Sudden Unexpected Death Research Articles

Abstract 4116148: Seasonal Variation of Unexpected Sudden Cardiac Death

Introduction: Data on the occurrence of unexpected sudden cardiac death (SCD) in different seasons are scanty and needs further exploration. Methods: Consecutive series of all unexpected SCD victims (n=5,869) who underwent medico-legal autopsy obligated by the Finnish law were prospectively collected from the geographically defined area in the Northern Finland during a twenty years period from 1998 to 2017. The seasonal variation of SCD and its possible causes were assessed in this large SCD victim cohort. Results: Unexpected SCD occurred more frequently during the first quarter of a year (from January to March) than during the other quarters (Figure 1). The occurrence of SCD during the twenty years follow-up was 4.5±0.24 during the first quarter of the year per month and 3.9±0.12 during the other quarters of the year per month on average (SCDs during the quarter of a year per month on average per 100,000 inhabitants per year, p<0.001) (Figure 2). The weather was colder during the first quarter of the year (average temperature -9.1 degrees centigrade) than during the other quarters (average temperature +5.7 degrees centigrade). The snow cover was the largest during the first quarter of the year. Conclusion: Unexpected SCD occurred more commonly during the first quarter of a year (from January to March) than during the other quarters (from April to December). Cold weather, and perhaps winter-time physical activities in cold environment such as removal of snow, may have contributed to the increased occurrence of SCD during the first quarter of the year.

Parental obesity and the risk of sudden unexpected infant death.

To clarify the possible role of accidental asphyxiation/suffocation for infants in shared sleeping situations. As it has recently been shown that there is an association between maternal obesity and sudden unexpected infant death (SUID) an index was calculated by dividing parental body mass index (BMI) by the shared sleeping surface area. A much higher index was derived for an obese individual on a narrow sleeping area such as a sofa (50) compared to a thin adult on a queen-sized mattress (5). The index may be a way of semi-quantitating high, and low, risk shared sleeping situations.

Mortality in older adults with epilepsy: An understudied entity.

Despite the recognition of Sudden Unexpected Death in Epilepsy (SUDEP) and other risks of premature mortality in people with epilepsy (PWE), mortality in older PWE remains an understudied entity. This review provides a comprehensive overview of the multifaceted causes of premature mortality in older adults with epilepsy and emphasizes the need for targeted interventions to reduce mortality and enhance the quality of life in this vulnerable population. It underscores the heightened prevalence of epilepsy among older adults and the interplay of intrinsic and extrinsic factors contributing to their mortality. Further, this paper delves into the nuances of diagnosing SUDEP in older adults and the underestimation of its incidence due to misclassification and lack of standardized protocols. Factors such as frailty, comorbidities, and the bidirectional relationship between epilepsy and conditions such as dementia and stroke further compound the mortality risks. Key factors, including status epilepticus, comorbid conditions (such as cardiovascular diseases, cerebrovascular events, and neurodegenerative disorders), and external causes like accidents, falls, and suicide, are discussed. It also examines the implications of anti-seizure medications, particularly polypharmacy, and their adverse effects on this population. Future directions include implementing enhanced diagnostic protocols, developing treatment plans, and integrating real-time monitoring technologies to reduce the risk of sudden death and multifaceted premature mortality in this patient population. Increasing awareness among healthcare providers and families about the risks and management of epilepsy in older adults, along with fostering collaborative research efforts, is essential to improve mortality outcomes. PLAIN LANGUAGE SUMMARY: There is a heightened risk of mortality in older people with epilepsy due to many causes unique to their population. Despite the risk, Sudden Unexpected Death in Epilepsy and early mortality in older adults with epilepsy are underestimated. Unique contributing factors include comorbid conditions like dementia, stroke, and frailty, adverse effects from polypharmacy, and increased risks of cardiovascular complications and external injuries such as falls and suicide. A careful consideration of all these factors can help mitigate the mortality in older adults with epilepsy.

Maternal Obesity and Sudden Unexpected Infant Death.

Maternal Obesity and Sudden Unexpected Infant Death.

Complex Febrile Seizures: Usual and the Unusual.

