Screening for autism spectrum disorder (ASD) during well-child pediatric check-ups reduces the age of
diagnosis, allowing more time for critical early intervention. Furthermore, universal screening mitigates
disparities in the age of diagnosis for minorities, and has been demonstrated to be feasible in community-
based primary care settings. However, limited follow-up of toddlers who screened negative is a notable gap in
the literature that contributed to the United States Preventive Services Task Force’s (USPSTF) determination
of insufficient evidence to recommend universal ASD screening at present. Follow-up of children who are not
identified at risk is cost- and labor-intensive, but is critical to determine the sensitivity of toddler ASD screening.
This study will be among the first to use rigorous prospective detection strategies in a large, low-risk sample
that previously had concurrent detection. The goal of the proposed study is to find missed cases by
rescreening children who were not identified with ASD during the course of three prior screening studies that
administered the Modified Checklist for Autism in Toddlers, Revised, with Follow-Up during toddler well child
visits. This includes those who screened negative as toddlers, as well as children who screened positive but
either were lost to follow-up or were evaluated and not diagnosed with ASD. The specific aims are to measure
prospective sensitivity using rigorous case confirmation for potential missed cases. We will identify patterns in
toddler screening outcomes for these missed cases; we predict that children whose first screen was younger
and those who did not complete multiple screens are more likely to be missed cases compared to those
screened at older toddler visits and rescreened by age three. Finally, we will examine whether missed cases
are more likely to have milder ASD symptoms, greater likelihood of psychiatric comorbidities, and be female
compared to children who demonstrated risk as toddlers but were not diagnosed with ASD until they were
older. Although these characteristics have been hypothesized, rigorous evidence is lacking to demonstrate
differences between children with ASD missed by toddler screening. The majority of the multi-site sample (total
n = 8,751) screened negative at one or more pediatric visits between 1 and 3 years old (n = 8,091). In addition,
we will rescreen children who screened positive but did not attend the evaluation (n = 426), which often signals
lack of parent concern, and children evaluated and classified as nonASD (n = 234), who may have developed
clinically significant ASD symptoms as they aged. Parents will be invited to enroll and rescreen their child, now
7-14 years old, using a secure web-based portal. All at risk children, and a random sample of low-risk cases,
will be invited for a comprehensive, research-reliable evaluation; final ASD outcomes will be used to calculate
prospective sensitivity, which will be compared to literature reporting sensitivity based on record review
strategies. Results of this proposed study will directly address a gap identified by the USPSTF, and will
address the Interagency Autism Coordinating Committee’s Question 1 about early detection of ASD.
