Autism Spectrum Disorder Diagnoses and Congenital Cytomegalovirus

OBJECTIVE To examine the association between congenital cytomegalovirus (cCMV) and autism spectrum disorder (ASD) administrative diagnoses in US children. METHODS Cohort study using 2014 to 2020 Medicaid claims data. We used diagnosis codes to identify cCMV (exposure), ASD (outcome), and covariates among children enrolled from birth through ≥4 to <7 years. Covariates include central nervous system (CNS) anomaly or injury diagnosis codes, including brain anomaly, microcephaly within 45 days of birth, cerebral palsy, epilepsy, or chorioretinitis. We used Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals, overall and stratified by sex, birth weight and gestational age outcome (low birth weight or preterm birth), and presence of CNS anomaly or injury. RESULTS Among 2 989 659 children, we identified 1044 (3.5 per 10 000) children with cCMV and 74 872 (25.0 per 1000) children with ASD. Of those with cCMV, 49% also had CNS anomaly or injury diagnosis codes. Children with cCMV were more likely to have ASD diagnoses (hazard ratio: 2.5; 95% confidence interval: 2.0–3.2, adjusting for birth year, sex, and region). This association differed by sex and absence of CNS anomaly or injury but not birth outcome. CONCLUSIONS Children with (versus without) cCMV diagnoses in Medicaid claims data, most of whom likely had symptomatic cCMV, were more likely to have ASD diagnoses. Future research investigating ASD risk among cohorts identified through universal cCMV screening may help elucidate these observed associations.