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Exposure to different sources of second-hand smoke during pregnancy and its effect on urinary cotinine and tobacco-specific nitrosamine (NNAL) concentrations
  1. Constantine I Vardavas1,2,
  2. Eleni Fthenou3,
  3. Evridiki Patelarou1,
  4. Emmanouil Bagkeris1,4,
  5. Sharon Murphy5,
  6. Stephen S Hecht5,
  7. Gregory N Connolly2,
  8. Leda Chatzi1,
  9. Manolis Kogevinas1,4,6,7
  1. 1Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece
  2. 2Center for Global Tobacco Control, Department of Society, Human Development and Health, Harvard School of Public Health, Boston, Massachusetts, USA
  3. 3Department of Histology, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece
  4. 4Center for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
  5. 5Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA
  6. 6Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain
  7. 7CIBER Epidemiologia y Salud Pública (CIBERESP), Spain
  1. Correspondence to Dr Constantine I Vardavas, Center for Global Tobacco Control, Department of Society, Human Development and Health, Harvard School of Public Health, Boston, Massachusetts, USA; vardavas{at}


Background To date, no research exists on the role that different sources of exposure to second-hand smoke (SHS) have on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and nicotine uptake, assessed via urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and cotinine concentrations of non-smoking pregnant women, nor the differences in NNAL concentrations among pregnant women who quit smoking in comparison to those who do not.

Methods As part of the ‘Rhea’ mother childbirth cohort in Crete, Greece, 1317 mother–child pairs were followed-up until delivery, while among a subsample, maternal urine was assessed for its NNAL (n=117) and cotinine concentrations (n=377).

Results Pregnant women who continued to smoke during pregnancy were found to have geometric mean urinary NNAL concentrations of 0.612 pmol/ml, in comparison to the 0.100 pmol/ml of ex-smokers and 0.0795 pmol/ml of non-smokers exposed to SHS. Exposure to SHS in the home was associated with a 4.40 ng/ml increase in urinary cotinine levels, while reported exposure to SHS in cars was associated with an even higher (8.73 ng/ml) increase in cotinine concentrations and was strongly related to NNAL concentrations. Exposure to SHS in the workplace and in public places was also shown to increase cotinine and NNAL concentrations. The NNAL:cotinine ratio was found to be higher among pregnant women who were exposed to SHS but did not smoke (p<0.001).

Conclusions Using cotinine levels as an indicator of NNK, exposure due to SHS during pregnancy leads to an underestimation of exposure to NNK uptake. Moreover, each source of exposure contributed to the increase in cotinine levels, indicating the importance of avoiding SHS exposure from any source.

  • Smoking
  • cessation
  • pregnancy
  • fetal health
  • passive smoking
  • SHS
  • toxicology
  • prevalence
  • environmental tobacco smoke
  • advertising and promotion
  • packaging and labelling
  • electronic nicotine delivery devices
  • public policy
  • cotinine
  • second-hand smoke
  • smoking-caused disease
  • carcinogens
  • harm reduction
  • taxation and price
  • advocacy

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  • Funding This work was supported by a Flight Attendant Medical Research Institute grant (Clinical Investigator Award 072058). This work was also partly supported by the EU Integrated Project NewGeneris, 6th Framework Programme (Contract No. FOOD-CT-2005-016320) and by the EU-funded project HiWATE, 6th Framework Programme (Contract No. Food-CT-2006-036224).

  • Competing interests None.

  • Ethics approval University Hospital of Crete, Institutional Review Board (IRB).

  • Provenance and peer review Not commissioned; externally peer reviewed.