An evaluation of pathologists' application of the diagnostic criteria from the San Diego definition of SIDS and unclassified sudden infant death.

Despite being widely used, few studies have assessed the utility of the San Diego definition of sudden infant death syndrome (SIDS). The purpose of this study was to evaluate pathologists' application of the San Diego definition in all cases of sudden unexpected death in infancy (SUDI) that occurred in Queensland, Australia, between 2010 and 2014. Key coronial documents of 228 cases of SUDI were reviewed independently by three reviewers and classified according to the San Diego definition. Clear guidance regarding the evidentiary threshold for classification and interpretation of the San Diego definition was provided. All reviewers classified cases identically in 202 cases (88.6%). Consensus was achieved on the classification of the remaining 26 deaths following case discussion. After review, 79 cases were classified as SIDS, a one third reduction compared with the original classification, mainly due to a high probability of accidental asphyxia. The number of cases classified as undetermined (USID) almost doubled (75/228, 32.9%), and there was more than a fivefold increase in cases classified as asphyxia (43/228, 18.9%). Natural conditions decreased by approximately one third (21/228, 9.2%). This study demonstrates that with clear guidelines for interpretation, the San Diego definition can be applied reliably, with discrepancies resolved through a process of peer review.

Inconsistent classification of unexplained sudden deaths in infants and children hinders surveillance, prevention and research: recommendations from The 3rd International Congress on Sudden Infant and Child Death.

This report details the proceedings and conclusions from the 3rd International Congress on Unexplained Deaths in Infants and Children, held November 26-27, 2018 at the Radcliffe Institute at Harvard University. The Congress was motivated by the increasing rejection of the diagnosis Sudden Infant Death Syndrome (SIDS) in the medical examiner community, leading to falsely depressed reported SIDS rates and undermining the validity and reliability of the diagnosis, which remains a leading cause of infant and child mortality. We describe the diagnostic shift away from SIDS and the practical issues contributing to it. The Congress was attended by major figures and opinion leaders in this area from countries significantly engaged in this problem. Four categories (International Classification of Diseases (ICD)-11 categories of MH11, MH12, MH14, PB00-PB0Z) were recommended for classification, and explicit definitions and guidance were provided for death certifiers. SIDS was reframed as unexplained sudden death in infancy or SIDS/MH11 to emphasize that either term signifies the lack of explanation following a rigorous investigation. A distinct category for children over the age of 1 was recommended (MH12). Definitions and exclusions were provided for the alternative categories of accidental asphyxia and undetermined. As recommended, unexplained sudden death in infancy or SIDS on a death certificate will code a unique, trackable entity, accurately reflecting the inability to determine a definitive explanation, while satisfying surveillance needs and reliable identification for research efforts. The conclusions will be submitted to the World Health Organization for inclusion in the upcoming ICD-11.

Neuronal apoptosis in the brainstem medulla of sudden unexpected death in infancy (SUDI), and the importance of standardized SUDI classification.

The purpose of this study was to examine the neuronal expression of apoptotic markers in the rostral medulla of a newly characterized dataset of sudden unexpected death in infancy (SUDI), and to determine the impact of diagnostic groupings on these findings and whether they pertain to the intrinsic apoptotic pathway. Immunohistochemical staining was quantified to determine the percentage of neurons positive for active caspase-9 (specific to the intrinsic apoptotic pathway), active caspase-3 (common to the intrinsic and extrinsic apoptotic pathways) and Terminal deoxynucleotidyl transferase mediated dUTP nick-end labelling (TUNEL) (labels DNA fragmentation) in nine nuclei of the rostral medulla. Expression was compared between groups of SUDI infants where the cause of death was initially classified by a forensic pathologist or subsequently after reclassification by an expert panel using the San Diego Criteria. 68 SUDI infants were studied and originally classified as explained SUDI (n = 12), Sudden Infant Death Syndrome (SIDS) (n = 27) and undetermined (n = 29). Reclassification resulted in a decrease in the number of explained SUDI cases to 7 and a decrease in the number of undetermined cases to 4, with a corresponding increase in the number of SIDS cases to 57 (8 SIDS I; 49 SIDS II). The expression of apoptotic markers was similar in explained SUDI and SIDS I infants. However, TUNEL expression was greater in the cuneate (p < 0.001), vestibular (p = 0.01) and hypoglossal (p < 0.001) nuclei and active caspase-3 expression was lower in the arcuate nucleus (p = 0.037) in SIDS II compared to explained Sudden Unexpected Death in Infancy (eSUDI) infants. Compared to SIDS I infants, SIDS II infants had greater TUNEL expression in the dorsal motor nucleus of the vagus (p < 0.01) and greater active caspase-9 expression in the medial and spinal vestibular nuclei (p = <0.01). Changes in apoptotic expression predominated in SIDS II infants. We postulate that these are due to a combination of contributing risk factors including the presence of an upper respiratory tract infection and bed-sharing/co-sleeping. The absence of changes in active caspase-9 expression compared to eSUDI indicates that the intrinsic apoptotic pathway is not upregulated in SIDS.

