Clustering of co-occurring conditions in autism spectrum disorder during early childhood: A retrospective analysis of medical claims data

Abstract

Individuals with autism spectrum disorder (ASD) are frequently affected by co-occurring medical conditions (COCs), which vary in severity, age of onset, and pathophysiological characteristics. The presence of COCs contributes to significant heterogeneity in the clinical presentation of ASD between individuals and a better understanding of COCs may offer greater insight into the etiology of ASD in specific subgroups while also providing guidance for diagnostic and treatment protocols. This study retrospectively analyzed medical claims data from a private United States health plan between years 2000 and 2015 to investigate patterns of COC diagnoses in a cohort of 3,278 children with ASD throughout their first 5 years of enrollment compared to 279,693 children from the general population without ASD diagnoses (POP cohort). Three subgroups of children with ASD were identified by k-means clustering using these COC patterns. The first cluster was characterized by generally high rates of COC diagnosis and comprised 23.7% (n = 776) of the cohort. Diagnoses of developmental delays were dominant in the second cluster containing 26.5% (n = 870) of the cohort. Children in the third cluster, making up 49.8% (n = 1,632) of the cohort, had the lowest rates of COC diagnosis, which were slightly higher than rates observed in the POP cohort. A secondary analysis using these data found that gastrointestinal and immune disorders showed similar longitudinal patterns of prevalence, as did seizure and sleep disorders. These findings may help to better inform the development of diagnostic workup and treatment protocols for COCs in children with ASD. Autism Res 2019, 12: 1272-1285. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Medical conditions that co-occur with autism spectrum disorder (ASD) vary significantly from person to person. This study analyzed patterns in diagnosis of co-occurring conditions from medical claims data and observed three subtypes of children with ASD. These results may aid with screening for co-occurring conditions in children with ASD and with understanding ASD subtypes.

Keywords: k-means clustering; autism spectrum disorder; co-occurring condition; comorbidity; medical claims; retrospective analysis.

Figure 1.

Summary of dates relevant to the study’s design and cohort definitions. The total study period spanned from January 1, 2000 to September 30, 2015 and included children must have been born between the years 2000 and 2010. The first date of a child’s coverage enrollment (index date) must have been within 1 year of the child’s birth year, and at least 5 years of continuous coverage (medical, pharmacy, and behavioral) must have followed the index date and been reached before the end of the study period. Autism spectrum disorder diagnoses were only considered if they were made at least 2 years after the birth year and prior to the end of the year 2012.

Figure 2.

Prevalence of each of the seven co-occurring condition categories across the 5-year enrollment period in (A) the autism spectrum disorder (ASD) cohort and general population with no ASD diagnosis (POP) cohort, and (B) the three ASD clusters. Dots signify the prevalence is at least as great as the indicated value.

Figure 3.

Proportions of the autism spectrum disorder (ASD) cohort, general population with no ASD diagnosis (POP) cohort, and three ASD clusters with a diagnosis in each co-occurring condition category during each 6-month interval of the 5-year enrollment period: (A) auditory disorders, (B) developmental delays, (C) gastrointestinal symptoms, (D) immune-related conditions, (E) psychiatric disorders, (F) seizures, and (G) sleep disorders.

Figure 4.

Frequency distributions for the number of co-occurring condition categories diagnosed during the 5-year enrollment period in an individual in the autism spectrum disorder (ASD) cohort, general population with no ASD diagnosis (POP) cohort, and three ASD clusters.

Figure 5.

Cumulative distribution functions for the time of first autism spectrum disorder (ASD) diagnosis in the ASD cohort and its three clusters.

Figure 6.

Differences in prevalence of the seven co-occurring condition categories between the autism spectrum disorder (ASD) cohort and general population with no ASD diagnosis (POP) cohort over time, with categories following similar patterns grouped together: (A) auditory disorders, (B) developmental delays, (C) gastrointestinal conditions clustered with immune-related disorders, (D) psychiatric disorders, and (E) seizures clustered with sleep disorders.