a 24 meses y mayores de 24 meses). ResultadosSe incluyó a 179 niños y 78 niñas. La edad media ± DE fue de 5,5 ± 3,75 años. La concentración sérica media de la proteína S100β en todo el grupo fue 0,156 (0,140-0,172) μg/l. En los menores de 12 meses, la concentración sérica de S100β fue de 0,350 (0,280-0,421) μg/l; 0,165 (0,139-0,190) μg/l en el grupo entre 12 y 24 meses y 0,121 (0,109-0,133) μg/l en el grupo de niños mayores de 24 meses. Se observó una relación inversa entre la edad y la concentración sérica de S100β, que desciende conforme se incrementa la edad. No se observaron diferencias en cuanto al sexo. ConclusionesLa concentración de S100β permanece estable a partir de los 2 años de edad, siendo posible establecer unos valores de referencia de S100β para mayores de 2 años. En los 2 primeros años de vida, la concentración de S100β sérica es más elevada cuanto menor es la edad del niño. No se observan diferencias en el valor de S100β sérica entre ambos sexos." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Arroyo Hernández M, Rodríguez Suárez J, Álvarez Menéndez F. Valores de referencia de la proteína S100β en población pediátrica. An Pediatr (Barc). 2016;84:254–259." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1271 "Ancho" => 1621 "Tamanyo" => 74429 ] ] "descripcion" => array:1 [ "en" => "Serum S100β protein levels by age. The results are also disaggregated by sex (dark grey for males and light grey for females). The age groups between which significant differences were found are represented by the letters ‘a’ (<12 months) and ‘b’ (12–24 months and >24 months)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1069 "Ancho" => 3050 "Tamanyo" => 192118 ] ] "descripcion" => array:1 [ "en" => "(A) Regression analysis: logarithmic curve fit for the entire dataset. The figure shows the goodness of fit of the model (R2). (B) Linear regression model for the data obtained from patients aged up to 2 years. The figure shows the goodness of fit (R2 and R) and the linear regression equation." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Percentile \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">S100β concentration in μg/L (95% CI)</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><12 months (n=33) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12–24 months (n=36) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">>24 months (n=188) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">2.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.076 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.030 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.043 (0.027–0.048) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.119 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.043 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.048 (0.041–0.051) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.145 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.066 (0.025–0.111) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.053 (0.049–0.060) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.187 (0.148–0.244) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.113 (0.087–0.138) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.071 (0.064–0.078) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.296 (0.209–0.428) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.168 (0.127–0.193) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.100 (0.093–0.107) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.483 (0.383–0.630) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.209 (0.175–0.244) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.135 (0.125–0.148) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.645 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.276 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.206 (0.178–0.236) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.734 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.328 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.246 (0.228–0.456) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">97.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.830 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.331 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.410 (0.249–0.520) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1035595.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Serum S100β concentrations in the three age groups considered in the study, expressed as mean and 95% confidence interval (CI)." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:26 [ 0 => array:3 [ "identificador" => "bib0135" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ 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We also thank Roche Diagnostics for their disinterested collaboration in this project." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/23412879/0000008400000005/v1_201604260918/S2341287916300060/v1_201604260918/en/main.assets" "Apartado" => array:4 [ "identificador" => "26005" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23412879/0000008400000005/v1_201604260918/S2341287916300060/v1_201604260918/en/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287916300060?idApp=UINPBA00005H"]

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Serum S100β protein reference values in a paediatric population

Valores de referencia de la proteína S100β en población pediátrica

M. Arroyo Hernándeza,

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mireiaah@yahoo.es

Corresponding author.

, J. Rodríguez Suárezb, F. Álvarez Menéndezc

a Servicio de Pediatría, Hospital San Agustín, Avilés, Asturias, Spain

b Área de Gestión Clínica de Pediatría, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain

c Servicio de Bioquímica Clínica, Área de Gestión Clínica Laboratorio de Medicina, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain

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it is detected in minimal concentrations in peripheral blood&#46; Its mean half-life ranges between 25<span class="elsevierStyleHsp" style=""></span>min and 2<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">5&#8211;8</span></a> This protein may be of interest in cases of acute neurologic pathology&#44; such as brain injury or neonatal hypoxic-ischaemic encephalopathy&#46; Diagnostic strategies based on biomarkers have been proposed as an alternative to computed tomography in the management of brain injury&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The serum concentrations of S100&#946; reported in healthy adults range between 0&#46;02 and 0&#46;05<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;dL&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">11&#8211;14</span></a> These values cannot be extrapolated to children&#44; 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between June 2008 and May 2010&#44; following approval by the Regional Clinical Research Ethics Committee&#46; We obtained the signed informed consent of the parents or guardians of all children included in the study&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">We collected blood samples from healthy children aged 0&#8211;14 years as part of the preoperative evaluation for minor surgeries&#46; In addition to these samples&#44; we included blood samples from children seen at the paediatric emergency department that were collected for a variety of processes&#46; We excluded samples obtained from children with diseases that could lead to elevated S100&#946; serum concentrations&#44; such as acute or chronic diseases of the central nervous system &#40;CNS&#41;&#44; bone fractures&#44; Down syndrome&#44; kidney failure&#44; or developmental delay&#44; and samples from children that had experienced a febrile seizure in the week preceding the blood being drawn&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">We divided the sample into three age groups&#58; 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and multifactorial ANOVA with the Tukey HSD post hoc test &#40;more than two groups&#41;&#46; We set the level of statistical significance at <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0045" class="elsevierStylePara elsevierViewall">We included 257 patients in the study&#44; of whom 179 were male &#40;69&#46;7&#37;&#41; and 78 female &#40;30&#46;4&#37;&#41;&#46; More than half of the blood samples &#40;67&#46;3&#37;&#41; were obtained from preoperative evaluations&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The mean age and standard deviation of the boys were 5&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;75 years&#44; with a median of 4&#46;76 years&#46; In girls&#44; the mean age was 4&#46;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;19 years and the median 3&#46;40 years&#46; We did not find statistically significant differences in age between the sexes &#40;Student&#39;s <span class="elsevierStyleItalic">t</span>&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;096&#41;&#44; and 26&#46;8&#37; of the children were aged less than 2 years&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The mean serum concentration of the S100&#946; protein in the overall sample was 0&#46;156 &#40;0&#46;140&#8211;0&#46;172&#41;<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#46; The means in each age group were 0&#46;350 &#40;0&#46;280&#8211;0&#46;421&#41;<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L in children aged less than 12 months&#44; 0&#46;165 &#40;0&#46;139&#8211;0&#46;190&#41;<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L in children aged 12&#8211;24 months&#44; and 0&#46;121 &#40;0&#46;109&#8211;0&#46;133&#41;<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L in children aged more than 24 months&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">When we considered the sex of the patients&#44; the concentration was significantly higher in girls &#40;0&#46;191 &#91;0&#46;153&#8211;0&#46;230&#93;<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#41; than in boys &#40;0&#46;141 &#91;0&#46;126&#8211;1&#46;156&#93;<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#41; &#40;Student&#39;s <span class="elsevierStyleItalic">t</span>&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;018&#41;&#46; The analysis by age group did not show significant differences between the sexes &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;137&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;690 and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;129&#44; respectively&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The multifactorial ANOVA showed that the mean serum concentrations of S100&#946; differed significantly between age groups &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#44; while a significant difference in mean concentrations was not found between the sexes &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;141&#41;&#46; There was a significant interaction effect between both factors &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;017&#41;&#44; which indicates that the observed protein concentration differences between age groups are not the same in both sexes&#46; The serum levels of S100&#946; were higher in females than in males &#40;although these differences were not statistically significant&#41;&#44; especially in the youngest age group&#46; As for the differences observed between age groups&#44; the post hoc analysis showed that the protein concentration was significantly higher in the group of individuals aged less than 12 months compared to the other two groups &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">We calculated percentiles and 95&#37; CIs for the three age groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; We were unable to calculate the 95&#37; CI for every percentile for the group aged 1&#8211;2 years due to the small sample size&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">The regression analysis showed an inverse correlation between age and serum concentrations of the protein&#44; which decreased as aged increased&#44; with the decrease being most pronounced in the early years of life&#46; The separate analysis of protein concentrations in patients aged 2 years and less showed a linear relationship between