Febrile seizures account for 2 to 14% of all childhood seizures, and one-third of febrile seizures are complex febrile seizures. Despite this, there is a lack of clinical equipoise in the diagnosis and management of complex febrile seizures and this results in significant practice variability amongst physicians. Although febrile seizures are generally noted to be benign phenomenon, complex febrile seizures carry the risk of subsequent epilepsy. Furthermore, long-term neurodevelopmental sequelae have been observed in some cohorts. The presence of both simple and complex febrile seizures have also been documented in sudden unexpected death in childhood cohorts, and there may be similarities in the underlying pathophysiology to sudden unexpected death in epilepsy. Finally, in some cases the presence of complex febrile seizures may herald the onset of a devastating developmental and epileptic encephalopathy (i.e., Dravet syndrome) or Febrile-Infection Related Epilepsy Syndrome (FIRES). In this narrative review the authors explore the current state of management of complex febrile seizures, their neurological sequelae and morbidity as well as rare epilepsy syndromes and conditions associated with them.

Ictal asystole is a rare complication of epilepsy

Ictal bradyarrhythmia (IB) and ictal asystole (IA) are rare complications of epilepsy. Onset latency of IB/IA implicates central nervous parasympathetic pathways, causing asystole, subsequent cerebral hypoxaemia, and potentially inducing a paradoxal, therapeutic effect by terminating both the seizure and the IA. This is a case report of a 68-year-old woman with mesial temporal lobe epilepsy and hippocampal sclerosis and IA. Association of IB/IA and sudden unexpected death in epilepsy lacks evidence and pacemaker therapy is rarely indicated. Treatment aims to minimize seizures and reduce the risk of falls.

Improving Consistency in Classifying Child Maltreatment for Sudden Unexpected Infant Deaths.

Develop guidelines for child death review teams that will improve the consistency in classifying child maltreatment (CM) and distinguish between classification of exposure to hazards and neglect for sleep-related sudden unexpected infant deaths (SUID). Sleep-related SUID (n = 25 797) were identified from the National Fatality Review-Case Reporting System between 2004 and 2018. Key variables considered when classifying CM among sleep-related SUID were identified. Logistic regression was used to assess the strength of associations and identify factors that distinguished between exposure to hazards and neglect. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Guidelines were developed based on these findings. Among the 13 034 sleep-related SUID with CM identified, hazards in the infant sleep environment were strongly associated with classification of both exposure to hazards and neglect, as were supervisor impairment and child welfare substantiation of the death. Comparing neglect to exposure to hazards, there was no association with sleep environment hazards with ORs ranging from 0.8 to 1.3 (95% CI 0.4-3.0), but sleep-related SUID were approximately twice as likely to be classified as neglect when the supervisor was impaired (OR 2.3, 95% CI 2.0-2.7) or child welfare action was taken (OR 1.8, 95% CI 1.5-2.0). The guidelines recommend classification of exposure to hazards for sleep environment hazards with elevation to neglect if the supervisor was impaired or child welfare substantiated the death. Among sleep-related SUID, classification of exposure to hazards is based on presence of sleep environment hazards, whereas neglect is based on supervisor impairment and child welfare action.

Collaboration to Reduce Sudden Unexpected Infant Death With Child Fatality Review and Outreach.

Sudden unexpected infant death (SUID) is the leading cause of postneonatal infant mortality in the United States, with disproportionately high rates in Baltimore City and Baltimore County in Maryland. This Advocacy Case Study describes the collaboration between the City and County Child Fatality Review teams to decrease infant mortality. B'more for Healthy Babies, formed in 2009 by the Bureau of Maternal Child Health in Baltimore City with the goal of reducing infant mortality through policy change, service improvements, community mobilization, and behavior change has had a sustained effort to respond to SUID. Recognizing that infants born in Baltimore City often reside in Baltimore County (and vice versa), collaboration with Baltimore County has been essential to increasing B'more for Healthy Babies' scope, reach, and effectiveness. Public health messaging campaigns, creation, and dissemination of a "SLEEP SAFE" testimonial video, and Safe Sleep Summits have involved caregivers, healthcare providers, and community partners. Outcomes of this ongoing collaboration demonstrate a decrease in sleep-related infant mortality rates. Our findings also highlight the need for continued, real time monitoring of sleep-related infant mortality trends with a coordinated, multidisciplinary, and crossjurisdictional response. This initiative can serve as a model of cross-sector communication that can be replicated in other similar geographic locations to further reduce SUID.

