Autopsy in Sudden Unexplained Death in Youth: indispensable or in some cases redundant?

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A. C. van der Gugten, Tess M. Wemeijer, B. A. Semmekrot, R. B.J. Smit, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9452325/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Objective Sudden Unexplained Death in Youth (SUDY) requires thorough investigation to identify underlying causes and guide prevention strategies. In the Netherlands, cases are investigated using the standardized Postmortem Evaluation of Sudden Unexplained Death in Infants and Children (PESUDIC), in which autopsy is offered as a standard component. However, its invasive nature and associated time burden may limit parental acceptance. This study evaluated to what extent the cause of death can be established using a limited set of diagnostic tests compared to the standard procedure including autopsy. Study Design In this observational study, children >2 years of age who died suddenly and unexpectedly and underwent PESUDIC, including imaging and autopsy, were included. Two expert panels, consisting of a forensic and a pediatric specialist, independently assessed early diagnostic tests available before autopsy. Cases were classified by level of diagnostic certainty and need for autopsy. Panel conclusions were compared with the reference standard: a multidisciplinary audit incorporating all available information, including autopsy findings. Results Sixty-six cases were included (median age 12 years (IQR 4–14.7), 63% male). Panels identified indicative information for a cause of death in 60 patients (91%). Nevertheless, autopsy was required in most cases (n=59) to confirm the diagnosis. In 7 cases (10.6%), panels were sufficiently confident to establish the cause of death without autopsy with complete agreement with the reference standard. Causes included obstructive gastrointestinal pathology (n=5) and diabetic ketoacidosis with dehydration (n=2). Conclusions In approximately 10% of children with SUDY, sufficient certainty regarding the cause of death can be obtained without autopsy. Autopsy child death review SUDY Forensic Medicine What is Known Autopsy in sudden unexplained death in youth is worldwide recognized as the gold standard for postmortem examination. However, its invasive nature and associated time burden may limit parental acceptance. What is New: In 7 of 60 sudden and unexplained deceased minors (10%), sufficient certainty regarding the cause of death can be obtained by other minimal invasive diagnostic test, so without the need of an autopsy. Causes without the need of an autopsy included obstructive gastrointestinal pathology and diabetic ketoacidosis with dehydration. Introduction Sudden Unexplained Death in Youth (SUDY) refers to the sudden and initially unexplained—yet presumed natural—death of an individual under the age of 18, excluding perinatal and unnatural deaths. The unexpected death of a child without a clear cause has a profound emotional and psychological impact on both the family and healthcare professionals. In such cases, a comprehensive postmortem investigation may offer clarity regarding the cause of death and help identify potentially preventable factors.[ 1 ] In the Netherlands, SUDY is estimated to affect approximately 50 children each year.[ 2 ] These cases are investigated using the Dutch Postmortem Evaluation of Sudden Death in Infants and Children (PESUDIC) protocol, an extensive, stepwise diagnostic approach. The PESUDIC procedure includes a thorough review of the medical history, external physical examination, biochemical and microbiological analyses, radiological imaging, and full autopsy, and concludes with a multidisciplinary panel discussion to reach consensus on the cause of death.[ 3 ] The purpose of the procedure is to establish the cause of death, in order to contribute to the parents’ grieving process of the sudden loss of their child and to help identify potentially preventable factors. Cases showing indications of an unnatural cause of death are excluded from the PESUDIC procedure. Parental consent is required for each step of the procedure. Between 2016 and 2021, the PESUDIC procedure was able to determine the cause of death in 58% of investigated children, while an additional 13% had a plausible cause identified.[ 3 ] The PESUDIC procedure had been preceded by a two-year pilot of this post mortem procedure, between 2012–2013, called the NODO procedure (in Dutch: Nader Onderzoek DoodsOorzaak) which was evaluated for cost-effectiveness by Price Waterhouse Cooper.[ 4 ] In the NODO procedure, an autopsy was offered as more or less mandatory so 90% of parents agreed to an autopsy. Conventional autopsy by a trained pediatric pathologist is considered the gold standard for identifying the cause of death.[ 5 – 8 ] In the PESUDIC procedure, 60% of parents consented to autopsy.[ 3 ] In recent years, alternative diagnostic methods such as postmortem whole-body magnetic resonance imaging (MRI) and computed tomography (CT) have been increasingly utilized in the investigation of sudden child deaths. However, studies conducted on relatively small cohorts, report wide ranges of concordance rates (18–83%) between imaging findings and autopsy results.[ 9 – 11 ] Also, other diagnostic modalities like microbiological, metabolic or genetic testing can be decisive in ascertaining the cause of death.[ 12 ] However, results from such diagnostic test are not immediately available, whereas decisions regarding whether or not to perform an autopsy must be made before these results are known. To date, it has not been systematically evaluated in which cases the cause of death can be established with sufficient certainty based solely on initial diagnostic results. The aim of the present study is therefore to assess the diagnostic value of autopsy and to determine in which cases the cause of death can be reliably identified without need for autopsy. Methods Study population Data were used from children who participated in the NODO procedure (2012–2013) and the PESUDIC procedure (2016–2022). Inclusion criteria for these procedures have been previously published.[ 3 , 4 , 10 ] In summary, diagnostic investigations following sudden unexplained death in children are conducted on a voluntary basis. Parents can choose which components of the diagnostic process they consent to participate in. Most diagnostic procedures take place shortly after death, and autopsy is performed within 1 to 2 days postmortem, depending on local availability. We have focused on an age category (2 to 18 years) beyond Sudden Unexplained Death in Infancy (SUDI) in order to make the data from this study more comparable with that from studies of adults. Because imaging and autopsy were important diagnostic and outcome tests of the reference standard, only children who underwent imaging and autopsy were included. Data collection Comprehensive and standardized data regarding medical history, postmortem physical examination, and diagnostic outcomes from the PESUDIC procedure were systematically recorded in the local electronic health records of all Dutch University Medical Centers. A dedicated Castor database (Ciwit BV. Castor Electronic Data Capture. 