Skip to main content

Advertisement

SpringerLink
Log in

Prenatal tobacco use and the risk of mood disorders in offspring: a systematic review and meta-analysis

  • Review
  • Published:
Social Psychiatry and Psychiatric Epidemiology Aims and scope Submit manuscript

Abstract

Purpose

It is plausible that offspring born to mothers using tobacco during pregnancy may have increased risk of mood disorders (depression and bipolar disorders); however, mixed results have been reported. We conducted a systematic review and meta-analysis to investigate the magnitude and consistency of associations reported between prenatal tobacco use and mood disorders in offspring.

Methods

We systematically searched EMBASE, SCOPUS, PubMed and Psych-INFO for studies on mood disorders and prenatal tobacco use. Methodological quality of studies was assessed with the revised Newcastle–Ottawa Scale. We estimated pooled relative risk (RR) with inverse variance weighted random-effects meta-analysis. We performed leave-one-out analyses, and stratified analyses by a subgroup (depression and bipolar disorder). Potential publication bias was assessed by inspection of the funnel plot and Egger’s test for regression asymmetry. This study protocol was prospectively registered in PROSPERO (CRD42017060037).

Results

Eight cohort and two case–control studies were included in the final meta-analysis. We found an increased pooled relative risk of mood disorders in offspring exposed to maternal prenatal tobacco use RRs 1.43 (95% CI 1.27–1.60) compared to no prenatal tobacco use. Similarly, the pooled relative risks of bipolar and depressive disorders in offspring were 1.44, (95% CI 1.15–1.80) and 1.44, (95% CI 1.21–1.71), respectively. Moreover, the pooled estimated risk of mood disorders was not significantly attenuated in the studies that reported sibling comparison results [RR = 1.21 (95% CI 1.04–1.41)].

Conclusion

Taken together, there was strong evidence for a small (RR < 2) association between prenatal tobacco use and mood disorders in offspring.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Availability of data and material

All data generated or analyzed during this review were included in this article and attached as supplementary files.

References

  1. Sadock BJ, Sadock VA, Ruiz P (2015) Kaplan and Sadock’s synopsis of psychiatry 11th edition: behavioral sciences/clinical psychiatry, book chapter 8. Wolters Kluwer, Alphen aan den Rijn

    Google Scholar 

  2. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders: DSM-IV-TR. American Psychiatric Association, Washington, DC

    Google Scholar 

  3. Malhi GS, Mann JJ (2018) Depression. Lancet 392(10161):2299–2312

    PubMed  Google Scholar 

  4. Kessler RC, Bromet EJ (2013) The epidemiology of depression across cultures. Annu Rev Public Health 34(1):119–138

    PubMed Central  PubMed  Google Scholar 

  5. Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA et al (2011) Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry 68(3):241–251

    PubMed Central  PubMed  Google Scholar 

  6. James SB, Alcott SV (2007) Mood disorders. Kaplan & Sadock’s synopsis of psychiatry: behavioral sciences/clinical psychiatry, 10th edn. Lippincott Williams & Wilkins, Philadelphia, pp 530–533

    Google Scholar 

  7. Thase ME (2009) Neurobiological aspects of depression. In: Gotlib IH, Hammen CL (eds) Handbook of depression. The Guilford Press, New York, pp 187–217

    Google Scholar 

  8. Kim DR, Bale TL, Epperson CN (2015) Prenatal programming of mental illness: current understanding of relationship and mechanisms. Curr Psychiatry Rep 17(2):5

    PubMed Central  PubMed  Google Scholar 

  9. Slotkin TA, Tate CA, Cousins MM, Seidler FJ (2006) Prenatal nicotine exposure alters the responses to subsequent nicotine administration and withdrawal in adolescence: serotonin receptors and cell signaling. Neuropsychopharmacology 31(11):2462–2475

    CAS  PubMed  Google Scholar 

  10. Slotkin TA (1998) Fetal nicotine or cocaine exposure: which one is worse? J Pharmacol Exp Ther 285(3):931–945

    CAS  PubMed  Google Scholar 

  11. Fluharty M, Taylor AE, Grabski M, Munafò MR (2017) The association of cigarette smoking with depression and anxiety: a systematic review. Nicotine Tobacco Res 19(1):3–13