Brief resolved unexplained event: New diagnosis in infants.

QUESTION: For many years, the term apparent life-threatening event (ALTE) was associated with sudden infant death syndrome, and parents who described an acute event in their infants were sent to the hospital for admission. I understand that for infants new terminology is recommended. What is the current approach to a near-death experience of an infant? ANSWER: A recent clinical practice guideline revised the name and definition of an ALTE to a brief resolved unexplained event (BRUE). The diagnosis of BRUE in infants younger than 1 year of age is made when infants experience 1 of the following BRUE symptoms: a brief episode (ie, less than 1 minute and usually less than 20 to 30 seconds) that is entirely resolved (infant is at baseline), which remains unexplained after the history and physical examination are completed, and includes an event characterized by cyanosis or pallor; absent, decreased, or irregular breathing; hypertonia or hypotonia; or altered responsiveness. Low-risk infants should not be admitted to the hospital and overtesting is discouraged.

Assigning cause for sudden unexpected infant death.

We have reached a conundrum in assigning cause of death for sudden unexpected infant deaths. We summarize the discordant perspectives and approaches and how they have occurred, and recommend a pathway toward improved consistency. This lack of consistency affects pediatricians and other health care professionals, scientific investigators, medical examiners and coroners, law enforcement agencies, families, and support or advocacy groups. We recommend that an interdisciplinary international committee be organized to review current approaches for assigning cause of death, and to identify a consensus strategy for improving consistency. This effort will need to encompass intrinsic risk factors or infant vulnerability in addition to known environmental risk factors including unsafe sleep settings, and must be sufficiently flexible to accommodate a progressively expanding knowledge base.

Reclassification of SIDS cases--a need for adjustment of the San Diego classification?

A study was undertaken reclassifying cases of sudden infant death syndrome (SIDS) taken from two geographically separate locations utilizing the San Diego definition with subclassifications. One hundred twenty-eight infant cases were examined from files at Forensic Science South Australia in Adelaide, SA, Australia over a 7.5-year period from July 1999 to January 2007. Thirty-one cases (24%) had initially been diagnosed as SIDS and 30 (23%) as undetermined while 67 (52%) had an explainable cause of death. After reclassification, the number of SIDS cases had increased to 49 of the 128 cases, now representing 38% of the cases; category IB SIDS constituted 10 (20%) and II SIDS 39 (80%) of the SIDS cases. No cases were classified as IA SIDS. Two hundred eighteen infant cases were identified from the files of the Department of Forensic Medicine, Aarhus University, Denmark over a 16-year period from 1992 to 2007. Eighty-two (38%) were originally diagnosed as SIDS, 128 (59%) with identifiable causes of death, and 8 (4%) as unexplained. After review, 77 (35%) cases were reclassified as SIDS, a decrease of 6%. Twenty (26%) infants were classified as category IB SIDS and 57 (74%) as II SIDS. None of the cases met the criteria for IA SIDS. Problems arose in assessing cases with failure to thrive, fever, and possible asphyxia. Modifications to the San Diego subclassifications might improve the consistency of categorizing these cases.

Application of a classification system focusing on potential asphyxia for cases of sudden unexpected infant death.

