The Association of Prenatal Dietary Factors with Child Autism Diagnosis and Autism-Related Traits Using a Mixtures Approach: Results from the Environmental Influences on Child Health Outcomes Cohort.

Background: Previous research on the role of maternal diet in relation to autism has focused on examining individual nutrient associations. Few studies have examined associations with multiple nutrients using mixtures approaches, which may better reflect true exposure scenarios.

Objectives: This study aims to examine associations of nutrient mixtures with children's autism diagnosis and trait scores within a large, diverse population.

Methods: Participants were drawn from the United States Environmental influences on Child Health Outcomes (ECHO) consortium. Maternal prenatal diet was reported via validated food frequency questionnaires. Children's autism-related traits were measured using the Social Responsiveness Scale (SRS) and autism diagnoses were from parent reports of physician diagnosis. Bayesian kernel machine regression was used to examine the overall mixture effect and interactions between a set of 5 primary nutrients (folate, vitamin D, omega 3 and omega 6 fatty acids, and iron), adjusted for potential confounders, in relationship to child outcomes. Secondary analyses were conducted in a subset of cohorts with an expanded set of 14 nutrients. Traditional linear and logistic regression models were also analyzed for comparison of results to mixture models.

Results: A total of 2614 participants drawn from 7 ECHO cohorts were included in primary analysis. Mixture analyses suggested that increasing the overall 5-nutrient mixture was associated with lower SRS scores. Individual U-shaped associations and bivariate interactions between folate and omega 3 fatty acids were suggested. In the subset included in the secondary analyses of the 14-nutrient mixture, a modest inverse trend remained, but individual nutrient associations were altered, with vitamin D demonstrating higher relative importance than other nutrients. Strong associations with autism diagnosis were not observed.

Conclusions: In this large sample, we found evidence for combined nutrient effects with broader autism-related traits. Because results for individual nutrients were sensitive to mixture components, replication of combined associations between nutrients and autism-related outcomes is needed.