Background: Although the effects of alcohol on metabolic processes in the body have been studied widely, there do not appear to be any previous reports clarifying how substance abuse changes metabolic profiles of pregnant women during the first trimester of pregnancy. Objective: Our aim was to evaluate the effect of substance abuse, especially alcohol use, on the metabolic profile of pregnant women during the first trimester. Study design: We applied mass spectrometry based non-targeted metabolite profiling of serum collected during routine visit to the hospital between gestational weeks 9 + 0 to 11 + 6 from controls (n = 55), alcohol users (n = 19), drug users (n = 24) and tobacco smokers (n = 40). Results: We observed statistically significantly differences among the study groups in serum levels of glutamate, glutamine, and serotonin (p-values Conclusion: The present study shows that alcohol and drug use were associated with increased glutamate, and decreased glutamine levels, and alcohol use is associated with decreased serotonin levels. This study serves as a proof-of-concept that the metabolite profile of human first trimester serum samples could be used to detect alcohol exposure during pregnancy. (C) 2018 Elsevier B.V. All rights reserved.Peer reviewe