Using Sudden Unexpected Infant Death-Case Registry Data to Drive Prevention.

Sudden unexpected infant death (SUID) is a major contributor to infant death and a persistent public health issue. After an initial decline after the 1994 "Back to Sleep" campaign, SUID numbers plateaued. Currently, ∼10 infants die suddenly and unexpectedly each day in the United States. In 2019, we established a surveillance system for SUID in Cook County, Illinois, partnering our academic medical center, the Cook County Medical Examiner's Office, and child death review to create the Cook County SUID Case Registry. Our data show that, in Cook County, including the city of Chicago, ∼1 infant dies unexpectedly during sleep every week. Of these SUID, ∼25% were because of suffocation/possible suffocation. SUID peaks at 30 to 60 days old. SUID rates are 15 times higher in non-Hispanic Black infants and 3 times higher in Hispanic infants, compared with white infants. Nearly all involved 1 or more unsafe sleep factors. SUID are concentrated in community areas experiencing high hardship. Through our Community Partnership Approaches for Safe Sleep-Chicago team, we have developed collaborative prevention approaches in affected communities, allowing for conversations with families and those who support them to better understand barriers to safe sleep that they experience. These partnerships and our data allow for tailoring of informed prevention approaches to address upstream factors driving disproportionate infant mortality in historically disinvested communities, as well as optimizing the immediate risks posed by the infant sleep environment. Data from our system show the number of SUID declining modestly since our prevention work began.

Unexplained Infant Deaths Without Unsafe Sleep Factors: 2011 to 2020.

To describe sudden unexpected infant deaths (SUIDs) occurring in safe sleep environments and explore differences in selected characteristics. We examined SUID from 22 jurisdictions from 2011 to 2020 and classified them as unexplained, no unsafe sleep factors (U-NUSF). Data were derived from the Sudden Unexpected Infant Death and Sudden Death in the Young Case Registry, a population-based Centers for Disease Control and Prevention surveillance system built on the National Center for Fatality Review and Prevention's child death review program. SUID classified as U-NUSF included infants who were (1) awake, under supervision, and witnessed to become unresponsive or (2) found unresponsive in a safe sleep environment after sleep (unwitnessed). We calculated frequencies and percentages for demographics, birth and environmental characteristics, medical history, and death investigation findings. Most of the 117 U-NUSF SUID occurred before 4 months of age. Witnessed deaths most commonly occurred at <1 month of age (28%), whereas unwitnessed deaths most commonly occurred at ages 2 to 3 months (44%) Among all U-NUSF, 69% occurred in the infant's home (62% witnessed, 77% unwitnessed). All unwitnessed deaths occurred in a crib; most witnessed deaths occurred while being held (54%) or in a car seat traveling (18%). Most infants (84%) had no history of abuse or neglect. Abnormal autopsy findings were reported in 46% of deaths (49% witnessed, 42% unwitnessed). Characterizing these deaths is key to advancing our knowledge of SUID etiology. Our study revealed a heterogeneous group of infants, suggesting physiologic, genetic, or environmental etiologies.

Trend in the prevalence, awareness, treatment and control of hypertension among adult over in Nigeria over a 4-year period

