European Journal of Epidemiology

, Volume 29, Issue 7, pp 499–506 | Cite as

In-utero exposure to maternal smoking is not linked to tobacco use in adulthood after controlling for genetic and family influences: a Swedish sibling study

  • Mina Rydell
  • Fredrik Granath
  • Sven Cnattingius
  • Cecilia Magnusson
  • Maria Rosaria Galanti


Previous studies have linked maternal smoking during pregnancy with regular tobacco use in offspring, but findings are not consistent and confounding from genetic and environmental factors have not fully been taken into account. A comparison between siblings discordant for prenatal smoking exposure adjusts for confounding by shared familial (i.e., genetic and environmental) factors. We investigated the association between prenatal exposure to maternal smoking during pregnancy and the risk of regular smoking or snus (Swedish moist smokeless tobacco) use in young adult offspring, using a population based matched cohort study. The cohort consisted of 1,538 randomly sampled same-sex sibling pairs, discordant for maternal smoking during pregnancy, 19–27 years old, participating in a survey conducted in Sweden 2010–2011. Lifetime and current history of tobacco use was self-reported in the survey, and information about maternal smoking during pregnancy was retrieved from the Medical Birth Register. Conditional logistic regression and stratified Cox proportional hazards regression were used to calculate odds ratios, hazard ratios, and corresponding 95 % confidence intervals. Analyses of exposure-discordant siblings did not reveal significant associations between prenatal exposure to maternal smoking and lifetime or current daily tobacco use, intensity of use, or time to onset of daily tobacco use. These findings suggest that the previously reported higher risks of tobacco use in offspring of mothers who smoked during pregnancy, compared with offspring of non-smoking mothers, were likely due to confounding from genetic or environmental factors.


Prenatal exposure delayed effects Cigarette smoking Smoking Tobacco Smokeless tobacco Matched-pair analyses 


