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Self-reported nicotine exposure and plasma levels of cotinine in early and late pregnancy
Abstract
BACKGROUND: The accuracy of maternal self-reported smoking information, especially exposure to environmental tobacco smoke, has been questioned. This study aimed to validate self-reported smoking, smoking cessation, and environmental tobacco smoke exposure in early and late pregnancy, using the biomarker cotinine as the gold standard. METHODS: Prospective cohort study of 953 pregnant Swedish women between 1996 and 1998. In-person interviews and cotinine measurements were performed at 6-12 and 31-34 completed weeks of gestation. All women were asked about nicotine exposures throughout pregnancy, including cigarette smoking, oral snuff, nicotine replacement therapy, and environmental tobacco smoke exposure. RESULTS: The validity of self-reported daily smoking was high in early and late pregnancy. However, among women reporting smoking cessation before the first interview and between the first and second interviews, 13% and 25% misreported active smoking, respectively. According to cotinine measurements, 22% of non-smoking women were exposed to environmental tobacco smoke in early pregnancy, and 8% were exposed in late pregnancy. Self-reported information on environmental tobacco smoke exposure in early and late pregnancy misclassified most exposed women as unexposed. CONCLUSION: The results of this study indicate that self-reported smoking information among pregnant women can be trusted. However, among women reporting smoking cessation during pregnancy, the misclassification rate increased with recency of quitting. Environmental tobacco smoke exposure was common among non-smokers, and the low validity of self-reported environmental tobacco smoke exposure suggests that future studies on environmental tobacco smoke exposure and risks of pregnancy outcomes may have to rely on biomarker assessments.
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“Nevertheless, a study performed in Sweden comparing self-reported nicotine exposure and plasma levels of cotinine in early and late pregnancy concluded that self-reported information on nicotine exposure had acceptable validity [49].”
From The effect of swedish snuff (snus) on offspring birthweight: a sibling analysis (2013) · cites this paper as [49]
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“Cotinine is a nicotine-specific metabolite, and detectable levels can, besides tobacco smoke, also be caused by other nicotine products including oral snuff and nicotine replacement therapy (9).”
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Solomon, L., & Quinn, V. P. (2004) · Nicotine & Tobacco Research · doi:10.1080/14622200410001669132 · Cited by 179
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“For these reasons, it is often used as a marker of smoking exposure.(63) Nicotine readily gains access to the fetus via the placenta.”
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Prevalence and determinants of adolescent tobacco smoking in Addis Ababa, Ethiopia
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Determinants of maternal and fetal exposure and temporal trends of perfluorinated compounds
Ode, A., Rylander, L., Lindh, C. H., Källén, K., Jönsson, B., Gustafsson, P., Olofsson, P., Ivarsson, S. A., & Rignell‐Hydbom, A. (2013) · Environmental Science and Pollution Research · doi:10.1007/s11356-013-1573-5 · Cited by 90
“2ng/ml) were defined as nonsmokers and those having a level higher than 15ng/ml were defined as active smokers (George et al. 2006).”
Tarasi, B., Cornuz, J., Clair, C., & Baud, D. (2022) · BMC Public Health · doi:10.1186/s12889-022-14881-4 · Cited by 91
“These numbers should be interpreted cautiously as up to 25% of pregnant women with cigarette use prior to pregnancy incorrectly indicated that they ceased smoking during pregnancy [7].”
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“Self-reporting of smoking behavior in pregnant women has been shown to impart a certain degree of bias (30, 35), because some women who smoke falsely report a “nonsmoking” status (54).”
BackgroundRazaz, N., Villamor, E., Muraca, G. M., Bonamy, A. E., & Cnattingius, S. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(20)30151-0 · Cited by 97
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Betel nut chewing during pregnancy, Madang province, Papua New Guinea
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“The maternal steady state levels of serum cotinine (the major metabolite of nicotine) resulting from this exposure are representative of those found in pregnant smokers (Holloway et al., 2006; George et al., 2006).”
