ORCID Profile
0000-0001-6022-2703
Current Organisation
Nanyang Technological University
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Publisher: ISTES Organization
Date: 23-10-2023
DOI: 10.46328/IJTE.557
Publisher: Springer Science and Business Media LLC
Date: 10-05-2019
Publisher: No publisher found
Date: 2023
Publisher: Informa UK Limited
Date: 10-2022
Publisher: Cold Spring Harbor Laboratory
Date: 14-06-2022
DOI: 10.1101/2022.06.08.22275892
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, a population-based birth cohort of 1074 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 blood 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 by subscales of the Child Behavior Checklist and the Strengths and Difficulties Questionnaire, respectively. Multivariable linear regression analyses demonstrated (i) associations between higher prenatal di(2-ethylhexyl) phthalate (DEHP) levels and increased activity in maternal non-oxidative energy metabolism pathways, specifically non-oxidative pyruvate metabolism and the Warburg Effect, and (ii) associations between increased activity in these pathways and increased offspring ASD symptomology at 2 and 4 years of age. Mediation analyses suggested 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. Interventions targeting maternal metabolic activity in pregnancy may be beneficial in reducing the potential risk to the developing fetus.
Publisher: Elsevier BV
Date: 2022
Location: United States of America
No related grants have been discovered for Christina Ratnam-Lim.