Increased maternal non-oxidative energy metabolism mediates association between prenatal di-(2-ethylhexyl) phthalate (DEHP) exposure and offspring autism spectrum disorder symptoms in early life: A birth cohort study

Autism Spectrum Disorder Neurodevelopment Phthalic Acids Cohort Studies 03 medical and health sciences Pregnancy Diethylhexyl Phthalate Metabolomics Humans GE1-350 Endocrine disrupting chemicals Autism spectrum disorder Child 0303 health sciences Infant, Newborn Australia Infant Environmental Exposure Environmental sciences Maternal Exposure Pyruvate metabolism Child, Preschool Prenatal Exposure Delayed Effects Female Environmental Pollutants Energy Metabolism Warburg Effect
DOI: 10.1016/j.envint.2022.107678 Publication Date: 2022-12-06T17:18:26Z
ABSTRACT
Prenatal phthalate exposure has previously been linked to the development of autism spectrum disorder (ASD). However, underlying biological mechanisms remain unclear. We investigated whether maternal and child central carbon metabolism is involved as part Barwon Infant Study (BIS), a population-based birth cohort 1,074 Australian children. estimated daily intakes using third-trimester urinary metabolite concentrations other relevant indices. The metabolome serum in third trimester, cord at plasma 1 year were measured by nuclear magnetic resonance. used Small Molecule Pathway Database principal component analysis construct composite scores reflecting metabolic pathways. ASD symptoms 2 4 years 596 674 children subscales Child Behavior Checklist Strengths Difficulties Questionnaire, respectively. Multivariable linear regression analyses demonstrated (i) prospective associations between higher prenatal di-(2-ethylhexyl) (DEHP) levels upregulation non-oxidative energy pathways, (ii) these pathways increased offspring age. Counterfactual mediation indicated that mechanism which DEHP influences early childhood through shift pregnancy towards are inefficient compared oxidative metabolism. These results highlight importance period suggest further investigation molecular mediator adverse impact environmental exposures such phthalates warranted.
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