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Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder.

ABSTRACT: Objective: To estimate phenotypic and familial association between early-life injuries and attention-deficit/hyperactivity disorder (ADHD) and the genetic contribution to the association using polygenic risk score for ADHD (PRS-ADHD) and genetic correlation analyses.Methods: Children born in Denmark between 1995-2010 (n = 786,543) were followed from age 5 years until a median age of 14 years (interquartile range: 10-18 years). Using ICD-10 diagnoses, we estimated hazard ratios (HRs) and absolute risks of ADHD by number of hospital/emergency ward-treated injuries by age 5. In a subset of ADHD cases and controls born 1995 to 2005 who had genetic data available (n = 16,580), we estimated incidence rate ratios (IRRs) for the association between PRS-ADHD and number of injuries before age 5 and the genetic correlation between ADHD and any injury before age 5.Results: Injuries were associated with ADHD (HR = 1.61; 95% CI, 1.55-1.66) in males (HR = 1.59; 1.53-1.65) and females (HR = 1.65; 1.54-1.77), with a dose-response relationship with number of injuries. The absolute ADHD risk by age 15 was 8.4% (3+ injuries) vs 3.1% (no injuries). ADHD was also associated with injuries in relatives, with a stronger association in first- than second-degree relatives. PRS-ADHD was marginally associated with the number of injuries in the general population (IRR = 1.06; 1.00-1.14), with a genetic correlation of 0.53 (0.21-0.85).Conclusions: Early-life injuries in individuals and their relatives were associated with a diagnosis of ADHD. However, even in children with the most injuries, more than 90% were not diagnosed with ADHD by age 15. Despite a low positive predictive value and that the impact of unmeasured factors such as parental behavior remains unclear, results indicate that the association is partly explained by genetics, suggesting that early-life injuries may represent or herald early behavioral manifestations of ADHD.

SUBMITTER: Wimberley T

PROVIDER: S-EPMC7612325 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceAppropriate diagnosis of attention-deficit/hyperactivity disorder (ADHD) can improve some short-term outcomes in children and adolescents, but little is known about the association of a diagnosis with their quality of life (QOL).ObjectiveTo compare QOL in adolescents with and without an ADHD diagnosis.Design, setting, and participantsThis cohort study followed an emulated target trial design using prospective, observational data from the Longitudinal Study of Australian Children, a representative, population-based prospective cohort study with biennial data collection from 2006 to 2018 with 8 years of follow-up (ages 6-7 to 14-15 years). Propensity score matching was used to ensure children with and without ADHD diagnosis were well matched on a wide range of variables, including hyperactive/inattentive (H/I) behaviors. Eligible children were born in 1999 to 2000 or 2003 to 2004 and did not have a previous ADHD diagnosis. All incident ADHD cases were matched with controls. Data were analyzed from July 2021 to January 2022.ExposuresIncident parent-reported ADHD diagnosis at age 6 to 7, 8 to 9, 10 to 11, 12 to 13, or 14 to 15.Main outcomes and measuresQuality of life at age 14 to 15 was measured with Child Health Utility 9D (CHU9D) and 8 other prespecified, self-reported measures mapped to the World Health Organization's QOL domains. Pooled regression models were fitted for each outcome, with 95% CIs and P values calculated using bootstrapping to account for matching and repeat observations.ResultsOf 8643 eligible children, a total of 393 adolescents had an ADHD diagnosis (284 [72.2%] boys; mean [SD] age, 10.03 [0.30] years; mean [SD] H/I Strengths and Difficulties Questionnaire score, 5.05 [2.29]) and were age-, sex-, and H/I score-matched with 393 adolescents without ADHD diagnosis at time zero. Compared with adolescents without diagnosis, those with an ADHD diagnosis reported similar QOL on CHU9D (mean difference, -0.03; 95% CI, -0.07 to 0.01; P = .10), general health (mean difference, 0.11; 95% CI, -0.04 to 0.27; P = .15), happiness (mean difference, -0.18; 95% CI, -0.37 to 0.00; P = .05), and peer trust (mean difference, 0.65; 95% CI, 0.00 to 1.30; P = .05). Diagnosed adolescents had worse psychological sense of school membership (mean difference, -2.58; 95% CI, -1.13 to -4.06; P < .001), academic self-concept (mean difference, -0.14; 95% CI, -0.02 to -0.26; P = .02), and self-efficacy (mean difference, -0.20; 95% CI, -0.05 to -0.33; P = .007); displayed more negative social behaviors (mean difference, 1.56; 95% CI, 0.55 to 2.66; P = .002); and were more likely to harm themselves (odds ratio, 2.53; 95% CI, 1.49 to 4.37; P < .001) than adolescents without diagnosis.Conclusions and relevanceIn this cohort study, ADHD diagnosis was not associated with any self-reported improvements in adolescents' QOL compared with adolescents with similar levels of H/I behaviors but no ADHD diagnosis. ADHD diagnosis was associated with worse scores in some outcomes, including significantly increased risk of self-harm. A large, randomized clinical trial with long-term follow-up is needed.

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Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder.

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