2016. Version 2024.2.4.1, Amsterdam) was developed to capture diagnostic procedures and outcomes using standardized data collection forms. All diagnostic procedures were conducted in accordance with the national PESUDIC protocol, encompassing medical history, physical examination, laboratory testing, microbiological analysis, DNA sampling, imaging, and autopsy guidelines. Outcome measures Conclusions on the cause of death were made in a multidisciplinary audit as part of the PESUDIC procedure; this was the reference standard in our study. In the audit, all the diagnostic results, including microbiological results, toxicology, radiology, autopsy and, when applicable, metabolic and genetic results, combined with medical history and forensic external examination, were taken into account. A cause of death was categorized as explained, plausible or unexplained. An explained cause had an abnormal postmortem finding corroborating with the history or a full explanation of the death provided by an indisputable postmortem finding. A cause of death was considered as plausible in cases where a postmortem finding did not fit with the medical history or vice versa. The cause of death remained unexplained in cases with an absence of history and postmortem findings related to a lethal condition. For the descriptions in this study, the explained and plausible categories were grouped together as having a determined cause of death. Two expert panels, each comprising a pediatrician and a forensic physician (BS, EP, CO, RS), all experts in this field, independently reviewed the diagnostic test results for each patient available prior to the commencement of the autopsy. The diagnostic information provided to the panels included the medical history, postmortem physical examination, biochemical analyses (blood, spinal fluid, vitreous humor, urine), imaging studies, as well as rapid microbiological and toxicological tests. The panels were tasked with determining whether a presumed cause of death could be identified based on these data. A presumed cause of death was defined when at least one directional indication was identified in the medical history, external examination, or ancillary investigations. Additionally, they evaluated whether an autopsy was necessary due to uncertainty regarding the cause of death. In cases of disagreement of the two panels on the need for autopsy, a third panel was consulted (JR, TW), and discussions continued until consensus was achieved. Statistical methods For data analysis SPSS 28 for Windows (IBM Corp. Released 2021. IBM SPSS Statistics for Windows, Version 28.0. Armonk, NY: IBM Corp) was used. The data were summarized with descriptive analyses. No statistical analyses were performed due to the low numbers and variety of cases. Results Between 2012 and 2022, a total of 126 children above 2 years of age underwent the PESUDIC or NODO procedure and in 80 children the procedure included imaging and autopsy. From 12 patients who underwent the NODO procedure it was impossible to obtain the data. In two cases, doubts arose regarding a natural cause of death during the procedure. These cases were excluded from this dataset. A total of 66 patients were included in the study. See Table 1 for more details. Characteristics Cases n = 66 (%) Sex - male 42 (63.6) Age – median (IQR) (years) 12 years (IQR 4 – 14.7) Age groups 2-4 years: 5-8 years: 9-12 years: 13-15 years: 16-18 years: 19 (28.7) 7 (10.6) 13 (19.7) 17 (25.8) 10 (15.2) Cause of death certainty Unexplained: Plausible: Explained: 11 (16.7) 6 (9.1) 49 (74.2) Category cause of death determined* Cardiovascular: Gastrointestinal: Neurological: Infectious: Other $ : 20 (36.4) 10 (18.2) 3 (5.5) 16 (29.1) 6 (10.9) * The explained and plausible categories were grouped together as having a determined cause of death. $ Other were metabolic disorder, foreign body in main bronchus, renal insufficiency, diabetic ketoacidosis (three times). Table 1 - Basis characteristics of included cases and outcomes according to the reference standard, the multidisciplinary audit. The panel reviewed the results of all the diagnostic tests available in the 66 cases. A medical history, postmortem physical examination and imaging (46 computed tomography, 27 MRI) were performed in all these children. Biochemical analysis was done in 95% of cases (n=63, blood in 42, cerebrospinal fluid in 34, vitreous humor in 23, urine in 27). Toxicological rapid tests were performed in 44% of cases (n=29) and microbiological rapid tests (nose and throat viral panel pcr) in 38% (n = 25). Category cause of death according to the audit Panel, no autopsy necessary Panel, autopsy necessary Total Cardiovascular 0 20 20 Gastrointestinal 5 5 10 Neurological 0 3 3 Infectious 0 16 16 Other 2 4 6 Unexplained 0 11 11 Total 7 59 66 Table 2 - Overview of causes of death according to the audit and the number of cases in which the panels considered an autopsy necessary or unnecessary. The panels were able to identify a presumed cause of death in 60 patients (91%), whilst in 6 they were unable to determine any likely cause. Among the cases with a presumed cause, both panels agreed in 50 instances about the presumed cause (83%). Imaging, biochemical analysis and history were the diagnostic tools most frequently providing valuable information for cause-of-death assessment. In 59 cases, panels expressed insufficient certainty regarding the cause of death and therefore deemed an autopsy necessary. In 7 cases (10,6%), both panels concurred that the cause of death was established with enough certainty to forgo an autopsy; of these, 2 initially required the involvement of a third panel to reach consensus. In all 7 cases, there was complete agreement between the panels’ determination and the definitive diagnosis established by the multidisciplinary audit following autopsy. See table 2 for details . The cause of death in these 7 cases were gastrointestinal obstructions in 5 cases (congenital mesenteric defect with sigmoid and small bowel herniation, intussusception, volvulus with lymphatic malformation as leading point, congenital mesenteric defect with small bowel intussusception and distal volvulus, strangulation with closed loop and internal herniation), and in the 2 other cases a diabetic ketoacidosis debut with dehydration. In cases with a gastrointestinal cause of death, imaging proved to be the key diagnostic tool, whereas in the two instances of diabetic ketoacidosis, biochemical analysis was crucial for diagnosis. Discussion The aim of the present study was to evaluate the diagnostic utility of autopsy and to determine in which cases the cause of death can be established with sufficient confidence to forgo an autopsy. Our study demonstrates that at the time when a decision regarding autopsy performance must be made, there is sufficient certainty about the cause of death based on pre-autopsy diagnostic results in 10% of cases. To the best of our knowledge, no similar study has been conducted before. In general, autopsy is considered to be the diagnostic test that offers the most certainty about the cause of death. In our national PESUDIC procedure, parents need to consent to every element of the procedure. Overall, approximately 60% of parents consented to an autopsy, of which only half agreed to include brain examination.