Sex differences in the age of childhood autism diagnosis and the impact of co-occurring conditions

Abstract

Sex differences in the age of autism diagnosis during childhood have been documented consistently but remain poorly understood. In this study, we used electronic health records data from a diverse, academic medical center to quantify differences in the age of autism diagnosis between boys and girls and identify associations between the age of diagnosis and co-occurring neurodevelopmental, psychiatric, and medical conditions. An established computable phenotype was used to identify all autism diagnoses within the Duke University Health System between 2014 and 2021. Co-occurring neurodevelopmental and psychiatric diagnoses as well as visits to specific medical and supportive services were identified in the 2 years prior to the autism diagnosis. Cox proportional hazards models were fitted to quantify associations between diagnosis age and sex with and without controlling for the presence of each co-occurring diagnosis and visit type. Records from 1438 individuals (1142 boys and 296 girls) were included. Girls were more likely to be diagnosed either before age 3 ((Formula presented.) = 497.720, p < 0.001) or after age 11 ((Formula presented.) = 4.014, p = 0.047), whereas boys were more likely to be diagnosed between ages 3 and 11 ((Formula presented.) = 5.532, p = 0.019). Visits for anxiety ((Formula presented.) = 4.200, p = 0.040) and mood disorders ((Formula presented.) = 7.033, p = 0.008) were more common in girls and associated with later autism diagnosis (HR = 0.615, p < 0.001; and HR = 0.493, p < 0.001). Visits for otolaryngology were more common in boys and associated with an earlier autism diagnosis (HR = 1.691, p < 0.001). After controlling for these conditions, associations between sex and diagnosis age were reduced and not statistically significant. These results show that the age of autism diagnosis differs in girls compared to boys, but these differences were neutralized when controlling for co-occurring neurodevelopmental and psychiatric conditions prior to autism diagnosis. Understanding sex differences and the possible mediating role of other diagnoses may suggest targets for intervention to promote earlier and more equitable diagnosis.