Association Between Prescribed Hypnotics in Infants and Toddlers and Later ADHD: A Large Cohort Study from Norway

As previously indicated an association may exist between early sleep problems in infants and toddlers, and a diagnosis of attention deficit hyperactivity disorder (ADHD). The aim of this study was to study if this association could be replicated in a complete nationwide cohort of children. Prospective cohort study using national registries. All children born in Norway from January 2004 to December 2010 were included (N = 410,555). Information on hypnotic drugs dispensed to children 0-3 years of age outside of institutions was collected from the Norwegian Prescription Database and used as a proxy for sleep problems. The outcome ADHD (ICD-10), as diagnosed by specialists in the Child Mental Health Service, was obtained from the Norwegian Patient Registry. Data were analysed using weighted estimation in Cox regression. The unadjusted weighted hazard ratio (wHR) for a later diagnosis of ADHD in children dispensed two or more prescriptions for any hypnotic drug, compared to zero prescriptions, was 2.30 [95% confidence interval (CI) 1.63-3.23] for girls and 1.75 (95% CI 1.48-2.07) for boys. For the sedative antihistamine trimeprazine the corresponding wHR was 3.71 (95% CI 1.83-7.52) for girls and 2.78 (95% CI 2.04-3.80) for boys. After adjusting for parental ADHD and parental education the wHR for trimeprazine users was 2.81 (95% CI 1.34-5.88) for girls and 2.33 (95% CI 1.70-3.20) for boys. Infants and toddlers who were dispensed hypnotics had an increased risk of ADHD at school age. This association was most pronounced with the use of trimeprazine, a drug traditionally prescribed to toddlers for sleep problems in Norway. After adjusting for parental ADHD and educational level the risk for ADHD among the trimeprazine users was still more than twice the risk among controls.