Current classification schemes for sudden unexpected infant death (SUID) may not be optimal for capturing scene events that potentially predispose to asphyxia. (1) To compare causes of death in a group of SUID cases assigned by multiple reviewers using our recently published classification scheme for SUID that is based on asphyxial risk at the death scene, and (2) To compare these newly assigned causes of death to that originally assigned by the medical examiners of record who performed the autopsies. Five reviewers independently assigned causes of death for 117 cases of SUID, including 83 originally diagnosed as sudden infant death syndrome (SIDS), accessioned into the San Diego SIDS/SUDC Research Project from the San Diego County Medical Examiner's Office. The diagnostic categories are: A: SIDS; B: Unexplained-Potentially Asphyxia; C: Unexplained-Other Potential Causes of Death; D: Unclassified-Other; E: Unclassified; and F: Known Cause of Death. The reviewers collectively opined that conditions at the death scene contributed to or caused death in 32-50% of all of the 117 cases as well as in 40-59% of the 83 originally diagnosed SIDS cases. Another cause of death was considered plausible in 2-12% of the SIDS cases. Application of this new classification system resulted in 55-69% decrease in SIDS diagnoses. Asphyxia as a potential contributor to, or as the specific cause of death, appears to exist in a large percentage of cases designated as SIDS using other classification schemes. When certifiers use a classification system that focuses upon potential asphyxia in determining the cause of death the incidence of SIDS dramatically declines.

Sudden unexpected death in infancy in Denmark.

BACKGROUND: Incidence of sudden unexpected death in infancy (SUDI) and sudden infant death syndrome (SIDS) differs among studies and non-autopsied cases are difficult to assess. OBJECTIVES: To investigate causes of sudden death in infancy in a nationwide setting. Validate the use of the ICD-10 code for SIDS (R95) in the Danish Cause of Death registry. DESIGN: A retrospective analysis of all infant deaths (< 1 year of age) in Denmark in 2000-2006. All death certificates and autopsy reports were read. RESULTS: We identified 192 SUDI cases (10% of total deaths, 0.42 per 1000 births) with autopsy performed in 87% of cases. In total, 49% of autopsied SUDI cases were defined as SIDS (5% of all deaths, 0.22 per 1000 births); Cardiac cause of death was denoted in 24% of cases. The Danish Cause of Death Registry misclassified 30% of SIDS cases. CONCLUSIONS: A large proportion of infant deaths are SUDI, and the majority of these are caused by cardiac disease or SIDS. Autopsy is not always performed and valuable information is subsequently lost. Cause of Death registry data is not accurate in describing SIDS.

Use of child death review to inform sudden unexplained infant deaths occurring in a large urban setting.

OBJECTIVE: To illustrate the benefits and utility of the child death review (CDR) reporting system when examining risk factors associated with infant death occurring within two subgroups of sudden unexpected infant deaths (SUID)-unintentional suffocation and sudden infant death syndrome (SIDS)-in a large urban county in Wisconsin. DESIGN: Retrospective CDR data were analysed, 2007-2008, for Milwaukee County, Wisconsin. PATIENTS OR SUBJECTS: Unintentional suffocation and SIDS infant deaths under 1 year of age in Milwaukee County, Wisconsin, 2007-2008, with a CDR record indicating a death in a sleep environment. Main outcome measure Study examined demographic characteristics, bed-sharing, incident sleep location, position of child when put to sleep, position of child when found, child's usual sleep place, crib in home, and other objects found in sleep environment. RESULTS: Unintentional suffocation (n=11) and SIDS (n=40) classified deaths with CDR data made up 18% (51/283) of all infant deaths in Milwaukee County from 2007 to 2008. The majority of infants who died of unintentional suffocation (n=9, 81.8%) or SIDS (n=26, 65.0%) were black and under the age of 3 months. Bed-sharing was involved in most of the unintentional suffocation deaths (n=10, 90.9%) and the SIDS deaths (n=28, 70.0%). All unintentional suffocation deaths (n=11, 100%) and the majority of SIDS deaths (n=31, 77.5%) took place in a non-crib sleeping environment. CONCLUSIONS: The study demonstrates how CDR provides enhanced documentation of risk factors to help steer prevention efforts regarding SUID deaths in a community and reaffirms infants in an unsafe sleep environment have an increased risk of death.

