Introduction
In 2013, in a population of 3,870,773 inhabitants younger than 20, 1,112 persons (0.29 per 1 million) died in the Netherlands [
1]. Of the children who died in 2014, the majority (
n=645) were younger than 1 year. These figures show that there is a low risk of death before the age of 20 years in the Netherlands. But in these rare cases the cause of death should be thoroughly investigated to prevent further cases of early demise in case of genetic-based diseases or disorders. Furthermore, determining cause of death can help parents in overcoming the grief of losing their child [
2].
In the last decades there has been increasing interest in the use of postmortem radiology, especially postmortem CT and postmortem MRI, as an adjunct to the conventional autopsy. Most studies have been performed in foetuses and neonates and almost exclusively in hospitals or forensic populations [
3‐
8]. Little is known about the value of postmortem CT in a paediatric population in whom a natural cause of death is assumed. A change in Dutch law in October 2010, whereby consultation with a municipal coroner became mandatory in all paediatric deaths (Article 10A of the Burial Act), led to the implementation of the so-called NODO procedure [
9]. This is a procedure in which in case of an assumed natural unexpected death a thorough postmortem evaluation, including postmortem radiology, is offered to the parents of the deceased child. The NODO procedure consists of a stepwise approach under the guidance of a forensic physician and a paediatrician, including a home visit by the forensic physician to assess the circumstances where the body was found, a full medical and medico–social history, an external examination, radiologic examination (conventional radiography in children ages <5 years, and postmortem CT in all cases), laboratory examination, genetic testing and conventional autopsy. The last step of the NODO procedure, the conventional autopsy, required consent from both parents during the time of the study. If during the NODO procedure an indication of a non-natural cause arises the procedure is aborted and a legal investigation is initiated. The findings of this stepwise procedure are discussed in a consensus meeting in which all relevant medical disciplines participate and during this meeting a final cause of death, if possible, is determined. A more in-depth presentation of the NODO procedure, including the legal implications, is presented in Appendix A.
The aim of this observational study was to assess the value of postmortem CT in diagnosing the cause of death in children with an assumed natural unexpected death.
Materials and methods
Patients
Between October 2012 and December 2013 two Dutch University Hospitals — the Emma Children’s Hospital – Academic Medical Center Amsterdam (AMC) and the Wilhelmina Children’s Hospital – University Medical Centre Utrecht (UMCU) — acted as national centres for the NODO procedure.
All consecutive children ages <18 years who fulfilled the criteria for the NODO procedure and who were referred to one of the two national centres were included in the study. In all cases, informed consent for the autopsy was requested by a trained paediatrician who explained the additional value of the autopsy. From this study population, those children who did not undergo postmortem radiologic examination and those for whom no permission for autopsy was given were excluded from the final data analysis because in these cases the reference standard was missing. We also excluded cases where during the NODO procedure an indication of a non-natural cause arose, the reason being that in these cases the final cause of death resulting from the forensic autopsy was unknown to us.
The internal review board of the AMC issued a waiver for retrospective anonymized chart reviews, therefore no approval was requested.
Postmortem skeletal survey
The NODO protocol dictates that a skeletal survey be performed in all children ages <5 years, according to the guidelines of the Royal College of Radiologists and the Royal College of Paediatrics and Child Health [
10].
For this study, the skeletal survey was scored independently by one of three paediatric radiologists (E.J.B. with 29 years of experience, R.-J.N. with 14 years of experience, and R.R.vR. with 12 years of experience). We used the reports of the initial skeletal survey.
Postmortem computed tomography
A full-body postmortem CT was performed in all children. The protocol consisted of a scan of the head/neck (parameters of 120 kV, 285 mAs, 0.9-mm slice thickness, 0.45-mm increment, pitch 0.392, collimation 64 × 0.625, with bone and brain reconstructions) and chest/abdomen/extremities (parameters of 120 kV, 250 mAs, 3.0-mm slice thickness, 2.0-mm increment, pitch 0.983, collimation 64 × 0.625, with bone and soft-tissue reconstructions). CT scans were performed on a Philips Brilliance (64 multi-detector CT; Philips Medical Systems, Best, the Netherlands) at the AMC and a Philips Brilliance (16 multi-detector CT; Philips) at the UMCU.
