Published online August 21, 2006
PEDIATRICS Vol. 118 No. 3 September 2006, pp. e747-e754 (doi:10.1542/peds.2005-2875)
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ARTICLE

Urinary S100B Protein Concentrations Are Increased in Intrauterine Growth-Retarded Newborns

Pasquale Florio, MD, PhDa, Emanuela Marinoni, MD, PhDb, Romolo Di Iorio, MD, PhDb, Moataza Bashir, MDc, Sabina Ciotti, MDd, Renata Sacchi, MDd, Matteo Bruschettini, MDd, Mario Lituania, MDd, Giovanni Serra, MDd, Fabrizio Michetti, MD, PhDe, Felice Petraglia, MDa and Diego Gazzolo, MD, PhDd,f

a Department of Pediatrics, Obstetrics, and Reproductive Medicine, University of Siena, Siena, Italy
b Laboratory of Perinatal Medicine and Molecular Biology, Department of Obstetrics and Neonatal Health, "La Sapienza" University, Rome, Italy
c Department of Neonatology, University Hospital, Cairo, Egypt
d Department of Pediatrics, Obstetrics and Gynecology, and Neuroscience, Giannina Gaslini Children's University Hospital, Genoa, Italy
e Institute of Anatomy and Cell Biology, Catholic University, Rome, Italy
f Department of Fetal and Neonatal Medicine, G. Garibuldi Hospital, Catania, Italy

BACKGROUND. Intrauterine growth retardation is one of the major causes of perinatal mortality and morbidity. To date, there are no reliable methods to detect brain damage in these patients.

METHODS. We conducted a case-control study in tertiary NICUs from December 2001 to December 2003 with 42 intrauterine growth retardation infants and 84 controls. Routine laboratory variables, neurologic outcome at 7-day follow-up, ultrasound imaging, and urine concentrations of S100B protein were determined at 5 time points. Urine S100B levels were measured by an immunoluminometric assay at first urination, 24, 48, and 72 hours, and 7 days after birth. Routine laboratory parameters and neurologic patterns were assessed at the same time as urine sampling.

RESULTS. S100B protein was significantly higher at all of the monitoring time points in urine taken from intrauterine growth retardation newborns than in control infants. When intrauterine growth retardation infants were corrected for the presence of abnormal (group A) or normal (group B) neurologic examination 7 days after birth, S100B was significantly higher at all of the predetermined monitoring time points in group A infants than in group B or controls. At a cutoff of 7.37 multiples of median at first urination, S100B achieved a sensitivity of 95% and a specificity of 99.1% as a single marker for predicting an adverse neurologic outcome. Twenty of 126 patients had neurologic abnormalities, making an overall prevalence of the disease in our population of 15.9% (pretest probability). With respect to the performance of S100B in predicting brain damage, its positive and negative predictive values were 91.0% and 99.0%, respectively.

CONCLUSIONS. Increased urine S100B protein levels in intrauterine growth retardation newborns in the first week after birth suggest the presence of brain damage reasonably because of intrauterine hypoxia. Longitudinal S100B protein measurements soon after birth are a useful tool to identify which intrauterine growth retardation infants are at risk of possible neurologic sequelae.

Key Words: brain damage • brain protein • S100B protein • newborn • IUGR

Abbreviations: IUGR—intrauterine growth retardation • CNS—central nervous system • SNAP-PE—Score for Neonatal Acute Physiology-Perinatal Extension • MoM—multiples of median • ROC—receiver operating curve • CI—confidence interval

Accepted Mar 22, 2006.