    Google Scholar 

  12. Al Mamun A, O’Callaghan FV, Alati R, O’Callaghan M, Najman JM, Williams GM et al (2006) Does maternal smoking during pregnancy predict the smoking patterns of young adult offspring? A birth cohort study. Tob Control 15(6):452–457

    PubMed  Google Scholar 

  13. D’Onofrio BM, Singh AL, Iliadou A, Lambe M, Hultman CM, Grann M et al (2010) Familial confounding of the association between maternal smoking during pregnancy and offspring criminality: a population-based study in Sweden. Arch Gen Psychiatry 67(5):529–538

    PubMed Central  PubMed  Google Scholar 

  14. Knopik VS, McGeary J, Nugent N, Francazio S, Heath AC (2010) Smoking during pregnancy, maternal xenobiotic metabolism genes, and child externalizing behavior: a case-crossover design. Behav Genet 40(6):799–800

    Google Scholar 

  15. Lange S, Probst C, Rehm J, Popova S (2018) National, regional, and global prevalence of smoking during pregnancy in the general population: a systematic review and meta-analysis. Lancet Glob Health 6(7):e769–e776

    PubMed  Google Scholar 

  16. Quinn PD, Rickert ME, Weibull CE, Johansson ALV, Lichtenstein P, Almqvist C et al (2017) Association between maternal smoking during pregnancy and severe mental illness in offspring. JAMA Psychiatry 74(6):589–596

    PubMed Central  PubMed  Google Scholar 

  17. Sutin AR, Flynn HA, Terracciano A (2017) Maternal cigarette smoking during pregnancy and the trajectory of externalizing and internalizing symptoms across childhood: similarities and differences across parent, teacher, and self reports. J Psychiatr Res 91:145–148

    PubMed Central  PubMed  Google Scholar 

  18. Talati A, Bao Y, Kaufman J, Shen L, Schaefer CA, Brown AS (2013) Maternal smoking during pregnancy and bipolar disorder in offspring. Am J Psychiatry 170(10):1178–1185

    PubMed Central  PubMed  Google Scholar 

  19. Ashford J, van Lier PA, Timmermans M, Cuijpers P, Koot HM (2008) Prenatal smoking and internalizing and externalizing problems in children studied from childhood to late adolescence. J Am Acad Child Adolesc Psychiatry 47(7):779–787

    PubMed  Google Scholar 

  20. Ekblad M, Gissler M, Lehtonen L, Korkeila J (2010) Prenatal smoking exposure and the risk of psychiatric morbidity into young adulthood. Arch Gen Psychiatry 67(8):841–849

    PubMed  Google Scholar 

  21. Indredavik MS, Brubakk A-M, Romundstad P, Vik T (2007) Prenatal smoking exposure and psychiatric symptoms in adolescence. Acta Paediatr 96(3):377–382

    PubMed Central  PubMed  Google Scholar 

  22. Menezes AMB, Murray J, Laszlo M, Wehrmeister FC, Hallal PC, Goncalves H et al (2013) Happiness and depression in adolescence after maternal smoking during pregnancy: birth cohort study. PLoS One 8(11):e80370

    PubMed Central  CAS  PubMed  Google Scholar 

  23. Monshouwer K, Huizink AC, Harakeh Z, Raaijmakers QA, Reijneveld SA, Oldehinkel AJ et al (2011) Prenatal smoking exposure and the risk of behavioral problems and substance use in adolescence: the TRAILS study. Eur Addict Res 17(6):342–350

    PubMed  Google Scholar 

  24. Dolan CV, Geels L, Vink JM, van Beijsterveldt CE, Neale MC, Bartels M et al (2016) Testing causal effects of maternal smoking during pregnancy on offspring’s externalizing and internalizing behavior. Behav Genet 46(3):378–388

    CAS  PubMed  Google Scholar 

  25. Talati A, Wickramaratne PJ, Wesselhoeft R, Weissman MM (2017) Prenatal tobacco exposure, birthweight, and offspring psychopathology. Psychiatry Res 252:346–352

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D et al (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. Jama 283(15):2008–2012

    CAS  PubMed  Google Scholar 

  27. Reviews UOYCF (2009) Dissemination. Systematic reviews: CRD’s guidance for undertaking reviews in health care. University of York, Centre for Reviews & Dissemination

