Abstract
The MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) Study was launched in 2006 as the
first epidemiologic cohort of younger siblings of children with autism spectrum disorders (ASD) to begin follow-
up before and during the prenatal period when ASD is likely to originate. In contrast to population-based cohorts
that require large sample sizes given a relatively low prevalence of ASD (1 in 44) and typically are not able to
conduct gold standard diagnosis of ASD, the enriched-risk design offers greater efficiency by enrolling
participants at high familial risk for developing ASD (>20%) and other neurodevelopmental concerns (15-20%).
Other cohorts of high-risk younger siblings recruited postnatally, with the exception of the EARLI study that is no
longer enrolling. Early enrollment provides an opportunity to examine a broad array of environmental exposures
and early biomarkers. Given increasing prevalence of ASD, it is critical to invest in studies identifying factors
responsible for increasing risk and the mechanisms underlying ASD etiology, which are not yet well-understood.
This project addresses both gaps by maintaining and enhancing the infrastructure of the MARBLES enriched-
risk cohort. The MARBLES study has enrolled over 522 pregnancies for 533 children and collected nearly 28,000
samples, comprehensive data on exposures, medical history, diet, lifestyle, and home factors, measured
methylation, expression, immune, nutrient, and contaminant markers, and conducted rich characterization of
neurodevelopmental outcomes using gold-standard clinical assessments. The MARBLES study employed a
multi-pronged recruitment approach that includes a variety of community outreach activities that resulted in a
sociodemographically diverse cohort allowing examination of differences in distributions and associations of a
multitude of environmental factors across race, ethnicity, nativity, parental education, and other socioeconomic
indicators. The MARBLES team has a history of supporting both scientific and workforce diversity and will
continue to expand these efforts. We propose to continue to enroll and follow participants under a streamlined
protocol that will now accommodate Spanish-speaking families, and expand our online presence to more widely
share resources for one of the only enriched-risk ASD cohorts in the U.S. with prospectively collected pregnancy
data and biosamples and deep evaluation of risk factors, mediators, and outcomes, to advance discovery of
etiologic factors and early biomarkers for ASD. We will further work to understand the racial, ethnic, and
sociodemographic disparities that exist in the diagnosis of ASD that are likely driven by structural racism14 by
collecting information from our participants on experienced discrimination and by linking to neighborhood-level
factors. Completion of these aims will markedly enrich MARBLES resources, expedite collaborative sharing, and
allow us and future collaborators to better address questions on predictors of ASD in an enriched-risk cohort,
while more thoroughly adjusting for confounding factors including those resulting from structural racism, and will
add understanding of how experienced discrimination plays a role in these families’ care and well-being.
