A Meta-Analysis of Urinary Cotinine Cut-Off Concentrations in Children Under Five Years for Assessing Environmental Tobacco Smoke Exposure
Sharifah Mazrah Sayed Mohamed Zain, Nadia Mohamad, Zurahanim Fasha Anual, Imanul Hassan Abdul Shukor, Wan Nurul Farah Wan AzmiBackground
Environmental tobacco smoke (ETS) exposure is a preventable risk factor for adverse health outcomes in early childhood. Urinary cotinine is widely used as a non-invasive biomarker of ETS exposure; however, variation in reported cut-off concentrations limits comparability across studies. No prior systematic review has quantitatively synthesised urinary cotinine cut-off values for children under five years. This review aimed to systematically summarise and evaluate these cut-off concentrations in early childhood.
Methods
A systematic review and meta-analysis were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines and a prospectively published protocol (PROSPERO CRD42024556969). PubMed, Embase, Scopus, and the Cochrane Library were searched from inception to February 2025. Observational and experimental studies reporting urinary cotinine cut-off concentrations to classify ETS exposure among children under five years were included. Study quality was assessed using the Newcastle–Ottawa Scale. Random-effects meta-analyses were performed to estimate pooled urinary cotinine cut-off concentrations for ETS exposure classification, stratified by unit of measurement (ng/mL vs ng/mg creatinine).
Results
Twelve studies were included. Reported urinary cotinine cut-off concentrations ranged from 0.05 to 30 ng/mL for unadjusted values and from 2.47 to 120 ng/mg creatinine for creatinine-adjusted values. Meta-analysis yielded pooled reference values of 5.90 ng/mL (95% CI: 5.53–6.27) and 50.36 ng/mg creatinine (95% CI: 47.53–53.20), respectively.
Conclusion
Urinary cotinine is a valid biomarker for assessing ETS in young children, but inconsistent cut-off values limit comparability. The pooled estimates may aid interpretation in surveillance and research but should not be used as universal thresholds. Standardized, age-appropriate cut-offs are needed to strengthen exposure assessment and inform child-focused tobacco control policies.