Assessing tobacco smoke exposure in pregnancy from self-report, urinary cotinine and NNAL: a validation study using the New Hampshire Birth Cohort Study

Janet L. Peacock, Thomas J. Palys, Yuliya Halchenko, Vicki Sayarath, Cindy A. Takigawa, Sharon E. Murphy, Lisa A. Peterson, Emily R. Baker, Margaret R. Karagas

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Objectives Accurate assessment of tobacco smoke exposure is key to evaluate its effects. We sought to validate and establish cut-offs for self-reported smoking and secondhand smoke (SHS) exposure during pregnancy using urinary cotinine and 4-(methylnitrosamino)-1-(-3-pyridyl)-1-butanol (NNAL) in a large contemporary prospective study from the USA, with lower smoking prevalence than has previously been evaluated. Design Prospective birth cohort. Setting Pregnancy clinics in New Hampshire and Vermont, USA. Participants 1396 women enrolled in the New Hampshire Birth Cohort Study with self-reported smoking, urinary cotinine, NNAL and pregnancy outcomes. Primary and secondary outcome measures Cut-offs for urinary cotinine and NNAL concentrations were estimated from logistic regression models using Youden's method to predict SHS and active smoking. Cotinine and NNAL were each used as the exposure in separate multifactorial models for pregnancy outcomes. Results Self-reported maternal smoking was: 72% non-smokers, 5.7% ex-smokers, 6.4% SHS exposure, 6.2% currently smoked, 10% unreported. Cotinine and NNAL levels were low and highly intercorrelated (r=0.91). Geometric mean cotinine, NNAL were 0.99 ng/mL, 0.05 pmol/mL, respectively. Cotinine cut-offs for SHS, current smoking were 1.2 ng/mL and 1.8 ng/mL (area under curve (AUC) 95% CI: 0.52 (0.47 to 0.57), 0.90 (0.85 to 0.94)). NNAL cut-off for current smoking was 0.09 pmol/mL (AUC=0.82 (95% CI 0.77 to 0.87)). Using cotinine and NNAL cut-offs combined gave similar AUC to cotinine alone, 0.87 (95% CI 0.82 to 0.91). Cotinine and NNAL gave almost identical effect estimates when modelling pregnancy outcomes. Conclusions In this population, we observed high concordance between self-complete questionnaire smoking data and urinary cotinine and NNAL. With respect to biomarkers, either cotinine or NNAL can be used as a measure of tobacco smoke exposure overall but only cotinine can be used to detect SHS.

Original languageEnglish (US)
Article number054535
JournalBMJ open
Issue number2
StatePublished - Feb 7 2022

Bibliographical note

Funding Information:
Funding Research supported in this publication was supported in part by the National Institutes of Health: P20GM104416, P42ES007373, P01 ES022832, UC2ES026533, UH30D023275, UG3OD023275 and US EPA RD83544201.

Publisher Copyright:
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.


  • epidemiology
  • perinatology
  • statistics & research methods

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


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