Mediators and Modifiers of Prenatal Environmental Exposures and Child Neurodevelopment: DNA methylation, Prenatal Diet, and Cognitive Stimulation (MEND) - Prenatal neurotoxic exposures can have long-lasting neurodevelopmental effects. Most studies focus on isolated exposure-outcome associations, ignoring the synergistic effects of multiple exposures and mechanisms of action. The proposed study, Mediators and Modifiers of Prenatal Environmental Exposures and Child Neurodevelopment: DNA methylation, Prenatal Diet, and Cognitive Stimulation study (MEND), addresses these gaps, leveraging extant and prospective data collected in the NIH Environmental Influences on Child Outcomes (ECHO) Program to study the effects of phthalates and organophosphate flame retardants (OPFRs) on child neurobehavior. These compounds are ubiquitous and believed to exert neurotoxicity through shared mechanisms. Our study will follow over 650 participants recruited from rural and urban communities in Washington State. Our long-term goals are to identify mechanisms of neurotoxic exposure and actionable targets for intervention that could attenuate the effects of those exposures. We propose the following: Aim 1. Examine the relationship between prenatal exposure to phthalates and OPFRs, cord blood DNA methylation, and child neurobehavior and assess prenatal dietary oxidative balance as a modifier. Aim 2(a) Use machine learning to develop multi-outcome neurobehavioral phenotypic profiles; (b) Employ these profiles to examine the relationships between prenatal phthalates and OPFRs, cord blood DNA methylation, prenatal dietary oxidative balance, and child neurobehavior; (c) Explore whether parental cognitive stimulation modifies the relationship between prenatal phthalates and OPFRs and child neurobehavioral outcomes, including established constructs and novel phenotypic profiles. Aim 3(a) Retain participants using tailored strategies such as sharing ECHO-wide and individual results and (b) implement the ECHO protocol with high fidelity. The
