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

1
Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
2
The Fenway Institute, Fenway Health, Boston, MA 02215, USA
3
Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, MA 02115, USA
4
Division of Pediatric Pulmonary Medicine, Golisano Children’s Hospital at Strong, University of Rochester Medical Center, Rochester, NY 14642, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this manuscript.
Metabolites 2019, 9(3), 42; https://doi.org/10.3390/metabo9030042
Received: 14 January 2019 / Revised: 14 February 2019 / Accepted: 28 February 2019 / Published: 5 March 2019
(This article belongs to the Special Issue Metabolomics in Epidemiological Studies)
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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. View Full-Text
Keywords: metabolomics; ages and stages questionnaire (ASQ); autism; endocannabinoid; serotonin; tryptophan metabolism; tyrosine metabolism; N-formylanthranilic acid; childhood development metabolomics; ages and stages questionnaire (ASQ); autism; endocannabinoid; serotonin; tryptophan metabolism; tyrosine metabolism; N-formylanthranilic acid; childhood development
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Kelly, R.S.; Boulin, A.; Laranjo, N.; Lee-Sarwar, K.; Chu, S.H.; Yadama, A.P.; Carey, V.; Litonjua, A.A.; Lasky-Su, J.; Weiss, S.T. Metabolomics and Communication Skills Development in Children; Evidence from the Ages and Stages Questionnaire. Metabolites 2019, 9, 42.

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