Skip to main content

A review of the causes and risk factors for sudden unexpected death in the young

Abstract

Sudden unexpected death in the young (SUDY) is a tragic event resulting in the fatality of seemingly healthy individuals between the ages of one and 40 years. Whilst studies have been performed on sudden unexpected death in infants, children, and adults respectively, little is known about trends in risk factors and causes of death of SUDY cases. Understanding the factors surrounding these deaths could lead to targeted interventions for at-risk individuals. Hence, a systematic approach to investigate the reported possible causes of SUDY was employed using three major databases and Primo, wherein 67 relevant articles were identified and 2 additional guidelines were read. Sudden unexpected death in epilepsy and sudden cardiac events were well-established causes of death with risk factors such as male predominance, substance use and a familial history identified. It was acknowledged that while the cause of death is established following post-mortem examination in many cases, some remain non-specific or undetermined. Considering the genetic etiology, these cases would be ideal candidates for molecular autopsies in the future. Thus, this review emphasized the significance of acquiring the relevant information to aid in resolving cause of death of these SUDY cases and subsequently highlighted the potential for further studies on risk factors and the value of molecular autopsies.

This is a preview of subscription content, access via your institution.

Fig. 1

Data availability

Not applicable.

Code availability

Not applicable.

References

  1. Dewar LJ, Krahn AD, Green MS, Tibbits GF, Sanatani S. Current practices regarding the investigation of sudden unexpected death in the young (SUDY) in Canada. Can J Cardiol. 2012. https://doi.org/10.1016/j.cjca.2012.07.494.

    Article  Google Scholar 

  2. World Health Organization. Global Health Observatory (GHO) data: mortality and global health estimates. 2019. https://www.who.int/gho/mortality_burden_disease/en/. Accessed 4 Nov 2019.

  3. World Health Organization. Children: reducing mortality. 2019. https://www.who.int/news-room/fact-sheets/detail/children-reducing-mortality. Accessed 9 Mar 2020.

  4. World Health Organization. World health statistics 2019: monitoring health for the SDGs, sustainable development goals. Geneva; 2019.

  5. World Health Organization. WHO international statistical classification of diseases and related health problems 10th revision (ICD-10) version for 2010. 2010. https://icd.who.int/browse10/2010/en#R96. Accessed 4 Nov 2019.

  6. Byard R. Sudden death in the young. 3rd ed. Cambridge: Cambridge University Press; 2010.

    Book  Google Scholar 

  7. Bowker T, Wood D, Davies M, et al. Sudden, unexpected cardiac or unexplained death in England: a national survey. QJ Med. 2003. https://doi.org/10.1093/qjmed/hcg038.

    Article  Google Scholar 

  8. Mason JK. Forensic medicine for lawyers. 3rd ed. London: Butterworths Legal Publishers; 1995.

    Google Scholar 

  9. Mathews S, Martin LJ, Coetzee D, Scott C, Naidoo T, Brijmohun Y, et al. The South African child death review pilot: a multiagency approach to strengthen healthcare and protection for children. S Afr Med J. 2016. https://doi.org/10.7196/SAMJ.2016.v106i9.11234.

    Article  PubMed  Google Scholar 

  10. Haas EA. Sudden unexplained death in childhood: an overview. In: Duncan JR, Byard RW, editors. SIDS sudden infant and early childhood death: The past, the present and future. Adelaide: Adelaide University Press; 2018. p. 51–71.

    Chapter  Google Scholar 

  11. van Deventer B, Rossouw S, du Toit-Prinsloo L. Sudden and unexpected childhood deaths investigated at the Pretoria Medico-Legal Laboratory, South Africa, 2007 - 2011. 2016. https://doi.org/10.7196/SAMJ.2016.v106i10.11028

  12. Grønborg S, Uldall P. Mortality and causes of death in children referred to a tertiary epilepsy center. Eur J Paediatr Neurology. 2014. https://doi.org/10.1016/j.ejpn.2013.08.004.

    Article  Google Scholar 

  13. Sveinsson O, Andersson T, Mattsson P, Carlsson S, Tomson T. Clinical risk factors in SUDEP: a nationwide population-based case-control study. Neurology. 2020. https://doi.org/10.1212/WNL.0000000000008741.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Einarsdottir AB, Sveinsson O, Olafsson E. Sudden unexpected death in epilepsy. a nationwide population-based study. Epilepsia. 2019. https://doi.org/10.1111/epi.16349

  15. Karlovich E, Devinsky O, Brandsoy M, Friedman D. SUDEP among young adults in the San Diego County Medical Examiner Office. Epilepsia. 2020. https://doi.org/10.1111/epi.16443.

