Comorbidities in autism spectrum disorder and their etiologies
Authors: Khachadourian Vahe , Mahjani Behrang , Sandin Sven , Kolevzon Alexander , Buxbaum Joseph D. , Reichenberg Abraham , Janecka Magdalena 
Published: March 2022

ABSTRACTImportancePerinatal 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.ObjectiveTo examine the burden and pattern of comorbidities in individuals with ASD, and evaluate the associations between perinatal exposures linked with ASD and distinct comorbidities.DesignWe 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.SettingAll data in SPARK are collected remotely to allow participants to complete the study protocol at their convenience.ParticipantsTo 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.ExposuresPerinatal 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 MeasuresOutcomes were based on parent report of professional diagnosis of neurological, cognitive, psychiatric, and physical disorders.ResultsChildren 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, father’s and mother’s 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 RelevanceIndividuals 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.KEY POINTSQuestionDoes the pattern of comorbidities in individuals with autism spectrum disorder vary by pre- and postnatal exposures?FindingsThe burden of pre- and postnatal exposures and comorbidity in children with autism spectrum disorder (ASD) is significantly higher than in their non-ASD siblings. Distinct pre- and postnatal exposures were associated with different patterns of comorbidities.MeaningChildren with ASD experience a significantly higher burden of comorbidities which may arise due to distinct etiological factors.