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.
Similar content being viewed by others
References
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 164:942–948
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:e43
Biederman J (2005) Attention-deficit/hyperactivity disorder: a selective overview. Biol Psychiatry 57:1215–1220
Banerjee TD, Middleton F, Faraone SV (2007) Environmental risk factors for attention-deficit hyperactivity disorder. Acta Paediatr 96:1269–1274
Faraone SV, Doyle AE (2001) The nature and heritability of attention-deficit/hyperactivity disorder. Child Adolesc Psychiatr Clin N Am 10:299–316
Viltart O, Vanbesien-Mailliot CC (2007) Impact of prenatal stress on neuroendocrine programming. Sci World J 7:1493–1537
Talge NM, Neal C, Glover V (2007) Antenatal maternal stress and long-term effects on child neurodevelopment: how and why? J Child Psychol Psychiatry 48:245–261
Welberg LA, Seckl JR (2001) Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol 13:113–128
Gitau R, Cameron A, Fisk NM, Glover V (1998) Fetal exposure to maternal cortisol. Lancet 352:707–708
Hansen D, Lou HC, Olsen J (2000) Serious life events and congenital malformations: a national study with complete follow-up. Lancet 356:875–880
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 71:615–618
Huttunen MO, Niskanen P (1978) Prenatal loss of father and psychiatric disorders. Arch Gen Psychiatry 35:429–431
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 65:146–152
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 180:502–508
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 41:1470–1477
Seckl J (2004) Prenatal glucocorticoids and long-term programming. Euro J Endocrinol 151:U49–U62
Weinstock M (2001) Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Prog Neurobiol 65:427–451
Weinstock M (2005) The potential influence of maternal stress hormones on development and mental health of the offspring. Brain Behav Immun 19:296–308
Osterweis M, Solomon F, Green M (1984) Bereavement: reactions, consequences, and care. National Academy Press, Washington, DC
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 219–239
Skodol AE, Shrout PE (1989) Use of DSM-III axis IV in clinical practice: rating etiologically significant stressors. Am J Psychiatry 146:61–66
Levav I, Krasnoff L, Dohrenwend BS (1981) Israeli PERI life event scale: ratings of events by a community sample. Isr J Med Sci 17:176–183
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 361:363–367
Pedersen CB, Gotzsche H, Moller JO, Mortensen PB (2006) The Danish Civil Registration System. A cohort of eight million persons. Dan Med Bull 53:441–449
Knudsen LB, Olsen J (1998) The Danish Medical Birth Registry. Dan Med Bull 45:320–323
Munk-Jorgensen P, Mortensen PB (1997) The Danish Psychiatric Central Register. Dan Med Bull 44:82–84
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 46:263–268
The Danish Medicines Agency (2009) Register of Medicinal Product Statistics. http://www.dkma.dk/1024/visUKLSArtikel.asp?artikelID=10895. Accessed 8 June 2009
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)
SAS Institute (1997) SAS/STAT software: changes and enhancements, release 6.12. SAS Institute, Cary, NC
Avison WR, Gotlib IH (1994) Stress and mental health: contemporary issues and prospects for the future. Plenum, New York
Brown GW, Harris TO (1989) Life events and illness. Guilford Press, New York
Elliott GR, Eisdorfer C (1982) Stress and human health. Springer, New York
Miller TW (1996) Theory and assessment of stressful life events. International Universities Press, Madison, CT
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 70:263–274
Weinstock M (2007) Gender differences in the effects of prenatal stress on brain development and behaviour. Neurochem Res 32:1730–1740
Berger-Sweeney J, Hohmann CF (1997) Behavioral consequences of abnormal cortical development: insights into developmental disabilities. Behav Brain Res 86:121–142
Staller J, Faraone SV (2006) Attention-deficit hyperactivity disorder in girls: epidemiology and management. CNS Drugs 20:107–123
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Li, J., Olsen, J., Vestergaard, M. et al. Attention-deficit/hyperactivity disorder in the offspring following prenatal maternal bereavement: a nationwide follow-up study in Denmark. Eur Child Adolesc Psychiatry 19, 747–753 (2010). https://doi.org/10.1007/s00787-010-0113-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00787-010-0113-9