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

Marco M Hefti; Hannah C Kinney; Jane B Cryan; Elisabeth A Haas; Amy E Chadwick; Laura A Crandall; Felicia L Trachtenberg; Dawna D Armstrong; Marjorie Grafe; Henry F Krous

doi:10.1007/s12024-015-9724-2

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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

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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

Marco M Hefti, Hannah C Kinney, Jane B Cryan, Elisabeth A Haas, Amy E Chadwick, Laura A Crandall, Felicia L Trachtenberg, Dawna D Armstrong, Marjorie Grafe and Henry F Krous

Forensic science, medicine, and pathology, Vol.12(1), pp.4-13

03/2016

DOI: 10.1007/s12024-015-9724-2

PMCID: PMC4752958

PMID: 26782961

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Abstract

The purpose of this study was to determine the major subcategories and clinicopathologic features of sudden unexpected death in young children in a large retrospective cohort, and to confirm the association of sudden unexplained death in children (abbreviated by us for unexplained deaths as SUDC) with hippocampal pathology and/or febrile seizures. We undertook analysis of a retrospective cohort of 151 cases, of which 80% (121/151) were subclassified as SUDC, 11% (16/151) as explained, 7% (10/151) as undetermined, and 3% (4/151) as seizure-related. There were no significant differences between SUDC and explained cases in postnatal, gestational, or postconceptional age, frequency of preterm birth, gender, race, or organ weights. In contrast, 96.7% (117/121) of the SUDC group were discovered during a sleep period compared to 53.3% (8/15) of the explained group (p < 0.001), and 48.8% (59/121) of the SUDC cases had a personal and/or family history of febrile seizures compared to 6.7% (1/15) of the explained group (p < 0.001). Of the explained deaths, 56% (9/16) were subclassified as infection, 31% (5/16) cardiac, 6% (1/16) accidental, and 6% (1/16) metabolic. Two of the three cases specifically tested for cardiac channelopathies at autopsy based upon clinical indications had genetic variants in cardiac genes, one of uncertain significance. Bacterial cultures at autopsy typically revealed organisms interpreted as contaminants. Two of the four seizure-related deaths were witnessed, with two of the brains from these cases showing generalized malformations. Hippocampal anomalies, including a specific combination we termed hippocampal maldevelopment associated with sudden death, were found in almost 50% (40/83) of the SUDC and undetermined cases in which hippocampal sections were available. This study highlights the key role for the hippocampus, febrile seizures, and sleep in SUDC pathophysiology. It also demonstrates the role of known predisposing conditions such as cardiac channelopathies and infections in causing sudden unexpected death in childhood, and the need for improved ancillary testing and protective strategies in these cases, even when the cause of death is established at autopsy.

Death, Sudden - etiology

Seizures, Febrile - mortality

Humans

Child, Preschool

Fever - mortality

Infant

Infection - mortality

Male

Hippocampus - pathology

Heart Diseases - congenital

Heart Diseases - mortality

Sleep

Metabolic Diseases - mortality

Channelopathies - mortality

Female

Forensic Pathology

Retrospective Studies

Hippocampus - abnormalities

Child

Accidents - mortality

Cohort Studies

Details

Title: Subtitle: 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
Creators: Marco M Hefti - Division of Neuropathology, Department of Pathology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY, 10029, USA. marco.hefti@mountsinai.org
Hannah C Kinney - Department of Pathology, Boston Children's Hospital, Boston, MA, USA
Jane B Cryan - Division of Neuropathology, Beaumont Hospital, Beaumont Road, Dublin 9, Ireland
Elisabeth A Haas - Department of Pathology, Rady Children's Hospital-San Diego, San Diego, CA, USA
Amy E Chadwick - Department of Pathology, Rady Children's Hospital-San Diego, San Diego, CA, USA
Laura A Crandall - Department of Neurology, NYU Langone Medical Center, New York, NY, USA
Felicia L Trachtenberg - New England Research Institutes, Watertown, MA, USA
Dawna D Armstrong - Department of Pathology, Emeritus, Baylor College of Medicine, Houston, TX, USA
Marjorie Grafe - Department of Pathology, Oregon Health and Science University, Portland, OR, USA
Henry F Krous - Department of Pediatrics, UCSD School of Medicine, La Jolla, CA, USA
Resource Type: Journal article
Publication Details: Forensic science, medicine, and pathology, Vol.12(1), pp.4-13
DOI: 10.1007/s12024-015-9724-2
PMID: 26782961
PMCID: PMC4752958
NLM abbreviation: Forensic Sci Med Pathol
ISSN: 1547-769X
eISSN: 1556-2891
Publisher: United States
Grant note: P01 HD036379 / NICHD NIH HHS
Language: English
Date published: 03/2016
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984047658302771

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