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40 years!
Last updated:
4/23/2024
Years published: 2010, 2017, 2020, 2024
NORD gratefully acknowledges Laura Gould, MSc, Research Assistant Professor, NYU Grossman School of Medicine and Orrin Devinsky, MD, Professor, Departments of Neurology, Neurosurgery and Psychiatry, Chief of Service, NYU Epilepsy Service, for assistance in the preparation of this report.
Summary
Sudden unexplained death in childhood (SUDC) is the sudden death of a child 12 months of age or older that remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene and review of the clinical history. These deaths elude our scientific understanding. SUDC cannot be predicted or prevented at this time. According to the U.S. Centers for Disease Control and Prevention, in 2021, 450 children between the ages of 1-18 years died suddenly without a clear cause of death determined. Most of these children were toddlers, aged 1-4 years (55%); an incidence of 1.6 deaths per 100,000 toddler aged children. Research and awareness of SUDC remains limited.
Most deaths due to SUDC were in previously healthy toddlers, aged 1 to 4 years. Characteristics associated with SUDC are male sex, sleeping in the prone position and winter season. These children were in good health prior to death or had mild symptoms of illness such as cold symptoms or fever. Some children who died from SUDC had a history of febrile seizures or a family history of febrile seizures.
A febrile seizure is a convulsion in a child that may be caused by a spike in body temperature, often from an infection. Children aged 3 months to 5 or 6 years may have febrile seizures and they occur in ~3% of the general population. There is a slight tendency for them to run in families. If a child’s parents, brothers or sisters, or other close relatives have had febrile seizures, the child is a bit more likely to have them. In comparison, in about 30% of deaths from SUDC, there is a history of febrile seizures which is a 10-fold increase.
By definition, the cause(s) of SUDC are unknown. However, due to the lack of standardizations of death investigations, it is important that doctors rule out previously undiagnosed cardiac disorders affecting the heart rhythm that are often due to genetic abnormalities, infections and neurological conditions.
The history of febrile seizures in some children with SUDC and their family members means there is a possible association with sudden unexpected death in epilepsy (SUDEP). SUDEP is defined as the sudden, unexpected, non-traumatic, non-drowning death in an individual with epilepsy, witnessed or unwitnessed, in which the postmortem examination does not reveal an anatomical or toxicological cause for the death. Most children who had a SUDEP death that was witnessed had a terminal convulsion called a tonic-clonic seizure. Rare video analyses from crib cameras of SUDC showed convulsive seizures immediately before death, so seizure related deaths may be more common than medical history suggests.
Examinations of the brains in a subset of children after SUDC reveal subtle findings of an area deep in the temporal lobe called the hippocampus. It is unknown whether these are a cause of seizures, a result of past seizures, are a normal variant in development and whether they have a direct association with the death. Such findings are also common in explained deaths. Recent proteomic research identifies some differences in brain tissue from SUDC (with and without febrile seizures) and explained deaths.
Children who die of SUDC are generally toddlers (55%), between 1 and 4 years of age, but older children can also die of SUDC. According to the CDC, non-Hispanic black/African American children have a >2-fold risk of SUDC versus non-Hispanic white, Asian or Pacific Islander and American Indian/Alaska Native children. Health disparities may also play a role in this distribution. Nearly 90% are born full-term and nearly half are first born.
SUDC is not a diagnosis but a category of death. SUDC describes the sudden death of a child greater than 12 months of age that has undergone a thorough investigation and does not reveal evidence of an unnatural death. Death investigations also vary widely and therefore the extent to which known causes of death have been ruled should be reviewed.
In 2019, the National Association of Medical Examiners Panel on Sudden Unexpected Death in Pediatrics published national guidelines regarding the investigation, certification and family needs associated with sudden death in children:
Unexplained Pediatric Deaths: Investigation, Certification and Family Needs (https://www.ncbi.nlm.nih.gov/books/NBK577018/ )
Clinical Testing and Work Up
The investigation of the child’s death should be comprehensive including investigation of the scene where the child was found unresponsive, interviews with caregivers, a review of the child’s medical history and their family medical history and a complete autopsy with other testing as clinically indicated.
