Metabolomics investigation of the deleterious consequences of prenatal alcohol exposure in subjects with fetal alcohol syndrome.

Prenatal alcohol exposure is associated with a series of physical (cranial malformations, growth deficits, abnormal brain development) and neurological (cognitive and behavioral disorders) alterations, which altogether constitute the characteristic phenotype of the fetal alcohol syndrome. However, the pathophysiology of this condition is poorly understood, which poses considerable difficulties on its diagnosis because of the lack of sensitive and specific biomarkers. Herein, we propose the application of state-of-the-art metabolomics approaches with the aim of getting deeper insights into the specific molecular mechanisms behind this complex disease. For this purpose, we enrolled a cohort of young individuals (6-18 years), comprising both patients affected by fetal alcohol syndrome and healthy controls matched for age (FAS: N = 15, age = 13.1 ± 3.4; CNT: N = 18, age = 13.5 ± 2.7) and sex (FAS: 66.7% males; CNT: 66.7% males), from whom urine samples were collected for subsequent UHPLC-HRMS untargeted analysis. The teratogenic effects of alcohol were mirrored in profound disruptions in a multitude of central metabolic pathways (e.g., energy homeostasis, lipid metabolism, oxidative stress), which could be responsible for the clinical manifestations of this disorder. These metabolomics alterations suggest the existence of presistent biochemical disturbances that may contribute to the long-term clinical manifestations observed in affected individuals. These findings open the door to define novel diagnostic biomarkers and therapeutic targets for more efficient clinical management of fetal alcohol syndrome and related complications.