European Child & Adolescent Psychiatry

, Volume 19, Issue 10, pp 747–753 | Cite as

Attention-deficit/hyperactivity disorder in the offspring following prenatal maternal bereavement: a nationwide follow-up study in Denmark

  • Jiong Li
  • Jørn Olsen
  • Mogens Vestergaard
  • Carsten Obel
Original Contribution

Abstract

Severe prenatal stress exposure has been found to increase the risk of neuropsychiatric conditions like schizophrenia. We examined the risk of attention-deficit/hyperactivity disorder (ADHD) in the offspring following prenatal maternal bereavement, as a potential source of stress exposure. We conducted a nationwide population-based cohort study including all 1,015,912 singletons born in Denmark from 1987 to 2001. A total of 29,094 children were born to women who lost a close relative during pregnancy or up to 1 year before pregnancy. These children were included in the exposed cohort and other children were in the unexposed cohort. We used Cox regression to estimate hazard ratios for ADHD, defined as the first-time ADHD hospitalization or first-time ADHD medication after 3 years of age. Boys born to mothers who were bereaved by unexpected death of a child or a spouse, had a 72% increased risk of ADHD [hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.09–2.73]. Boys born to mothers who lost a child or a spouse during 0–6 months before pregnancy and during pregnancy had a HR of 1.47 (95% CI 1.00–2.16) and 2.10 (95% CI 1.16–3.80), respectively. Our findings suggest that prenatal maternal exposure to severe stress may increase the risk of ADHD in the offspring.

Keywords

Attention-deficit/hyperactivity disorder (ADHD) Stress Bereavement Fetal programming Child psychiatry 

Notes

Acknowledgments

The study was supported by the Danish Medical Research Council (project no. 271-05-0616, project no. 271-07-0437), Gigtforeningen (R54-A596-B286), Nordic Cancer Union (2008), and NordForsk (070331).

Conflict of interest statement

None.