SUDC is a multidisciplinary problem and requires coordination among the professionals involved to effectively investigate a case of SUDC and provide appropriate communication and effective medical follow-up for family members. Families need effective communication regarding the ramifications of the child’s final cause of death and what screening recommendations are appropriate to consider. Asking the family’s primary care physician to collaborate with the medical examiner or coroner who performed the death investigation can be an excellent way to streamline communication in an emotionally traumatic and confusing situation.
Since genetic disorders can contribute to sudden death, evaluation of family members is indicated. This can include but is not limited to inherited heart arrhythmia seizure disorders and metabolic disorders. It is valuable to confirm a family diagnosis and assess the risk in the living family members following an unexplained death. Clinical evaluation of family members following a sudden death may identify other affected members. First degree relatives (parents and siblings of the person who has died) should speak to their primary physician for a referral to a cardiologist with expertise in electrophysiology and special training to evaluate genetic cardiac disorders and other referrals as clinically indicated.
SUDC is a category of death and diagnosis of exclusion which means that it is only determined after the death and thorough investigation of the clinical history, scene of death and autopsy reveal no other cause. Because the determination of SUDC is made after death, there is no treatment.
SUDC Registry and Research Collaborative (SUDCRRC) at NYU Langone Health
The purpose of the SUDCRRC is to increase the understanding of the characteristics, circumstances, medical histories and pathologies of children from ages 1 months through 18 years who have died suddenly and unexpectedly, and in some instances, without explanation. The SUDC Registry and Research Collaborative analyzes cases of sudden unexpected deaths in these children to understand risk factors and causes (including genetic studies on the child who died and both parents) and develop preventative measures. The SUDCRRC is available to review cases for evaluation through Oct 2028. For more information: www.sudcrrc.org
North American SUDEP Registry
NYU Comprehensive Epilepsy Center
223 East 34th St New York, NY 10016
P: 855-432-8555
http://sudepregistry.org/
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, in the main, contact:
www.centerwatch.com
For more information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
Centers for Disease Control and Prevention, National Center for Health Statistics. National Vital Statistics System, Mortality 2018-2021 on CDC WONDER Online Database, released in 2021. Data are from the Multiple Cause of Death Files, 2018-2021, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. https://wonder.cdc.gov/ucd-icd10-expanded.html accessed April 9, 2024.
Gould L, Reid CA, Rodriguez AJ, Devinsky O; for SUDC Video Working Group. Video analyses of sudden unexplained deaths in toddlers. Neurology. 2024;102(3):e208038. doi:10.1212/WNL.0000000000208038
Gould L, Delavale V, Plovnick C, Wisniewski T, Devinsky O. Are brief febrile seizures benign? A systematic review and narrative synthesis. Epilepsia. 2023;64(10):2539-2549. doi:10.1111/epi.17720
Leitner DF, William C, Faustin A, et al. Proteomic differences in hippocampus and cortex of sudden unexplained death in childhood. Acta Neuropathol. 2022;143(5):585-599. doi:10.1007/s00401-022-02414-7
Halvorsen M, Gould L, Wang X, et al. De novo mutations in childhood cases of sudden unexplained death that disrupt intracellular Ca2+ regulation. Proc Natl Acad Sci U S A. 2021;118(52):e2115140118. doi:10.1073/pnas.2115140118
Leitner DF, McGuone D, William C, et al. Blinded review of hippocampal neuropathology in sudden unexplained death in childhood reveals inconsistent observations and similarities to explained paediatric deaths. Neuropathol Appl Neurobiol. 2022;48(1):e12746. doi:10.1111/nan.12746
Harowitz J, Crandall L, McGuone D, Devinsky O. Seizure-related deaths in children: The expanding spectrum. Epilepsia. 2021 Feb 14. doi: 10.1111/epi.16833. Epub ahead of print. PMID: 33586153.