During the NODO procedure the postmortem CT was reviewed by one of three experienced paediatric radiologists (the same as for the postmortem skeletal survey). For this study the scans were reviewed by two paediatric radiologists, one reviewer per centre (R.-J.N. and R.R.vR.). The radiologists did not have access to clinical data.
Other data
In all cases a full clinical and social history was obtained, a full physical exam was performed, laboratory investigations including blood culture, basic haematological workup, renal/liver and pancreatic functions, and electrolytes were obtained. In select patients additional genetic, metabolic and virology testing was performed. The results of these tests were correlated with imaging in cases where clinically significant findings (e.g., cause of death) were found on imaging. A full analysis of the other medical tests performed in the NODO procedure is outside the scope of this study. The cause of death was obtained from the pathology reports that were finalised after a consensus meeting with all participating disciplines.
Data analysis
The patients were grouped into two categories based on the autopsy outcome. The first category was composed of cases where the full autopsy procedure led to a definitive cause of death. This population was used to calculate sensitivity. The second category was composed of cases where the full autopsy procedure did not lead to a cause of death, including those with sudden infant death syndrome (SIDS) and sudden unexpected death in epilepsy (SUDEP). For this study these three categories were combined into one group.
Discussion
In the last decades there has been an increasing interest in the use of postmortem radiology; initially the focus was on adults, often in forensic radiology [
12‐
14]. However in the last several years there has been a strong increase in interest in postmortem radiology in children [
15]. This has been recognised within the European Society of Paediatric Radiology, and in 2015 the society initiated a task force on postmortem radiology [
16].
Our study shows that postmortem CT detected the cause of death in a minority of cases (12.9%) in a group of children who unexpectedly died of an apparent natural cause and in whom a cause of death was found. Based on the findings of this study, an autopsy could have been avoided in some children based on CT findings. In the majority of cases (74.1%) postmortem CT was not of added value in diagnosing the cause of death. One important explanation for this relatively low yield of postmortem CT could be the case mix, with a high rate of infection and cardiovascular causes of death. Postmortem CT did not yield clinically relevant findings in the majority of these cases.
The four excluded cases in whom an indication for a non-natural cause of death was found, although excluded from the final analysis, show that postmortem CT might, however, have a significant outcome on the final diagnosis of the cause of death in children and where findings might lead to legal investigations.
In the NODO procedure postmortem CT was used instead of postmortem MRI during this study. The main reason for this was the fact that the postmortem CT was initially planned to screen for potential non-natural causes of death, in which case the NODO procedure has to be aborted. For this purpose postmortem CT is sufficient because it rules out, for example, intracranial and thoracoabominal haemorrhages and fractures. The second reason is, given the high demand for MRI studies, access to MRI scanners is limited, particularly during regular office hours. In the current literature there is overwhelming evidence that in foetuses (which were excluded from the NODO procedure) and neonates, postmortem MRI is superior to postmortem CT [
8,
17].
The Magnetic Resonance Imaging Autopsy Study (MaRIAS) from London showed that a minimal invasive autopsy consisting of a postmortem MRI in combination with postmortem blood sampling via a needle puncture had a high concordance rate, ranging from 53.6% to 81%, with the conventional autopsy [
8]. It is also of interest to note that in the MaRIAS the concordance rate dropped significantly with increasing age, albeit with a much smaller number of older children. A smaller sub-study consisting of 82 cases from the MaRIAS cohort directly compared postmortem MRI versus postmortem CT [
17]. This study showed that although postmortem CT was significantly less accurate compared to postmortem MRI in foetuses younger than the gestational age of 24 weeks, the modalities’ performance was not significantly different for foetuses older than 24 weeks’ gestational age, neonates and children.
