Skip to main content
Log in

Maternal Smoking During Pregnancy and Adverse Outcomes in Offspring: Genetic and Environmental Sources of Covariance

  • Original Research
  • Published:
Behavior Genetics Aims and scope Submit manuscript

Abstract

Maternal smoking during pregnancy (SDP) has been associated with several psychiatric outcomes in the offspring; studies have questioned whether the associations are causal, however. We analyzed all children born in Sweden between 1983 and 2009 to investigate the effect of SDP on multiple indicators of adverse outcomes in three areas: pregnancy outcomes (birth weight, preterm birth and being born small for gestational age), long-term cognitive abilities (low academic achievement and general cognitive ability) and externalizing behaviors (criminal conviction, violent criminal conviction and drug misuse). SDP was associated with all outcomes. Within-family analyses of the pregnancy outcomes were consistent with a causal interpretation as the associations persisted when siblings discordant for SDP were compared. For the cognitive and externalizing outcomes, the results were not consistent with causal effects; when comparing differentially exposed siblings none of the associations remained significant. In quantitative genetic models genetic factors explained the majority of the associations between SDP and cognitive and externalizing outcomes. The results suggest that the associations between SDP in mothers and cognition and externalizing behaviors in their offspring is primarily due to genetic effects that influence the behaviors in both generations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Agrawal A, Knopik VS, Pergadia ML, Waldron M, Bucholz KK, Martin NG, Heath AC, Madden PAF (2008) Correlates of cigarette smoking during pregnancy and its genetic and environmental overlap with nicotine dependence. Nicotine Tob Res 10:567–578

    Article  PubMed  Google Scholar 

  • Bates D, Maechler M, Bolker B (2012) lme4: Linear mixed-effects models using S4 classes [computer program]

  • Boker S, Neale M, Maes H, Wilde M, Spiegel M, Brick T, Spies J, Estabrook R, Kenny S, Bates T, Mehta P, Fox J (2011) OpenMx: an open source extended structural equation modeling framework. Psychometrika 76:306–317

    Article  PubMed Central  PubMed  Google Scholar 

  • Boker SM, Neale MC, Maes HH, Wilde MJ, Spiegel M, Brick TR, Estabrook R, Bates TC, Mehta P, von Oertzen T, Gore RJ, Hunter MD, Hackett DC, Karch J, Brandmaier AM (2012) OpenMx User Guide, Release 1.2.0-1919

  • Centre for Epidemiology (2012) The Swedish Medical Birth Register—A Summary of Content and Quality Socialstyrelsen

  • Cnattingius S (2004) The epidemiology of smoking during pregnancy: smoking prevalence, maternal characteristics, and pregnancy outcomes. Nicotine Tob Res 6(Suppl 2):S125–S140

    Article  PubMed  Google Scholar 

  • D’Onofrio BM, Turkheimer E, Eaves LJ, Corey LA, Berg K, Solaas MH, Emery RE (2003) The role of the Children of Twins design in elucidating causal relations between parent characteristics and child outcomes. J Child Psychol Psychiatry 44:1130–1144

    Article  PubMed  Google Scholar 

  • D’Onofrio BM, Van Hulle CA, Waldman ID, Rodgers JL, Harden KP, Rathouz PJ, Lahey BB (2008) Smoking during pregnancy and offspring externalizing problems: an exploration of genetic and environmental confounds. Dev Psychopathol 20:139–164

    PubMed Central  PubMed  Google Scholar 

  • D’Onofrio BM, Singh AL, Iliadou A, Lambe M, Hultman CM, Grann M, Neiderhiser JM, Langstrom N, Lichtenstein P (2010a) Familial confounding of the association between maternal smoking during pregnancy and offspring criminality: a population-based study in Sweden. Arch Gen Psychiatry 67:529–538

    Article  PubMed Central  PubMed  Google Scholar 

  • D’Onofrio BM, Singh AL, Iliadou A, Lambe M, Hultman CM, Neiderhiser JM, Langstrom N, Lichtenstein P (2010b) A quasi-experimental study of maternal smoking during pregnancy and offspring academic achievement. Child Dev 81:80–100

    Article  PubMed Central  PubMed  Google Scholar 

  • D’Onofrio BM, Rickert ME, Langstrom N, Donahue KL, Coyne CA, Larsson H, Ellingson JM, Van Hulle CA, Iliadou AN, Rathouz PJ, Lahey BB, Lichtenstein P (2012) Familial confounding of the association between maternal smoking during pregnancy and offspring substance use and problems. Arch Gen Psychiatry 69:1140–1150

    Article  PubMed Central  PubMed  Google Scholar 

  • D’Onofrio BM, Lahey BB, Turkheimer E, Lichtenstein P (2013) Critical need for family-based, quasi-experimental designs in integrating genetic and social science research. Am J Public Health 103(Suppl 1):S46–S55

    Article  PubMed Central  PubMed  Google Scholar 

  • Donovan SJ, Susser E (2011) Commentary: advent of sibling designs. Int J Epidemiol 40:345–349