    Article  PubMed  Google Scholar 

  16. Kiani R, Tyrer F, Jesu A, Bhaumik S, Gangavati S, Walker G, et al. Mortality from sudden unexpected death in epilepsy (SUDEP) in a cohort of adults with intellectual disability. J Intellect Disabil Res. 2014. https://doi.org/10.1111/jir.12047.

    Article  PubMed  Google Scholar 

  17. Sveinsson O, Andersson T, Carlsson S, Tomson T. The incidence of SUDEP: a nationwide population-based cohort study. Neurology. 2017. https://doi.org/10.1212/WNL.0000000000004094.

    Article  PubMed  Google Scholar 

  18. Sillanpää M, Shinnar S. SUDEP and other causes of mortality in childhood-onset epilepsy. Epilepsy Behav. 2013. https://doi.org/10.1016/j.yebeh.2013.04.016.

    Article  PubMed  Google Scholar 

  19. Verducci C, Hussain F, Donner E, Moseley BD, Buchhalter J, Hesdorffer D, et al. SUDEP in the North American SUDEP registry: the full spectrum of epilepsies. Neurology. 2019. https://doi.org/10.1212/WNL.0000000000007778.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Vlooswijk MCG, Majoie HJM, De Krom MCTFM, Tan IY, Aldenkamp AP. SUDEP in the Netherlands: a retrospective study in a tertiary referral center. Seizure. 2007. https://doi.org/10.1016/j.seizure.2006.11.002

  21. Mu J, Liu L, Zhang Q, et al. Causes of death among people with convulsive epilepsy in rural West China: a prospective study. Neurology. 2011. https://doi.org/10.1212/WNL.0b013e318223c784.

    Article  PubMed  Google Scholar 

  22. Ngugi AK, Bottomley C, Fegan G, Chengo E, Odhiambo R, Bauni E, et al. Premature mortality in active convulsive epilepsy in rural Kenya: causes and associated factors. Neurology. 2014. https://doi.org/10.1212/WNL.0000000000000123.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Shankar R, Jalihal V, Walker M, et al. A community study in Cornwall UK of sudden unexpected death in epilepsy (SUDEP) in a 9-year population sample. Seizure. 2014. https://doi.org/10.1016/j.seizure.2014.02.005.

    Article  PubMed  Google Scholar 

  24. Ryu HU, Hong JP, Han SH, Choi EJ, et al. Seizure frequencies and number of anti-epileptic drugs as risk factors for sudden unexpected death in epilepsy. J Korean Med Sci. 2015. https://doi.org/10.3346/jkms.2015.30.6.788.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pollanen MS, Kodikara S. Sudden unexpected death in epilepsy : a retrospective analysis of 24 adult cases. 2012. https://doi.org/10.1007/s12024-011-9263-4

  26. Opeskin K, Harvey AS, Cordner SM, Berkovic SF. Sudden unexpected death in epilepsy in Victoria. J Clin Neurosci. 2000. https://doi.org/10.1054/jocn.1999.0137.

    Article  PubMed  Google Scholar 

  27. Aurlien D, Larsen JP, Gjerstad L, Taubøll E. Increased risk of sudden unexpected death in epilepsy in females using lamotrigine: a nested, case-control study. Epilepsia. 2012. https://doi.org/10.1111/j.1528-1167.2011.03334.x.

    Article  PubMed  Google Scholar 

  28. Brennan M, Scott S, Bergin P. Sudden unexpected death in epilepsy (SUDEP) in New Zealand: a retrospective review. NZ Med J. 2020;133:65–71.

    Google Scholar 

  29. Melez İE, Arslan MN, Melez DO, Şanli AN, Koç S. Sudden unexpected death in epilepsy: a retrospective autopsy study of 112 epileptic patients. Noro Psikiyatr Ars. 2017. https://doi.org/10.5152/npa.2016.14863

  30. Ge Y, Ding D, Zhang Q, et al. Incidence of sudden unexpected death in epilepsy in community-based cohort in China. Epilepsy Behav. 2017. https://doi.org/10.1016/j.yebeh.2017.08.024.

    Article  PubMed  Google Scholar 

  31. Holst AG, Winkel BG, Risgaard B, Nielsen JB, Rasmussen PV, Haunsø S, et al. Epilepsy and risk of death and sudden unexpected death in the young: a nationwide study. Epilepsia. 2013. https://doi.org/10.1111/epi.12328.