[ 3 ] The reasons for declining this procedure are currently being investigated in a qualitative study. Possible reasons include the invasiveness of the procedure, time required to complete it, no perceived benefit from autopsy, religion, and fear of mutilation.[ 13 – 16 ] Besides parental reluctance, an autopsy is a time-consuming and costly procedure. When parents do consent to autopsy, the practitioner will typically proceed with the examination, regardless of their professional opinion on its necessity. To make an informed decision and to properly counsel parents, it is essential to clearly establish in which cases an autopsy is not required to reach a definitive conclusion regarding the cause of death. Based on the findings of this study, it can be concluded that when there is a documented history of new-onset diabetes mellitus confirmed by clinical chemistry results (in blood, cerebrospinal fluid of vitreous humor), performing an autopsy does not provide additional diagnostic value. Similarly, in cases where a clear obstructive gastrointestinal cause of death is evident from the medical history and imaging, an autopsy is unlikely to contribute further. Our previous study showed that autopsy provided a decisive cause of death in almost half of the cases it was performed. Although the autopsy plays an important role in excluding certain causes, this means that the other half of all causes determined were identified through other investigations than autopsy, like genetic testing or microbiological testing or combinations of these.[ 3 ] The discrepancy with our study is determined by the difference in methodology of our diagnostic study and by the fact that some results (e.g. genetic testing) are not available at the moment that a decision on whether or not to perform an autopsy, has yet to be made. One consideration for the future is to allow more time before deciding to perform an autopsy, in some cases, for example by awaiting the results of microbiological diagnostics. A limitation of our study is its observational design, including that not all investigations were performed in every case. Additionally, only patients who underwent both imaging and autopsy were included. Among the children who did not undergo autopsy (46 in total), some were excluded because the cause of death was already clearly established. Within the PESUDIC procedure, this rationale was documented for five children over the age of two years. Among these, four had an infectious cause of death, and one was attributed to midgut volvulus. The age distribution of the children who did not underwent autopsy was equal to the children included in the study. Regarding causes of death, an infectious cause was identified in nearly 50% of the children who did not undergo autopsy. Conclusion Our study demonstrates that autopsy remains crucial in the diagnostic evaluation of the cause of death in children who have died suddenly and unexpectedly without explanation. In a small subset of cases, autopsy can be omitted because the cause of death is already clearly established. This information might be helpful for physicians in asking for informed consent to autopsy in cases of child death. Declarations Medical ethical review The study proposal was reviewed by the Medical Research Ethics Committee of the University Medical Center Utrecht (reference number 18–174/C). The committee issued a statement confirming that this study does not fall under the Dutch Medical Research Involving Human Subjects Act. Funding The grant for this research was provided by the Netherlands Organization for Health Research and Development (ZonMw) to Maastricht University in 2022, number 10480012120002. Author Contribution AG, WD, EP devised the study design. AG compiled dossiers and panels. The three expert panels consisted of a pediatrician and a forensic physician (BS, EP, CO, RS, SR, TW). Each author contributed to the writing phase and provided feedback on the article. Data Availability All data supporting the findings of this study are available upon request. Other research that used these data is acceseble at: https://pubmed.ncbi.nlm.nih.gov/37852434/. References Wojcik MH, Krous HF, Goldstein RD (2023) Sudden unexplained death in childhood: current understanding. Pediatr Emerg Care 39(12):979–983 Centraal Bureau Statistiek. CBS Statline Overledenen; doodsoorzaak (uitgebreide lijst), leeftijd, geslacht 2022 (Updated 23–06– 2022). Available from: https://opendata.cbs.nl/#/CBS/nl/dataset/ 7233/table?ts=1656511974367. Pries AM, Ruskamp JM, Edelenbos E, Fuijkschot J, Semmekrot B, Verbruggen KT et al (2024) A systematic approach to evaluate sudden unexplained death in children. J Pediatr 264:113780 PWC. NODO-evaluatieonderzoek: Onderzoek naar de effectiviteit van de NODO-procedure in het achterhalen van de aard van het onverwacht en onverklaard overlijden van minderjarigen in Nederland. Staatscourant 2013 Nr. 11750;27-02-2017 Rodrigues FS, Correa de Oliveira I, Nunes Lima Cat M, Lopes Mattos MC, Andrioli Silva G (2021). Agreement between clinical and anatomopathological diagnoses in pediatric intensive care. Rev Paul Pediatr. Mar12:39:e2019263. Roulson J, Benbow EW, Hasleton PS. Discrepancies between clinical and autopsy diagnosis and the value of post mortem histology; a meta-analysis and review. Histopathology. 2005;47:551–9. Ribeiro MP, Duoarte-Neto AN, Dolhnikoff M, Lndoso L, Lourenco B et al. Major discrepancy between clinical diagnosis of death and anatomopathological findings in adolescents with chronic diseases during 18-years. Clinics (Sao Paulo). 2023 Mar 25:78:100184. doi: 10.1016/j.clinsp.2023.100184. eCollection 2023. Tumer AR, Tumer L, Bilge Y, Sudden unexpected child deaths: forensic autopsy results in cases of sudden deaths during a 5-year period. J Trop Pediatr. 2005 Jun;51(3):131-5. doi: 10.1093/tropej/fmh099. Epub 2005 Apr 14 Proisy M, Marchand AJ, Loget P, Bouvet R, Roussey M, Pelé F et al (2013) Whole-body post-mortem computed tomography compared with autopsy in the investigation of unexpected death in infants and children. Eur Radiol 23(6):1711–1719 van Rijn RR, Beek EJ, van de Putte EM, Teeuw AH, Nikkels PGJ, Duijst W et al (2017) The value of postmortem computed tomography in paediatric natural cause of death: a Dutch observational study. Pediatr Radiol 47(11):1514–1522 Speelman AC, Engel-Hills PC, Martin LJ, van Rijn RR, Ofah AC (2022) Postmortem computed tomography plus forensic autopsy for determining the cause of death in child fatalities. Pediatr Radiol 52(13):2620–2629 Pries AM, van der Gugten AC, Moll HA, Klein WM, Fuijkschot J et al. Postmorten diagnostics in sudden unexpected death in infants and children: use and utility. Eur J of Pediatr 2025 Mar 5: 184:223 Holste C, Pilo C, Pettersson K, Radestad I, Papadogiannakis N. Mothers’attitudes towards perinatal autopsy after stillbirth. Acta Obsttet Gynaecol Scand. 