Using death certificates to characterize sudden infant death syndrome (SIDS): opportunities and limitations.

OBJECTIVE: To examine cause-of-death terminology written on death certificates for sudden infant death syndrome (SIDS) and to determine the adequacy of this text data in more fully describing circumstances potentially contributing to SIDS deaths. STUDY DESIGN: With 2003 and 2004 US mortality files, we analyzed all deaths that were assigned the underlying cause-of-death code for SIDS (R95). With the terminology written on the death certificates, we grouped cases into SIDS-related cause-of-death subcategories and then assessed the percentage of cases in each subcategory with contributory or possibly causal factors described on the certificate. RESULTS: Of the 4408 SIDS-coded deaths, we subcategorized 67.2% as "SIDS" and 11.0% as "sudden unexplained (or unexpected) infant death." The terms "probable SIDS" (2.8%) and "consistent with SIDS" (4.6%) were found less frequently. Of those death certificates that described additional factors, "bedsharing or unsafe sleep environment" was mentioned approximately 80% of the time. Most records (79.4%) did not mention any additional factors. CONCLUSION: Our death certificate analysis of the cause-of-death terminology provided a unique opportunity to more accurately characterize SIDS-coded deaths. However, the death certificate was still limited in its ability to more fully describe the circumstances leading to SIDS death, indicating the need for a more comprehensive source of SIDS data, such as a case registry.

Statewide systematic evaluation of sudden, unexpected infant death classification: results from a national pilot project.

The Centers for Disease Control and Prevention funded seven states, including Kentucky, to clarify statewide death certification practices in sudden, unexpected infant death and compare state performances with national expectations. Accurate assignment of the cause and manner of death in cases of sudden, unexpected infant death is critical for accurate vital statistics data to direct limited resources to appropriate targets, and to implement optimal and safe risk reduction strategies. The primary objectives are to (1) Compare SUID death certifications recommended by the KY medical examiners with the stated cause of death text field on the hard copy death electronic death certificates and (2) Compare KY and national SUID rates. Causes of death for SUID cases recommended by the medical examiners and those appearing on the hard copy and electronic death certificates in KY were collected retrospectively for 2004 and 2005. Medical examiner recommendations were based upon a classification scheme devised by them in 2003. Coroners hard copy death certificates and the cause of death rates in KY were compared to those occurring nationally. Eleven percent of infants dying suddenly and unexpectedly did not undergo autopsy during the study interval. The KY 2003 classification scheme for SIDS is at variance with the NICHD and San Diego SIDS definitions. Significant differences in causes of death recommended by medical examiners and those appearing on the hard copy and electronic death certificates were identified. SIDS rates increased in KY in contrast to decreasing rates nationally. Nationwide adoption of a widely used SIDS definition, such as that proposed in San Diego in 2004 as well as legislation by states to ensure autopsy in all cases of sudden unexpected infant death are recommended. Medical examiners' recommendations for cause of death should appear on death certificates. Multidisciplinary pediatric death review teams prospectively evaluating cases before death certification is recommended. Research into other jurisdictions death certification process is encouraged.

A practical classification schema incorporating consideration of possible asphyxia in cases of sudden unexpected infant death.

Although the rate of the sudden infant death syndrome (SIDS) has decreased over the last two decades, medical examiners and coroners are increasingly unwilling to use the SIDS diagnosis, particularly when there is an unsafe sleeping environment that might pose a risk for asphyxia. In order to reliably classify the infant deaths studied in a research setting in the mixed ancestory population in Cape Town, South Africa, we tested a classification system devised by us that incorporates the uncertainty of asphyxial risks at an infant death scene. We classified sudden infant deaths as: A) SIDS (where only a trivial potential for an overt asphyxial event existed); B) Unclassified-Possibly Asphyxial-Related (when any potential for an asphyxial death existed); C) Unclassified-Non-Asphyxial-Related (e.g., hyperthermia); D) Unclassified-No autopsy and/or death scene investigation; and E) Known Cause of Death. Ten infant deaths were classified according to the proposed schema as: SIDS, n = 2; Unclassified-Possibly Asphyxial-Related, n = 4; and Known Cause, n = 4. A conventional schema categorized the deaths as 6 cases, SIDS, and 4 cases, Known Cause, indicating that 4/6 (67%) of deaths previously classified as SIDS are considered related importantly to asphyxia and warrant their own subgroup. This new classification schema applies a simpler, more qualitative approach to asphyxial risk in infant deaths. It also allows us to test hypotheses about the role of asphyxia in sudden infant deaths, such as in brainstem defects in a range of asphyxial challenges.

