Maternal exposure to chemicals and offspring neurodevelopmental disabilities: informing public health actions by understanding nutritional modifiers and simulating interventions

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Project summary Humans are ubiquitously exposed to metals and per-and polyfluoroalkyl substances (PFAS), which are either established or suspected neurotoxicants in experimental and population settings. Exposure to these chemicals can be particularly harmful in utero, a critical period of fetal brain development. Four major literature gaps exist: 1) prospective studies of in utero exposure to these chemicals and child risk of neurodevelopmental disorders (NDs) are limited in the U.S, with most studies from predominantly White, European populations; 2) despite growing evidence that these chemicals may affect multiple NDs and systems, most studies are limited to a single ND outcome without consideration of comorbidities; 3) exposures rarely occur in isolation, yet combined exposure across different chemical classes remain unclear let alone chemical-nutrition interplay (nutrition may modify chemical toxicities); 4) most children’s environmental health studies focus on identifying risk factors with few that use or develop solution-oriented analytic methods that can directly inform public health actions. To fill these critical gaps, Dr. Choi proposes to investigate metals and PFAS in relation to clinician-diagnosed NDs considering comorbidities, while examining nutritional modifiers that may mitigate chemical toxicities and generating policy-relevant effect estimates via simulating intervention effects on chemicals and nutrition. To address this overarching goal, she will leverage rich existing resources (biospecimen data and clinical diagnoses of NDs and comorbidities across the lifespan) in the Boston Birth Cohort, a large prospective birth cohort with a significant representation of understudied low-income minorities. In K99, Dr. Choi will estimate the relations of metals and PFAS in maternal blood collected 24-72hours postpartum with NDs and comorbidities in offspring (Aim 1). Comorbidities will be considered with cluster analysis, to evaluate whether children with certain NDs and comorbidities are more vulnerable to the toxic effects of gestational chemical exposures. She will receive interdisciplinary training across NDs & comorbidities, chemical-nutrition, research translation, and advanced statistical methods (i.e., cluster analysis, mixtures analysis, causal inference) from a multidisciplinary mentorship team and via additional training activities including coursework, seminars, working groups, research dissemination activities targeted at lay audiences and policy settings, and national and international workshops or conferences. In R00, she will evaluate nutritional modifiers of the adverse chemical- ND relations identified in Aim 1 (Aim 2) and simulate intervention effects by estimating the number of NDs that could have been prevented had there been pregnancy interventions on chemicals, nutrition, and both chemicals and nutrition (Aim 3). This K99/R00 will position Dr. Choi as an innovative, independent researcher in environmental epidemiology, with a unique niche in NDs and comorbidities, chemical-nutrition interplay, research translation, and advanced methods. Our findings and activities will increase public awareness and serve as scientific evidence for future policies on the environment or nutrition to reduce the burdens of NDs.