2011 Nov;90(11):1287-90. Schirmann A, Boyle FM, Horey D, Siassakos D, Ellwood D et al. Understanding mothers’decision-making needs for autopsy consent after stillbirth: Framework analysis of a large survey. Birth 2018 Sep;45(3):255-262. Sullivan J, Monagle P. Bereaved parents’perceptions of the autopsy examination of their child. Pediatrics. 2011 Apr;127(4):e1013-20. doi: 10.1542/peds.2009-2027. Epub 2011 Mar 14. Wemeijer TM, van der Gugten AC et al. Onderzoek doodsoorzaak bij onverwacht overlijden kind. Ervaringen van ouders met de NODOK-procedure. NED TIJDSCHR GENEESKD. 2026;170:D8634 PESUDIC collaborative A. Custers 8 , E. Edelenbos 9 , J. Fuijkschot 10 , B. Levelink 8 , C. Oostdam 6 , P.J. Puiman 11 , E. van de Putte 1 , R. R van Rijn 12 , J.M. Ruskamp 1 , B.A. Semmekrot 4 , K.T. Verbruggen 13 , H. Vlaardingerbroek 14 , M.E. Wiesman 15 . Department of Paediatrics, University Medical Center Utrecht Wilhelmina Children’s Hospital, Utrecht, the Netherlands. Faculty of Law, Department of Criminal Law and Criminology, Maastricht University, Maastricht, The Netherlands. Forensic Medicine, GGD (Public Health Service) Ijsselland, Zwolle, The Netherlands. Canisius Wilhelmina Ziekenhuis, Department of Paediatrics, Nijmegen, the Netherlands. Forensic Medicine, GGD (Public Health Service) Utrecht, Zeist, The Netherlands. Forensic Medicine, GGD (Public Health Service) Fryslan, Leeuwarden, The Netherlands. Department of Pathology, Division of Laboratories, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, the Netherlands. Department of Paediatrics, Maastricht University Medical Center, Maastricht, the Netherlands. Department of Paediatrics, Amsterdam University Medical Center Emma Children’s Hospital, Amsterdam, the Netherlands. Department of Paediatrics, Radboud University Medical Center Amalia Children’s Hospital, Nijmegen, the Netherlands. Department of General Paediatrics, Erasmus University Medical Center Sophia Children’s Hospital, Rotterdam, the Netherlands. Department of Radiology and Nuclear Medicine, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, the Netherlands. Department of Paediatrics, University Medical Center Groningen Beatrix Children’s Hospital, Groningen, the Netherlands. Department of Paediatrics, Leiden University Medical Center, Leiden, the Netherlands. Department of Pediatrics, Medical Spectrum Twente (MST), Enschede, The Netherlands. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 08 May, 2026 Reviewers agreed at journal 30 Apr, 2026 Reviewers agreed at journal 29 Apr, 2026 Reviewers invited by journal 28 Apr, 2026 Editor assigned by journal 27 Apr, 2026 Submission checks completed at journal 27 Apr, 2026 First submitted to journal 17 Apr, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9452325","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":632701977,"identity":"41d10f64-01d3-4a5c-a3a5-a14ab0486073","order_by":0,"name":"A. C. van der Gugten","email":"","orcid":"","institution":"University Medical Center Utrecht Wilhelmina Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"A.","middleName":"C. van der","lastName":"Gugten","suffix":""},{"id":632701978,"identity":"b6e867c0-8232-4d97-ada3-64bb4b7979d2","order_by":1,"name":"Tess M. 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However, its invasive nature and associated time burden may limit parental acceptance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is New:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn 7 of 60 sudden and unexplained deceased minors (10%), sufficient certainty regarding the cause of death can be obtained by other minimal invasive diagnostic test, so without the need of an autopsy. Causes without the need of an autopsy included obstructive gastrointestinal pathology and diabetic ketoacidosis with dehydration.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eSudden Unexplained Death in Youth (SUDY) refers to the sudden and initially unexplained\u0026mdash;yet presumed natural\u0026mdash;death of an individual under the age of 18, excluding perinatal and unnatural deaths. The unexpected death of a child without a clear cause has a profound emotional and psychological impact on both the family and healthcare professionals. In such cases, a comprehensive postmortem investigation may offer clarity regarding the cause of death and help identify potentially preventable factors.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn the Netherlands, SUDY is estimated to affect approximately 50 children each year.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] These cases are investigated using the Dutch Postmortem Evaluation of Sudden Death in Infants and Children (PESUDIC) protocol, an extensive, stepwise diagnostic approach. The PESUDIC procedure includes a thorough review of the medical history, external physical examination, biochemical and microbiological analyses, radiological imaging, and full autopsy, and concludes with a multidisciplinary panel discussion to reach consensus on the cause of death.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] The purpose of the procedure is to establish the cause of death, in order to contribute to the parents\u0026rsquo; grieving process of the sudden loss of their child and to help identify potentially preventable factors.\u003c/p\u003e \u003cp\u003eCases showing indications of an unnatural cause of death are excluded from the PESUDIC procedure. Parental consent is required for each step of the procedure. Between 2016 and 2021, the PESUDIC procedure was able to determine the cause of death in 58% of investigated children, while an additional 13% had a plausible cause identified.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe PESUDIC procedure had been preceded by a two-year pilot of this post mortem procedure, between 2012\u0026ndash;2013, called the NODO procedure (in Dutch: Nader Onderzoek DoodsOorzaak) which was evaluated for cost-effectiveness by Price Waterhouse Cooper.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] In the NODO procedure, an autopsy was offered as more or less mandatory so 90% of parents agreed to an autopsy.\u003c/p\u003e \u003cp\u003eConventional autopsy by a trained pediatric pathologist is considered the gold standard for identifying the cause of death.[\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] In the PESUDIC procedure, 60% of parents consented to autopsy.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] In recent years, alternative diagnostic methods such as postmortem whole-body magnetic resonance imaging (MRI) and computed tomography (CT) have been increasingly utilized in the investigation of sudden child deaths. However, studies conducted on relatively small cohorts, report wide ranges of concordance rates (18\u0026ndash;83%) between imaging findings and autopsy results.