    Article  PubMed  Google Scholar 

  32. Gungor M, Arslan EA, Tezer Filik FI, Saygi S. SUDEP: the first case series in Turkey. Noro Psikiyatr Ars. 2016. https://doi.org/10.5152/npa.2015.7553.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Opeskin K, Berkovic SF. Risk factors for sudden unexpected death in epilepsy: a controlled prospective study based on coroners cases. Seizure. 2003. https://doi.org/10.1016/S1059-1311(02)00352-7.

    Article  PubMed  Google Scholar 

  34. Krexi D, Sheppard MN. Cardiovascular causes of maternal sudden death. Sudden arrhythmic death syndrome is leading cause in UK. Eur J Obstet Gynecol Reprod Biol. 2017. https://doi.org/10.1016/j.ejogrb.2017.03.006

  35. Braggion-Santos MF, Volpe GJ, Pazin-Filho A, Maciel BC, Marin-Neto JA, Schmidt A. Sudden cardiac death in Brazil: a community-based autopsy series (2006–2010). Arq Bras Cardiol. 2014. https://doi.org/10.5935/abc.20140178.

    Article  PubMed  Google Scholar 

  36. Finocchiaro G, Papadakis M, Dhutia H, Cole D, Behr ER, Tome M, et al. Obesity and sudden cardiac death in the young: clinical and pathological insights from a large national registry. Eur J Prev Cardiol. 2018. https://doi.org/10.1177/2047487317751291.

    Article  PubMed  Google Scholar 

  37. Amital H, Glikson M, Burstein M, Afek A, Sinnreich R, Weiss Y, et al. Clinical characteristics of unexpected death among young enlisted military personnel: results of a three-decade retrospective surveillance. Chest. 2004. https://doi.org/10.1378/chest.126.2.528.

    Article  PubMed  Google Scholar 

  38. Allan KS, Morrison LJ, Pinter A, Tu JV, Dorian P. Unexpected high prevalence of cardiovascular disease risk factors and psychiatric disease among young people with sudden cardiac arrest. J Am Heart Assoc. 2019. https://doi.org/10.1161/JAHA.118.010330.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Hellenthal N, Gaertner-Rommel A, Klauke B, Paluszkiewicz L, Stuhr M, Kerner T, et al. Molecular autopsy of sudden unexplained deaths reveals genetic predispositions for cardiac diseases among young forensic cases. Europace. 2017. https://doi.org/10.1093/europace/euw247.

    Article  PubMed  Google Scholar 

  40. Maron BJ, Olivotto I, Spirito P, Casey SA, Bellone P, Gohman TE, et al. Epidemiology of hypertrophic cardiomyopathy–related death. Circulation. 2000. https://doi.org/10.1161/01.cir.102.8.858.

    Article  PubMed  Google Scholar 

  41. Campuzano O, Sanchez-Molero O, Fernandez A, et al. Sudden arrhythmic death during exercise: a post-mortem genetic analysis. Sport Med. 2017. https://doi.org/10.1007/s40279-017-0705-3.

    Article  Google Scholar 

  42. Lewis ME, Lin FC, Nanavati P, Mehta N, Mounsey L, Nwosu A, et al. Estimated incidence and risk factors of sudden unexpected death. Open Heart. 2016. https://doi.org/10.1136/openhrt-2015-000321.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Risgaard B. Sudden cardiac death: a nationwide cohort study among the young. Dan Med J. 2016;63:1–18.

    Google Scholar 

  44. Winkel BG, Holst AG, Theilade J, Kristensen IB, Thomsen JL, Ottesen GL, et al. Nationwide study of sudden cardiac death in persons aged 1–35 years. Eur Heart J. 2011. https://doi.org/10.1093/eurheartj/ehq428.

    Article  PubMed  Google Scholar 

  45. Omerkić E, Baraković F, Kušljugić Z, Prašo M, Poljić A, Bijelic M, et al. Incidence of sudden cardiac death in Zivinice municipality, Bosnia and Herzegovina, during the year 2007. Acta Medica Saliniana. 2009;38:86–90.

    Google Scholar 

  46. Zhang J, Zhou X, Xing Q, et al. Epidemiological investigation of sudden cardiac death in multiethnic Xinjiang Uyghur autonomous region in Northwest China. BMC Public Health. 2019. https://doi.org/10.1186/s12889-019-6435-8.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Sanatani S, Wilson G, Smith CR, Hamilton RM, Williams WG, Adatia I. Sudden unexpected death in children with heart disease. Congenit Heart Dis. 2006. https://doi.org/10.1111/j.1747-0803.2006.00014.x.

