Influence of Prenatal Folate on Placental mtDNA and Autism Risk

Project: Research project

Project Details

Description

PROJECT ABSTRACT Autism spectrum disorders (ASD) are a growing concern, with more than 1 in every 68 children affected in
the US by the age of eight years. Complex interactions between genes and environmental factors are thought
to contribute to ASD risk. Evidence is accumulating for a potentially large role in ASD etiology and/or morbidity
for the early in-utero environment, including gestational nutrition. Maternal folic acid is one of the first
modifiable factors identified to date with the potential to reduce the risk of ASD by ~40%. In addition to being
essential for neurodevelopment, folate is critical for preventing apoptosis, and is involved in nuclear and
mitochondrial DNA synthesis and repair. Folic acid is associated with reduced ASD risk at a time in early
pregnancy when impaired mitochondrial function may influence processes highly dependent on energy, such
as neurodevelopment. In addition, our work was first to show that children with ASD are more likely to have
mitochondrial dysfunction (MD), mtDNA overreplication, and mtDNA deletions than typically developing
children. To this end, we propose to leverage data and samples from mother-child pairs in a large NIH-funded
cohort study to examine protection against mitochondrial abnormalities in placenta samples as a potential
pathway for ASD prevention through maternal dietary and supplemental folate intake. Samples will be obtained
from the Markers of Autism Risk in Babies: Learning Early Signs (MARBLES) study of >300 mothers who have
a child with confirmed ASD and became pregnant with another child, in order to understand what influences
the outcome of the younger sibling and to identify early markers of ASD. This is a significant advantage given
that samples and data on demographic, lifestyle, health, interpregnancy interval, dietary, and other potentially
relevant factors have been prospectively collected in this study since 2006, and children?s developmental
assessments and clinically confirmed diagnoses will be available. This project will provide evidence on whether
maternal and placental folate affects mitochondrial DNA and function, which then influence the developing
child?s neurobehavioral outcomes including ASD. Findings will inform folic acid prevention strategies.
StatusFinished
Effective start/end date2/1/161/31/18

Funding

  • National Institutes of Health: $235,063.00

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