[\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAlso, other diagnostic modalities like microbiological, metabolic or genetic testing can be decisive in ascertaining the cause of death.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] However, results from such diagnostic test are not immediately available, whereas decisions regarding whether or not to perform an autopsy must be made before these results are known. To date, it has not been systematically evaluated in which cases the cause of death can be established with sufficient certainty based solely on initial diagnostic results. The aim of the present study is therefore to assess the diagnostic value of autopsy and to determine in which cases the cause of death can be reliably identified without need for autopsy.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eData were used from children who participated in the NODO procedure (2012\u0026ndash;2013) and the PESUDIC procedure (2016\u0026ndash;2022). Inclusion criteria for these procedures have been previously published.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] In summary, diagnostic investigations following sudden unexplained death in children are conducted on a voluntary basis. Parents can choose which components of the diagnostic process they consent to participate in. Most diagnostic procedures take place shortly after death, and autopsy is performed within 1 to 2 days postmortem, depending on local availability. We have focused on an age category (2 to 18 years) beyond Sudden Unexplained Death in Infancy (SUDI) in order to make the data from this study more comparable with that from studies of adults. Because imaging and autopsy were important diagnostic and outcome tests of the reference standard, only children who underwent imaging and autopsy were included.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eData collection\u003c/h3\u003e\n\u003cp\u003eComprehensive and standardized data regarding medical history, postmortem physical examination, and diagnostic outcomes from the PESUDIC procedure were systematically recorded in the local electronic health records of all Dutch University Medical Centers. A dedicated Castor database (Ciwit BV. Castor Electronic Data Capture. 2016. Version 2024.2.4.1, Amsterdam) was developed to capture diagnostic procedures and outcomes using standardized data collection forms. All diagnostic procedures were conducted in accordance with the national PESUDIC protocol, encompassing medical history, physical examination, laboratory testing, microbiological analysis, DNA sampling, imaging, and autopsy guidelines.\u003c/p\u003e\n\u003ch3\u003eOutcome measures\u003c/h3\u003e\n\u003cp\u003eConclusions on the cause of death were made in a multidisciplinary audit as part of the PESUDIC procedure; this was the reference standard in our study. In the audit, all the diagnostic results, including microbiological results, toxicology, radiology, autopsy and, when applicable, metabolic and genetic results, combined with medical history and forensic external examination, were taken into account. A cause of death was categorized as explained, plausible or unexplained. An explained cause had an abnormal postmortem finding corroborating with the history or a full explanation of the death provided by an indisputable postmortem finding. A cause of death was considered as plausible in cases where a postmortem finding did not fit with the medical history or vice versa. The cause of death remained unexplained in cases with an absence of history and postmortem findings related to a lethal condition. For the descriptions in this study, the explained and plausible categories were grouped together as having a determined cause of death.\u003c/p\u003e \u003cp\u003eTwo expert panels, each comprising a pediatrician and a forensic physician (BS, EP, CO, RS), all experts in this field, independently reviewed the diagnostic test results for each patient available prior to the commencement of the autopsy. The diagnostic information provided to the panels included the medical history, postmortem physical examination, biochemical analyses (blood, spinal fluid, vitreous humor, urine), imaging studies, as well as rapid microbiological and toxicological tests. The panels were tasked with determining whether a presumed cause of death could be identified based on these data. A presumed cause of death was defined when at least one directional indication was identified in the medical history, external examination, or ancillary investigations. Additionally, they evaluated whether an autopsy was necessary due to uncertainty regarding the cause of death. In cases of disagreement of the two panels on the need for autopsy, a third panel was consulted (JR, TW), and discussions continued until consensus was achieved.\u003c/p\u003e\n\u003ch3\u003eStatistical methods\u003c/h3\u003e\n\u003cp\u003eFor data analysis SPSS 28 for Windows (IBM Corp. Released 2021. IBM SPSS Statistics for Windows, Version 28.0. Armonk, NY: IBM Corp) was used. The data were summarized with descriptive analyses. No statistical analyses were performed due to the low numbers and variety of cases.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBetween 2012 and 2022, a total of 126 children above 2 years of age underwent the PESUDIC or NODO procedure and in 80 children the procedure included imaging and autopsy. From 12 patients who underwent the NODO procedure it was impossible to obtain the data. In two cases, doubts arose regarding a natural cause of death during the procedure. These cases were excluded from this dataset. \u0026nbsp;A total of 66 patients were included in the study. \u003cem\u003eSee Table 1 for more details.\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCases\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en = 66 (%)\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSex - male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e42 (63.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge \u0026ndash; median (IQR) (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e12 years (IQR 4 \u0026ndash; 14.7)\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge groups\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41.9027%;\"\u003e\n \u003cp\u003e2-4 years: \u003c/p\u003e\n \u003cp\u003e5-8 years: \u003c/p\u003e\n \u003cp\u003e9-12 years: \u003c/p\u003e\n \u003cp\u003e13-15 years: \u003c/p\u003e\n \u003cp\u003e16-18 years: \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.8487%;\"\u003e\n \u003cp\u003e19 \u0026nbsp; (28.7)\u003c/p\u003e\n \u003cp\u003e7 \u0026nbsp; \u0026nbsp;(10.6)\u003c/p\u003e\n \u003cp\u003e13 (19.7)\u003c/p\u003e\n \u003cp\u003e17 \u0026nbsp; (25.8)\u003c/p\u003e\n \u003cp\u003e10 \u0026nbsp; (15.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCause of death certainty\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41.9027%;\"\u003e\n \u003cp\u003eUnexplained: \u003c/p\u003e\n \u003cp\u003ePlausible:\u003c/p\u003e\n \u003cp\u003eExplained: \u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.8487%;\"\u003e\n \u003cp\u003e11 \u0026nbsp; (16.7)\u003c/p\u003e\n \u003cp\u003e6 \u0026nbsp; \u0026nbsp;(9.1)\u003c/p\u003e\n \u003cp\u003e49 \u0026nbsp; (74.