    Article  PubMed Central  PubMed  Google Scholar 

  • Ellingson JM, Rickert ME, Lichtenstein P, Langstrom N, D’Onofrio BM (2012) Disentangling the relationships between maternal smoking during pregnancy and co-occurring risk factors. Psychol Med 42:1547–1557

    Article  PubMed Central  PubMed  Google Scholar 

  • Frisell T, Lichtenstein P, Langstrom N (2011) Violent crime runs in families: a total population study of 12.5 million individuals. Psychol Med 41:97–105

    Article  PubMed  Google Scholar 

  • Frisell T, Oberg S, Kuja-Halkola R, Sjolander A (2012a) Sibling comparison designs: bias from non-shared confounders and measurement error. Epidemiology 23:713–720

    Article  PubMed  Google Scholar 

  • Frisell T, Pawitan Y, Langstrom N (2012b) Is the association between general cognitive ability and violent crime caused by family-level confounders? PLoS ONE 7:e41783

    Article  PubMed Central  PubMed  Google Scholar 

  • Gaysina D, Fergusson DM, Leve LD, Horwood J, Reiss D, Shaw DS, Elam KK, Natsuaki MN, Neiderhiser JM, Harold GT (2013) Maternal smoking during pregnancy and offspring conduct problems: evidence from 3 independent genetically sensitive research designs. JAMA Psychiatry 70:956–963

  • Gilman SE, Gardener H, Buka SL (2008) Maternal smoking during pregnancy and children’s cognitive and physical development: a causal risk factor? Am J Epidemiol 168:522–531

    Article  PubMed Central  PubMed  Google Scholar 

  • Glantz MD, Chambers JC (2006) Prenatal drug exposure effects on subsequent vulnerability to drug abuse. Dev Psychopathol 18:893–922

    Article  PubMed  Google Scholar 

  • Heath AC, Kendler KS, Eaves LJ, Markell D (1985) The resolution of cultural and biological inheritance: informativeness of different relationships. Behav Genet 15:439–465

    Article  PubMed  Google Scholar 

  • Huizink AC, Mulder EJ (2006) Maternal smoking, drinking or cannabis use during pregnancy and neurobehavioral and cognitive functioning in human offspring. Neurosci Biobehav Rev 30:24–41

    Article  PubMed  Google Scholar 

  • Karlsgodt KH, Glahn DC, van Erp TG, Therman S, Huttunen M, Manninen M, Kaprio J, Cohen MS, Lonnqvist J, Cannon TD (2007) The relationship between performance and fMRI signal during working memory in patients with schizophrenia, unaffected co-twins, and control subjects. Schizophrenia Res 89:191–197

    Article  Google Scholar 

  • Kendler KS, Neale MC, MacLean CJ, Heath AC, Eaves LJ, Kessler RC (1993) Smoking and major depression. A causal analysis. Arch Gen Psychiatry 50:36–43

    Article  PubMed  Google Scholar 

  • Kendler KS, Sundquist K, Ohlsson H, Palmer K, Maes H, Winkleby MA, Sundquist J (2012) Genetic and familial environmental influences on the risk for drug abuse: a national Swedish adoption study. Arch Gen Psychiatry 69:690–697

    Article  PubMed Central  PubMed  Google Scholar 

  • Knopik VS (2009) Maternal smoking during pregnancy and child outcomes: real or spurious effect? Dev Neuropsychol 34:1–36

    Article  PubMed Central  PubMed  Google Scholar 

  • Knopik VS, Maccani MA, Francazio S, McGeary JE (2012) The epigenetics of maternal cigarette smoking during pregnancy and effects on child development. Dev Psychopathol 24:1377–1390

    Article  PubMed Central  PubMed  Google Scholar 

  • Kuja-Halkola R, D’Onofrio BM, Iliadou AN, Langstrom N, Lichtenstein P (2010) Prenatal smoking exposure and offspring stress coping in late adolescence: no causal link. Int J Epidemiol 39:1531–1540

    Article  PubMed Central  PubMed  Google Scholar 

  • Lahey BB, D’Onofrio BM (2010) All in the family: comparing siblings to test causal hypotheses regarding environmental influences on behavior. Curr Dir Psychol Sci 19:319–323

    Article  PubMed Central  PubMed  Google Scholar 

  • Lambe M, Hultman C, Torrang A, Maccabe J, Cnattingius S (2006) Maternal smoking during pregnancy and school performance at age 15. Epidemiology 17:524–530

    Article  PubMed  Google Scholar 

  • Langley K, Heron J, Smith GD, Thapar A (2012) Maternal and paternal smoking during pregnancy and risk of ADHD symptoms in offspring: testing for intrauterine effects. Am J Epidemiol 176:261–268

    Article  PubMed Central  PubMed  Google Scholar 

  • Lindqvist R, Lendahls L, Tollbom O, Aberg H, Hakansson A (2002) Smoking during pregnancy: comparison of self-reports and cotinine levels in 496 women. Acta Obstet Gynecol Scand 81:240–244

