The cerebrospinal fluid proteome of preterm infants predicts neurodevelopmental outcome

Abstract

BackgroundSurvival rate increases for preterm infants, but long-term neurodevelopmental outcome predictors are lacking. Our primary aim was to determine whether a specific proteomic profile in cerebrospinal fluid (CSF) of preterm infants differs from that of term infants and to identify novel biomarkers of neurodevelopmental outcome in preterm infants.MethodsTwenty-seven preterm infants with median gestational age 27 w + 4 d and ten full-term infants were enrolled prospectively. Protein profiling of CSF were performed utilizing an antibody suspension bead array. The relative levels of 178 unique brain derived proteins and inflammatory mediators, selected from the Human Protein Atlas, were measured.ResultsThe CSF protein profile of preterm infants differed from that of term infants. Increased levels of brain specific proteins that are associated with neurodevelopment and neuroinflammatory pathways made up a distinct protein profile in the preterm infants. The most significant differences were seen in proteins involved in neurodevelopmental regulation and synaptic plasticity, as well as components of the innate immune system. Several proteins correlated with favorable outcome in preterm infants at 18–24 months corrected age. Among the proteins that provided strong predictors of outcome were vascular endothelial growth factor C, Neurocan core protein and seizure protein 6, all highly important in normal brain development.ConclusionOur data suggest a vulnerability of the preterm brain to postnatal events and that alterations in protein levels may contribute to unfavorable neurodevelopmental outcome.

Identification of Central Nervous System Oncologic Disease Biomarkers in EVs from Cerebrospinal Fluid (CSF) of Pediatric Patients: A Pilot Neuro-Proteomic Study

“…Among these there was basigin (or CD147), whose isoform 2 stimulates matrix metalloproteinases that play a key role in regulating tumor growth [29]. Prospective protein profiling of CSF from LP from 27 preterm infants showed that the proteome can predict neurodevelopmental outcomes [30]. In the proteomic study of CSF from children with the syndromic CLN3-Batten, a fatal neurodegenerative disease caused by mutations in the endolysosomal transmembrane CLN3 protein, a protein implicated in axonal development, were identified as candidate biomarkers [31].…”