Association Between Receipt of General Anesthesia During Childhood and Attention Deficit Hyperactive Disorder and Neurodevelopment

Figures

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  Fig. 1. Study design. ICD-10 = 10th revision of the International Classification of Diseases.

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  Fig. 2. Forest plot for sensitivity analysis of alternative definitions of ADHD. HRs and 95% CIs were calculated using a Cox proportional hazards model to assess the relationship between general anesthesia and various definitions of ADHD, adjusting for age at the index date, sex, calendar year of birth (2008 or 2009), birth weight, birth residence (Seoul/metropolitan, city, or rural area), economic status (low, middle, or high), and perinatal diseases. Recurrent ADHD 1 year apart was defined as two principal diagnoses of ICD-10 code F90.X after 72 months of age and 1 year apart between diagnoses. Wide-ranging ADHD was defined as at least a principal or second diagnosis of ICD-10 code F90.X after 72 months of age. ADHD with medication was defined as at least a principal diagnosis of ICD-10 code F90.X after 72 months of age with a prescription of methylphenidate. All outcomes were identified for at least one year (window period) after the index date. Filled rounds indicate aHRs and black lines indicate 95% CIs. ADHD = attention deficit hyperactivity disorder, PY = person-years, CI = confidence interval, HR = hazard ratio, aHR = adjusted hazard ratio, ICD-10 = 10th revision of the…

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  Fig. 3. Forest plot of the association between GA and ADHD according to the intensity of GA and participant’s condition after GA. HRs and 95% CIs were calculated using a Cox proportional hazards model, adjusting for age at the index date, sex, calendar year of birth (2008 or 2009), birth weight, birth residence (Seoul, metropolitan, city, or rural area), economic status (low, middle, or high), and perinatal diseases. To estimate the intensity of GA and participants’ condition after GA, the exposure was divided according to the duration of GA (less than 1 hour, 1–2 hours, 2–3 hours, or over 3 hours), number of GA exposures (once, twice, or thrice or over), duration of admission at the time of GA (less than 3 days [median] or 3 days or over), and admission to the ICU (yes or no). All outcomes were identified for at least one year (window period) after the index date. Filled rounds indicate aHRs and black lines indicate 95% CIs. ADHD = attention deficit hyperactivity disorder, CI = confidence interval, aHR = adjusted hazard ratio, ICU = intensive care unit, GA = general anesthesia.

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  Fig. 4. Sensitivity analysis for the association between general anesthesia and ADHD based on the 1:1 propensity score matching method. RRs and 95% CIs were calculated using a modified Poisson regression to assess the relationship between general anesthesia and ADHD in the second cohort. ADHD as main outcome was defined as at least a principal diagnosis of ICD-10 code F90.X after 72 months old. Recurrent ADHD 1 year apart was defined as two principal diagnoses of ICD-10 code F90.X after 72 months of age and 1 year apart between diagnoses. Wide-ranging ADHD was defined as at least a principal or second diagnosis of ICD-10 code F90.X after 72 months of age. ADHD with medication was defined as at least a principal diagnosis of ICD-10 code F90.X after 72 months of age with a prescription of methylphenidate. All outcomes were identified for at least one year (window period) after the index date. Filled rounds indicate aRRs and black lines indicate 95% CIs. ADHD = attention deficit hyperactivity disorder, CI = confidence interval, RR = risk ratio, aRR = adjusted risk ratio, ICD-10 = 10th revision of the International Classification of Diseases.

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  Fig. 5. Forest plot for the association between general anesthesia and each domain of K-ASQ. ORs and their 95% CIs were calculated using generalized estimated equations with the logit link function to assess the associations between general anesthesia exposure and adverse results of the K-ASQ in children. The results of each domain were stratified into appropriate, need for follow-up, and recommendations for further evaluation categories. The results of need for follow-up and recommendation for further evaluation, which mean a score below −1 and −2 standard deviations for age, were considered adverse results. All outcomes were identified for at least one year (window period) after the index date. Filled rounds indicate aORs and black lines indicate 95% CIs. K-ASQ = Korean-Ages and Stages Questionnaire, CI = confidence interval, OR = odds ratio, aOR = adjusted odds ratio.