European Journal of Pediatrics

, Volume 171, Issue 1, pp 173–179 | Cite as

Stressful life events in childhood and risk of infectious disease hospitalization

  • Nete Munk Nielsen
  • Anne Vinkel Hansen
  • Jacob Simonsen
  • Anders Hviid
Original Paper


Individuals exposed to high levels of stress might have an increased risk of infectious diseases. However, most of the previous studies have been conducted among adults. To examine the effect of childhood stress, we conducted a nationwide cohort study including all Danish children born from 1977 to 2004. Stressful life events (SFLE) included parental death, death of sibling or parental divorce. Outcome was defined as hospitalizations due to less severe (LSID) or severe infectious diseases (SID). Children were followed until the age of 15 years. The association between SFLE and risk of infections was evaluated through rate ratios (RR) comparing infectious disease incidence ratios in children with and without a history of SFLE. Overall, children exposed to SFLE were at 13% increased risk of LSID (RR = 1.13 (1.10–1.15)), but at no increased risk of SID hospitalization (RR = 1.05 (0.97–1.14)). Looking at the specific type of SFLE, parental divorce increased the risk of LSID (RR = 1.11 (1.09–1.14)) and SID hospitalization (1.11 (1.02–1.21)) by 11%, whereas no increased risk of LSID and SID hospitalization was observed following parental death. Finally, a 34% increased risk of LSID hospitalization (RR = 1.34 (1.23–1.45)) was observed following death of sibling, in contrast to no increased risk of SID hospitalization. Conclusion: Childhood exposure to SFLE, especially parental divorce seems to increase the risk of infectious disease hospitalization. Although we cannot determine whether our observations are the result of a biological effect of stress, adoption of unhealthy behaviours or increased likelihood of hospitalization, our findings do have public health relevance as a considerable proportion of the children today will be exposed to SFLE, the majority to parental divorce.


Stressful life events Childhood Infectious disease hospitalizations Nationwide study 



The study was supported by research grants from the Lundbeck Foundation, Aase and Ejnar Danielsen's Foundation, The Dagmar Marshall Foundation and The Health Insurance Foundation

