The complex inter-relationships between genetics and the environment that influence risk for autism spectrum disorder (ASD) are complicated. They may include environmental triggers in genetically susceptible individuals and may operate through complicated physiological pathways. The focus of this proposal is to explore one of these intricate webs. We begin with the fact that ASD risk appears to be increased in children born to women who are obese at the start of pregnancy, who gain excessive weight during pregnancy, and / or who suffer complications associated with poor metabolic health, like chronic and gestational forms of hypertension and diabetes. The public health implications of these findings are enormous given that over half of pregnant women are overweight or obese and the incidence of ASD continues to rise. These statistics provide persuasive motivation to implement this proposal which seeks to understand modifiable risk factors that influence obesity and poor metabolic health in pregnant women, both for their own wellness and also to optimize neurobehavioral development in their developing fetuses. The mechanism hypothesized in this proposal begins with maternal exposure during pregnancy to phthalates, a set of chemicals that are widespread in the environment and that are found in many consumer products, including vinyl flooring, food packaging, medical supplies, pill coatings, and personal care products. We hypothesize that increased contact with phthalates alters metabolism in pregnant women and results in characteristic clinical manifestations and measurable shifts in metabolic byproducts throughout the body known as the metabolome. Together these maternal biomarkers elucidate a pathway leading from phthalate contact to aberrant brain development and increased autism risk in children. This proposal harnesses the unique resources of an NIEHS-funded prospective cohort of mothers and their children at elevated-risk for ASD, MARBLES (Markers of Autism Risk in Babies ? Learning Early Signs) to examine the impact of phthalates on maternal clinical metabolic endpoints and child neurobehavioral outcomes using existing data. New analyses on archived blood samples will allow exploration of the role of the maternal metabolome in this etiologic pathway linking phthalates to elevated ASD risk.
The proposed research plan will examine whether exposure in pregnant women and their fetuses to an upstream set of environmental chemicals called phthalates increases the occurrence of autism spectrum disorder (ASD) and related neurobehavioral outcomes through a pathway of maternal metabolic impairment evidenced by key clinical findings and molecular biomarkers. Identification of women with metabolic health issues whose fetuses are at heightened risk for ASD based on biomarker profiles will target prevention efforts that can be applied before, during and after pregnancy and widening the window during which interventions can be implemented to ameliorate symptoms.