  28. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M et al (2015) Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 4:1

    PubMed Central  PubMed  Google Scholar 

  29. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M et al (2017) The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. The Ottawa Hospital Research Institute. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 27 Apr 2019

  30. Borenstein M, Hedges L, Higgins J, Rothstein H (2005) Comprehensive meta-analysis version 2. Biostat, Englewood, p 104

    Google Scholar 

  31. Borenstein M, Hedges LV, Higgins JP, Rothstein HR (2010) A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods 1(2):97–111

    PubMed  Google Scholar 

  32. Patsopoulos NA, Evangelou E, Ioannidis JP (2008) Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation. Int J Epidemiol 37(5):1148–1157

    PubMed Central  PubMed  Google Scholar 

  33. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ (Clin Res Ed) 327(7414):557–560

    Google Scholar 

  34. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ (Clin Res Ed) 315(7109):629–634

    CAS  Google Scholar 

  35. Hill SY, Lowers L, Locke-Wellman J, Shen S (2000) Maternal smoking and drinking during pregnancy and the risk for child and adolescent psychiatric disorders. J Stud Alcohol 61(5):661–668

    PubMed Central  CAS  PubMed  Google Scholar 

  36. Taylor AE, Carslake D, De Mola CL, Rydell M, Nilsen TIL, Bjørngaard JH et al (2017) Maternal smoking in pregnancy and offspring depression: a cross cohort and negative control study. Sci Rep 7(1):1–8

    Google Scholar 

  37. Biederman J, Martelon M, Woodworth KY, Spencer TJ, Faraone SV (2017) Is maternal smoking during pregnancy a risk factor for cigarette smoking in offspring? A longitudinal controlled study of adhd children grown up. J Atten Disord 21(12):975–985

    PubMed  Google Scholar 

  38. Chudal R, Brown AS, Gissler M, Suominen A, Sourander A (2015) Is maternal smoking during pregnancy associated with bipolar disorder in offspring? J Affect Disord 171:132–136

    PubMed  Google Scholar 

  39. Meier SM, Plessen KJ, Verhulst F, Mors O, Mortensen PB, Pedersen CB et al (2017) Familial confounding of the association between maternal smoking during pregnancy and internalizing disorders in offspring. Psychol Med 19:1–10. https://doi.org/10.1017/S0033291716003627

    Article  Google Scholar 

  40. Lambers DS, Clark KE (1996) The maternal and fetal physiologic effects of nicotine. Semin Perinatol 20(2):115–126

    CAS  PubMed  Google Scholar 

  41. Rogers JM (2009) Tobacco and pregnancy. Reprod Toxicol (Elmsf NY) 28(2):152–160

    CAS  Google Scholar 

  42. Levin ED, Slotkin TA (1998) Chapter 34—developmental neurotoxicity of nicotine. In: Slikker W, Chang LW (eds) Handbook of developmental neurotoxicology. Academic Press, San Diego, pp 587–615

    Google Scholar 

  43. Slikker W, Xu ZA, Levin ED, Slotkin TA (2005) Mode of action: disruption of brain cell replication, second messenger, and neurotransmitter systems during development leading to cognitive dysfunction—developmental neurotoxicity of nicotine. Crit Rev Toxicol 35(8–9):703–711

    CAS  PubMed  Google Scholar 

  44. Ernst M, Moolchan ET, Robinson ML (2001) Behavioral and neural consequences of prenatal exposure to nicotine. J Am Acad Child Adolesc Psychiatry 40(6):630–641

    CAS  PubMed  Google Scholar 

  45. Suter M, Ma J, Harris A, Patterson L, Brown KA, Shope C et al (2011) Maternal tobacco use modestly alters correlated epigenome-wide placental DNA methylation and gene expression. Epigenetics 6(11):1284–1294

    PubMed Central  CAS  PubMed  Google Scholar 

  46. Richmond RC, Simpkin AJ, Woodward G, Gaunt TR, Lyttleton O, McArdle WL et al (2015) Prenatal exposure to maternal smoking and offspring DNA methylation across the lifecourse: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC). Hum Mol Genet 24(8):2201–2217