Conflict of interest



  1. 1.
    Agid O, Shapira B, Zislin J, Ritsner M, Hanin B, Murad H, Troudart T, Bloch M, Heresco-Levy U, Lerer B (1999) Environment and vulnerability to major psychiatric illness: a case control study of early parental loss in major depression, bipolar disorder and schizophrenia. Mol Psychiatry 4:163–172PubMedCrossRefGoogle Scholar
  2. 2.
    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
  3. 3.
    Atkinson RL, Atkinson RC, Smith EE, Bem DJ, Nolen-Hoeksema S (1996) Stress, health and coping. In: Klein CP, Galloway K, Hester A, Welch S (eds) Hilgard's introduction to psychology, 12th edn. Harcourt Brace & Company, Orlando, pp 476–508Google Scholar
  4. 4.
    Benfield T, Jensen JS, Nordestgaard BG (2007) Influence of diabetes and hyperglycaemia on infectious disease hospitalisation and outcome. Diabetologia 50:549–554PubMedCrossRefGoogle Scholar
  5. 5.
    Benfield T, Lange P, Vestbo J (2008) Chronic obstructive pulmonary disease stage and risk of hospitalization for infectious disease. Chest 134:46–53CrossRefGoogle Scholar
  6. 6.
    Bleeker SE, Rksen-Lubsen G, Grobbee DE, Donders AR, Moons KG, Moll HA (2007) Validating and updating a prediction rule for serious bacterial infection in patients with fever without source. Acta Paediatr 96:100–104PubMedCrossRefGoogle Scholar
  7. 7.
    Boyce WT, Chesney M, Alkon A, Tschann JM, Adams S, Chesterman B, Cohen F, Kaiser P, Folkman S, Wara D (1995) Psychobiologic reactivity to stress and childhood respiratory illnesses: results of two prospective studies. Psychosom Med 57:411–422PubMedGoogle Scholar
  8. 8.
    Boyce WT, Jensen EW, Cassel JC, Collier AM, Smith AH, Ramey CT (1977) Influence of life events and family routines on childhood respiratory tract illness. Pediatrics 60:609–615PubMedGoogle Scholar
  9. 9.
    Brown LP, Cowen EL (1988) Children's judgments of event upsettingness and personal experiencing of stressful events. Am J Community Psychol 16:123–135PubMedCrossRefGoogle Scholar
  10. 10.
    Burns VE, Carroll D, Ring C, Harrison LK, Drayson M (2002) Stress, coping, and hepatitis B antibody status. Psychosom Med 64:287–293PubMedCrossRefGoogle Scholar
  11. 11.
    Caserta MT, O'Connor TG, Wyman PA, Wang H, Moynihan J, Cross W, Tu X, Jin X (2008) The associations between psychosocial stress and the frequency of illness, and innate and adaptive immune function in children. Brain Behav Immun 22:933–940PubMedCrossRefGoogle Scholar
  12. 12.
    Cohen S, Frank E, Doyle WJ, Skoner DP, Rabin BS, Gwaltney JM Jr (1998) Types of stressors that increase susceptibility to the common cold in healthy adults. Health Psychol 17:214–223PubMedCrossRefGoogle Scholar
  13. 13.
    Cohen S, Miller GE, Rabin BS (2001) Psychological stress and antibody response to immunization: a critical review of the human literature. Psychosom Med 63:7–18PubMedGoogle Scholar
  14. 14.
    Cohen S, Tyrrell DA, Smith AP (1991) Psychological stress and susceptibility to the common cold. N Engl J Med 325:606–612PubMedCrossRefGoogle Scholar
  15. 15.
    Drummond PD, Hewson-Bower B (1997) Increased psychosocial stress and decreased mucosal immunity in children with recurrent upper respiratory tract infections. J Psychosom Res 43:271–278PubMedCrossRefGoogle Scholar
  16. 16.
    Elkind D (1981) The hurried child. Addison-Wesley Publishing Co, MasssachusettsGoogle Scholar
  17. 17.
    Ellneby Y (1999) Om børn og stress -og hvad vi kan gøre ved det. Hans Reitzels Forlag, KøbenhavnGoogle Scholar
  18. 18.
    Eng PM, Kawachi I, Fitzmaurice G, Rimm EB (2005) Effects of marital transitions on changes in dietary and other health behaviours in US male health professionals. J Epidemiol Community Health 59:56–62PubMedCrossRefGoogle Scholar
  19. 19.