  1. 1.
    Al Mamun A, O’Callaghan FV, Alati R, et al. Does maternal smoking during pregnancy predict the smoking patterns of young adult offspring? A birth cohort study. Tob Control. 2006;15(6):452–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Lawlor DA, O’Callaghan MJ, Mamun AA, Williams GM, Bor W, Najman JM. Early life predictors of adolescent smoking: findings from the Mater-University study of pregnancy and its outcomes. Paediatr Perinat Epidemiol. 2005;19(5):377–87.PubMedCrossRefGoogle Scholar
  3. 3.
    O’Callaghan FV, O’Callaghan M, Najman JM, Williams GM, Bor W, Alati R. Prediction of adolescent smoking from family and social risk factors at 5 years, and maternal smoking in pregnancy and at 5 and 14 years. Addiction. 2006;101(2):282–90.PubMedCrossRefGoogle Scholar
  4. 4.
    O’Callaghan FV, Al Mamun A, O’Callaghan M, et al. Maternal smoking during pregnancy predicts nicotine disorder (dependence or withdrawal) in young adults—a birth cohort study. Aust N Z J Public Health. 2009;33(4):371–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Agrawal A, Knopik VS, Pergadia ML, et al. Correlates of cigarette smoking during pregnancy and its genetic and environmental overlap with nicotine dependence. Nicotine Tob Res. 2008;10(4):567–78.PubMedCrossRefGoogle Scholar
  6. 6.
    Cornelius MD, Leech SL, Goldschmidt L, Day NL. Prenatal tobacco exposure: is it a risk factor for early tobacco experimentation? Nicotine Tob Res. 2000;2(1):45–52.PubMedCrossRefGoogle Scholar
  7. 7.
    Griesler P, Kandel D, Davies M. Maternal smoking in pregnancy, child behaviour problems, and adolescent smoking. J Res Adolesc. 1998;8(2):159–85.CrossRefGoogle Scholar
  8. 8.
    Kandel DB, Wu P, Davies M. Maternal smoking during pregnancy and smoking by adolescent daughters. Am J Public Health. 1994;84(9):1407–13.PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Kandel DB, Griesler PC, Schaffran C. Educational attainment and smoking among women: risk factors and consequences for offspring. Drug Alcohol Depend. 2009;104:S24–33.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Kardia SL, Pomerleau CS, Rozek LS, Marks JL. Association of parental smoking history with nicotine dependence, smoking rate, and psychological cofactors in adult smokers. Addict Behav. 2003;28(8):1447–52.PubMedCrossRefGoogle Scholar
  11. 11.
    Lieb R, Schreier A, Pfister H, Wittchen HU. Maternal smoking and smoking in adolescents: a prospective community study of adolescents and their mothers. Eur Addict Res. 2003;9(3):120–30.PubMedCrossRefGoogle Scholar
  12. 12.
    Oncken C, McKee S, Krishnan-Sarin S, O’Malley S, Mazure C. Gender effects of reported in utero tobacco exposure on smoking initiation, progression and nicotine dependence in adult offspring. Nicotine Tob Res. 2004;6(5):829–33.PubMedCrossRefGoogle Scholar
  13. 13.
    Tehranifar P, Liao Y, Ferris JS, Terry MB. Life course socioeconomic conditions, passive tobacco exposures and cigarette smoking in a multiethnic birth cohort of U.S. women. Cancer Causes Control. 2009;20(6):867–76.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Rydell M, Cnattingius S, Granath F, Magnusson C, Galanti MR. Prenatal exposure to tobacco and future nicotine dependence: population-based cohort study. Br J Psychiatry. 2012;200(3):202–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Cornelius MD, Goldschmidt L, Day NL. Prenatal cigarette smoking: long-term effects on young adult behaviour problems and smoking behaviour. Neurotoxicol Teratol. 2012;34(6):554–9.PubMedCrossRefGoogle Scholar
  16. 16.
    Rydell M, Magnusson C, Cnattingius S, Granath F, Svensson A, Galanti MR. Exposure to maternal smoking during pregnancy as a risk factor for tobacco use in adult offspring. Am J Epidemiol. 2014. doi:10.1093/aje/kwu074.
  17. 17.
    Slotkin TA, Tate CA, Cousins MM, Seidler FJ. Prenatal nicotine exposure alters the responses to subsequent nicotine administration and withdrawal in adolescence: serotonin receptors and cell signalling. Neuropsychopharmacology. 2006;31(11):2462–75.PubMedCrossRefGoogle Scholar
  18. 18.
    Levin ED, Lawrence S, Petro A, Horton K, Seidler FJ, Slotkin TA. Increased nicotine self-administration following prenatal exposure in female rats. Pharmacol Biochem Behav. 2006;85(3):669–74.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Hellstrom-Lindahl E, Nordberg A. Smoking during pregnancy: a way to transfer the addiction to the next generation? Respiration. 2002;69(4):289–93.PubMedCrossRefGoogle Scholar
  20. 20.
    Buka SL, Shenassa ED, Niaura R. Elevated risk of tobacco dependence among offspring of mothers who smoked during pregnancy: a 30-year prospective study. A J Psychiatry. 2003;160(11):1978–84.CrossRefGoogle Scholar
  21. 21.
    Cornelius MD, Leech SL, Goldschmidt L, Day NL. Is prenatal tobacco exposure a risk factor for early adolescent smoking? A follow-up study. Neurotoxicol Teratol. 2005;27(4):667–76.PubMedCrossRefGoogle Scholar
  22. 22.