Abstract Background Hypertension is the commonest risk factor for most cardiovascular and cerebrovascular diseases, also the commonest cause of sudden unexpected death in the country. Despite concerted efforts to reduce the burden of this condition through increasing awareness, treatment and control rate of hypertension among adults in Nigeria. The rates of hypertension awareness (60%), treatment (34%), and control (12%) have been reported recently These figures need to change for the improved health of the citizens. Objective The study assessed the trend in the prevalence, levels of awareness, treatment, and control of hypertension among adults in urban setting in Nigeria, Sub-Sahara Africa. Methods This was a retrospective study. Data collected from opportunistic screening of adults aged 15 years and above in 4 urban communities during May Measurement Month from 2020 to 2023 was analyzed. Standardized protocol was used to collected data on socio-demographics and anthropometric measurements, blood pressure and pulse rate were measured using digital blood pressure monitors after patient have rested for at least 15 minutes. Hypertension was defined based on the 7th Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of Hypertension. Data was analyzed using SPSS 22 and p-value &amp;lt;0.05 was statistically significant Results We analyzed data of 2676participants. The mean age was 40.4years (SD 15·04), 68·5% of whom were women, 2.8% had diabetes mellitus, and 50·9% were overweight/obese. A third of the participants (33·9%) had hypertension, more than half of whom (57·2%) were aware that they were diagnosed of hypertension. The prevalence reduced from 39.7% in 2020 to 26.8% in 2023. Among those diagnosed, 66.5% were taking medication, and among those taking medication 32.5% had controlled blood pressure. We noted an increasing improvement in the rate of awareness from 35.4% to 72.5%, treatment from 46.7% to 82.6% and control from 5.7% to 52.3% over the 4-year period, p-value 0.000 (figure 1). When comparing between the hypertensives and non-hypertensives; higher age group (55years and above), the presence of diabetic mellitus and overweight/obesity showed statistically significant association, all at p-value of 0.000 each (table 1). Conclusion Hypertension is still a major problem among urban dwellers in Akwa Ibom State, with almost every one out of three adults have the condition. Though there is a decreasing trend in the prevalence and increasing trend in the awareness, treatment and control of hypertension, these rates are still suboptimal. Urgent measures are needed to reduce the prevalence and improve hypertension control among this population.

Focal granule cell bilamination of the dentate gyrus-its prevalence across the human age spectrum and review of the literature.

The prevalence of focal granule cell bilamination (FGCB) in the hippocampal dentate gyrus varies from 0% to 44%, depending on age and study population. FGCB is commonly thought to be a specific feature of temporal lobe epilepsy (TLE) but its prevalence in cases without TLE is unclear. Using formalin-fixed, paraffin-embedded hippocampal sections, this retrospective postmortem study evaluated the prevalence of FGCB and other granule cell pathologies in infants (1-12 months of age, n = 16), children (4-10 years, n = 6), and adults (28-91 years, n = 15) with no known history of epilepsy or seizures. We found FGCB in 6% of infants, 17% of children, and 27% of adults. We then compared our findings with those in published reports of sudden unexpected deaths in infancy (SUDI), childhood (SUDC), and epilepsy (SUDEP), and in surgical specimens from patients with TLE. The reported prevalence of FGCB in those studies was 6%-19% in infants, 0%-17% in children, and 0%-2% in adults in non-seizure-related cases and 9% in children and 3%-25% in adults with TLE. Our findings highlight the presence of FGCB in individuals with no known epilepsy/seizure-related histories in proportions similar to those reported in individuals with clinical epilepsy.

Caregiver burden and therapeutic needs in Dravet syndrome - A national UK cross-sectional questionnaire study

Background and objectivesDravet Syndrome is a severe developmental and epileptic encephalopathy with significant care needs for affected individuals and families. Our objective was to characterise the caregiver burden and therapeutic needs of families caring for an individual with Dravet Syndrome from child to adulthood, to examine age related differences in co-morbidities, and identify current gaps in health and social care. MethodsCross-sectional national survey conducted by the patient advocacy group Dravet Syndrome UK (DSUK) emailed to registered families caring for an individual with a confirmed diagnosis of Dravet syndrome. To characterise the sample, quantitative data on demographics, diagnostic journey, co-morbidities, therapies, healthcare utilisation, social care and funding, and impact on family life were collected. Qualitative data were analysed using grounded theory to develop a model of impact and service need. Results165 out of 381 families (43 %) responded. 90 % of adult Dravet syndrome patients waited >12 months to receive a diagnosis, compared to 25 % families with a young child (p < 0.001). 96 % reported intellectual disability as co-morbidity, more frequently observed in older Dravet syndrome individuals (p < 0.001), alongside autism/autistic-like symptoms (χ2 = 15.3, df = 3 p = 0.001) and scoliosis (χ2 = 28.4, df = 3, p < 0.001). Sleep problems are associated with greater impact on caregiver's mental well-being (χ2 = 13.2, df = 2, p < 0.001). 77 % of families wished more discussions about sudden unexpected death in epilepsy (SUDEP) and 50 % rated the paediatric to adult transition experience as ‘poor’. 90 % of caregivers were unable to continue working as normal with negative impact on their quality of life (p = 0.024) and mental well-being (p = 0.007). DiscussionFamilies are profoundly impacted by Dravet syndrome. Their experience changes over time as people with Dravet syndrome become older and present with increasing levels of health, cognitive and behavioural comorbidities. Families will benefit from improved communication with health care professionals, psychosocial interventions and better access to social care.

