RT Journal Article SR Electronic T1 Exploring the gateway hypothesis of e-cigarettes and tobacco: a prospective replication study among adolescents in the Netherlands and Flanders JF Tobacco Control JO Tob Control FD BMJ Publishing Group Ltd SP tobaccocontrol-2021-056528 DO 10.1136/tobaccocontrol-2021-056528 A1 Thomas Martinelli A1 Math J J M Candel A1 Hein de Vries A1 Reinskje Talhout A1 Vera Knapen A1 Constant P van Schayck A1 Gera E Nagelhout YR 2021 UL http://tobaccocontrol.bmj.com/content/early/2022/05/08/tobaccocontrol-2021-056528.abstract AB Background Studies demonstrated that adolescent e-cigarette use is associated with subsequent tobacco smoking, commonly referred to as the gateway effect. However, most studies only investigated gateways from e-cigarettes to tobacco smoking. This study replicates a cornerstone study revealing a positive association between both adolescent e-cigarette use and subsequent tobacco use; and tobacco and subsequent e-cigarette use in the Netherlands and Flanders.Design The longitudinal design included baseline (n=2839) and 6-month (n=1276) and 12-month (n=1025) follow-up surveys among a school-based cohort (mean age: 13.62). Ten high schools were recruited as a convenience sample. The analyses involved (1) associations of baseline e-cigarette use and subsequent tobacco smoking among never smokers; (2) associations of e-cigarette use frequency at baseline and tobacco smoking frequency at follow-up; and (3) the association of baseline tobacco smoking and subsequent e-cigarette use among non-users of e-cigarettes.Findings Consistent with prior findings, baseline e-cigarette use was associated with higher odds of tobacco smoking at 6-month (OR=1.89; 95% CI 1.05 to 3.37) and 12-month (OR=5.63; 95% CI 3.04 to 10.42) follow-ups. More frequent use of e-cigarettes at baseline was associated with more frequent smoking at follow-ups. Baseline tobacco smoking was associated with subsequent e-cigarette use (OR=3.10; 95% CI 1.58 to 6.06 at both follow-ups).Conclusion Our study replicated the positive relation between e-cigarette use and tobacco smoking in both directions for adolescents. This may mean that the gateway works in two directions, that e-cigarette and tobacco use share common risk factors, or that both mechanisms apply.Data are available upon reasonable request. Anonymised data and protocols are available upon reasonable request from the corresponding author (martinelli@ivo.nl).