In a study by Proisy et al. [
5] conventional autopsy revealed a cause of death in 18 of 47 cases (38.3%). In 16 of these 18 cases postmortem CT showed concordant findings [
5]. In a paediatric forensic case series Sieswerda-Hoogendoorn et al. [
7] showed that the case mix is an important factor in predicting the sensitivity and specificity of postmortem CT. These studies show that, especially in older children, data are still lacking with respect to the accuracy of postmortem CT and postmortem MRI. Albeit in a small sample size, our study showed that in cases where the cause of death was related to the gastrointestinal tract the sensitivity was 100%, and for cardiovascular causes this was 16.7%. For all other causes of death the sensitivity was lower (decreasing to 0% for endocrinological causes, for example). The single case where infection was diagnosed as cause of death on postmortem CT was a case of an incarcerated inguinal hernia, with massive air in all vessels, so one could argue that this case actually should be considered as a gastrointestinal cause of death. Our study is one of the larger paediatric postmortem CT studies in non-forensic cases, yet in order to assess the true value of postmortem CT larger prospective multicentre studies are needed.
A drawback of our retrospective nested cohort study is the fact that not all children who were eligible, despite the fact that it is mandatory by law, were indeed referred for the NODO procedure. The mortality data of 2013, which are presented in the introduction, are the best available; more specific data for Dutch inhabitants younger than 18 years are not available. We also do not know the proportion of these children eligible for the NODO procedure. Based on the data from Statistics Netherlands, we estimate that close to 200 cases per year could have been included. There were significant differences across the Netherlands, where some areas didn’t submit a single case for the NODO procedure. The reason for this is unknown. It might — despite education and widespread information of the involved medical specialties — be related to recent implementation of the procedure in the Netherlands. We also cannot exclude the risk that selection bias has occurred because we do not have access to the death certificates of all children in the Netherlands. However we have good contacts in the field of forensic medicine and as far as we can assess there doesn’t seem to be a significant selection bias in our population. A second drawback is the fact that in nine cases no consent for autopsy was obtained. We therefore excluded these patients from our study; in one of these cases anterior rib fractures resulting from resuscitation were found, and in one case retroperitoneal and perirenal free air, possibly related to an infectious cause, was found. A final drawback is the fact that we could not evaluate the interobserver variance among the involved radiologists. The number of cases and their often distinctive findings would make it almost impossible to truly assess the interobserver variance. On the other hand, the study reflects a real-life situation where in general a single radiologist reviews the postmortem CT and interprets the findings.
In order for postmortem imaging to have a real impact in clinical practice both radiologists and pathologists need to work together or acquire a new skill set. In general, where radiologists lack pathological knowledge, pathologists lack radiologic knowledge; therefore during the NODO procedure, the ideal situation is a full child death review where all involved specialties discuss the cases. If this cannot be achieved, combined training in radiology and pathology could be a viable option [
18‐
20].
Acknowledgements
The authors would like to thank all personnel involved in the NODO procedure.
Besides the named authors, the following persons are a collaborators in the Dutch NODO Group: J. Doosje (GGD GHOR, the Netherlands); Mrs. E. Edelenbos (Department of Paediatrics, Free University Medical Center, Amsterdam, the Netherlands); W. Fetter (Department of Paediatrics, Free University Medical Center, Amsterdam, the Netherlands); Mrs. E.A. Landsmeer (Rivierduinen, GGZ K & J, Leiden, the Netherlands); S.P.H. Letmaath (GGD, Drenthe, the Netherlands); Mrs. M. L’Hoir (GGD GHOR, the Netherlands); J.C. Mulder (Landelijke Werkgroep Wiegendood van de NVK); Mrs. T. Naujocks (Community Health Service, Groningen, the Netherlands); Y. Schat (GGD GHOR, the Netherlands); M. de Vries (GGD GHOR, the Netherlands); F. Woonink (Department of Forensic Medicine, Public Health Service, region Utrecht, the Netherlands). All members participated in the development of the NODO procedure and were involved in the evaluation of the NODO procedure.
The NODO procedure was funded by the Dutch Ministry of Security and Justice.
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.