    CAS  PubMed  Google Scholar 

  47. Stroud LR, Papandonatos GD, Rodriguez D, McCallum M, Salisbury AL, Phipps MG et al (2014) Maternal smoking during pregnancy and infant stress response: test of a prenatal programming hypothesis. Psychoneuroendocrinology 48:29–40

    PubMed Central  CAS  PubMed  Google Scholar 

  48. 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(4):1377–1390

    PubMed Central  PubMed  Google Scholar 

  49. Tehranifar P, Wu H-C, McDonald JA, Jasmine F, Santella RM, Gurvich I et al (2018) Maternal cigarette smoking during pregnancy and offspring DNA methylation in midlife. Epigenetics 13(2):129–134

    PubMed Central  PubMed  Google Scholar 

  50. Klose RJ, Bird AP (2006) Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 31(2):89–97

    CAS  PubMed  Google Scholar 

  51. Varghese FP, Brown ES (2001) The hypothalamic-pituitary-adrenal axis in major depressive disorder: a brief primer for primary care physicians. Prim Care Companion J Clin Psychiatry 3(4):151–155

    PubMed Central  PubMed  Google Scholar 

  52. Mello AF, Mello MF, Carpenter LL, Price LH (2003) Update on stress and depression: the role of the hypothalamic-pituitary-adrenal (HPA) axis. Rev Bras Psiquiatr (Sao Paulo Braz 1999) 25(4):231–238

    Google Scholar 

  53. He X, Lu J, Dong W, Jiao Z, Zhang C, Yu Y et al (2017) Prenatal nicotine exposure induces HPA axis-hypersensitivity in offspring rats via the intrauterine programming of up-regulation of hippocampal GAD67. Arch Toxicol 91(12):3927–3943

    CAS  PubMed  Google Scholar 

  54. Zhang C, Fan SJ, Sun AB, Liu ZZ, Liu L (2019) Prenatal nicotine exposure induces depression like behavior in adolescent female rats via modulating neurosteroid in the hippocampus. Mol Med Rep 19(5):4185–4194

    PubMed Central  CAS  PubMed  Google Scholar 

  55. Lieb R, Isensee B, Höfler M, Pfister H, Wittchen H-U (2002) Parental major depression and the risk of depression and other mental disorders in offspring: a prospective-longitudinal community study. Arch Gen Psychiatry 59(4):365–374

    PubMed  Google Scholar 

  56. Halligan SL, Murray L, Martins C, Cooper PJ (2007) Maternal depression and psychiatric outcomes in adolescent offspring: a 13-year longitudinal study. J Affect Disord 97(1–3):145–154

    PubMed  Google Scholar 

  57. Hannigan LJ, Eilertsen EM, Gjerde LC, Reichborn-Kjennerud T, Eley TC, Rijsdijk FV et al (2018) Maternal prenatal depressive symptoms and risk for early-life psychopathology in offspring: genetic analyses in the Norwegian Mother and Child Birth Cohort Study. Lancet Psychiatry 5(10):808–815

    PubMed  Google Scholar 

  58. Brion M-J, Victora C, Matijasevich A, Horta B, Anselmi L, Steer C et al (2010) Maternal smoking and child psychological problems: disentangling causal and noncausal effects. Pediatrics 126(1):e57–e65

    PubMed  Google Scholar 

  59. Kuja-Halkola R, D’Onofrio BM, Larsson H, Lichtenstein P (2014) Maternal smoking during pregnancy and adverse outcomes in offspring: genetic and environmental sources of covariance. Behav Genet 44(5):456–467

    PubMed Central  PubMed  Google Scholar 

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

    PubMed Central  PubMed  Google Scholar 

  61. Kabir Z, Connolly GN, Alpert HR (2011) Secondhand smoke exposure and neurobehavioral disorders among children in the United States. Pediatrics 128(2):263–270

    PubMed  Google Scholar 

  62. Tiesler CMT, Heinrich J (2014) Prenatal nicotine exposure and child behavioural problems. Eur Child Adolesc Psychiatry 23(10):913–929

    PubMed Central  PubMed  Google Scholar 

  63. Markou A, Kosten TR, Koob GF (1998) Neurobiological similarities in depression and drug dependence: a self-medication hypothesis. Neuropsychopharmacology 18(3):135–174