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCategory cause of death determined*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 41.9027%;\"\u003e\n \u003cp\u003eCardiovascular: \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eGastrointestinal: \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNeurological: \u0026nbsp;\u003c/p\u003e\n \u003cp\u003eInfectious: \u0026nbsp;\u003c/p\u003e\n \u003cp\u003eOther\u003csup\u003e$\u003c/sup\u003e: \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 27.8487%;\"\u003e\n \u003cp\u003e20 \u0026nbsp; (36.4)\u003c/p\u003e\n \u003cp\u003e10 \u0026nbsp; (18.2)\u003c/p\u003e\n \u003cp\u003e3 \u0026nbsp; \u0026nbsp;(5.5)\u003c/p\u003e\n \u003cp\u003e16 \u0026nbsp;(29.1)\u003c/p\u003e\n \u003cp\u003e6 \u0026nbsp; \u0026nbsp;(10.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e* The explained and plausible categories were grouped together as having a determined cause of death.\u003c/p\u003e\n \u003cp\u003e\u003csup\u003e$\u003c/sup\u003e Other were metabolic disorder, foreign body in main bronchus, renal insufficiency, diabetic ketoacidosis (three times).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eTable 1 - Basis characteristics of included cases and outcomes according to the reference standard, the multidisciplinary audit.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe panel reviewed the results of all the diagnostic tests available in the 66 cases. A medical history, postmortem physical examination and imaging (46 computed tomography, 27 MRI) were performed in all these children. Biochemical analysis was done in 95% of cases (n=63, blood in 42, cerebrospinal fluid in 34, vitreous humor in 23, urine in 27). Toxicological rapid tests were performed in 44% of cases (n=29) and microbiological rapid tests (nose and throat viral panel pcr) in 38% (n = 25).\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategory cause of death according to the audit\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePanel, no autopsy necessary\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePanel, autopsy necessary\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCardiovascular \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGastrointestinal \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eNeurological \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eInfectious\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eUnexplained\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e7\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e59\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e66\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003eTable 2 - Overview of causes of death according to the audit and the number of cases in which the panels considered an autopsy necessary or unnecessary.\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe panels were able to identify a presumed cause of death in 60 patients (91%), whilst in 6 they were unable to determine any likely cause. Among the cases with a presumed cause, both panels agreed in 50 instances about the presumed cause (83%). Imaging, biochemical analysis and history were the diagnostic tools most frequently providing valuable information for cause-of-death assessment. In 59 cases, panels expressed insufficient certainty regarding the cause of death and therefore deemed an autopsy necessary. In 7 cases (10,6%), both panels concurred that the cause of death was established with enough certainty to forgo an autopsy; of these, 2 initially required the involvement of a third panel to reach consensus. In all 7 cases, there was complete agreement between the panels\u0026rsquo; determination and the definitive diagnosis established by the multidisciplinary audit following autopsy. \u003cem\u003eSee table 2 for details\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eThe cause of death in these 7 cases were gastrointestinal obstructions in 5 cases (congenital mesenteric defect with sigmoid and small bowel herniation, intussusception, volvulus with lymphatic malformation as leading point, congenital mesenteric defect with small bowel intussusception and distal volvulus, strangulation with closed loop and internal herniation), and in the 2 other cases a diabetic ketoacidosis debut with dehydration. In cases with a gastrointestinal cause of death, imaging proved to be the key diagnostic tool, whereas in the two instances of diabetic ketoacidosis, biochemical analysis was crucial for diagnosis.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe aim of the present study was to evaluate the diagnostic utility of autopsy and to determine in which cases the cause of death can be established with sufficient confidence to forgo an autopsy. Our study demonstrates that at the time when a decision regarding autopsy performance must be made, there is sufficient certainty about the cause of death based on pre-autopsy diagnostic results in 10% of cases.\u003c/p\u003e \u003cp\u003eTo the best of our knowledge, no similar study has been conducted before. In general, autopsy is considered to be the diagnostic test that offers the most certainty about the cause of death. In our national PESUDIC procedure, parents need to consent to every element of the procedure. Overall, approximately 60% of parents consented to an autopsy, of which only half agreed to include brain examination.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] The reasons for declining this procedure are currently being investigated in a qualitative study. Possible reasons include the invasiveness of the procedure, time required to complete it, no perceived benefit from autopsy, religion, and fear of mutilation.[\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] Besides parental reluctance, an autopsy is a time-consuming and costly procedure. When parents do consent to autopsy, the practitioner will typically proceed with the examination, regardless of their professional opinion on its necessity. To make an informed decision and to properly counsel parents, it is essential to clearly establish in which cases an autopsy is not required to reach a definitive conclusion regarding the cause of death.\u003c/p\u003e \u003cp\u003eBased on the findings of this study, it can be concluded that when there is a documented history of new-onset diabetes mellitus confirmed by clinical chemistry results (in blood, cerebrospinal fluid of vitreous humor), performing an autopsy does not provide additional diagnostic value. Similarly, in cases where a clear obstructive gastrointestinal cause of death is evident from the medical history and imaging, an autopsy is unlikely to contribute further.\u003c/p\u003e \u003cp\u003eOur previous study showed that autopsy provided a decisive cause of death in almost half of the cases it was performed. Although the autopsy plays an important role in excluding certain causes, this means that the other half of all causes determined were identified through other investigations than autopsy, like genetic testing or microbiological testing or combinations of these.