concentration and age&#44; and the regression model obtained was statistically significant &#40;ANOVA&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">In recent years&#44; there has been a growing interest in the use of biomarkers in the management of different pathologies and biological processes&#8212;which requires their determination to be easy&#44; quick and economical&#8212;and in learning the normal concentration patterns of these proteins in the populations of interest and the concentration patterns in the pathologies in which they are meant to be applied&#46; When it comes to CNS pathologies&#44; biomarkers with an adequate sensitivity and specificity are not yet available&#46; In the paediatric field&#44; protein S100&#946; could be a potentially useful biomarker in different biological fluids&#44; such as peripheral blood&#44; cord blood&#44; urine&#44; cerebrospinal fluid&#44; etc&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">There are often ethical and legal obstacles to performing clinical research in children&#44; which limits the number of patients included in studies&#46; This frequently leads to the extrapolation of values found in adults to paediatric patients&#46; However&#44; the influence of age&#44; which is associated with different degrees of organ and system development and maturation&#44; periods of rapid growth&#44; and differences in hepatic and renal metabolism&#44; may preclude the possibility of making such extrapolations&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">To our knowledge&#44; our study is the first conducted in Spain to analyse S100&#946; concentrations in healthy paediatric patients&#44; which is why we had a keen interest in obtaining data on the concentration patterns of this protein in our setting using the method available to us &#40;electrochemiluminescence&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Most of the samples we used were obtained from preoperative evaluations for minor surgical interventions&#44; to which we added samples from children with other conditions &#40;the largest number corresponded to children with fever without source&#41; and observed that this circumstance did not influence serum S100&#946; levels or the presence of bilirubin in blood&#44; which was consistent with what Kleindienst et al&#46; had reported in adults&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">18</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The first studies in paediatric patients did not address the potential effects of age&#44; but observed that concentrations were higher than in adults&#46; The study by Gazzolo et al&#46; was the first to provide data on paediatric patients broken down by age group&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">2</span></a> The highest serum levels of S100&#946; have been reported in healthy infants&#44; decreasing in later ages&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">3&#44;19</span></a> Higher concentrations of S100&#946; in newborns with lower gestational ages have been found in other biological fluids&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">20&#44;21</span></a> The variation in the serum concentration of this protein between the early months of life and later ages may be due to differences in the blood&#8211;brain barrier and brain circulation&#44; as well as to the function of the protein&#44; with evidence of a gradual decrease in the serum concentration of S100&#946;&#46; This reduction could reflect a reduced release of this trophic factor at more advanced stages of brain maturation&#46; Other evidence has described a possible increase in serum S100&#946; from age 7 years on&#44; which may be related to height growth and nerve elongation&#44;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">2&#44;15</span></a> a fact that we did not observe in our sample&#46; This hypothesis is supported by the presence of S100&#946; in peripheral nerves and by its stimulating action on neurite outgrowth&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">2</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Previous studies on serum S100&#946; concentrations in children have provided few data for the first years of life&#44; and it is common for the youngest age group to be the least represented<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">3</span></a> or for the age distribution of the children to not be reported&#44;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">1</span></a> with the exception of the study conducted by Bouvier&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">16</span></a> This may be related to the difficulty of obtaining samples in this age group&#46; Thus&#44; we considered that including 69 children in this age range in the study would provide highly relevant data for elucidating concentration patterns of S100&#946; in this age group&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">We also observed an inverse correlation between serum S100&#946; concentrations and age&#44; consistent with previous evidence&#44;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">2</span></a> with concentrations being significantly higher in the first 2 years of life and essentially starting to decrease from age 1 year until reaching a stable mean value for all subsequent age groups&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Different age intervals have been suggested for analysis&#44; and reference values for serum S100&#946; concentrations in children aged more and less than 3 years proposed in recent years&#44; with mean S100&#946; values similar to the mean for our sample&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">9&#44;16&#44;22</span></a> The differences observed between the various studies that use electrochemiluminescence methods are probably due to differences in the age distributions of their samples&#46; Our findings suggest that serum S100&#946; concentrations are stable from age 2 years with levels similar to those described in adults&#44;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">9&#44;22&#44;23</span></a> which makes it possible to establish reference values for children aged more than 2 years&#44; in whom the mean serum concentration of S100&#946; is 0&#46;120<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L &#40;0&#46;083&#41; with a 50th percentile of 