Uncovering Diaphragm Cramp in SIDS and Other Sudden Unexpected Deaths.

The diaphragm is the primary muscle of respiration. Here, we disclose a fascinating patient's perspective that led, by clinical reasoning alone, to a novel mechanism of spontaneous respiratory arrests termed diaphragm cramp-contracture (DCC). Although the 7-year-old boy survived its paroxysmal nocturnal "bearhug pain apnea" episodes, essentially by breathing out to breathe in, DCC could cause sudden unexpected deaths in children, especially infants. Diaphragm fatigue is central to the DCC hypothesis in SIDS. Most, if not all, SIDS risk factors contribute to it, such as male sex, young infancy, rebreathing, nicotine, overheating and viral infections. A workload surge by a roll to prone position or REM-sleep inactivation of airway dilator or respiratory accessory muscles can trigger pathological diaphragm excitation (e.g., spasms, flutter, cramp). Electromyography studies in preterm infants already show that diaphragm fatigue and sudden temporary failure by transient spasms induce apneas, hypopneas and forced expirations, all leading to hypoxemic episodes. By extension, prolonged spasm as a diaphragm cramp would induce sustained apnea with severe hypoxemia and cardiac arrest if not quickly aborted. This would cause a sudden, rapid, silent death consistent with SIDS. Moreover, a unique airway obstruction could develop where the hypercontracted diaphragm resists terminal inspiratory efforts by the accessory muscles. It would disappear postmortem. SIDS autopsy evidence consistent with DCC includes disrupted myofibers and contraction band necrosis as well as signs of agonal breathing from obstruction. Screening for diaphragm injury from hypoxemia, hyperthermia, viral myositis and excitation include serum CK-MM and skeletal troponin-I. Active excitation could be visualized on ultrasound or fluoroscopy and monitored by respiratory inductive plethysmography or electromyography.

Early mortality in STXBP1-related disorders.

Pathogenic variants in STXBP1 cause a spectrum of disorders mainly consisting of developmental and epileptic encephalopathy (DEE), often featuring drug-resistant epilepsy. An increased mortality risk occurs in individuals with drug-resistant epilepsy and DEE, with sudden unexpected death in epilepsy (SUDEP) often the major cause of death. This study aimed to identify the rate and causes of mortality in STXBP1-related disorders. Through an international call, we analyzed data on individuals with STXBP1 pathogenic variants, who passed away from causes related to their disease. We estimated a mortality rate of 3.2% (31/966), based on the STXBP1 Foundation and the STXBP1 Global Connect registry. In total, we analyzed data on 40 individuals (23 males) harboring pathogenic STXBP1 variants, collected from different centers worldwide. They died at a median age of 13years (range: 11months-46years). The most common cause of death was SUDEP (36%), followed by pulmonary infections and respiratory complications (33%). The incidence of SUDEP peaked in mid-childhood, while non-SUDEP causes were more frequent in early childhood or adulthood (p = 0.006). In the most severe phenotypes, death was related to non-SUDEP causes (p = 0.018). We found a mortality rate in STXBP1-related disorders similar to other DEEs, with an early age at death and SUDEP as well as pulmonary infections as the main cause of death. These findings assist in prognostic evaluation and genetic counseling for the families. They help to define the mortality risk of STXBP1-related disorders and implement preventative strategies.

