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.
Environ Int
; 171: 107678, 2023 01.
Article
in En
| MEDLINE
| ID: mdl-36516674
ABSTRACT
Prenatal phthalate exposure has previously been linked to the development of autism spectrum disorder (ASD). However, the underlying biological mechanisms remain unclear. We investigated whether maternal and child central carbon metabolism is involved as part of the Barwon Infant Study (BIS), a population-based birth cohort of 1,074 Australian children. We estimated phthalate daily intakes using third-trimester urinary phthalate metabolite concentrations and other relevant indices. The metabolome of maternal serum in the third trimester, cord serum at birth and child plasma at 1 year were measured by nuclear magnetic resonance. We used the Small Molecule Pathway Database and principal component analysis to construct composite metabolite scores reflecting metabolic pathways. ASD symptoms at 2 and 4 years were measured in 596 and 674 children by subscales of the Child Behavior Checklist and the Strengths and Difficulties Questionnaire, respectively. Multivariable linear regression analyses demonstrated (i) prospective associations between higher prenatal di-(2-ethylhexyl) phthalate (DEHP) levels and upregulation of maternal non-oxidative energy metabolism pathways, and (ii) prospective associations between upregulation of these pathways and increased offspring ASD symptoms at 2 and 4 years of age. Counterfactual mediation analyses indicated that part of the mechanism by which higher prenatal DEHP exposure influences the development of ASD symptoms in early childhood is through a maternal metabolic shift in pregnancy towards non-oxidative energy pathways, which are inefficient compared to oxidative metabolism. These results highlight the importance of the prenatal period and suggest that further investigation of maternal energy metabolism as a molecular mediator of the adverse impact of prenatal environmental exposures such as phthalates is warranted.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phthalic Acids
/
Prenatal Exposure Delayed Effects
/
Diethylhexyl Phthalate
/
Environmental Pollutants
/
Autism Spectrum Disorder
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Newborn
/
Pregnancy
Country/Region as subject:
Oceania
Language:
En
Journal:
Environ Int
Year:
2023
Document type:
Article
Affiliation country:
Australia