0&#46;100<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#46; In a study of a sample of 186 children&#44; Bouvier proposed calculating reference values for different age subgroups in children aged less than 3 years &#40;0&#8211;3 months&#44; 4&#8211;9 months&#44; 10&#8211;24 months&#44; 25&#8211;36 months&#41; and found no significant differences between the groups&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">16</span></a> While it is possible that such differences in the serum concentrations of S100&#946; do exist in the early months of life&#44; we consider that these divisions are not too practical&#46; In our sample&#44; we identified two age subgroups in children younger than 2 years with significantly different values &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46; Thus&#44; we propose reference values for children aged less than 1 year&#44; children aged 1&#8211;2 years&#44; and children aged more than 2 years&#46; Since one of the potential clinical applications of the determination of protein S100&#946; levels would be its use in the management of children with traumatic brain injury&#44; the age groups we propose would fit those proposed for the management of this pathology&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">24&#44;25</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Gazzolo et al&#46; reported higher concentrations of S100&#946; in females&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">21</span></a> which they attributed to sex differences in the pattern of cerebral maturation&#44; both in the intrauterine period and in adulthood&#44;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">2</span></a> while the potential interaction of sex hormones with S100&#946; cannot be ruled out&#46; However&#44; subsequent studies have not observed these differences in healthy children&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">3&#44;26</span></a> When we compared S100&#946; levels in males and females in our sample for each age group &#40;because variations in the sex distribution of different age groups could be a source of bias&#41;&#44; we found no significant differences in the serum concentrations of this protein&#46; However&#44; the serum S100&#946; levels seemed higher in females in the youngest age group&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">We think it is worth noting that the reference values for S100&#946; protein serum concentrations described in this study are the first proposed for the paediatric population of Spain&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Limitations of the study</span><p id="par0130" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0135" class="elsevierStylePara elsevierViewall">The study was conducted in a single centre&#44; so the data may not be representative of other paediatric populations&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0140" class="elsevierStylePara elsevierViewall">The study included few children aged less than 2 years&#46;</p></li></ul></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0145" class="elsevierStylePara elsevierViewall">When we analysed serum S100&#946; values in a sample of healthy children&#44; we observed the following&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">1&#46;</span><p id="par0150" class="elsevierStylePara elsevierViewall">The concentration of S100&#946; remains stable after age 2 years&#44; so that reference values for S100&#946; can be established for individuals aged more than 2 years&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">2&#46;</span><p id="par0155" class="elsevierStylePara elsevierViewall">In the first two years of life&#44; the serum concentration of S100&#946; is higher&#44; the younger the child&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">3&#46;</span><p id="par0160" class="elsevierStylePara elsevierViewall">There were no differences in the serum levels of S100&#946; between the sexes&#46;</p></li></ul></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Funding</span><p id="par0165" class="elsevierStylePara elsevierViewall">XI Grants for Clinical Research and Epidemiology in Paediatrics of the Fundaci&#243;n Ernesto S&#225;nchez-Villares &#40;2008&#41;&#46; Funds received&#58; 2500 euro&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">S100&#946; protein has been proposed as a potential biomarker for both chronic and acute neurological disorders&#46; Reference values of this protein are well defined in adults but not in children&#44; in whom serum levels appear to vary with age&#46; Reference values for serum S100&#946; in children from 0 to 14 years are presented&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A prospective study was conducted on 257 healthy children&#44; who were divided into three age groups &#40;under 12 months&#44; 12&#8211;24 months and over 24 months&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The study included 179 boys and 78 girls&#44; with a mean age of 5&#46;5 &#40;3&#46;75&#41; years&#46; The mean serum concentration of protein S100&#946; was 0&#46;156 &#40;0&#46;140&#8211;0&#46;172&#41;<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#46; In children under 12 months&#44; serum S100&#946; concentration was 0&#46;350 &#40;0&#46;280&#8211;0&#46;421&#41;<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L&#59; 0&#46;165 &#40;0&#46;139&#8211;0&#46;190&#41;<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L in the group between 12 and 24 months and 0&#46;121 &#40;0&#46;109&#8211;0&#46;133&#41;<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;L in children older than 24 months&#46; An inverse relationship was observed between age and serum S100&#946;&#44; which declines as age increases&#46; No differences were observed between sexes&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The concentration of S100&#946; remains stable after two years of age&#44; being possible to establish a baseline of S100&#946; for over two years&#46; During the first two years of life&#44; S100&#946; serum concentration is higher&#44; the lower the age of the child&#46; No differences in serum S100&#946; levels between sexes are observed&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La prote&#237;na S100&#946; se ha propuesto como posible biomarcador en patolog&#237;a neurol&#243;gica&#44; tanto cr&#243;nica como aguda&#46; Los valores normales de esta