Neurological abnormalities in full-term asphyxiated newborns and salivary S100B testing: the "Cooperative Multitask against Brain Injury of Neonates" (CoMBINe) international study

PLoS One. 2015 Jan 8;10(1):e0115194. doi: 10.1371/journal.pone.0115194. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Asphyxia Neonatorum / complications
  • Asphyxia Neonatorum / diagnosis*
  • Biomarkers / analysis
  • Brain Injuries / complications
  • Brain Injuries / diagnosis*
  • Brain Injuries / diagnostic imaging
  • Case-Control Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Immunoassay
  • Infant, Newborn
  • Intensive Care Units, Neonatal
  • Longitudinal Studies
  • Magnetic Resonance Imaging
  • Male
  • Prognosis
  • ROC Curve
  • Radiography
  • S100 Proteins / analysis*
  • Saliva / metabolism
  • Sensitivity and Specificity

Substances

  • Biomarkers
  • S100 Proteins

Grants and funding

This work is part of the I.O. PhD International Program under the auspices of the Italian Society of Neonatology and was partially supported by grants to DG from Stella Cometa, I Colori della Vita Foundations, Italy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.