    Isohanni M, Moilanen I, Rantakallio P. Determinants of teenage smoking, with special reference to non-standard family background. Br J Addict. 1991;86(4):391–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Munafo MR, Wileyto EP, Murphy MFG, Collins BN. Maternal smoking during late pregnancy and offspring smoking behaviour. Addict Behav. 2006;31(9):1670–82.PubMedCrossRefGoogle Scholar
  24. 24.
    Porath AJ, Fried PA. Effects of prenatal cigarette and marijuana exposure on drug use among offspring. Neurotoxicol Teratol. 2005;27(2):267–77.PubMedCrossRefGoogle Scholar
  25. 25.
    Roberts KH, Munafo MR, Rodriguez D, et al. Longitudinal analysis of the effect of prenatal nicotine exposure on subsequent smoking behaviour of offspring. Nicotine Tob Res. 2005;7(5):801–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Kendler KS, Chen XN, Dick D, et al. Recent advances in the genetic epidemiology and molecular genetics of substance use disorders. Nat Neurosci. 2012;15(2):181–9.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Lahey BB, D’Onofrio BM. All in the family: comparing siblings to test causal hypotheses regarding environmental influences on behaviour. Curr Dir Psychol Sci. 2010;19(5):319–23.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    D’Onofrio BM, Rickert ME, Langstrom N, et al. Familial confounding of the association between maternal smoking during pregnancy and offspring substance use and problems. Arch Gen Psychiatry. 2012;69(11):1140–50.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Benowitz NL. Nicotine and smokeless tobacco. CA Cancer J Clin. 1988;38(4):244–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Benowitz NL, Porchet H, Sheiner L, Jacob P 3rd. Nicotine absorption and cardiovascular effects with smokeless tobacco use: comparison with cigarettes and nicotine gum. Clin Pharmacol Ther. 1988;44(1):23–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Sullivan KM, Bottorff J, Reid C. Does mother’s smoking influence girls’ smoking more than boys’ smoking? A 20-year review of the literature using a sex- and gender-based analysis. Subst Use Misuse. 2011;46(5):656–68.PubMedCrossRefGoogle Scholar
  32. 32.
    The National Board of Health and Welfare. The Swedish medical birth register: a summary of content and quality. Stockholm, Sweden: The National Board of Health and Welfare; 2003.Google Scholar
  33. 33.
    Ekbom A. The Swedish multi-generation register. Methods Mol Biol. 2011;675:215–20.PubMedCrossRefGoogle Scholar
  34. 34.
    Statistics Sweden. Tables on the population in Sweden 2009. Örebro: Statistics Sweden; 2010.Google Scholar
  35. 35.
    Statistics Sweden. Registret över befolkningens utbildning [The Swedish Register of Education]. Statistics Sweden. Accessed Febr 13 2014.
  36. 36.
    The National Board of Health and Welfare. Graviditeter, förlossningar och nyfödda barn: Medicinska födelseregistret 1973–2011, Assisterad befruktning 1991–2010 [Pregnancies, Deliveries and Newborn Infants: The Swedish Medical Birth Register 1973–2012, Assisted Reproduction, treatment 1991–2011]: The National Board of Health and Welfare, 2013.Google Scholar
  37. 37.
    Dluzen DE, Anderson LI. Estrogen differentially modulates nicotine-evoked dopamine release from the striatum of male and female rats. Neurosci Lett. 1997;230(2):140–2.PubMedCrossRefGoogle Scholar
  38. 38.
    The National Board of Health and Welfare. Folkhälsorapport 2009 [Public Health Report 2009]. Stockholm: The National Board of Health and Welfare; 2009.Google Scholar
  39. 39.
    Slomkowski C, Rende R, Novak S, Lloyd-Richardson E, Niaura R. Sibling effects on smoking in adolescence: evidence for social influence from a genetically informative design. Addiction. 2005;100(4):430–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Frisell T, Öberg S, Kuja-Halkola R, Sjölander A. Sibling comparison designs: bias from non-shared confounders and measurement error. Epidemiology. 2012;23(5):713–20.PubMedCrossRefGoogle Scholar
  41. 41.
    Connor Gorber S, Schofield-Hurwitz S, Hardt J, Levasseur G, Tremblay M. The accuracy of self-reported smoking: a systematic review of the relationship between self-reported and cotinine-assessed smoking status. Nicotine Tob Res. 2009;11(1):12–24.PubMedCrossRefGoogle Scholar
  42. 42.
    Swedish National Institute of Public Health. Tobacco habits—results 2012. Swedish National Institute of Public Health, Östersund, Sweden. 2013. Accessed 29 July 2013.

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Mina Rydell
    • 1
  • Fredrik Granath
    • 2
  • Sven Cnattingius
    • 2
  • Cecilia Magnusson
    • 1
    • 3
  • Maria Rosaria Galanti
    • 1
    • 3
  1. 1.Department of Public Health SciencesKarolinska InstitutetStockholmSweden
  2. 2.Department of MedicineKarolinska InstitutetStockholmSweden
  3. 3.Centre for Epidemiology and Community MedicineStockholm County CouncilStockholmSweden

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