Metabolomics and Communication Skills Development in Children; Evidence from the Ages and Stages Questionnaire

Abstract

We hypothesized metabolomic profiling could be utilized to identify children who scored poorly on the communication component of the Ages and Stages Questionnaire (ASQ); which assesses development in childhood, and to provide candidate biomarkers for autism spectrum disorders (ASD). In a population of three-year-old children, 15 plasma metabolites, were significantly (p < 0.05) different between children who were categorized as having communication skills that were “on schedule” (n = 365 (90.6%)) as compared to those “requiring further monitoring/evaluation” (n = 38 (9.4%)) according to multivariable regression models. Five of these metabolites, including three endocannabinoids, were also dysregulated at age one (n = 204 “on schedule”, n = 24 “further monitoring/evaluation”) in the same children. Stool metabolomic profiling identified 11 significant metabolites. Both the plasma and stool results implicated a role for tryptophan and tyrosine metabolism; in particular, higher levels of N-formylanthranilic acid were associated with an improved communication score in both biosample types. A model based on the significant plasma metabolites demonstrated high sensitivity (88.9%) and specificity (84.5%) for the prediction of autism by age 8. These results provide evidence that ASQ communication score and metabolomic profiling of plasma and/or stool may provide alternative approaches for early diagnosis of ASD, as well as insights into the pathobiology of these conditions.

Keywords

• metabolomics
• ages and stages questionnaire (ASQ)
• autism
• endocannabinoid
• serotonin
• tryptophan metabolism
• tyrosine metabolism
• N-formylanthranilic acid
• childhood development