Timing and tempo of pubertal development and substance use in adolescence: a cohort study in the Danish National Birth Cohort.

study questionAre the age at reaching different pubertal milestones, and the tempo of pubertal progression, associated with cigarette smoking, alcohol intake, or recreational drug use in adolescence? SUMMARY ANSWER: Earlier age at pubertal development was associated with a higher risk of smoking cigarettes, drinking alcohol (only boys), and using recreational drugs in adolescence, and a faster tempo tended to be associated with higher risks, mainly in girls, while any associations in boys appeared less clear. WHAT IS KNOWN ALREADY: Girls and boys with an earlier age at pubertal development are suggested to have a higher risk of engaging in risk-taking behaviours, which include use of substances, primarily studied for smoking and alcohol. The potential impact of pubertal tempo has been studied less. STUDY DESIGN SIZE DURATION: In this cohort study, 8063 girls and boys born from 2000 to 2003 by mothers in the Danish National Birth Cohort participated. Information on covariates was obtained from pregnancy interviews and a follow-up questionnaire at age 7. Information on pubertal development was obtained from questionnaires completed by the girls and boys throughout puberty, starting at age 11, and information on substance use, covering cigarette smoking, alcohol, and recreational drug use, was obtained from a questionnaire completed at a mean age of 18 years and 4 months. PARTICIPANTS/MATERIALS SETTING

methodsA multinomial logistic regression model was used to obtain adjusted relative risk ratios (RRRs) of smoking, drinking alcohol, and using recreational drugs (non-medical use of psychoactive substances) per 1 year earlier timing of pubertal development (Tanner stages of breast/genital and pubic hair development, menarche, first ejaculation, and voice break) and for tempo per one-unit (Tanner stages per year) faster tempo. Additionally, we also analysed categories of pubertal timing (15% earliest, 70% (ref.), 15% latest) and tempo (15% fastest, 70% (ref.), 15% slowest). The timing and tempo of the development of Tanner stages were derived using a non-linear mixed-effects model. MAIN RESULTS AND THE ROLE OF CHANCE: At the age of 18 years, 19% of girls and 20% of boys reported smoking at least monthly, 69% of girls and 71% of boys reported consuming alcohol more frequently than once a month, and 17% of girls and 30% of boys reported use of recreational drugs (primarily hash or pot) at some point during the past year. In girls, the RRR per 1-year earlier breast development was 1.20 (95% CI, 1.08-1.34) for smoking daily or weekly and 1.10 (95% CI, 0.97-1.25) for smoking monthly, and in boys, the RRR per 1-year earlier genital development was 1.09 (95% CI, 0.94-1.27) for smoking daily or weekly and 1.17 (95% CI, 1.02-1.34) for smoking monthly compared to no smoking. In girls, earlier age at menarche, but no other milestone, was associated with lower risk of alcohol consumption at age 18, whereas in boys, earlier age at genital development was associated with higher risk of drinking alcohol weekly (RRR 1.13 (95% CI, 0.99-1.30) per 1-year earlier timing) and 2-4 times/month (RRR 1.07 (95% CI, 0.96-1.19) per 1-year earlier timing) compared to drinking alcohol ≤1 time/month. In girls, the RRR per 1-year earlier breast development was 1.31 (95% CI, 1.07-1.59) for using recreational drugs monthly and 1.04 (95% CI, 0.93-1.15) for using recreational drugs <1 time/month. In boys, the RRR per 1-year earlier genital development was 1.17 (95% CI, 0.97-1.43) for using recreational drugs monthly and 1.16 (95% CI, 1.03-1.30) for using recreational drugs <1 time/month compared to no recreational drug use. Faster pubertal tempo tended to be associated with higher risk of smoking, drinking alcohol, and using recreational drugs, mainly in girls. LIMITATIONS REASONS FOR CAUTION: Information on pubertal development was self-reported, introducing a risk of misclassification of pubertal timing and tempo. Furthermore, the self-reported information on smoking habits, alcohol intake, and recreational drug use might be under-reported due to social stigmatization. We were not able to explore associations with snus or e-cigarettes, although this may be highly relevant. WIDER IMPLICATIONS OF THE

findingsThe findings suggest that girls and boys with earlier and maybe faster pubertal development may be high-risk groups for smoking cigarettes, drinking alcohol, and using recreational drugs. The associations were observed across various pubertal milestones, and the consistent findings across these strengthen the conclusion and support what has previously been shown primarily for pubertal timing and smoking. Our findings on pubertal tempo suggest that preventive strategies could benefit from targeting early developers and also fast-developing girls. This study was performed in a Danish cohort, and the findings are likely transferable to other Western populations with a comparable smoking, alcohol, and drug use culture. STUDY FUNDING/COMPETING INTERESTS: This study has been supported by the Lundbeck Foundation (R396-2022-265). The project was further co-funded by the European Union (ERC, BIOSFER, 101071773). Views and opinions expressed are those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible for them. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.