BackgroundAssociation Between Maternal Body Mass Index in Early Pregnancy and Incidence of Cerebral Palsy
Villamor, E., Tedroff, K., Peterson, M. D., Johansson, S., Neovius, M., Petersson, G., & Cnattingius, S. (2017) · JAMA · doi:10.1001/jama.2017.0945 · Cited by 84
Fetal Exposure to Perfluorinated Compounds and Attention Deficit Hyperactivity Disorder in Childhood
Ode, A., Källén, K., Gustafsson, P., Rylander, L., Jönsson, B., Olofsson, P., Ivarsson, S. A., Lindh, C. H., & Rignell‐Hydbom, A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0095891 · Cited by 88
“2 and 15 ng/ml were related to second-hand smokers [47].”
Tsai, H.-J., Liu, X., Mestan, K. K. L., Yu, Y., Zhang, S., Fang, Y., Pearson, C., Ortiz, K., ZUCKERMAN, B. S., Bauchner, H., et al. (2008) · Human Genetics · doi:10.1007/s00439-008-0485-9 · Cited by 81
“However, previous studies have demonstrated fair agreement between self-reported smoking amounts with serum and urinary levels of cotinine, a biochemical marker of cigarette smoke (George et al. 2006; KlebanoV et al. 2001; Peacock et al. 1998).”
ResultBaba, S., Wikström, A., Stephansson, O., & Cnattingius, S. (2013) · BJOG: An International Journal of Obstetrics & Gynaecology · doi:10.1111/1471-0528.12067 · Cited by 80
Self-citationHoyt, A. T., Canfield, M. A., Romitti, P. A., Botto, L. D., Anderka, M., Krikov, S. V., Tarpey, M. K., & Feldkamp, M. L. (2016) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2016.07.022 · Cited by 79
Smoking and quit attempts during pregnancy and postpartum: a longitudinal UK cohort
Cooper, S. E., Orton, S., Leonardi‐Bee, J., Brotherton, E., Vanderbloemen, L., Bowker, K., Naughton, F., USSHER, M. H., Pickett, K. E., Sutton, S. R., et al. (2017) · BMJ Open · doi:10.1136/bmjopen-2017-018746 · Cited by 74
Advanced Maternal Age and Stillbirth Risk in Nulliparous and Parous Women
Waldenström, U., Cnattingius, S., Norman, M., & Schytt, E. (2015) · Obstetrics and Gynecology · doi:10.1097/aog.0000000000000947 · Cited by 73
“The validity of smoking information has previously shown to be high.(20) Level of education (elementary school or less, high school, and college or university) was obtained by linkage to the nationwide Swedish Population and Education Register.”
MethodCotinine Validation of Self-Reported Smoking During Pregnancy in the Swedish Medical Birth Register
Mattsson, K., Källén, K., Rignell‐Hydbom, A., Lindh, C. H., Jönsson, B., Gustafsson, P., Olofsson, P., Ivarsson, S. A., & Rylander, L. (2015) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntv087 · Cited by 72
Long-Term Reprogramming of Cardiovascular Function in Infants of Active Smokers
Cohen, G., Jeffery, H. E., Lagercrantz, H., & Katz‐Salamon, M. (2010) · Hypertension · doi:10.1161/hypertensionaha.109.142695 · Cited by 70
Influence of smoking and snuff cessation on risk of preterm birth
Baba, S., Wikström, A.-K., Stephansson, O., & Cnattingius, S. (2012) · European Journal of Epidemiology · doi:10.1007/s10654-012-9676-8 · Cited by 69
Prenatal environmental tobacco smoke exposure and early childhood body mass index
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“Methods: In a nationwide study of 851,371 singleton births in Sweden from 1999 to 2010, we used multiple logistic regression models to examine associations between cessation or continuation of snuff use or smoking and risks for stillbirth (at 28 weeks or later) and early neonatal mortality (death during the first week…”
BackgroundInfluentialMaternal tobacco use and extremely premature birth – a population‐based cohort study
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Brief report: maternal smoking during pregnancy and autism spectrum disorders
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“Furthermore, selfreported data have been validated against serum cotinine levels and found to be reasonably accurate, although underreporting of smoking exists (George et al. 2006).”
Transgenerational effects of fetal and neonatal exposure to nicotine
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“It was shown that self-reported smoking correlates well with serum cotinine levels [43,44], but the self-reported ETE was less reliable [44].”
