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

• DOI: 10.1016/j.envint.2022.107678
• Publication Date: 2022-12-06T17:18:26Z
• Authors: Sarah Thomson; Katherine Drummond; Martin O'Hely; Christos Symeonides; Chitra Chandran; Toby Mansell; Richard Saffery; Peter Sly; Jochen Mueller; Peter Vuillermin; Anne-Louise Ponsonby
• Keywords: 0301 basic medicine; 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

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.