Comorbidities in autism spectrum disorder and their etiologies

Abstract

Importance: Perinatal exposures have been associated with autism spectrum disorder (ASD). It is unknown whether perinatal exposures are also associated with the burden of comorbidities in ASD across different medical domains. Objective: To examine the burden and pattern of comorbidities in individuals with ASD, and evaluate the associations between perinatal exposures linked with ASD and distinct comorbidities. Design: We used data from family-based study (SPARK) which recruited families with one or more children with a clinically confirmed ASD diagnosis across clinical sites throughout the US. Setting: All data in SPARK are collected remotely to allow participants to complete the study protocol at their convenience. Participants: To minimize recall bias of early-life exposures, we restricted the sample to individuals born between 1999 and 2019 who were less than 18 years of age at the time of registration into the study. The final analytic sample included 40,582 children with ASD and 11,389 non-ASD siblings. Exposures: Perinatal exposures including preterm birth, prenatal infection, fetal alcohol syndrome, hypoxia at birth, bleeding into the brain during delivery, lead poisoning, brain infections, and traumatic brain injury. Main Outcomes and Measures: Outcomes were based on parent report of professional diagnosis of neurological, cognitive, psychiatric, and physical disorders. Results: Children with ASD had a substantially higher prevalence of all comorbidities compared to their siblings without an ASD diagnosis (all p-values <0.05). ADHD was the most common comorbidity, affecting 1 in every 3 children with ASD. In logistic regression models adjusted for covariates (annual household income, parental education, parental ages at childbirth, year of birth, age of the child at evaluation, race, and ethnicity), different exposures were associated with distinct patterns of comorbidities in ASD cases, including associations between preterm birth and difficulty gaining weight (OR=2.38; 95%CI=2.09-2.71) and traumatic brain injury and seizure or epilepsy (OR=4.75; 95%CI=3.25-6.95). We observed a similar pattern of associations in non-ASD siblings. Conclusions and Relevance: Individuals with ASD experience a greater burden of perinatal exposures and comorbidities. The higher burden of comorbidities in this population could be partly attributable to the higher rates of perinatal exposures. Study findings, if replicated in other samples, can inform the etiology of comorbidity in ASD.