Duncan JR, Byard RW. Determining the prevalence of sudden and unexplained death in childhood (SUDC): a national Australian perspective. Int J Legal Med. 2021 May;135(3):793-800. doi: 10.1007/s00414-020-02445-3. Epub 2020 Oct 23. PMID: 33097983.
Crandall LG, Lee JH, Friedman D, et al. Evaluation of concordance between original death certifications and an expert panel process in the determination of sudden unexplained death in childhood. JAMA Netw Open. 2020;3(10):e2023262. Published 2020 Oct 1. doi:10.1001/jamanetworkopen.2020.23262
McGuone D, Crandall LG, Devinsky O. Sudden unexplained death in childhood: a neuropathology review. Front Neurol. 2020;11:582051. Published 2020 Oct 16. doi:10.3389/fneur.2020.582051
McGuone D, Leitner D, William C, et al. Neuropathologic changes in sudden unexplained death in childhood. J Neuropathol Exp Neurol. 2020;79(3):336-346. doi:10.1093/jnen/nlz136
Phoon CKL, Halvorsen M, Goldstein DB, et al. Sudden unexpected death in asymptomatic infants due to PPA2 variants. Mol Genet Genomic Med. 2020;8(1):e1008. doi:10.1002/mgg3.1008
The National Association of Medical Examiners’ Panel on Sudden Unexpected Death in Pediatrics, Bundock EA, Corey TS, et al., eds. Unexplained Pediatric Deaths: Investigation, Certification, and Family Needs. San Diego (CA): Academic Forensic Pathology International; 2019.
Hoch MJ, Bruno MT, Faustin A, Cruz N, Mogilner AY, Crandall L, Wisniewski T, Devinsky O, Shepherd TM. 3T MRI whole-brain microscopy discrimination of subcortical anatomy, Part 2: basal forebrain. AJNR Am J Neuroradiol. 2019 Jul;40(7):1095-1105. doi:10.3174/ajnr.A6088. Epub 2019 Jun 13.PMID: 31196861
Hoch MJ, Bruno MT, Faustin A, Cruz N, Crandall L, Wisniewski T, Devinsky O, Shepherd TM.3T MRI whole-brain microscopy discrimination of subcortical anatomy, Part 1: brain stem. AJNR Am J Neuroradiol. 2019 Mar;40(3):401-407. doi: 10.3174/ajnr.A5956. Epub 2019 Jan 31.PMID: 30705073
Crandall LG, Lee J, Stainman R, Friedman D, Devinsky O. Sudden deaths in children: potential role of febrile seizures and other risk factors, JAMA Open Network, April 2019.
Duncan JR, Byard RW, eds. SIDS Sudden Infant and Early Childhood Death: The Past, the Present and the Future. Adelaide (AU): University of Adelaide Press; May 2018.
Crandall L, Devinsky O. Sudden unexplained death in children. The Lancet Child and Adolescent Health, Vol 1, September 2017.
