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Nicotine Tob Res. 2014 Feb;16(2):145-54. doi: 10.1093/ntr/ntt127. Epub 2013 Aug 13.

Nicotine dependence and biochemical exposure measures in the second trimester of pregnancy.

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Division of Primary Care, University of Nottingham, Medical School, Queen's Medical Centre, Nottingham, UK;



The Heaviness of Smoking Index (HSI) is validated to measure nicotine dependence in nonpregnant smokers, and in these smokers, mean salivary and serum cotinine levels are related by a ratio of 1.25. However, as nicotine metabolism increases during gestation, these findings may differ in pregnancy. We investigated the validity of HSI in pregnancy by comparing this with 3 biochemical measures; in a search for a less-invasive cotinine measure in pregnancy, we also explored the relationship between mean blood and salivary cotinine levels.


Cross-sectional analyses using baseline data from the Smoking, Nicotine, and Pregnancy Trial. Participants were 16-46 years old, 12-24 weeks gestation, smoked more than 5 cigarettes per day, and had exhaled carbon monoxide (CO) readings of at least 8 ppm. Linear regression was used to examine correlations between HSI and blood cotinine and salivary cotinine and exhaled CO. Correlation between blood and salivary cotinine was investigated using linear regression through the origin.


HSI scores were associated with blood cotinine (R² = 0.20, n = 662, p < .001), salivary cotinine (R² = 0.11, n = 967, p < .001), and exhaled CO (R² = 0.13, n = 1,050, p < .001). Salivary and blood cotinine levels, taken simultaneously, were highly correlated (R² = 0.91, n = 628, p < .001) and the saliva:blood level ratio was 1.01 (95% CI 0.99-1.04).


Correlations between HSI and biochemical measures in pregnancy were comparable with those obtained outside pregnancy, suggesting that HSI has similar validity in pregnant smokers. Salivary and blood cotinine levels are roughly equivalent in pregnant smokers.

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