Background/Objectives: Our understanding of the transdiagnostic factors that influence health-related quality of life (HRQOL) in individuals with neurodivergent conditions is very sparse and highly siloed by diagnosis labels. Research on transdiagnostic predictors of HRQOL across neurodevelopmental conditions is needed to enable care models that address shared needs of neurodivergent individuals beyond diagnostic boundaries. Our objective was to identify transdiagnostic factors associated with HRQOL in children with autism, epilepsy, or comorbid autism/epilepsy. Methods: This cross-sectional study included 37 autistic and/or epileptic children (mean age = 9.2; SD = 3.9; boys = 28). Parents provided sociodemographic information and completed the following measures: Social Communication Questionnaire (measure of severity of autistic symptoms); Parenting Stress Index, Fourth Edition; Pediatric Quality of Life Inventory; and the Behavioral Assessment System for Children, Third Edition. Child intellectual functioning was measured using age-appropriate scales: the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition: Canadian or the Wechsler Intelligence Scale for Children-Fifth Edition: Canadian. Results: Higher autistic symptom severity (OR = 0.851 95% CI: 0.732-0.988, p = 0.034) and parenting stress (OR = 0.687 95% CI: 0.493-0.959, p = 0.027) were associated with poorer HRQOL. Full Scale IQ and adaptive skills showed trend level associations with HRQOL. Sociodemographic factors including maternal education, child sex, and child age as well as child diagnosis were not associated with HRQOL. Conclusions: In this transdiagnostic sample of children, autism symptom severity and parenting stress were shared predictors of HRQOL. Interventions targeting child autistic symptoms and parents' levels of stress could result in improved HRQOL in neurodivergent populations.
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