Crandall LG. Inexplicable Child Deaths: Medicolegal Death Investigation Resources from the SUDC Foundation and the SUDC Registry and Research Collaborative. Acad Forensic Pathol. 2017;7(2):xxiv-xxvi. doi:10.1177/192536211700700205
Ackerman MJ, Andrew TA, Baker AM, et al. An Association of Hippocampal Malformations and Sudden Death? We Need More Data. Forensic Sci Med Pathol. 2016;12(2):229-231. doi:10.1007/s12024-016-9765-1
Halvorsen M, Petrovski S, Shellhaas R, Tang Y, Crandall L, Goldstein D, Devinsky O. Mosaic mutations in early-onset genetic diseases Genet Med. 2016 Jul;18(7):746-9. doi: 10.1038/gim.2015.155. Epub 2015 Dec 30. PMID: 26716362 Free PMC Article available
Hefti MM, Cryan JB, Haas EA, Chadwick AE, Crandall LA, Trachtenberg FL, Armstrong DD, Grafe M, Krous HF, Kinney HC. Hippocampal malformation associated with sudden death in early childhood: a neuropathologic study: Part 2 of the investigations of The San Diego SUDC Research Project, Forensic Sci Med Pathol. 2016 Mar;12(1):14-25. doi: 10.1007/s12024-015-9731-3. Epub 2016 Jan 19. PMID: 26782962
Hefti MM, Kinney HC, Cryan JB, et al. Sudden unexpected death in early childhood: general observations in a series of 151 cases: Part 1 of the investigations of the San Diego SUDC Research Project. Forensic Sci Med Pathol. 2016;12(1):4-13. doi:10.1007/s12024-015-9724-2
Bagnall RD, Weintraub RG, Ingles J, et al. A Prospective study of sudden cardiac death among children and young adults. N Engl J Med. 2016;374(25):2441-2452. doi:10.1056/NEJMoa1510687
Hesdorffer DC, Crandall LA, Friedman D, Devinsky O; Sudden unexplained death in childhood: A comparison of cases with and without a febrile seizure history. Epilepsia. 2015 Aug;56(8):1294-300. doi: 10.1111/epi.13066. Epub 2015 Jun 29
Rudd R, Capizzi Marain L, Crandall L. To hold or not to hold: medicolegal death investigation practices during unexpected child death investigations and the experiences of next of kin. Am J Forensic Med Pathol. 2014 Jun;35(2):132-9.
Rudd, R. & D’Andrea, L. Professional support requirements and grief interventions for parents bereaved by an unexplained death at different time periods in the grief process. International Journal of Emergency Mental Health and Human Resilience. 2013;15(1), 51-68.
Treacy A, Cryan J, McGarvey C, Devaney D, Matthews TG. Sudden unexplained death in childhood. An audit of the quality of autopsy reporting. Ir Med J. 2013 Mar;106(3):70-2. PMID: 23951973
McGarvey C, O’Regan M, Cryan J, Treacy A, Hamilton K, Devaney D and Matthews T. Sudden unexplained death in childhood (1–4 years) in Ireland: an epidemiological profile and comparison with SIDS Arch Dis Child 2012 Aug;97(8):692-7. doi: 10.1136/archdischild-2011-301393. Epub 2012 Jun 9.
Holm IA, Poduri A, Crandall L, et al. Inheritance of febrile seizures in sudden unexplained death in toddlers. Pediatr Neurol. 2012;46(4):235-239. doi:10.1016/j.pediatrneurol.2012.02.007
Baker AM, Crandall L. To hold or not to hold. Forensic Sci Med Pathol. 2009;5(4):321-323. doi:10.1007/s12024-009-9123-7
Kinney HC, Chadwick AE, Crandall LA, et al. Sudden death, febrile seizures, and hippocampal and temporal lobe maldevelopment in toddlers: a new entity. Pediatr Dev Pathol. 2009;12(6):455-463. doi:10.2350/08-09-0542.1
Krous HF, Wahl C, Chadwick AE. Sudden unexpected death in a toddler with Williams syndrome. Forensic Sci Med Pathol. 2008;4(4):240-5. doi: 10.1007/s12024-008-9035-y. Epub 2008 Apr 4.
Kinney HC, Armstrong DL, Chadwick AE, et al. Sudden death in toddlers associated with developmental abnormalities of the hippocampus: a report of five cases. Pediatr Dev Pathol. 2007;10:208-223.
Krous H, Chadwick A, Miller D, Crandall L, Kinney H. Sudden death in toddlers with viral meningitis, massive cerebral edema, and neurogenic pulmonary edema and hemorrhage: Report of two cases. Pediatr Dev Pathol. 2007;10:463-469.
Masoumi H, Kinney HC, Chadwick AE, Rubio A, Krous HF. Sudden unexpected death in childhood associated with cardiac rhabdomyoma, involuting adrenal ganglioneuroma, and megalencephaly: another expression of tuberous sclerosis? Pediatr Dev Pathol. 2007;10:129-133.
Krous HF, Chadwick AE, Crandall L, Nadeau-Manning. Sudden unexpected death in childhood: A report of 50 Cases. Pediatric Dev Pathol. 2005;8:307-319.
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