The EARLI Study As a Resource for Autism Etiologic Research

Background: Infant sibling studies have been at the vanguard of autism spectrum disorder (ASD) research over the past decade, providing important new knowledge about the earliest emerging signs of ASD and expanding our understanding of the developmental course of this complex disorder.  Studies focused on siblings of children with ASD also have unrealized potential for contributing to ASD etiologic research.  Moving the targeted time of enrollment back from infancy toward conception creates tremendous opportunities for optimally studying risk factors and risk biomarkers during the pre-, peri- and neonatal periods.  By doing so, a traditional sibling study, which already incorporates close developmental follow-up of at-risk infants through the third year of life, is essentially reconfigured as an enriched-risk pregnancy cohort study.  

Objectives: To describe, in detail, the design, data collection approach, and progress to date for the Early Autism Risk Longitudinal Investigation (EARLI) – a multisite, autism enriched risk pregnancy  cohort study that has now been in the field for 2 ½ of its planned ten years.  Our goal is to provide a larger segment of the autism research community with a more in-depth understanding of EARLI in order to catalyze collaborative opportunities and maximize the scientific return from this valuable cohort.

Methods: ASD enriched-risk prospective pregnancy cohort study.

Results: EARLI has enrolled 200 of a projected 850 women who are mothers of a child with ASD (proband) at the start of a subsequent pregnancy.  80% of currently enrolled families also have a participating biologic father.  Proband diagnostic status is confirmed at enrollment and biologic samples collected.  In depth longitudinal exposure data are collected at multiple points in pregnancy via self-report, biosampling, and environmental sampling.  Biosamples are collected at delivery and babies (siblings) are followed for exposure (with serial biosamples) and developmental outcomes until age three.  138 at-risk siblings have been born into the cohort to date, with 69 six month and 32 12-month follow-up visits completed thus far.  Self-report instrument completeness has been very good and biologic sampling compliance has also been strong.  The EARLI biorepository already contains nearly 2000 aliquots each of serum plasma and whole blood, 1500 aliquots of extracted DNA, over 4000 urine sample aliquots, 150 semen sample aliquots, 550 placental biopsies, 425 breast milk aliquots and 200 meconium samples.  Detailed maternal interviews have been completed on 99% of the subjects and the median number of weekly pregnancy diaries is 0.9 – close to the target of 1 per week.  Dust samples have been collected at 94% of all home visits.  At least one blood sample is available on 99.5% of all enrolled mother and 97% of enrolled fathers.

Conclusions: The EARLI study is building a comprehensive resource for analyses of potential autism risk factors and biomarkers.  As an NIH Autism Center of Excellence Network, EARLI seeks to proactively engage members of the autism research community to explore alternative approaches by which EARLI can best advance our understanding of autism etiology.