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] The discrepancy with our study is determined by the difference in methodology of our diagnostic study and by the fact that some results (e.g. genetic testing) are not available at the moment that a decision on whether or not to perform an autopsy, has yet to be made. One consideration for the future is to allow more time before deciding to perform an autopsy, in some cases, for example by awaiting the results of microbiological diagnostics.\u003c/p\u003e \u003cp\u003eA limitation of our study is its observational design, including that not all investigations were performed in every case. Additionally, only patients who underwent both imaging and autopsy were included. Among the children who did not undergo autopsy (46 in total), some were excluded because the cause of death was already clearly established. Within the PESUDIC procedure, this rationale was documented for five children over the age of two years. Among these, four had an infectious cause of death, and one was attributed to midgut volvulus. The age distribution of the children who did not underwent autopsy was equal to the children included in the study. Regarding causes of death, an infectious cause was identified in nearly 50% of the children who did not undergo autopsy.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur study demonstrates that autopsy remains crucial in the diagnostic evaluation of the cause of death in children who have died suddenly and unexpectedly without explanation. In a small subset of cases, autopsy can be omitted because the cause of death is already clearly established. This information might be helpful for physicians in asking for informed consent to autopsy in cases of child death.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eMedical ethical review\u003c/h2\u003e \u003cp\u003e The study proposal was reviewed by the Medical Research Ethics Committee of the University Medical Center Utrecht (reference number 18\u0026ndash;174/C). The committee issued a statement confirming that this study does not fall under the Dutch Medical Research Involving Human Subjects Act.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003e The grant for this research was provided by the Netherlands Organization for Health Research and Development (ZonMw) to Maastricht University in 2022, number 10480012120002.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAG, WD, EP devised the study design. AG compiled dossiers and panels. The three expert panels consisted of a pediatrician and a forensic physician (BS, EP, CO, RS, SR, TW). Each author contributed to the writing phase and provided feedback on the article.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data supporting the findings of this study are available upon request. Other research that used these data is acceseble at: https://pubmed.ncbi.nlm.nih.gov/37852434/.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eWojcik MH, Krous HF, Goldstein RD (2023) Sudden unexplained death in childhood: current understanding. Pediatr Emerg Care 39(12):979\u0026ndash;983\u003c/li\u003e\n \u003cli\u003eCentraal Bureau Statistiek. CBS Statline Overledenen; doodsoorzaak (uitgebreide lijst), leeftijd, geslacht 2022 (Updated 23\u0026ndash;06\u0026ndash; 2022). Available from: https://opendata.cbs.nl/#/CBS/nl/dataset/ 7233/table?ts=1656511974367.\u003c/li\u003e\n \u003cli\u003ePries AM, Ruskamp JM, Edelenbos E, Fuijkschot J, Semmekrot B, Verbruggen KT et\u0026nbsp;al (2024) A systematic approach to evaluate sudden unexplained death in children. J Pediatr 264:113780\u003c/li\u003e\n \u003cli\u003ePWC. NODO-evaluatieonderzoek: Onderzoek naar de effectiviteit van de NODO-procedure in het achterhalen van de aard van het onverwacht en onverklaard overlijden van minderjarigen in Nederland. Staatscourant 2013 Nr. 11750;27-02-2017\u003c/li\u003e\n \u003cli\u003eRodrigues FS, Correa de Oliveira I, Nunes Lima Cat M, Lopes Mattos MC, Andrioli Silva G (2021). Agreement between clinical and anatomopathological diagnoses in pediatric intensive care. Rev Paul Pediatr. Mar12:39:e2019263.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eRoulson J, Benbow EW, Hasleton PS. Discrepancies between clinical and autopsy diagnosis and the value of post mortem histology; a meta-analysis and review. Histopathology. 2005;47:551\u0026ndash;9.\u003c/li\u003e\n \u003cli\u003eRibeiro MP, Duoarte-Neto AN, Dolhnikoff M, Lndoso L, Lourenco B et al. Major discrepancy between clinical diagnosis of death and anatomopathological findings in adolescents with chronic diseases during 18-years.\u0026nbsp;Clinics (Sao Paulo). 2023 Mar 25:78:100184. doi: 10.1016/j.clinsp.2023.100184.\u0026nbsp;eCollection 2023.\u003c/li\u003e\n \u003cli\u003eTumer AR, Tumer L, Bilge Y, Sudden unexpected child deaths:\u0026nbsp;forensic autopsy results in cases of sudden deaths during a 5-year period. J Trop Pediatr. 2005 Jun;51(3):131-5. doi: 10.1093/tropej/fmh099.\u0026nbsp;Epub 2005 Apr 14\u003c/li\u003e\n \u003cli\u003eProisy M, Marchand AJ, Loget P, Bouvet R, Roussey M, Pel\u0026eacute; F et\u0026nbsp;al (2013) Whole-body post-mortem computed tomography compared with autopsy in the investigation of unexpected death in infants and children. Eur Radiol 23(6):1711\u0026ndash;1719\u003c/li\u003e\n \u003cli\u003evan Rijn RR, Beek EJ, van de Putte EM, Teeuw AH, Nikkels PGJ, Duijst W et\u0026nbsp;al (2017) The value of postmortem computed tomography in paediatric natural cause of death: a Dutch observational study. Pediatr Radiol 47(11):1514\u0026ndash;1522\u003c/li\u003e\n \u003cli\u003eSpeelman AC, Engel-Hills PC, Martin LJ, van Rijn RR, Ofah AC (2022) Postmortem computed tomography plus forensic autopsy for determining the cause of death in child fatalities. Pediatr Radiol 52(13):2620\u0026ndash;2629\u003c/li\u003e\n \u003cli\u003ePries AM, van der Gugten AC, Moll HA, Klein WM, Fuijkschot J et al. Postmorten diagnostics in sudden unexpected death in infants and children: use and utility. Eur J of Pediatr 2025 Mar 5: 184:223\u003c/li\u003e\n \u003cli\u003eHolste C, Pilo C, Pettersson K, Radestad I, Papadogiannakis N. Mothers\u0026rsquo;attitudes towards perinatal autopsy after stillbirth. Acta Obsttet Gynaecol Scand. 2011 Nov;90(11):1287-90.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSchirmann A, Boyle FM, Horey D, Siassakos D, Ellwood D et al. Understanding mothers\u0026rsquo;decision-making needs for autopsy consent after stillbirth: Framework analysis of a large survey. Birth 2018 Sep;45(3):255-262.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eSullivan J, Monagle P. Bereaved parents\u0026rsquo;perceptions of the autopsy examination of their child. Pediatrics. 2011 Apr;127(4):e1013-20.\u0026nbsp; doi: 10.1542/peds.2009-2027. Epub 2011 Mar 14.