Risk of Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder in Children With Hypoxic-Ischemic Encephalopathy

PURPOSE: This study investigated the risk of ASD and ADHD in children who have survived hypoxic-ischemic encephalopathy (HIE), one of the common conditions during birth resulting in neonatal brain injury. METHODS: A population-based cohort study analyzed electronic medical records of term infants with HIE born in public hospital in Hong Kong from 1st January 2004 to 31st December 2018 with followed-up until 31st Dec 2024. The association of HIE with ADHD and ASD was examined using log-binomial regression models adjusting sequentially for age, sex, and socioeconomic status (SES). RESULTS: A total of 533,230 children were included of which 349 cases had a diagnosis of HIE. Compared to children without history of HIE, the RR of ADHD in children with HIE was 1.94 (CI 1.40-2.68, p < 0.001) in the unadjusted model, 1.83 (CI 1.32, 2.52, p < 0.001) when adjusting for age & sex, and 1.84 (CI 1.34, 2.55, p < 0.001) when adjusting for age, sex and socioeconomic status (SES). The relationship between ASD and HIE did not reach statistical significance, RR = 1.58 (p = 0.08, CI 0.93, 2.68) adjusted for age, sex and SES. A significant interaction effect was found between HIE and the age of mothers, the RR of ADHD was 4.25 (CI 2.14, 8.46) in mothers under 24 years of age. CONCLUSION: Children with HIE, especially those born to younger mothers, were associated with elevated risk of ADHD. The relationship between ASD and HIE remained inconclusive, suggesting the need for further research to clarify this potential association.