    Article  PubMed  Google Scholar 

  48. Chaturvedi M, Satoskar M, Khare MS, Kalgutkar AD. Sudden, unexpected and natural death in young adults of age between 18 and 35 years : a clinicopathological study. Indian J Pathol Microbiol. 2011;54:47–50.

    Article  Google Scholar 

  49. Corrado D, Basso C, Rizzoli G, Schiavon M, Thiene G. Does sports activity enhance the risk of sudden death in adolescents and young adults? J Am Coll Cardiol. 2003. https://doi.org/10.1016/j.jacc.2003.03.002.

    Article  PubMed  Google Scholar 

  50. Nagata M, Ninomiya T, Doi Y, Hata J, Ikeda F, Mukai N, et al. Temporal trends in sudden unexpected death in a general population: the hisayama study. Am Heart J. 2013. https://doi.org/10.1016/j.ahj.2013.02.028.

    Article  PubMed  Google Scholar 

  51. Ågesen FN, Risgaard B, Zachariasardóttir S, et al. Sudden unexpected death caused by stroke: A nationwide study among children and young adults in Denmark. Int J Stroke. 2018. https://doi.org/10.1177/1747493017724625.

    Article  PubMed  Google Scholar 

  52. Dempers J, Van Vuuren RJ. Sudden unexplained death in adults – an approach. Contin Med Educ. 2006;24:116–20.

    Google Scholar 

  53. Shankar R, Cox D, Jalihal V, Brown S, Hanna J, McLean B. Sudden unexpected death in epilepsy (SUDEP): development of a safety checklist. Seizure. 2013. https://doi.org/10.1016/j.seizure.2013.07.014.

    Article  PubMed  Google Scholar 

  54. Burns KM, Bienemann L, Camperlengo L, et al. The sudden death in the young case registry: Collaborating to understand and reduce mortality. Pediatrics. 2017. https://doi.org/10.1542/peds.2016-2757.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Hesdorffer DC, Tomson T, Benn E, Sander JW, Nilsson L, Langan Y, et al. Combined analysis of risk factors for SUDEP. Epilepsia. 2011. https://doi.org/10.1111/j.1528-1167.2010.02952.x.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Harden C, Tomson T, Gloss D, et al. Practice guideline summary: Sudden unexpected death in epilepsy incidence rates and risk factors. Neurology. 2017. https://doi.org/10.1212/wnl.0000000000003685.

    Article  PubMed  Google Scholar 

  57. Maron BJ, Friedman RA, Kligfield P, et al. Assessment of the 12-lead ECG as a screening test for detection of cardiovascular disease in healthy general populations of young people (12–25 years of age) a scientific statement from the American Heart Association and the American College of Cardiology. Circulation. 2014. https://doi.org/10.1161/CIR.0000000000000025.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Farwell D, Gollob MH. Electrical heart disease: Genetic and molecular basis of cardiac arrhythmias in normal structural hearts. Can J Cardiol. 2007. https://doi.org/10.1016/s0828-282x(07)71001-2.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Skinner JR, Crawford J, Smith W, et al. Prospective, population-based long QT molecular autopsy study of postmortem negative sudden death in 1 to 40 year olds. Heart Rhythm. 2011. https://doi.org/10.1016/j.hrthm.2010.11.016.

    Article  PubMed  Google Scholar 

  60. Maron BJ. Sudden death in young athletes. Circulation. 1980;62:218–29.

    CAS  Article  Google Scholar 

  61. Tiemensma M, Burger EH. Sudden and unexpected deaths in an adult population, Cape Town, South Africa, 2001–2005. S Afr Med J. 2012. https://doi.org/10.7196/samj.5363.

    Article  PubMed  Google Scholar 

  62. Berg AT, Nickels K, Wirrell EC, Geerts AT, Callenbach PMC, Arts WF, et al. Mortality risks in new-onset childhood epilepsy. Pediatrics. 2013. https://doi.org/10.1542/peds.2012-3998.

    Article  PubMed  PubMed Central  Google Scholar 

  63. de la Grandmaison GL. Is there progress in the autopsy diagnosis of sudden unexpected death in adults? Forensic Sci Int. 2004;156:138–44.