    CAS  PubMed  Google Scholar 

  64. Rose JE, Behm FM, Ramsey C, Ritchie JC Jr (2001) Platelet monoamine oxidase, smoking cessation, and tobacco withdrawal symptoms. Nicotine Tob Res 3(4):383–390

    CAS  PubMed  Google Scholar 

  65. Schlotz W, Phillips DI (2009) Fetal origins of mental health: evidence and mechanisms. Brain Behav Immun 23(7):905–916

    PubMed  Google Scholar 

  66. Thapar A, Rutter M (2009) Do prenatal risk factors cause psychiatric disorder? Be wary of causal claims. Br J Psychiatry J Ment Sci 195(2):100–101

    Google Scholar 

  67. Al-Sahab B, Saqib M, Hauser G, Tamim H (2010) Prevalence of smoking during pregnancy and associated risk factors among Canadian women: a national survey. BMC Pregnancy Childbirth 10(1):24

    PubMed Central  PubMed  Google Scholar 

  68. Muhajarine N, D’Arcy C, Edouard L (1997) Prevalence and predictors of health risk behaviours during early pregnancy: Saskatoon Pregnancy and Health Study. Can J Public Health Revue Canadienne de Sante Publique. 88(6):375–379

    CAS  PubMed  Google Scholar 

  69. Stewart DE, Streiner DL (1995) Cigarette smoking during pregnancy. Can J Psychiatry Revue Canadienne de Psychiatrie 40(10):603–607

    CAS  PubMed  Google Scholar 

  70. Nagahawatte NT, Goldenberg RL (2008) Poverty, maternal health, and adverse pregnancy outcomes. Ann N Y Acad Sci 1136:80–85

    PubMed  Google Scholar 

  71. Heaman MI, Chalmers K (2005) Prevalence and correlates of smoking during pregnancy: a comparison of aboriginal and non-aboriginal women in manitoba. Birth 32(4):299–305

    PubMed  Google Scholar 

  72. Roza SJ, Verhulst FC, Jaddoe VWV, Steegers EAP, Mackenbach JP, Hofman A et al (2008) Maternal smoking during pregnancy and child behaviour problems: the Generation R Study. Int J Epidemiol 38(3):680–689

    PubMed  Google Scholar 

Download references

Acknowledgements

We are so grateful to the Curtin University for providing us a wide range of available online databases.

Funding

No external funding obtained for this systematic review and meta-analysis.

Author information

Authors and Affiliations

  1. School of Public Health, Curtin University, Kent Street, Bentley, WA, 6102, Australia

    Bereket Duko, Getinet Ayano, Gavin Pereira, Kim Betts & Rosa Alati

  2. Telethon Kids Institute, Northern Entrance, Perth Children’s Hospital, 15 Hospital Ave, Nedlands, WA, 6009, Australia

    Gavin Pereira

  3. Centre for Fertility and Health (CeFH), Norwegian Institute of Public Health, Oslo, Norway

    Gavin Pereira

  4. Institute for Social Sciences Research, The University of Queensland, 80 Meier’s Rd, Indooroopilly, QLD, 4068, Australia

    Rosa Alati

Authors
  1. Bereket Duko
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Getinet Ayano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gavin Pereira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kim Betts
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rosa Alati
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

BD conceived the hypothesis, developed the methodology, identified all potential studies, extracted the data, assessed quality, conducted a meta-analysis, and wrote the first draft of the manuscript. GA reviewed abstracts and assessed the methodological quality of the included studies. GP reviewed the protocol, reviewed data extraction, data analysis and contributed to subsequent drafts of the manuscript. KB reviewed data extraction, data analysis and contributed to subsequent drafts of the manuscript. RA reviewed the protocol, reviewed data extraction, and synthesis and contributed to subsequent drafts of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Bereket Duko.

Ethics declarations

Conflict of interest

All authors have no conflicts of interest to disclose.

Code availability

Comprehensive Meta-Analysis (CMA) version 3.0 was used to analyze the data.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 13 kb)

Supplementary material 2 (DOCX 29 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Duko, B., Ayano, G., Pereira, G. et al. Prenatal tobacco use and the risk of mood disorders in offspring: a systematic review and meta-analysis. Soc Psychiatry Psychiatr Epidemiol 55, 1549–1562 (2020). https://doi.org/10.1007/s00127-020-01949-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00127-020-01949-y

Keywords

Search

Navigation