Trends in Sudden Unexpected Deaths in an Australian Population: Impact of the COVID-19 Pandemic

SARS-CoV-2 infection is associated with increased cardiovascular (CV) morbidity and mortality, manifesting as increased adverse outcomes in the first 30 days, extending to 12 months. This study aimed to investigate trends in sudden unexpected deaths between 2018 and 2022, with a focus on CV deaths. A retrospective analysis was performed on autopsy reports (n=9,330) obtained from New South Wales Coroners Court, Australia, specifically targeting cases of unexplained deaths that occurred between 2018 and 2022. Statistical analysis was conducted using chi-square tests and a post hoc analysis with Bonferroni correction, as well as analysis of variance with multiple comparisons. There were 349 (18.3%) CV deaths in 2018, 346 (18.0%) in 2019, 338 (17.5%) in 2020, 395 (21.9%) in 2021, and (23.4%) 413 in 2022 (p=0.0002). Among CV deaths, the number of deaths from sudden arrhythmic death syndrome were 25 (7.2%) in 2018, 26 (7.5%) in 2019, 18 (5.3%) in 2020, 52 (13.2%) in 2021, and 80 (19.4%) in 2022 (p=0.0001). Atherosclerosis was the most common cause of death among all CV categories; there were 196 (56.2%) atherosclerosis deaths in 2018, 207 (59.8%) in 2019, 192 (56.8%) in 2020, 221 (56.0%) in 2021, and 197 (47.7%) in 2022 (p=0.43). The average age of death from sudden arrhythmic death syndrome (42.8±19.1 years) across 2018-2022 was younger than atherosclerosis (56.2±12.4 years) and total groups (53.1±15.1 years) (p<0.001). Males comprised 76% of all CV deaths from 2018 to 2022 (p<0.0001). Compared with pre-pandemic data, a noteworthy increase in CV deaths was observed in occurrence with the escalation in COVID-19 cases in Australia. This may be attributed to direct or indirect factors, such as lifestyle modifications, disrupted access to routine cardiac care, or COVID-19 infection-triggered CV deaths.

Sudden unexpected atraumatic arterial dissection-related death after seizures

BackgroundTo date, it has been assumed that acute seizures which arise in the context of sudden, spontaneous, atraumatic, acute, arterial dissections (SAAADs) are downstream consequences of the dissections driven by syncope or focal brain lesions (FBLs). As this subject has not been formally investigated, likely due to its rarity, we reviewed published case reports (CRs) to examine the veracity of this assumption. MethodsWe included CR describing patients diagnosed with both acute seizures and arterial dissections in order to ascertain the temporal sequence between acute seizures and typical SAAAD symptoms. In addition, we quantified the frequency with which hypotension, bradycardia, and FBLs are associated with acute seizures in such cases. ResultsWe found 45 published CRs, six (13.3%) of which involved traumatic arterial dissections and 39 (86.7%) which involved SAAADs. Of the latter, twenty-one (53.8%) described seizures that followed typical SAAAD symptoms (SAFO), and 18 (46.2%) that preceded all such symptoms (SATO). On average, blood pressure and heart rate for both groups exceeded the normal range. Of the CRs that included magnetic resonance imaging (MRI) scans, 8 (100%) SAFO but only 6 (54.5%) SATO patients demonstrated FBLs (p<0.03). A conspicuously large fraction of SATO patients had known epilepsy compared with SAFO patients, (33.3% vs 4.8%; p<0.02). In addition, SATO epilepsy patients’ seizure semiologies frequently resembled their breakthrough seizures (BTS). The most common SAAAD associated with acute seizures was aortic dissection (AoD; 17/45; 37.8%). Nine CRs (20%) described patients who died soon after presentation, seven of which were associated with AoDs, including one epilepsy patient. Six of these seven AoDs occurred in patients who suffered from chronic hypertension (CHTN). All five deaths in the SATO group followed first ever seizures (FES) [four AoDs and one coronary artery dissection (CoAD)]. ConclusionAcute seizures arising in the context of SAAADs are not necessarily associated with hypotension or FBLs, and frequently appear to precede the associated dissections. These results suggest that seizures could act as triggers for SAAADs. In addition, sudden unexpected atraumatic acute arterial dissection-related death after seizure (SUADAS) might be a distinct cause of sudden death in epilepsy patients.

What Has the Sudden Unexpected Infant Death and Sudden Death in the Young Case Registry Learned About Consenting Families for DNA Banking and/or Genomic Research?