    Article  Google Scholar 

  64. Manu P, Kane JM, Correll CU. Sudden deaths in psychiatric patients. J Clin Psychiatry. 2011. https://doi.org/10.4088/JCP.10m06244gry.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Gullach AJ, Risgaard B, Lynge TH, Jabbari R, Glinge C, Haunsø S, et al. Sudden death in young persons with uncontrolled asthma - a nationwide cohort study in Denmark. BMC Pulm Med. 2015. https://doi.org/10.1186/s12890-015-0033-z.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Romero JL, Gálvez JLL, Gonzalez LR. Pulmonary embolism as a cause of unexpected sudden death in people aged 1–35 years. CorSalud. 2017;9:215–7.

    Google Scholar 

  67. Konstantinides S, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galiè N, et al. ESC guide-lines on the diagnosis and management of acute pulmonary embolism. Eur Heart J. 2014;35:3033–69.

    CAS  Article  Google Scholar 

  68. Sanchez O, Campuzano O, Fernández-Falgueras A, et al. Natural and undetermined sudden death: Value of post-mortem genetic investigation. PLoS ONE. 2016. https://doi.org/10.1371/journal.pone.0167358.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Dewar L, Alcaide M, Fornika D, Sanatani S, Balachandra T, Morin R, et al. Strategies to improve diagnosis in the investigation of sudden unexpected death in the young (SUDY) in Canada. Can J Cardiol. 2015. https://doi.org/10.1016/j.cjca.2015.07.538.

    Article  Google Scholar 

  70. Semsarian C, Hamilton RM. Key role of the molecular autopsy in sudden unexpected death. Heart Rhythm. 2012. https://doi.org/10.1016/j.hrthm.2011.07.034.

    Article  PubMed  Google Scholar 

  71. Centers for Disease Control and Prevention. Guidelines for death scene investigation of sudden, unexplained infant deaths: Recommendations of the interagency panel on sudden infant death syndrome. Morb Mortal Wkly Rep. 1996;45:1–5.

    Google Scholar 

  72. U.S. Department of Justice. Death Investigation: A Guide for the Scene Investigator. 1999.

  73. Centers for Disease Control and Prevention. Announcements: sudden death in the young registry. Morb Mortal Wkly Rep. 2016. https://doi.org/10.15585/mmwr.mm6512a5

  74. Centers for Disease Control and Prevention. Sudden unexpected infant death and sudden death in the young case registry. 2018. https://www.cdc.gov/sids/pdf/case-registry/SUID-SDY-case-registry-h.pdf. Accessed 10 Mar 2020.

  75. Chugh SS, Reinier K, Teodorescu C, Evanado A, Kehr E, Al Samara M, et al. Epidemiology of sudden cardiac death: clinical and research implications. Prog Cardiovasc Dis. 2008. https://doi.org/10.1016/j.pcad.2008.06.003.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Bennett T, Martin LJ, Heathfield LJ. A retrospective study of death scene investigation practices for sudden unexpected death of infants (SUDI) in Cape Town. South Africa Forensic Sci Med Pathol. 2019. https://doi.org/10.1007/s12024-019-00206-2.

    Article  PubMed  Google Scholar 

  77. Shanley JR, Risch EC, Bonner BL. U.S. child death review programs: assessing progress toward a standard review process. Am J Prev Med. 2010. https://doi.org/10.1016/j.amepre.2010.08.010

Download references

Funding

Postgraduate Publication Incentive, Faculty of Health Sciences, University of Cape Town. The first author received a scholarship from the National Research Foundation of South Africa (Grant number: 122641). The opinions, findings and conclusions or recommendations expressed herein our own, and not representative of the National Research Foundation.

Author information

Authors and Affiliations

Authors

Contributions

Yuvika Vandayar: Methodology, Funding acquisition, Writing—original draft. Laura Jane Heathfield: Conceptualization, Methodology, Visualization, Supervision, Writing – reviewing and editing, Funding acquisition, Project administration.

Corresponding author

Correspondence to Laura Jane Heathfield.

Ethics declarations

Ethics approval

This study received ethics approval from the University of Cape Town, Faculty of Health Sciences Human Research Ethics Committee (HREC REF: 219/2020).

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Conflicts of interest

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 13 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Vandayar, Y., Heathfield, L.J. A review of the causes and risk factors for sudden unexpected death in the young. Forensic Sci Med Pathol 18, 186–196 (2022). https://doi.org/10.1007/s12024-021-00444-3

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12024-021-00444-3

Keywords

  • Sudden unexpected death in young
  • Risk factors
  • Undetermined
  • Cause of death
  • Molecular autopsies
  • Sudden cardiac death