References

  1. 1.
    Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA (2007) The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry 164:942–948CrossRefPubMedGoogle Scholar
  2. 2.
    Brown RT, Freeman WS, Perrin JM, Stein MT, Amler RW, Feldman HM, Pierce K, Wolraich ML (2001) Prevalence and assessment of attention-deficit/hyperactivity disorder in primary care settings. Pediatrics 107:e43CrossRefPubMedGoogle Scholar
  3. 3.
    Biederman J (2005) Attention-deficit/hyperactivity disorder: a selective overview. Biol Psychiatry 57:1215–1220CrossRefPubMedGoogle Scholar
  4. 4.
    Banerjee TD, Middleton F, Faraone SV (2007) Environmental risk factors for attention-deficit hyperactivity disorder. Acta Paediatr 96:1269–1274CrossRefPubMedGoogle Scholar
  5. 5.
    Faraone SV, Doyle AE (2001) The nature and heritability of attention-deficit/hyperactivity disorder. Child Adolesc Psychiatr Clin N Am 10:299–316PubMedGoogle Scholar
  6. 6.
    Viltart O, Vanbesien-Mailliot CC (2007) Impact of prenatal stress on neuroendocrine programming. Sci World J 7:1493–1537Google Scholar
  7. 7.
    Talge NM, Neal C, Glover V (2007) Antenatal maternal stress and long-term effects on child neurodevelopment: how and why? J Child Psychol Psychiatry 48:245–261CrossRefPubMedGoogle Scholar
  8. 8.
    Welberg LA, Seckl JR (2001) Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol 13:113–128CrossRefPubMedGoogle Scholar
  9. 9.
    Gitau R, Cameron A, Fisk NM, Glover V (1998) Fetal exposure to maternal cortisol. Lancet 352:707–708CrossRefPubMedGoogle Scholar
  10. 10.
    Hansen D, Lou HC, Olsen J (2000) Serious life events and congenital malformations: a national study with complete follow-up. Lancet 356:875–880CrossRefPubMedGoogle Scholar
  11. 11.
    Li J, Vestergaard M, Obel C, Precht DH, Christensen J, Lu M, Olsen J (2009) Prenatal stress and cerebral palsy: a nationwide cohort study in Denmark. Psychosom Med 71:615–618CrossRefPubMedGoogle Scholar
  12. 12.
    Huttunen MO, Niskanen P (1978) Prenatal loss of father and psychiatric disorders. Arch Gen Psychiatry 35:429–431PubMedGoogle Scholar
  13. 13.
    Khashan AS, Abel KM, McNamee R, Pedersen MG, Webb RT, Baker PN, Kenny LC, Mortensen PB (2008) Higher risk of offspring schizophrenia following antenatal maternal exposure to severe adverse life events. Arch Gen Psychiatry 65:146–152CrossRefPubMedGoogle Scholar
  14. 14.
    O’Connor TG, Heron J, Golding J, Beveridge M, Glover V (2002) Maternal antenatal anxiety and children’s behavioural/emotional problems at 4 years: report from the Avon Longitudinal Study of Parents and Children. Br J Psychiatry 180:502–508CrossRefPubMedGoogle Scholar
  15. 15.
    O’Connor TG, Heron J, Glover V, the ALSPAC Study Team (2002) Antenatal anxiety predicts child behavioral/emotional problems independently of postnatal depression. J Am Acad Child Adoles Psychiatry 41:1470–1477CrossRefGoogle Scholar
  16. 16.
    Seckl J (2004) Prenatal glucocorticoids and long-term programming. Euro J Endocrinol 151:U49–U62CrossRefGoogle Scholar
  17. 17.
    Weinstock M (2001) Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Prog Neurobiol 65:427–451CrossRefPubMedGoogle Scholar
  18. 18.
    Weinstock M (2005) The potential influence of maternal stress hormones on development and mental health of the offspring. Brain Behav Immun 19:296–308CrossRefPubMedGoogle Scholar
  19. 19.
    Osterweis M, Solomon F, Green M (1984) Bereavement: reactions, consequences, and care. National Academy Press, Washington, DCGoogle Scholar
  20. 20.
    Rubin SS, Malkinson R (2001) Parental responses to child loss across the life cycle: clinical and research perspectives. In: Stroebe MS, Hansson RO, Stroebe W (eds) Handbook of bereavement research: consequences, coping, and care. American Psychological Association, Washington, DC, pp 219–239CrossRefGoogle Scholar
  21. 21.
    Skodol AE, Shrout PE (1989) Use of DSM-III axis IV in clinical practice: rating etiologically significant stressors. Am J Psychiatry 146:61–66PubMedGoogle Scholar
  22. 22.
    Levav I, Krasnoff L, Dohrenwend BS (1981) Israeli PERI life event scale: ratings of events by a community sample. Isr J Med Sci 17:176–183PubMedGoogle Scholar
  23. 23.
    Li J, Precht DH, Mortensen PB, Olsen J (2003) Mortality in parents after death of a child in Denmark: a nationwide follow-up study. Lancet 361:363–367CrossRefPubMedGoogle Scholar
  24. 24.
    Pedersen CB, Gotzsche H, Moller JO, Mortensen PB (2006) The Danish Civil Registration System. A cohort of eight million persons. Dan Med Bull 53:441–449PubMedGoogle Scholar
  25. 25.
    Knudsen LB, Olsen J (1998) The Danish Medical Birth Registry. Dan Med Bull 45:320–323PubMedGoogle Scholar
  26. 26.
    Munk-Jorgensen P, Mortensen PB (1997) The Danish Psychiatric Central Register. Dan Med Bull 44:82–84PubMedGoogle Scholar
  27. 27.
    Andersen TF, Madsen M, Jorgensen J, Mellemkjoer L, Olsen JH (1999) The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan Med Bull 46:263–268PubMedGoogle Scholar
  28. 28.
    The Danish Medicines Agency (2009) Register of Medicinal Product Statistics. http://www.dkma.dk/1024/visUKLSArtikel.asp?artikelID=10895. Accessed 8 June 2009
  29. 29.
    Denmark Statistics (1991) IDA—an integrated database for labor market research. Available at http://www.dst.dk/) (under IDA, Intergrated Database for Arbejdsmarkedsforskning) (in Danish)
  30. 30.
    SAS Institute (1997) SAS/STAT software: changes and enhancements, release 6.12. SAS Institute, Cary, NCGoogle Scholar
  31. 31.
    Avison WR, Gotlib IH (1994) Stress and mental health: contemporary issues and prospects for the future. Plenum, New YorkGoogle Scholar
  32. 32.
    Brown GW, Harris TO (1989) Life events and illness. Guilford Press, New YorkGoogle Scholar
  33. 33.
    Elliott GR, Eisdorfer C (1982) Stress and human health. Springer, New YorkGoogle Scholar
  34. 34.
    Miller TW (1996) Theory and assessment of stressful life events. International Universities Press, Madison, CTGoogle Scholar
  35. 35.
    Schneider ML, Roughton EC, Koehler AJ, Lubach GR (1999) Growth and development following prenatal stress exposure in primates: an examination of ontogenetic vulnerability. Child Dev 70:263–274CrossRefPubMedGoogle Scholar
  36. 36.
    Weinstock M (2007) Gender differences in the effects of prenatal stress on brain development and behaviour. Neurochem Res 32:1730–1740CrossRefPubMedGoogle Scholar
  37. 37.
    Berger-Sweeney J, Hohmann CF (1997) Behavioral consequences of abnormal cortical development: insights into developmental disabilities. Behav Brain Res 86:121–142CrossRefPubMedGoogle Scholar
  38. 38.
    Staller J, Faraone SV (2006) Attention-deficit hyperactivity disorder in girls: epidemiology and management. CNS Drugs 20:107–123CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Jiong Li
    • 1
  • Jørn Olsen
    • 1
    • 2
  • Mogens Vestergaard
    • 3
  • Carsten Obel
    • 3
  1. 1.Department of Epidemiology, The Danish Epidemiology Science Centre, Institute of Public HealthThe University of AarhusAarhusDenmark
  2. 2.Department of Epidemiology, School of Public HealthUniversity of CaliforniaLos AngelesUSA
  3. 3.Department of General Practice, Institute of Public HealthUniversity of AarhusAarhusDenmark

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