    Glaser R, Kiecolt-Glaser JK, Bonneau RH, Malarkey W, Kennedy S, Hughes J (1992) Stress-induced modulation of the immune response to recombinant hepatitis B vaccine. Psychosom Med 54:22–29PubMedGoogle Scholar
  20. 20.
    Glaser R, Kiecolt-Glaser JK, Speicher CE, Holliday JE (1985) Stress, loneliness, and changes in herpesvirus latency. J Behav Med 8:249–260PubMedCrossRefGoogle Scholar
  21. 21.
    Glaser R, Pearson GR, Bonneau RH, Esterling BA, Atkinson C, Kiecolt-Glaser JK (1993) Stress and the memory T-cell response to the Epstein–Barr virus in healthy medical students. Health Psychol 12:435–442PubMedCrossRefGoogle Scholar
  22. 22.
    Godbout JP, Glaser R (2006) Stress-induced immune dysregulation: implications for wound healing, infectious disease and cancer. J Neuroimmune Pharmacol 1:421–427PubMedCrossRefGoogle Scholar
  23. 23.
    Graham NM, Woodward AJ, Ryan P, Douglas RM (1990) Acute respiratory illness in Adelaide children. II: the relationship of maternal stress, social supports and family functioning. Int J Epidemiol 19:937–944PubMedCrossRefGoogle Scholar
  24. 24.
    Harland P, Reijneveld SA, Brugman E, Verloove-Vanhorick SP, Verhulst FC (2002) Family factors and life events as risk factors for behavioural and emotional problems in children. Eur Child Adolesc Psychiatry 11:176–184PubMedCrossRefGoogle Scholar
  25. 25.
    Herberth G, Weber A, Roder S, Elvers HD, Kramer U, Schins RP, Diez U, Borte M, Heinrich J, Schafer T, Herbarth O, Lehmann I (2008) Relation between stressful life events, neuropeptides and cytokines: results from the LISA birth cohort study. Pediatr Allergy Immunol 19:722–729PubMedCrossRefGoogle Scholar
  26. 26.
    Hoglund CO, Axen J, Kemi C, Jernelov S, Grunewald J, Muller-Suur C, Smith Y, Gronneberg R, Eklund A, Stierna P, Lekander M (2006) Changes in immune regulation in response to examination stress in atopic and healthy individuals. Clin Exp Allergy 36:982–992PubMedCrossRefGoogle Scholar
  27. 27.
    Huurre T, Junkkari H, Aro H (2006) Long-term psychosocial effects of parental divorce: a follow-up study from adolescence to adulthood. Eur Arch Psychiatry Clin Neurosci 256:256–263PubMedCrossRefGoogle Scholar
  28. 28.
    Jabaaij L, van Hattum J, Vingerhoets JJ, Oostveen FG, Duivenvoorden HJ, Ballieux RE (1996) Modulation of immune response to rDNA hepatitis B vaccination by psychological stress. J Psychosom Res 41:129–137PubMedCrossRefGoogle Scholar
  29. 29.
    Jose BS, van Oers HA, van de Mheen HD, Garretsen HF, Mackenbach JP (2000) Stressors and alcohol consumption. Alcohol Alcohol 35:307–312PubMedGoogle Scholar
  30. 30.
    Kang DH, Fox C (2001) Th1 and Th2 cytokine responses to academic stress. Res Nurs Health 24:245–257PubMedCrossRefGoogle Scholar
  31. 31.
    Kiecolt-Glaser JK, Garner W, Speicher C, Penn GM, Holliday J, Glaser R (1984) Psychosocial modifiers of immunocompetence in medical students. Psychosom Med 46:7–14PubMedGoogle Scholar
  32. 32.
    Knudsen LB, Olsen J (1998) The Danish medical birth registry. Dan Med Bull 45:320–323PubMedGoogle Scholar
  33. 33.
    Krogvold L, Wathne KO (2004) Treatment of serious infectious diseases in children. Tidsskr Nor Laegeforen 124:484–487PubMedGoogle Scholar
  34. 34.
    Lee S, Cho E, Grodstein F, Kawachi I, Hu FB, Colditz GA (2005) Effects of marital transitions on changes in dietary and other health behaviours in US women. Int J Epidemiol 34:69–78PubMedCrossRefGoogle Scholar
  35. 35.
    Maes M, Song C, Lin A, De Jongh R, Van Gastel A, Kenis G, Bosmans E, De Meester I, Benoy I, Neels H, Demedts P, Janca A, Scharpe S, Smith RS (1998) The effects of psychological stress on humans: increased production of pro-inflammatory cytokines and a Th1-like response in stress-induced anxiety. Cytokine 10:313–318PubMedCrossRefGoogle Scholar
