Metabolomic profiling of brain from infants who died from Sudden Infant Death Syndrome reveals novel predictive biomarkers

OBJECTIVE: Sudden Infant Death Syndrome (SIDS) is defined as the sudden death of an infant < 1 year of age that cannot be explained following a thorough investigation. Currently, no reliable clinical biomarkers are available for the prediction of infants who will die of SIDS. STUDY DESIGN: This study aimed to profile the medulla oblongata from postmortem human brain from SIDS victims (n=16) and compare their profiles with that of age-matched controls (n=7). RESULTS: Using LC-Orbitrap-MS, we detected 12 710 features in electrospray ionization' positive (ESI+) mode and 8243 in ESI mode from polar extracts of brain. Five features acquired in ESI+ mode produced a predictive model for SIDS with an area under the receiver operating characteristic curve (AUC) of 1 (confidence interval (CI): 0.995-1)and a predictive power of 97.4%. Three biomarkers acquired in ESI-mode produced a predictive model with an AUC of 0.866 (CI: 0.767-0.942) and a predictive power of 77.6%. We:confidently identified 5 of these features (I-(+)-ergothioneine, nicotinic acid, succinic acid, adenosine monophosphate and azelaic acid) and putatively identify another 4 out of the 15 in total. CONCLUSIONS: This study underscores the potential value of metabolomics for studying SIDS. Further characterization of the metabolome of postmortem SIDS brains could lead to the identification of potential antemortem biomarkers for novel prevention strategies for SIDS.