Continuing major inconsistencies in the classification of unexpected infant deaths.

The classification of the cause of unexpected infant deaths by both pathologists and researchers may be quite inconsistent. For example, if an infant is found lying face down on soft bedding the death may still be certified as 'sudden infant death syndrome (SIDS)', 'accidental suffocation', 'undetermined', 'unclassified sudden infant death (USID)', or 'sudden unexpected death in infancy (SUDI)'. As the San Diego definition of SIDS does not appear to be rigorously or consistently applied, clarifying 'mechanical asphyxia not determined with certainty' may help to more clearly separate SIDS from USID. Including a classification algorithm with the definition may also help to better define unsafe sleep factors and suffocation. This commentary reviews the current situation with regard to classifying these deaths and concludes that the absence of diagnostic pathological markers with conflicting classification systems has led to idiosyncratic certification practices.

Impact of changes in infant death classification on the diagnosis of sudden infant death syndrome.

This study evaluates the hypothesis that a decline in sudden infant death syndrome in Minnesota is associated with increases in other categories of sudden unexpected infant death. Matched birth and death certificates, autopsy reports, and home visit questionnaires were reviewed for 722 sudden unexpected infant deaths that occurred from January 1, 1996 through December 31, 2002. Descriptive data and cause of death were recorded. Cause of death was compared for 2 periods: early (1996-1998) and late (2000-2002). The age of the infant at death, sex, race, and infant death rates were similar between the 2 periods ( P = .637). Sudden infant death syndrome declined by 50.1% (P < .001). Overlay deaths increased 235.5% (P < .01). Asphyxia related deaths increased 259.6% (P < .001). Injury-related deaths increased 840.0% (P < .001). A decline in sudden infant death syndrome in Minnesota was associated with increased deaths in categories that are asphyxial in nature and are potentially preventable.

National and State Trends in Sudden Unexpected Infant Death: 1990-2015.

BACKGROUND: Sharp declines in sudden unexpected infant death (SUID) in the 1990s and a diagnostic shift from sudden infant death syndrome (SIDS) to unknown cause and accidental suffocation and strangulation in bed (ASSB) in 1999-2001 have been documented. We examined trends in SUID and SIDS, unknown cause, and ASSB from 1990 to 2015 and compared state-specific SUID rates to identify significant trends that may be used to inform SUID prevention efforts. METHODS: We used data from US mortality files to evaluate national and state-specific SUID rates (deaths per 100 000 live births) for 1990-2015. SUID included infants with an underlying cause of death, SIDS, unknown cause, or ASSB. To examine overall US rates for SUID and SUID subtypes, we calculated the percent change by fitting Poisson regression models. We report state differences in SUID and compared state-specific rates from 2000-2002 to 2013-2015 by calculating the percent change. RESULTS: SUID rates declined from 154.6 per 100 000 live births in 1990 to 92.4 in 2015, declining 44.6% from 1990 to 1998 and 7% from 1999 to 2015. From 1999 to 2015, SIDS rates decreased 35.8%, ASSB rates increased 183.8%, and there was no significant change in unknown cause rates. SUID trends among states varied widely from 41.5 to 184.3 in 2000-2002 and from 33.2 to 202.2 in 2013-2015. CONCLUSIONS: Reductions in SUID rates since 1999 have been minimal, and wide variations in state-specific rates remain. States with significant declines in SUID rates might have SUID risk-reduction programs that could serve as models for other states.