Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder

Serena B Gumusoglu; Brandon M Schickling; Donna A Santillan; Lynn M Teesch; Mark K Santillan

doi:10.1186/s11689-025-09601-z

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Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder

Journal article

Open access

Peer reviewed

Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder

Serena B Gumusoglu, Brandon M Schickling, Donna A Santillan, Lynn M Teesch and Mark K Santillan

Journal of neurodevelopmental disorders, Vol.17(1), 16

03/29/2025

DOI: 10.1186/s11689-025-09601-z

PMCID: PMC11954230

PMID: 40158086

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Abstract

Despite the power and promise of early detection and treatment in autism spectrum disorder (ASD), early-life biomarkers are limited. An early-life risk biosignature would advance the field's understanding of ASD pathogenies and targets for early diagnosis and intervention. We therefore sought to add to the growing ASD biomarker literature and evaluate whether fetal metabolomics are altered in idiopathic ASD. Banked cord blood plasma samples (N = 36 control, 16 ASD) were analyzed via gas chromatography and mass spectrometry (GC-MS). Samples were from babies later diagnosed with idiopathic ASD (non-familial, non-syndromic) or matched, neurotypical controls. Metabolite set enrichment analysis (MSEA) and biomarker prediction were performed (MetaboAnalyst). We detected 76 metabolites in all samples. Of these, 20 metabolites differed significantly between groups: 10 increased and 10 decreased in ASD samples relative to neurotypical controls (p < 0.05). MSEA revealed significant changes in metabolic pathways related to carbohydrate metabolism and glycemic control. Untargeted principle components analysis of all metabolites did not reveal group differences, while targeted biomarker assessment (using only Fructose 6-phosphate, D-Mannose, and D-Fructose) by a Random Forest algorithm generated an area under the curve (AUC) = 0.766 (95% CI: 0.612-0.896) for ASD prediction. Despite a high and increasing prevalence, ASD has no definitive biomarkers or available treatments for its core symptoms. ASD's earliest developmental antecedents remain unclear. We find that fetal plasma metabolomics differ with child ASD status, in particular invoking altered carbohydrate metabolism. While prior clinical and preclinical work has linked carbohydrate metabolism to ASD, no prior fetal studies have reported these disruptions in neonates or fetuses who go on to be diagnosed with ASD. Future work will investigate concordance with maternal metabolomics to determine maternal-fetal mechanisms.

Pregnancy

Autism Spectrum Disorder - blood

Autism Spectrum Disorder - metabolism

Biomarkers - blood

Biomarkers - metabolism

Carbohydrate Metabolism - physiology

Female

Fetal Blood - chemistry

Fetal Blood - metabolism

Fetus - metabolism

Gas Chromatography-Mass Spectrometry

Humans

Infant, Newborn

Male

Metabolomics

Details

Title: Subtitle: Disrupted fetal carbohydrate metabolism in children with autism spectrum disorder
Creators: Serena B Gumusoglu - Iowa's Hawkeye Intellectual and Developmental Disabilities Research Center (Hawk-IDDRC), Iowa City, USA
Brandon M Schickling - University of Iowa
Donna A Santillan - Iowa's Hawkeye Intellectual and Developmental Disabilities Research Center (Hawk-IDDRC), Iowa City, USA
Lynn M Teesch - University of Iowa
Mark K Santillan - Iowa's Hawkeye Intellectual and Developmental Disabilities Research Center (Hawk-IDDRC), Iowa City, USA. Mark-Santillan@uiowa.edu
Resource Type: Journal article
Publication Details: Journal of neurodevelopmental disorders, Vol.17(1), 16
DOI: 10.1186/s11689-025-09601-z
PMID: 40158086
PMCID: PMC11954230
NLM abbreviation: J Neurodev Disord
ISSN: 1866-1955
eISSN: 1866-1955
Publisher: BMC
Grant note: 22POST30908921 / American Heart Association 19IPLOI34760288 / American Heart Association P50HD10355601A1 / NIH HHS R01HD08994005 / NIH HHS 5T32HL007121-45 / NIH HHS
Language: English
Date published: 03/29/2025
Academic Unit: Psychiatry; Core Research Facilities; Iowa Neuroscience Institute; Obstetrics and Gynecology
Record Identifier: 9984805011902771

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