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“40 41 However, self-reported information on smoking cessation is often less reliable, and this potentially has an effect on the present findings with regards to smoking cessation and amount smoked prior to pregnancy.(41) In addition, it was not possible to determine with precision the exact nature of the timing and pa…”
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“The validity of selfreported smoking has been reported to be high among pregnant women in the Swedish Birth Registry.(9) However, one limitation was that some malformations may not have been detected and diagnosed at the physical examination after birth.”
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“Finally, data on current smoking were only collected through interviews and not verified by biomarkers such as cotinine assessment or exhaled carbon monoxide [30-33].”
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The Influence of In Utero Exposure to Smoking on Sleep Patterns in Preterm Neonates
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“smoke exposure is highest in early and late pregnancy [56].”
BackgroundRelationship of Maternal Snuff Use and Cigarette Smoking With Neonatal Apnea
Gunnerbeck, A., Wikström, A.-K., Bonamy, A.-K. E., Wickström, R., & Cnattingius, S. (2011) · Pediatrics · doi:10.1542/peds.2010-3811 · Cited by 51
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“The maternal steady state levels of serum cotinine (the major metabolite of nicotine) resulting from this exposure of 135.9 ± 7.86 ng/ml [13] are within the range of cotinine concentrations recently reported by George et al. [ 22 ] in pregnant smokers.”
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“Studies have shown a self-reported smoking habit being quite reliable among pregnant women, but it underestimates the real prevalence of smoking by 19–38%, depending on the defini-tions used (37,38).”
Muula, A. S., & Mpabulungi, L. (2007) · PubMed Central · doi:10.5555/afhs.2007.7.1.45 · Cited by 36
“It is possible, although expensive to estimate tobacco exposure quantitatively using blood, saliva or hair content of cotinine, a by-product of nicotine intake.(14-16) Assessment of current tobacco smoking can also be estimated by measuring exhaled carbon monoxide.”
BackgroundMattsson, K., Jönsson, I., Malmqvist, E., Larsson, H. E., & Rylander, L. (2015) · European Journal of Epidemiology · doi:10.1007/s10654-014-9985-1 · Cited by 36
“status during pregnancy in Swedish women has in previous studies been shown to be a valid measure [23].”
BackgroundMaternal smoking, passive tobacco smoke, and neural tube defects
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“Recent studies show that women underestimate their level of exposure to environmental smoke when compared with cotinine levels (DeLorenze et al., 2002; George et al., 2006b).”
BackgroundLupsa, I.-R., Nunes, B., Ligocka, D., Gurzău, A. E., Jakubowski, M., Casteleyn, L., Aerts, D., Biot, P., Hond, E. D., Castaño, A., et al. (2015) · Environmental Research · doi:10.1016/j.envres.2015.03.018 · Cited by 35
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“Cotinine is a major metabolite of nicotine with a longer halflife and thus a more accurate measure of total exposure than questionnaire methods.(16,17) The purpose of this prospective study was to evaluate the effect of smoking exposure on the fetus by both questionnaire assessment and urinary cotinine measurement in…”
BackgroundClinical Maternal-Fetal Medicine Online
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“exposure, and that self-reported exposure to secondhand smoke may not be a sensitive estimate for true exposure [14, 15].”
BackgroundPetre, M. A., Petrik, J., Ellis, R., Inman, M. D., Holloway, A. C., & Labiris, N. R. (2011) · International Journal of Toxicology · doi:10.1177/1091581810395332 · Cited by 32
“86 ng/mL(23) and is within the range of cotinine concentrations reported in pregnant smokers during both early pregnancy and late pregnancy.(24) At postnatal day 1 (PND1), litters were culled to eight to assure uniformity of litter size between treated and control litters.”