\u003c/li\u003e\n \u003cli\u003eWemeijer TM, van der Gugten AC et al. Onderzoek doodsoorzaak bij onverwacht overlijden kind. Ervaringen van ouders met de NODOK-procedure. NED TIJDSCHR GENEESKD. 2026;170:D8634\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePESUDIC collaborative\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA. Custers\u003csup\u003e8\u003c/sup\u003e, E. Edelenbos\u003csup\u003e9\u003c/sup\u003e, J. Fuijkschot\u003csup\u003e10\u003c/sup\u003e, B. Levelink\u003csup\u003e8\u003c/sup\u003e, C. Oostdam\u003csup\u003e6\u003c/sup\u003e, P.J. Puiman\u003csup\u003e11\u003c/sup\u003e,\u0026nbsp;E. van de Putte\u003csup\u003e1\u003c/sup\u003e,\u0026nbsp;R. R van Rijn\u003csup\u003e12\u003c/sup\u003e, J.M. Ruskamp\u003csup\u003e1\u003c/sup\u003e, B.A. Semmekrot\u003csup\u003e4\u003c/sup\u003e, K.T. Verbruggen\u003csup\u003e13\u003c/sup\u003e, H. Vlaardingerbroek\u003csup\u003e14\u003c/sup\u003e, M.E. Wiesman\u003csup\u003e15\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eDepartment of Paediatrics, University Medical Center Utrecht Wilhelmina Children\u0026rsquo;s Hospital, Utrecht, the Netherlands.\u003c/li\u003e\n \u003cli\u003eFaculty of Law, Department of Criminal Law and Criminology, Maastricht University, Maastricht, The Netherlands.\u003c/li\u003e\n \u003cli\u003eForensic Medicine, GGD (Public Health Service) Ijsselland, Zwolle, The Netherlands.\u003c/li\u003e\n \u003cli\u003eCanisius Wilhelmina Ziekenhuis, Department of Paediatrics, Nijmegen, the Netherlands.\u003c/li\u003e\n \u003cli\u003eForensic Medicine, GGD\u0026nbsp;(Public Health Service) Utrecht, Zeist, The Netherlands.\u003c/li\u003e\n \u003cli\u003eForensic Medicine, GGD (Public Health Service) Fryslan, Leeuwarden, The Netherlands.\u003c/li\u003e\n \u003cli\u003eDepartment of Pathology, Division of Laboratories, Pharmacy and Biomedical Genetics,\u0026nbsp;University Medical Center Utrecht, the Netherlands.\u003c/li\u003e\n \u003cli\u003eDepartment of Paediatrics, Maastricht University Medical Center, Maastricht, the Netherlands.\u003c/li\u003e\n \u003cli\u003eDepartment of Paediatrics, Amsterdam University Medical Center Emma Children\u0026rsquo;s Hospital, Amsterdam, the Netherlands.\u003c/li\u003e\n \u003cli\u003eDepartment of Paediatrics, Radboud University Medical Center Amalia Children\u0026rsquo;s Hospital, Nijmegen, the Netherlands.\u003c/li\u003e\n \u003cli\u003eDepartment of General Paediatrics, Erasmus University Medical Center Sophia Children\u0026rsquo;s Hospital, Rotterdam, the Netherlands.\u003c/li\u003e\n \u003cli\u003eDepartment of Radiology and Nuclear Medicine, Emma Children\u0026apos;s Hospital, Amsterdam UMC, University of Amsterdam, the Netherlands.\u003c/li\u003e\n \u003cli\u003eDepartment of Paediatrics, University Medical Center Groningen Beatrix Children\u0026rsquo;s Hospital, Groningen, the Netherlands.\u003c/li\u003e\n \u003cli\u003eDepartment of Paediatrics, Leiden University Medical Center, Leiden, the Netherlands.\u003c/li\u003e\n \u003cli\u003eDepartment of Pediatrics, Medical Spectrum Twente (MST), Enschede, The Netherlands.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Autopsy, child death review, SUDY, Forensic Medicine","lastPublishedDoi":"10.21203/rs.3.rs-9452325/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9452325/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cu\u003eObjective\u003c/u\u003e\u003cem\u003e\u003cbr\u003e\n \u003c/em\u003eSudden Unexplained Death in Youth (SUDY) requires thorough investigation to identify underlying causes and guide prevention strategies. In the Netherlands, cases are investigated using the standardized Postmortem Evaluation of Sudden Unexplained Death in Infants and Children (PESUDIC), in which autopsy is offered as a standard component. However, its invasive nature and associated time burden may limit parental acceptance. This study evaluated to what extent the cause of death can be established using a limited set of diagnostic tests compared to the standard procedure including autopsy.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eStudy Design\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eIn this observational study, children \u0026gt;2 years of age who died suddenly and unexpectedly and underwent PESUDIC, including imaging and autopsy, were included. Two expert panels, consisting of a forensic and a pediatric specialist, independently assessed early diagnostic tests available before autopsy. Cases were classified by level of diagnostic certainty and need for autopsy. Panel conclusions were compared with the reference standard: a multidisciplinary audit incorporating all available information, including autopsy findings.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eResults\u003c/u\u003e\u003cem\u003e\u003cbr\u003e\n \u003c/em\u003eSixty-six cases were included (median age 12 years (IQR 4–14.7), 63% male). Panels identified indicative information for a cause of death in 60 patients (91%). Nevertheless, autopsy was required in most cases (n=59) to confirm the diagnosis. In 7 cases (10.6%), panels were sufficiently confident to establish the cause of death without autopsy with complete agreement with the reference standard. Causes included obstructive gastrointestinal pathology (n=5) and diabetic ketoacidosis with dehydration (n=2).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConclusions\u003c/u\u003e\u003cbr\u003e\n In approximately 10% of children with SUDY, sufficient certainty regarding the cause of death can be obtained without autopsy.\u003c/p\u003e","manuscriptTitle":"Autopsy in Sudden Unexplained Death in Youth: indispensable or in some cases redundant?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-07 09:01:39","doi":"10.21203/rs.3.rs-9452325/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-08T13:34:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"61215691020113627012150989850728587845","date":"2026-04-30T21:53:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"222959954796670165732070456733081043453","date":"2026-04-29T19:05:26+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-28T15:10:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-27T10:30:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-27T09:43:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Pediatrics","date":"2026-04-17T19:34:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"affe7516-0994-4d97-ad55-61673b882e4b","owner":[],"postedDate":"May 7th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-08T13:34:53+00:00","index":26,"fulltext":""},{"type":"reviewerAgreed","content":"61215691020113627012150989850728587845","date":"2026-04-30T21:53:46+00:00","index":25,"fulltext":""},{"type":"reviewerAgreed","content":"222959954796670165732070456733081043453","date":"2026-04-29T19:05:26+00:00","index":24,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-07T09:01:39+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-07 09:01:39","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9452325","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9452325","identity":"rs-9452325","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}