prote&#237;na est&#225;n bien definidos en adultos&#44; no as&#237; en ni&#241;os&#44; en los que los valores s&#233;ricos parecen variar con la edad&#46; Nuestro objetivo es describir valores de referencia de S100&#946; s&#233;rica en ni&#241;os de 0 a 14 a&#241;os&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo en 257 ni&#241;os sanos&#46; Se establecieron 3 grupos por edad &#40;menores de 12 meses&#44; de 12 a 24 meses y mayores de 24 meses&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluy&#243; a 179 ni&#241;os y 78 ni&#241;as&#46; La edad media &#177; DE fue de 5&#44;5 &#177; 3&#44;75 a&#241;os&#46; La concentraci&#243;n s&#233;rica media de la prote&#237;na S100&#946; en todo el grupo fue 0&#44;156 &#40;0&#44;140-0&#44;172&#41; &#956;g&#47;l&#46; En los menores de 12 meses&#44; la concentraci&#243;n s&#233;rica de S100&#946; fue de 0&#44;350 &#40;0&#44;280-0&#44;421&#41; &#956;g&#47;l&#59; 0&#44;165 &#40;0&#44;139-0&#44;190&#41; &#956;g&#47;l en el grupo entre 12 y 24 meses y 0&#44;121 &#40;0&#44;109-0&#44;133&#41; &#956;g&#47;l en el grupo de ni&#241;os mayores de 24 meses&#46; Se observ&#243; una relaci&#243;n inversa entre la edad y la concentraci&#243;n s&#233;rica de S100&#946;&#44; que desciende conforme se incrementa la edad&#46; No se observaron diferencias en cuanto al sexo&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La concentraci&#243;n de S100&#946; permanece estable a partir de los 2 a&#241;os de edad&#44; siendo posible establecer unos valores de referencia de S100&#946; para mayores de 2 a&#241;os&#46; En los 2 primeros a&#241;os de vida&#44; la concentraci&#243;n de S100&#946; s&#233;rica es m&#225;s elevada cuanto menor es la edad del ni&#241;o&#46; No se observan diferencias en el valor de S100&#946; s&#233;rica entre ambos sexos&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Introducci&#243;n"
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          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Material y m&#233;todos"
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          2 => array:2 [
            "identificador" => "abst0035"
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          3 => array:2 [
            "identificador" => "abst0040"
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Arroyo Hern&#225;ndez M&#44; Rodr&#237;guez Su&#225;rez J&#44; &#193;lvarez Men&#233;ndez F&#46; Valores de referencia de la prote&#237;na S100&#946; en poblaci&#243;n pedi&#225;trica&#46; An Pediatr &#40;Barc&#41;&#46; 2016&#59;84&#58;254&#8211;259&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Serum S100&#946; protein levels by age&#46; The results are also disaggregated by sex &#40;dark grey for males and light grey for females&#41;&#46; The age groups between which significant differences were found are represented by the letters &#8216;a&#8217; &#40;&#60;12 months&#41; and &#8216;b&#8217; &#40;12&#8211;24 months and &#62;24 months&#41;&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#41; Regression analysis&#58; logarithmic curve fit for the entire dataset&#46; The figure shows the goodness of fit of the model &#40;<span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span>&#41;&#46; &#40;B&#41; Linear regression model for the data obtained from patients aged up to 2 years&#46; The figure shows the goodness of fit &#40;<span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span> and <span class="elsevierStyleItalic">R</span>&#41; and the linear regression equation&#46;</p>"
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                  \t\t\t\t</th><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">S100&#946; concentration in &#956;g&#47;L &#40;95&#37; CI&#41;</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#60;12 months &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12&#8211;24 months<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>36&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#62;24 months &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>188&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="char" valign="top">2&#46;5&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Serum S100&#946; concentrations in the three age groups considered in the study&#44; expressed as mean and 95&#37; confidence interval &#40;CI&#41;&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:26 [
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                          "etal" => false
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                      ]
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                      "autores" => array:1 [
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                          "etal" => false
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                      "titulo" => "Serum neuron-specific enolase&#44; S100B&#44; and myelin basic protein concentrations after inflicted and noninflicted traumatic brain injury in children"
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                        0 => array:2 [
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                          "autores" => array:6 [
                            0 => "R&#46; Berger"
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                            2 => "M&#46; Pierce"
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                            5 => "P&#46; Kochanek"
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        "titulo" => "Acknowledgments"
        "texto" => "<p id="par0175" class="elsevierStylePara elsevierViewall">We want to thank the <span class="elsevierStyleGrantSponsor" id="gs1">Fundaci&#243;n Ernesto S&#225;nchez Villares</span> for awarding us a grant for the amount of 2500 euro in the XI Convocatoria de Ayudas a la Investigaci&#243;n Cl&#237;nica y Epidemiol&#243;gica en Pediatr&#237;a &#40;2008&#41; for the project titled &#8220;Utilidad de la prote&#237;na S-100 beta en el estudio de los traumatismos craneoencef&#225;licos leves en una poblaci&#243;n pedi&#225;trica&#8221; &#91;Usefulness of S100&#946; protein in the study of mild traumatic brain injury in a paediatric population&#93;&#46;</p> <p id="par0180" class="elsevierStylePara elsevierViewall">We also thank Roche Diagnostics for their disinterested collaboration in this project&#46;</p>"
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Article information

