Patterns of Risk for Multiple Co-Occurring Medical Conditions Replicate Across Distinct Cohorts of Children with Autism Spectrum Disorder

Abstract

Children with autism spectrum disorder (ASD) may present with multiple medical conditions in addition to ASD symptoms. This study investigated whether there are predictive patterns of medical conditions that co-occur with ASD, which could inform medical evaluation and treatment in ASD, as well as potentially identify etiologically meaningful subgroups. Medical history data were queried in the multiplex family Autism Genetic Resource Exchange (AGRE). Fourteen medical conditions were analyzed. Replication in the Simons Simplex Collection (SSC) was attempted using available medical condition data on gastrointestinal disturbances (GID), sleep problems, allergy and epilepsy. In the AGRE cohort, no discrete clusters emerged among 14 medical conditions. GID and seizures were enriched in unaffected family members, and together with sleep problems, were represented in both AGRE and SSC. Further analysis of these medical conditions identified predictive co-occurring patterns in both samples. For a child with ASD, the presence of GID predicts sleep problems and vice versa, with an approximately 2-fold odds ratio in each direction. These risk patterns were replicated in the SSC sample, and in addition, there was increased risk for seizures and sleep problems to co-occur with GID. In these cohorts, seizure alone was not predictive of the other conditions co-occurring, but behavioral impairments were more severe as the number of co-occurring medical symptoms increased. These findings indicate that interdisciplinary clinical care for children with ASD will benefit from evaluation for specific patterns of medical conditions in the affected child and their family members.

Keywords: gastrointestinal disturbances; medical symptoms; seizure; sleep.

Figure 1

Odds ratios of co‐occurring medical symptoms. Graph depicts, for the AGRE and SCC cohorts, the odds ratio (adjusted for proband sex) of bivariate and trivariate combinations of a child having co‐occurring gastrointestinal disturbance (GID), sleep disturbance, and seizures. Table 3 reports the specific ranges of calculated ORs and results of significance tests. Note that for some combinations in the AGRE sample, such as those including seizures in the GID x sleep multivariate analysis, the confidence intervals are large, reflecting small sample numbers in the seizure category.