  36. 36.
    McEwen BS (1998) Protective and damaging effects of stress mediators. N Engl J Med 338:171–179PubMedCrossRefGoogle Scholar
  37. 37.
    Miller GE, Cohen S, Pressman S, Barkin A, Rabin BS, Treanor JJ (2004) Psychological stress and antibody response to influenza vaccination: when is the critical period for stress, and how does it get inside the body? Psychosom Med 66:215–223PubMedCrossRefGoogle Scholar
  38. 38.
    Mouton C, Fillion L, Tawadros E, Tessier R (1989) Salivary IgA is a weak stress marker. Behav Med 15:179–185PubMedCrossRefGoogle Scholar
  39. 39.
    Nielsen AM, Koefoed BG, Moller R, Laursen B (2006) Prevalence rates of recent illnesses in Danish children, 1994 and 2000. Ugeskr Laeger 168:373–378PubMedGoogle Scholar
  40. 40.
    Nielsen, L, Vinther Larsen, M, Nielsen, NR, Grønbæk, M (2007) [Stress among the youth] Stress blandt unge. The Danish National Board of Health, National Institute of Public Health, University of Southern Denmark. Ref Type: ReportGoogle Scholar
  41. 41.
    Nunes-Costa RA, Lamela DJ, Figueiredo BF (2009) Psychosocial adjustment and physical health in children of divorce. J Pediatr Rio J 85:385–396PubMedGoogle Scholar
  42. 42.
    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
  43. 43.
    Rodgers B, Power C, Hope S (1997) Parental divorce and adult psychological distress: evidence from a national birth cohort: a research note. J Child Psychol Psychiatry 38:867–872PubMedCrossRefGoogle Scholar
  44. 44.
    Shirtcliff EA, Coe CL, Pollak SD (2009) Early childhood stress is associated with elevated antibody levels to herpes simplex virus type 1. Proc Natl Acad Sci U S A 106:2963–2967PubMedCrossRefGoogle Scholar
  45. 45.
    Simonsen J, Frisch M, Ethelberg S (2008) Socioeconomic risk factors for bacterial gastrointestinal infections. Epidemiology 19:282–290PubMedCrossRefGoogle Scholar
  46. 46.
    Thrane N, Sondergaard C, Schonheyder HC, Sorensen HT (2005) Socioeconomic factors and risk of hospitalization with infectious diseases in 0- to 2-year-old Danish children. Eur J Epidemiol 20:467–474PubMedCrossRefGoogle Scholar
  47. 47.
    Van den BA, Aertgeerts B, Bruyninckx R, Aerts M, Buntinx F (2007) Signs and symptoms for diagnosis of serious infections in children: a prospective study in primary care. Br J Gen Pract 57:538–546Google Scholar
  48. 48.
    Wallerstein JS (1991) The long-term effects of divorce on children: a review. J Am Acad Child Adolesc Psychiatry 30:349–360PubMedCrossRefGoogle Scholar
  49. 49.
    Weitoft GR, Hjern A, Haglund B, Rosen M (2003) Mortality, severe morbidity, and injury in children living with single parents in Sweden: a population-based study. Lancet 361:289–295PubMedCrossRefGoogle Scholar
  50. 50.
    Worden JW, Davies B, McCown D (1999) Comparing parent loss with sibling loss. Death Stud 23:1–15PubMedCrossRefGoogle Scholar
  51. 51.
    Wyman PA, Moynihan J, Eberly S, Cox C, Cross W, Jin X, Caserta MT (2007) Association of family stress with natural killer cell activity and the frequency of illnesses in children. Arch Pediatr Adolesc Med 161:228–234PubMedCrossRefGoogle Scholar
  52. 52.
    Yamamoto K, Davis OL Jr, Dylak S, Whittaker J, Marsh C, van der Westhuizen PC (1996) Across six nations: stressful events in the lives of children. Child Psychiatry Hum Dev 26:139–150PubMedCrossRefGoogle Scholar
  53. 53.
    Zlotnik G (2001) Children and stress. Ugeskr Laeger 163:1121–1124PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Nete Munk Nielsen
    • 1
  • Anne Vinkel Hansen
    • 1
  • Jacob Simonsen
    • 1
  • Anders Hviid
    • 1
  1. 1.Department of Epidemiology ResearchStatens Serum InstitutCopenhagenDenmark

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