Since 2015, the Sudden Unexpected Infant Death (SUID) and Sudden Death in the Young (SDY) Case Registry has characterized sudden and unexpected deaths among young people (0-20 years). Families may provide informed consent to save biospecimens for banking and/or genomic research. We reviewed all consent-eligible cases to describe the frequency, time from death to consent, type (paper, phone, or electronic), and staffing method (Medical Examiner Office-based bereavement counselor vs outsourced genetic counselor). Of 5438 cases from January 2015 to January 2022, 3498 (64%) were eligible for consent and 391 (11%) were successfully consented. Half (54%) were obtained within 60 days of the death, 39% within 48 hours. Most were paper based (73%); 23% were obtained by phone, and 4% electronically. Consent rates varied by site from 3% to 66%. Higher consent rates were achieved within a Medical Examiner Office by a social worker or death investigator. Only 3% of consents attempted by a contracted genetic counselor were successful. Identified barriers include lack of available contact information, inability to reach family using the collected information, and lack of response when contacted. Consent rates were highest shortly after death when families were contacted by the Medical Examiner Office as part of bereavement outreach.

The power of hybridization capture - Illustrated using an expanded gene panel on 100 post mortem samples, focusing on sudden unexplained death

Sudden unexpected death (SUD) is an unexpected event that in many cases are caused by diseases with an underlying genetic background. Forensic molecular autopsy is an approach that has gained wide-spread attention, in part explained by the rapid progress of DNA sequencing techniques. The approach leverages genetic data in combination with medical autopsy findings in post-mortem samples to explore a potential underlying genetic cause of death.Traditional forensic approaches to molecular autopsy focus on a small panel of genes, say <200 genes, with strong association to heart conditions whereas clinical genetics tend to capture entire exomes while subsequently selecting targeted panels bioinformatically. The drop in price and the increased throughput has promoted wider exome sequencing as a viable method to discover genetic variants. We explore a targeted gene panel consisting of 2422 genes, selected based on their broad association to sudden unexplained death. A hybridization capture approach from Twist Bioscience based on double stranded DNA probes was used to target exons of the included genes. We selected and sequenced a total of 98 post-mortem samples from historical forensic autopsy cases where the cause of death could not be unambiguously determined based on medical findings and that had a previous negative molecular autopsy.In the current study, we focus on the performance of the hybridization capture technology on a 2422 gene panel and explore metrics related to sequencing success using a mid-end NextSeq 550 as well as a MiSeq FGx platform. With the latter we demonstrate that our sequence data benefits from 2×300bp sequencing increasing coverage, in particular, for difficult regions where shadow coverage, i.e. regions outside the probes, are utilized. The results further illustrate a highly uniform capture across the panel of genes (mean fold80=1.5), in turn minimizing excessive sequencing costs to reach sufficient coverage, i.e. 20X.We outline a stepwise procedure to select genes associated with SUD through virtual bioinformatical panels extracting tier of genes with increasing strength of association to SUD. We propose some prioritization strategies to filter variants with highest potential and show that the number of high priority genetic variant requiring manual inspections is few (0-3 for all tiers of genes) when all filters are applied.

Impact of COVID-19 Pandemic Interventions on Sudden Unexpected Death in Infancy Incidence in France

To study the impact of non-pharmaceutical interventions (NPIs) implemented during the COVID-19 pandemic on the monthly incidence of sudden unexpected death in infancy (SUDI) cases overall and those with a viral or bacterial identification. We conducted an interrupted time-series analysis using seasonally adjusted Poisson regression models from the French national prospective and multicenter SUDI registry, that included all SUDI cases under age one year who died from 2016 to 2021 in mainland France. Of 998 SUDI cases analyzed, 750 were recorded during the pre-pandemic period (January 2016 through March 2020) and 248 during the NPI period (April 2020 through December 2021). We found a significant seasonal pattern of overall monthly SUDI incidence, with a peak observed periodically from November to February. The monthly SUDI incidence decreased significantly from the pre-pandemic to NPI periods (adjusted incidence rate ratio 0.83 [95% confidence interval 0·72-0·96]). In particular, the monthly incidence of SUDI cases with a viral or bacterial identification decreased, while no significant difference was found for SUDI cases without a viral or bacterial identification. NPIs were associated with a significant change in the incidence of SUDI cases with a viral or bacterial identification. Further investigations are needed to analyze the pathophysiologic role of viruses and bacteria in the SUDI.