title: Neurological abnormalities in full-term asphyxiated newborns and salivary S100B testing: the "Cooperative Multitask against Brain Injury of Neonates" (CoMBINe) international study.
abstract: BACKGROUND
  Perinatal asphyxia (PA) is a leading cause of mortality and morbidity in newborns: its prognosis depends both on the severity of the asphyxia and on the immediate resuscitation to restore oxygen supply and blood circulation. Therefore, we investigated whether measurement of S100B, a consolidated marker of brain injury, in salivary fluid of PA newborns may constitute a useful tool for the early detection of asphyxia-related brain injury.
  
  
  METHODS
  We conducted a cross-sectional study in 292 full-term newborns admitted to our NICUs, of whom 48 suffered PA and 244 healthy controls admitted at our NICUs. Saliva S100B levels measurement longitudinally after birth; routine laboratory variables, neurological patterns, cerebral ultrasound and, magnetic resonance imaging were performed. The primary end-point was the presence of neurological abnormalities at 12-months after birth.
  
  
  RESULTS
  S100B salivary levels were significantly (P<0.001) higher in newborns with PA than in normal infants. When asphyxiated infants were subdivided according to a good (Group A; n = 15) or poor (Group B; n = 33) neurological outcome at 12-months, S100B was significantly higher at all monitoring time-points in Group B than in Group A or controls (P<0.001, for all). A cut-off >3.25 MoM S100B achieved a sensitivity of 100% (CI5-95%: 89.3%-100%) and a specificity of 100% (CI5-95%: 98.6%-100%) as a single marker for predicting the occurrence of abnormal neurological outcome (area under the ROC curve: 1.000; CI5-95%: 0.987-1.0).
  
  
  CONCLUSIONS
  S100B protein measurement in saliva, soon after birth, is a useful tool to identify which asphyxiated infants are at risk of neurological sequelae.
authors.affiliation: Department of Maternal, Fetal and Neonatal Medicine, "C. Arrigo" Children's Hospital Alessandria, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Gazzolo
authors.affiliation: Department of Cardiology and Laboratory Reasearch S. Donato Milanese University Hospital, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pluchinotta
authors.affiliation: Department of Neonatology, Cairo University, Cairo, Egypt.
authors.forename: Moataza
authors.initials: M
authors.lastname: Bashir
authors.affiliation: Department of Neonatology, Cairo University, Cairo, Egypt.
authors.forename: Hanna
authors.initials: H
authors.lastname: Aboulgar
authors.affiliation: Department of Neonatology, Cairo University, Cairo, Egypt.
authors.forename: Hala Mufeed
authors.initials: HM
authors.lastname: Said
authors.affiliation: Department of Neonatology, Cairo University, Cairo, Egypt.
authors.forename: Iskander
authors.initials: I
authors.lastname: Iman
authors.affiliation: Pediatric Intensive Care Unit, "Regina Margherita" Children's Hospital Turin, Turin, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ivani
authors.affiliation: Pediatric Intensive Care Unit, "Regina Margherita" Children's Hospital Turin, Turin, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Conio
authors.affiliation: Department of Maternal Fetal and Neonatal Health "G. Garibaldi" Hospital, Catania, Italy.
authors.forename: Lucia Gabriella
authors.initials: LG
authors.lastname: Tina
authors.affiliation: Department of Maternal Fetal and Neonatal Health "G. Garibaldi" Hospital, Catania, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nigro
authors.affiliation: Department of Biochemistry, Catania University, Catania, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Li Volti
authors.affiliation: Department of Biochemistry, Catania University, Catania, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Galvano
authors.affiliation: Institute of Anatomy and Cell Biology, Catholic University, Rome, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Michetti
authors.affiliation: Laboratory of Perinatal Medicine, Department of Obstetrics and Gynecology, University "La Sapienza", Rome, Italy.
authors.forename: Romolo
authors.initials: R
authors.lastname: Di Iorio
authors.affiliation: Laboratory of Perinatal Medicine, Department of Obstetrics and Gynecology, University "La Sapienza", Rome, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marinoni
authors.affiliation: Department of Pediatrics and Neonatology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Luc J
authors.initials: LJ
authors.lastname: Zimmermann
authors.affiliation: Department of Pediatrics and Neonatology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Antonio D W
authors.initials: AD
authors.lastname: Gavilanes
authors.affiliation: Department of Child Neurology, Maastricht University, Maastricht, The Netherlands.
authors.forename: Hans J S
authors.initials: HJ
authors.lastname: Vles
authors.affiliation: Department of Neonatology and Intensive Care of Neonate, Warsaw University, Warsaw, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Kornacka
authors.affiliation: Department of Neonatology and Intensive Care of Neonate, Warsaw University, Warsaw, Poland.
authors.forename: Darek
authors.initials: D
authors.lastname: Gruszfeld
authors.affiliation: Department of Pediatrics "G. Gaslini" Children's University Hospital, Genoa, Italy.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Frulio
authors.affiliation: Department of Pediatrics "G. Gaslini" Children's University Hospital, Genoa, Italy.
authors.forename: Renata
authors.initials: R
authors.lastname: Sacchi
authors.affiliation: Department of Pediatrics "G. Gaslini" Children's University Hospital, Genoa, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Ciotti
authors.affiliation: Department of Pediatrics "G. Gaslini" Children's University Hospital, Genoa, Italy.
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Risso
authors.affiliation: Department of Pediatrics "G. Gaslini" Children's University Hospital, Genoa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sannia
authors.affiliation: UOC of Obstetrics and Gynecology, "S. Iacopo" Hospital, Pistoia, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Florio
mesh_terms: D019540:Area Under Curve; D001238:Asphyxia Neonatorum / Q000150:complications / Q000175:diagnosis*; D015415:Biomarkers / Q000032:analysis; D001930:Brain Injuries / Q000150:complications / Q000175:diagnosis* / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007118:Immunoassay; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D011379:Prognosis; D012372:ROC Curve; D011859:Radiography; D009418:S100 Proteins / Q000032:analysis*; D012463:Saliva / Q000378:metabolism; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D009418:S100 Proteins