Exploration of circulating metabolites in infants with abusive head trauma

Abstract

Abusive head trauma (AHT) is a severe form of traumatic brain injury (TBI) and causes significant brain lesions by vigorous shaking. It is the leading cause of mortality and morbidity in children under 2 years of age. If not fatal, AHT can result in severe disabilities, often requiring long-term care. Clinical diagnosis of AHT is challenging, because symptoms are often non-specific, overlap with those of other diseases and relies on screening for intracranial, spinal, and ocular lesions. To date, no screening test has been developed to preselect children suspected to be victims of AHT for further clinical investigations. However, as recently demonstrated via analysis of serum proteomes of infant victims of AHT, large-scale omic analysis of blood serum samples could help identify molecules with high potential for early detection of human pathologies. Here, we investigated the circulating serum metabolome of infants with severe head trauma with a Glasgow Coma Scale (GCS) score of 3–4 and compared it to infants with no signs of head trauma during medico-legal examinations. Using liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS), we identified 53 metabolites with the most significant differences between the groups. Six metabolites were already known to be implicated in different gross pathologies associated with neurological diseases. In addition, our analysis revealed several lipids and lipid-like molecules, all with an increased profile in the peripheral blood circulation of infant victims of AHT. As we speculated some of the identified metabolites to come from specific brain regions affected by the shaking mechanism, we further performed a multi-omic integration by integrating metabolites showing evidence of their presence in the brain and publicly available proteomic data. As results, we found significant metabolite-protein correlations which could be closely associated with AHT, thus, providing evidence of tensions and supporting strong dynamic changes occurring within the brain during assault.