ISSN: 23412879
Original language: English

DOI:10.1016/j.anpede.2015.07.031

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Year/Month	Html	Pdf	Total

2024 November	6	8	14
2024 October	89	33	122
2024 September	92	25	117
2024 August	119	55	174
2024 July	121	36	157
2024 June	95	28	123
2024 May	108	47	155
2024 April	81	39	120
2024 March	68	33	101
2024 February	75	37	112
2024 January	93	43	136
2023 December	94	19	113
2023 November	85	25	110
2023 October	104	31	135
2023 September	74	27	101
2023 August	70	20	90
2023 July	82	25	107
2023 June	75	25	100
2023 May	101	25	126
2023 April	64	14	78
2023 March	107	23	130
2023 February	82	24	106
2023 January	66	24	90
2022 December	78	18	96
2022 November	53	31	84
2022 October	82	34	116
2022 September	34	22	56
2022 August	68	75	143
2022 July	59	74	133
2022 June	48	37	85
2022 May	59	56	115
2022 April	62	31	93
2022 March	50	49	99
2022 February	51	25	76
2022 January	45	35	80
2021 December	64	44	108
2021 November	64	46	110
2021 October	91	75	166
2021 September	56	36	92
2021 August	62	54	116
2021 July	45	37	82
2021 June	67	44	111
2021 May	66	43	109
2021 April	123	77	200
2021 March	112	43	155
2021 February	57	18	75
2021 January	61	26	87
2020 December	90	22	112
2020 November	49	22	71
2020 October	48	13	61
2020 September	55	20	75
2020 August	26	14	40
2020 July	36	17	53
2020 June	62	15	77
2020 May	59	32	91
2020 April	37	23	60
2020 March	51	21	72
2020 February	55	26	81
2020 January	56	16	72
2019 December	73	22	95
2019 November	36	13	49
2019 October	28	15	43
2019 September	46	17	63
2019 August	56	17	73
2019 July	35	32	67
2019 June	47	28	75
2019 May	60	24	84
2019 April	112	19	131
2019 March	42	21	63
2019 February	45	14	59
2019 January	46	26	72
2018 December	52	29	81
2018 November	73	35	108
2018 October	88	17	105
2018 September	41	14	55
2018 August	2	0	2
2018 June	3	0	3
2018 May	2	0	2
2018 April	35	0	35
2018 March	49	0	49
2018 February	8	0	8
2018 January	12	0	12
2017 December	13	0	13
2017 November	15	0	15
2017 October	11	0	11
2017 September	17	0	17
2017 August	15	0	15
2017 July	11	0	11
2017 June	57	14	71
2017 May	24	5	29
2017 April	7	10	17
2017 March	6	2	8
2017 February	11	5	16
2017 January	2	1	3
2016 December	23	16	39
2016 November	26	9	35
2016 October	26	18	44
2016 September	33	1	34
2016 August	39	6	45
2016 July	29	8	37
2016 June	0	9	9
2016 May	7	0	7

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