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Departments of,
1
Pediatrics and,
2
Obstetrics and Gynecology, Giannina Gaslini, Children’s University Hospital, I-16147 Genoa, Italy
3
Institute of Anatomy, Catholic University, Largo Francesco Vito, 1, I-00168 Rome, Italy
aAuthor for correspondence. Fax 39-0630154813; e-mail fabrizio.michetti{at}rm.unicatt.it.
To the Editor:
S100B is an acidic calcium-binding protein concentrated in the nervous system, where it is located mainly in glial cells (1). Measurements of the protein in cerebrospinal fluid and blood are used to detect brain distress, both in infants and in adults (2)(3), and in the perinatal period are correlated with brain maturation (4). Because collecting urine is a simpler procedure than collecting cerebrospinal fluid or blood, especially in infants in whom anemia of premature infants attributable to blood sampling is common, this study investigated whether S100B can be detected in urine of preterm and term infants.
Eighty-three women with normal physiological pregnancies (23 preterm, 60 term) whose deliveries occurred between 26–42 weeks of gestation were enrolled in the study. Gestational age was defined by the presence of ultrasonographic signs according to Campbell and Thoms (5) and by postnatal confirmation. Exclusion criteria were multiple pregnancies, intrauterine growth retardation, and third trimester maternal diseases. The study protocol was approved by the local Ethics Committee after consent was given by parents.
After birth, the first urination was collected, and S100B concentrations were measured in duplicate in all samples using a Lia-mat Sangtec 100 (AB Sangtec Medical, Bromma, Sweden) according to the manufacturer’s recommendations. Cord blood samples were collected at the same time and measured in 42 patients selected without conscious bias. The detection limit of the assay was 0.02 µg/L. The S100B concentrations in the groups are expressed as the mean ± SE. Statistical analysis was performed by Kolmogorov–Smirnov one-way ANOVA and Mann–Whitney U-test when data were not normally distributed. The relationship between the urine concentration of S100B and weeks of gestation was analyzed by linear regression analysis. P <0.05 was considered significant.
Normal clinical conditions and an absence of overt neurological injury were observed on discharge of all infants from the hospital. In the preterm group, gestational age at birth and birth weight were significantly lower than in the term group (P <0.01), whereas no differences were observed regarding delivery mode and Apgar score at the 1st and 5th min (P >0.05, not significant). Tests of renal function were within reference intervals and did not differ between the two groups (P >0.05, not significant). Urine concentrations of S100B were significantly higher in the preterm group, peaking in the earliest weeks of gestation and progressively decreasing near term, being undetectable or at the detection limit of the assay in the term group (3.17 ± 1.02 vs 0.70 ± 0.23 µg/L; P <0.001). The same pattern was found when S100B cord blood concentrations were measured in the same selected patients (data not shown). When urine S100B concentrations in preterm newborns were subgrouped according to gestational age and weight at birth (6), they were significantly higher in the very low birth weight group compared with both the low birth weight and term groups (P <0.001) and significantly higher in the low birth weight group than in the term group (P <0.001). A significant correlation between S100B urine concentrations and gestational age was observed when all newborns were considered (r = -0.79; P <0.001).
The data presented constitute the first observation of S100B in urine and offer a urinary S100B concentration reference curve (available from the authors) at different gestational ages. These findings also fit previous observations on cord blood S100B concentrations (4). Because renal function tests were normal in all examined infants, it did not appear to influence the results. The higher concentrations of S100B in preterm newborns may be related to the neurotrophic role possibly exerted by S100B (1). This possibility seems to be consistent with high concentrations of the trophic factor at earlier gestational ages, when brain maturation processes are more active, and lower concentrations at later stage of brain maturation.
In conclusion, the present S100B urinary pattern could provide the basis for a new and easier means of studying brain pathophysiological conditions, which have hitherto been investigated by measuring the protein in cerebrospinal fluid or blood.
Acknowledgments
Supported in part by grants from Ministero dell’Università Ricerca Scientifica e Tecnologica (MURST; to F.M. and D.G.), and by Sangtec Medical, Bromma, Sweden, and Byk Gulden Italia.
References
The following articles in journals at HighWire Press have cited this article:
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  P. Florio, E. Marinoni, R. Di Iorio, M. Bashir, S. Ciotti, R. Sacchi, M. Bruschettini, M. Lituania, G. Serra, F. Michetti, et al. Urinary S100B Protein Concentrations Are Increased in Intrauterine Growth-Retarded Newborns Pediatrics, September 1, 2006; 118(3): e747 - e754. [Abstract] [Full Text] [PDF]
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 D. Gazzolo, E. Marinoni, R. Di Iorio, M. Bruschettini, M. Kornacka, M. Lituania, U. Majewska, G. Serra, and F. Michetti Measurement of Urinary S100B Protein Concentrations for the Early Identification of Brain Damage in Asphyxiated Full-term Infants Arch Pediatr Adolesc Med, December 1, 2003; 157(12): 1163 - 1168. [Abstract] [Full Text] [PDF]
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 D. Gazzolo, M. Kornacka, M. Bruschettini, M. Lituania, L. Giovannini, G. Serra, U. Majewska, and F. Michetti Maternal Glucocorticoid Supplementation and S100B Protein Concentrations in Cord Blood and Urine of Preterm Infants Clin. Chem., July 1, 2003; 49(7): 1215 - 1218. [Full Text] [PDF]
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D. Gazzolo, F. Michetti, M. Bruschettini, N. Marchese, M. Lituania, S. Mangraviti, E. Pedrazzi, and P. Bruschettini Pediatric Concentrations of S100B Protein in Blood: Age- and Sex-related Changes Clin. Chem., June 1, 2003; 49(6): 967 - 970. [Full Text] [PDF]
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D. Gazzolo, M. Lituania, M. Bruschettini, P. Bruschettini, and F. Michetti S100B Protein Concentrations in Amniotic Fluid Are Higher in Monoamniotic than in Diamniotic Twins and Singleton Pregnancies Clin. Chem., June 1, 2003; 49(6): 997 - 999. [Full Text] [PDF]
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F. Michetti and D. Gazzolo S100B Protein in Biological Fluids: A Tool for Perinatal Medicine Clin. Chem., December 1, 2002; 48(12): 2097 - 2104. [Abstract] [Full Text] [PDF]
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L. V.C. Portela, A. B.L. Tort, D. V. Schaf, L. Ribeiro, D. B. Nora, R. Walz, L. N. Rotta, C. T. Silva, J. V. Busnello, F. Kapczinski, et al. The Serum S100B Concentration Is Age Dependent Clin. Chem., June 1, 2002; 48(6): 950 - 952. [Full Text] [PDF]
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D. Gazzolo, M. Bruschettini, R. Di Iorio, E. Marinoni, M. Lituania, M. Marras, R. Sarli, P. L. Bruschettini, and F. Michetti Maternal Nitric Oxide Supplementation Decreases Cord Blood S100B in Intrauterine Growth-retarded Fetuses Clin. Chem., April 1, 2002; 48(4): 647 - 650. [Full Text] [PDF]
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D. Gazzolo, M. Bruschettini, M. Lituania, G. Serra, W. Bonacci, and F. Michetti Increased Urinary S100B Protein as an Early Indicator of Intraventricular Hemorrhage in Preterm Infants: Correlation with the Grade of Hemorrhage Clin. Chem., October 1, 2001; 47(10): 1836 - 1838. [Full Text] [PDF]
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