    Article  PubMed  Google Scholar 

  • Ludvigsson JF, Otterblad-Olausson P, Pettersson BU, Ekbom A (2009) The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research. Eur J Epidemiol 24:659–667

    Article  PubMed Central  PubMed  Google Scholar 

  • Lundberg F, Cnattingius S, D’Onofrio B, Altman D, Lambe M, Hultman C, Iliadou A (2010) Maternal smoking during pregnancy and intellectual performance in young adult Swedish male offspring. Paediatr Perinat Epidemiol 24:79–87

    Article  PubMed Central  PubMed  Google Scholar 

  • McGue M, Osler M, Christensen K (2010) Causal inference and observational research: the utility of twins. Persp Psychol Sci 5:546–556

    Article  Google Scholar 

  • Muller KU, Mennigen E, Ripke S, Banaschewski T, Barker GJ, Buchel C, Conrod P, Fauth-Buhler M, Flor H, Garavan H, Heinz A, Lawrence C, Loth E, Mann K, Martinot JL, Pausova Z, Rietschel M, Strohle A, Struve M, Walaszek B, Schumann G, Paus T, Smolka MN (2013) Altered reward processing in adolescents with prenatal exposure to maternal cigarette smoking. JAMA Psychiatry 70:847–856

    Article  PubMed  Google Scholar 

  • Neale MC, Cardon LR (1992) Methodology for genetic studies of twins and families. Kluwer Academic Publishers, Dordrecht

    Book  Google Scholar 

  • Neuhaus JM, Kalbfleisch JD (1998) Between- and within-cluster covariate effects in the analysis of clustered data. Biometrics 54:638–645

    Article  PubMed  Google Scholar 

  • Neuhaus JM, McCulloch CE (2006) Separating between- and within-cluster covariate effects by using conditional and partitioning methods. J R Stat Soc Ser B 68:859–872

    Article  Google Scholar 

  • Paradis AD, Fitzmaurice GM, Koenen KC, Buka SL (2011) Maternal smoking during pregnancy and criminal offending among adult offspring. J Epidemiol Community Health 65:1145–1150

    Article  PubMed Central  PubMed  Google Scholar 

  • R Development Core Team (2012) R: A language and environment for statistical computing [computer program]

  • Silberg J, Rutter M, D’Onofrio B, Eaves L (2003) Genetic and environmental risk factors in adolescent substance use. J Child Psychol Psychiatry 44:664–676

    Article  PubMed  Google Scholar 

  • Skoglund C, Chen Q, D’Onofrio BM, Lichtenstein P, Larsson H (2013) Familial confounding of the association between maternal smoking during pregnancy and ADHD in offspring. J Child Psychol Psychiatry 55:61–68

  • Slotkin TA (2013) Maternal smoking and conduct disorder in the offspring. JAMA Psychiatry 70:901–902

    Article  PubMed  Google Scholar 

  • Statistics Sweden (1994) Fakta om den svenska familjen. Demografiska rapporter (1994:2). Stockholm

  • Thapar A, Rice F, Hay D, Boivin J, Langley K, van den Bree M, Rutter M, Harold G (2009) Prenatal smoking might not cause attention-deficit/hyperactivity disorder: evidence from a novel design. Biol Psychiatry 66:722–727

    Article  PubMed Central  PubMed  Google Scholar 

  • Therneau T (2012) A Package for Survival Analysis in S. R package version 2.36-14. [computer program]

  • Turkheimer E, Harden KP (2014) Behavior genetic research methods: testing quasi-causal hypotheses using multivariate twin data. In: Reis HT, Judd CM (eds) Handbook of research methods in personality and social psychology, 2nd edn. Cambridge University Press, Cambridge

  • Wakschlag LS, Pickett KE, Cook E Jr, Benowitz NL, Leventhal BL (2002) Maternal smoking during pregnancy and severe antisocial behavior in offspring: a review. Am J Public Health 92:966–974

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

Preliminary partial results were presented at the 42nd Annual Meeting of the Behavior Genetics Association; June 24, 2012; Edinburgh, Scotland. The study was supported by Grants from the National Institute of Child Health and Human Development (B.M.D., Grant Number HD061817); by the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework grant no 340-2013-5867, by the and Swedish Research Council for Health, Working Life and Welfare, and by the Swedish Prison and Probation Services.

Conflict of Interest

Author Kuja-Halkola R, Author D’Onofrio BM, Author Larsson H and Author Lichtenstein P declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Data was merged and anonymized by Statistics Sweden, an independent governmental agency. The key linking the personal number to the data was destroyed immediately after merging; therefore no informed consent was required.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ralf Kuja-Halkola.

Additional information

Edited by Valerie Knopik.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 984 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kuja-Halkola, R., D’Onofrio, B.M., Larsson, H. et al. Maternal Smoking During Pregnancy and Adverse Outcomes in Offspring: Genetic and Environmental Sources of Covariance. Behav Genet 44, 456–467 (2014). https://doi.org/10.1007/s10519-014-9668-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10519-014-9668-4

Keywords

Navigation