BackgroundBeer, R. J., Cnattingius, S., Susser, E., & Villamor, E. (2022) · Acta Paediatrica · doi:10.1111/apa.16375 · Cited by 30
Baheiraei, A., Banihosseini, S. Z., Heshmat, R., Mota, A., & Mohsenifar, A. (2011) · Paediatric and Perinatal Epidemiology · doi:10.1111/j.1365-3016.2011.01242.x · Cited by 31
Hearing loss, lead (Pb) exposure, and noise: a sound approach to ototoxicity exploration
Carlson, K., & Neitzel, R. L. (2018) · Journal of Toxicology and Environmental Health Part B · doi:10.1080/10937404.2018.1562391 · Cited by 31
“Smoking and environmental tobacco smoke are important exposures, although self-reported exposures have been shown to be unreliable (George et al. 2006).”
BackgroundSantiago, S. E., & Huffman, K. J. (2012) · Neuroscience Research · doi:10.1016/j.neures.2012.05.005 · Cited by 30
“…which has been demonstrated to result in pregnancy complications and physical abnormalities in offspring (Luck et al., 1985; Ernst et al., 2001; George et al., 2006b; Jaddoe et al., 2007; Ward et al., 2007), such as spontaneous abortions, smaller head circumferences, and lower birth weights in…”
BackgroundWahabi, H., Mandil, A., Alzeidan, R. A., Bahnassy, A., & Fayed, A. A. (2013) · BMC Public Health · doi:10.1186/1471-2458-13-1058 · Cited by 30
“This might have skewed our results, considering the high rate of misclassification reported for both active and SHS exposure in pregnancy [25,26]; however such misclassification was not detected, when self-reported SHS was compared to biomarker detected SHS, in some communities in the Middle East [27].”
ResultFasting, M. H., Øien, T., Storrø, O., Nilsen, T.-I. L., Johnsen, R., & Vik, T. (2008) · Early Human Development · doi:10.1016/j.earlhumdev.2008.05.009 · Cited by 30
“Moreover, even if some women who were classified as quitters might have smoked throughout pregnancy and some non-smoker could have been smokers or quitters [21], such misclassification would dilute the differences between the groups.”
BackgroundPrediction of stillbirth in women with overweight or obesity—A register-based cohort study
Åmark, H., Westgren, M., & Persson, M. (2018) · PLoS ONE · doi:10.1371/journal.pone.0206940 · Cited by 31
Heinonen, K., Räikkönen, K., Pesonen, A., ANDERSSON, S. M., Kajantie, E., Eriksson, J. G., Dieter Wolke, C., & Lano, A. (2011) · Early Human Development · doi:10.1016/j.earlhumdev.2011.02.002 · Cited by 32
“Previous studies comparing the serum cotinine concentrations and self-reports of smoking have, however, demonstrated a close correlation between these parameters during pregnancy [35,36].”
BackgroundResultKrstev, S., Marinković, J., Simić, S. B., Kocev, N. I., & Bondy, S. J. (2011) · International Journal of Public Health · doi:10.1007/s00038-011-0301-5 · Cited by 28
Moradzadeh, R., Mansournia, M. A., Baghfalaki, T., Nadrian, H., Gustafson, P., & McCandless, L. C. (2018) · Annals of Epidemiology · doi:10.1016/j.annepidem.2018.07.011 · Cited by 28
Lagunov, A., Anzar, M., Sadeu, J. C., Khan, M. I. R., Bruin, J. E., Woynillowicz, A. K., Buhr, M. M., Holloway, A. C., & Foster, W. G. (2010) · Reproductive Toxicology · doi:10.1016/j.reprotox.2010.12.004 · Cited by 27
Perinatal Biochemical Confirmation of Smoking Status by Trimester
Ashford, K. B., Wiggins, A. T., Rayens, E. A., Assef, S., Fallin‐Bennett, A., & Rayens, M. K. (2017) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntw332 · Cited by 27
Villamor, E., Norman, M., Johansson, S., & Cnattingius, S. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa783 · Cited by 27
“Smoking was determined by self-report at either the first prenatal visit or in the third trimester; this has been validated with cotinine markers [22].”
MethodTobacco-related Foetal Origin of Adult Diseases Hypothesis--population studies in Poland.
