Autism spectrum disorders (ASD) are a growing concern, with more than 1 in every 68 children affected inthe US by the age of eight years. Complex interactions between genes and environmental factors are thoughtto contribute to ASD risk. Evidence is accumulating for a potentially large role in ASD etiology and/or morbidityfor the early in-utero environment, including gestational nutrition. Maternal folic acid is one of the firstmodifiable factors identified to date with the potential to reduce the risk of ASD by ~40%. In addition to beingessential for neurodevelopment, folate is critical for preventing apoptosis, and is involved in nuclear andmitochondrial DNA synthesis and repair. Folic acid is associated with reduced ASD risk at a time in earlypregnancy when impaired mitochondrial function may influence processes highly dependent on energy, suchas neurodevelopment. In addition, our work was first to show that children with ASD are more likely to havemitochondrial dysfunction (MD), mtDNA overreplication, and mtDNA deletions than typically developingchildren. To this end, we propose to leverage data and samples from mother-child pairs in a large NIH-fundedcohort study to examine protection against mitochondrial abnormalities in placenta samples as a potentialpathway for ASD prevention through maternal dietary and supplemental folate intake. Samples will be obtainedfrom the Markers of Autism Risk in Babies: Learning Early Signs (MARBLES) study of >300 mothers who havea child with confirmed ASD and became pregnant with another child, in order to understand what influencesthe outcome of the younger sibling and to identify early markers of ASD. This is a significant advantage giventhat samples and data on demographic, lifestyle, health, interpregnancy interval, dietary, and other potentiallyrelevant factors have been prospectively collected in this study since 2006, and children’s developmentalassessments and clinically confirmed diagnoses will be available. This project will provide evidence on whethermaternal and placental folate affects mitochondrial DNA and function, which then influence the developingchild’s neurobehavioral outcomes including ASD. Findings will inform folic acid prevention strategies.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