Wojtyła, A., Goździewska, M., Paprzycki, P., & Biliński, P. (2012) · PubMed · Cited by 27
Maternal Smoking During Pregnancy and the Risk of Psychiatric Morbidity in Singleton Sibling Pairs
Ekblad, M. O., Lehtonen, L., Korkeila, J. J. A., & Gissler, M. (2017) · Nicotine & Tobacco Research · doi:10.1093/ntr/ntx001 · Cited by 26
Fa, S., Larsen, T. V., Bilde, K., Daugaard, T. F., Ernst, E. H., Olesen, R. H., Mamsen, L. S., Ernst, E., Larsen, A., & Nielsen, A. L. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0296-0 · Cited by 25
Gruslin, A., Cesta, C. E., Bell, M. D., Qiu, Q., Petre, M. A., & Holloway, A. C. (2009) · Reproductive Sciences · doi:10.1177/1933719109337038 · Cited by 24
“During the same interval, an even more pronounced decline in maternal mature IGF-II (1-67) levels was seen in this group.”
BackgroundInfluentialMaternal diet and dioxin-like activity, bulky DNA adducts and micronuclei in mother–newborns
Pedersen, M., Halldorsson, T. I., Autrup, H. N., Brouwer, A., Besselink, H. T., Loft, S. H., & Knudsen, L. E. (2012) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2012.04.006 · Cited by 23
Flenady, V., MacPhail, J. M., New, K., Devenish-Meares, P. P., & Smith, J. P. (2008) · Australian and New Zealand Journal of Obstetrics and Gynaecology · doi:10.1111/j.1479-828x.2008.00907.x · Cited by 23
Orton, S., Bowker, K., Cooper, S. E., Naughton, F., USSHER, M. H., Pickett, K. E., Leonardi‐Bee, J., Sutton, S. R., Dhalwani, N. N., & Coleman, T. J. (2014) · BMJ Open · doi:10.1136/bmjopen-2014-004915 · Cited by 23
The effect of swedish snuff (snus) on offspring birthweight: a sibling analysis
Juárez, S. P., & Merlo, J. (2013) · PLoS ONE · doi:10.1371/journal.pone.0065611 · Cited by 22
“Nevertheless, a study performed in Sweden comparing self-reported nicotine exposure and plasma levels of cotinine in early and late pregnancy concluded that selfreported information on nicotine exposure had acceptable validity [49].”
Maternal smoking during pregnancy and risks of suicidal acts in young offspring
Cnattingius, S., Svensson, T., Granath, F. N., & Iliadou, A. N. (2011) · European Journal of Epidemiology · doi:10.1007/s10654-011-9556-7 · Cited by 22
“The validity of self-reported smoking is generally high, but is lower among women stating that they recently changed smoking habits [33].”
BackgroundGrjibovski, A. M., Ehrenblad, B., & Yngve, A. (2008) · International Breastfeeding Journal · doi:10.1186/1746-4358-3-23 · Cited by 22
Metadata
- Authors
- GEORGE, L., GRANATH, F., JOHANSSON, A. L. V., & CNATTINGIUS, S.
- Affiliations
- Karolinska Institutet (SE)
- Karolinska University Hospital (SE)
- Corresponding author
- GEORGE, LENA
- Venue
- Acta Obstetricia Et Gynecologica Scandinavica
- Publisher
- Wiley
- Published
- 2006-11
- Volume
- 85
- Issue
- 11
- Pages
- 1331-1337
- ISSN
- 0001-6349 (ISSN-L)
- 1600-0412
- OpenAlex
- W1968549649
- Cited by
- 192
- References
- 21
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 5 · 2023: 5 · 2022: 14 · 2021: 7 · 2020: 13 · 2019: 8 · 2018: 10 · 2017: 8 · 2016: 5 · 2015: 11 · 2014: 11 · 2013: 11 · 2012: 14
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Obstetricia Et Gynecologica Scandinavica (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Epidemiology
- Keywords
- maternal smoking, self-reported smoking, cotinine, passive smoking, smoking cessation, misclassification, biomarker validation, oral snuff, nicotine replacement therapy, pregnancy, early pregnancy, late pregnancy
- MeSH terms
- Cotinine, Female, Humans, Nicotine, Pregnancy, Pregnancy Trimester, First, Pregnancy Trimester, Third, Prospective Studies, Self Disclosure, Smoking, Tobacco Smoke Pollution, Smoking Cessation, Maternal Exposure
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