A 10-year retrospective analysis of sudden unexpected death in the young investigated at Salt River Mortuary, Cape Town
Sudden unexpected death in the young (SUDY) is characterised by a rapid and unanticipated episode that results in the death of a seemingly healthy individual aged between one and 40 years . SUDY is thought to affect approximately 1–3 per 100 000 young people annually , however, the incidence of SUDY in African countries is largely unknown . Investigating cause of death, demographics, physical profile, as well as lifestyle and medical history pertaining to SUDY has previously assisted in identifying risk factors, which enables the development of intervention strategies to mitigate such cases in the future . In most countries, deaths that are sudden and unexplained are referred for medico-legal investigations to determine the ultimate cause of death, which may include a death scene investigation, autopsy, and a review of medical and social history. Cause of death for these cases is often reported to be cardiac or epileptic in nature , although a study conducted in Pretoria, South Africa found that the leading cause of death in SUD in children (SUDC) was of pulmonary origin. Cause of death in SUDY thus may be linked with age as well as geographical location . Cause of death may be diagnosed at autopsy or with ancillary investigations . However, some cases present with no macroscopic or microscopic pathologies, and the cause of death remains undetermined . These cases are termed ‘autopsy-negative’, and such outcomes may have a profound effect on the family and their ability to process and accept the death of a loved one . In South Africa, an ‘undetermined’ cause of death is a final categorisation which indicates uncertainty despite all efforts to determine the cause of death, while ‘under investigation’ is a temporary categorisation allocated to cases where cause of death is not known, however, the post-mortem investigation into cause of death determination is still in progress. Up to one third of autopsy-negative cases may be attributable to cardiac channelopathies, which can only be diagnosed through DNA testing . It is possible that the findings of a molecular autopsy could explain at least a portion of unexplained cases, which would bring some level of closure to relatives . Salt River Mortuary (SRM) (recently replaced by the Observatory Forensic Pathology Institute) is an academic mortuary that services the western metropole of the City of Cape Town in South Africa. The mortuary has a historically large caseload , with 4 500 unnatural death investigations in 2023 alone (in-house data). An assessment of SUDY cases has not previously been conducted in this region, and information regarding the frequency and profile of these cases, the presence of known risk factors, the scope of post-mortem investigations and the ultimate causes of death are currently unknown. The aim of this study was therefore to retrospectively explore these factors in SUDY admissions to SRM over a ten-year period (1 January 2010 – 31 December 2019).   Study population and case identification The autopsy records from all admissions to SRM that occurred between 2010 and 2019 ( n = 34 601) were reviewed using the Office Autopsy Database (HREC: R036/2014) to identify SUDY cases. The inclusion criteria were cases that were admitted to SRM between 1 January 2010 and 31 December 2019 (inclusive) as ‘sudden unexpected death’, with the age at death ranging between 365 days and 40 years. Cases involving partial or skeletonised human remains, were excluded as such cases could not be accurately attributed to the definition of sudden and unexpected death (SUD). Decomposed bodies were included as they met the inclusion criteria, but it is acknowledged that these cases may have skewed body mass index (BMI) data. Molecular autopsy candidates were selected based on the following criteria: SUDY cases admitted to SRM between 2010 and 2019, ‘Undetermined’, ‘under-investigation’ or ‘non-specific/semi-specific natural’ cause of death following a full post-mortem investigation with ancillary investigations, Clinical history of heart disease and/or family history of heart disease and/or sudden death. Data collection After applying the inclusion and exclusion criteria, 1 997 cases were identified, and medico-legal case files were retrieved. Variables pertaining to demographics, circumstances at death, known risk factors, details of post-mortem investigation, as well as medical and social histories were collected into Microsoft Excel (Table ). BMI was calculated using the conventional equation BMI = mass (kg)/height (m) 2 . For decedents < 18 years old, BMI was interpreted in relation to age and sex, based on the World Health Organization BMI-for-age-and-sex standards . For decedents ≥ 18 years old, a BMI < 18.5 was recorded as ‘underweight’, and a BMI > 24.9 was recorded as ‘overweight’. A BMI within the range of 18.5–24.9 was recorded as ‘normal’. Socioeconomic factors were obtained from routine questionnaires of next-of-kin during the post-mortem investigation, which are available in the case files. The effect of socioeconomic factors such as marital status has been associated with health and mortality in the literature . Marital status of adults was recorded where available. For minors (< 18 years of age), marital status of the minor’s mother/guardian was recorded. Highest level of education and annual household income were collected for minors, as details pertaining to these variables are routinely requested for these cases. Double entry validation was carried out on all included cases. The 10-year dataset was then cleaned to ensure consistency and uniformity before data analysis. Data analysis Descriptive statistics were carried out to summarise the data. Numerical data were assessed with the Shapiro-Wilk test for normality. Differences between numerical data were assessed using Student’s t-tests for normally distributed data and Wilcoxon rank-sum tests where data did not conform to normality. Associations between categorical data were assessed using Pearson’s Chi-squared test. Where assumptions of this test were violated Fisher’s Exact test was applied. Pairwise differences between proportions within categorical variables were assessed post-hoc with Bonferroni correction applied. A p-value of ≤ 0.05 was deemed statistically significant for all tests. Statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) Ver. 24 (IBM corp., Armonk, NY). Notably, details pertaining to every variable in this study were not always available for every case. This was also noted by Tiemensma et al. , and may be either due to missing documents, absence of a response, language barriers, or the details were not specified. As a result, the denominator for each variable is different, reflecting the variability in availability of data per variable.   The autopsy records from all admissions to SRM that occurred between 2010 and 2019 ( n = 34 601) were reviewed using the Office Autopsy Database (HREC: R036/2014) to identify SUDY cases. The inclusion criteria were cases that were admitted to SRM between 1 January 2010 and 31 December 2019 (inclusive) as ‘sudden unexpected death’, with the age at death ranging between 365 days and 40 years. Cases involving partial or skeletonised human remains, were excluded as such cases could not be accurately attributed to the definition of sudden and unexpected death (SUD). Decomposed bodies were included as they met the inclusion criteria, but it is acknowledged that these cases may have skewed body mass index (BMI) data. Molecular autopsy candidates were selected based on the following criteria: SUDY cases admitted to SRM between 2010 and 2019, ‘Undetermined’, ‘under-investigation’ or ‘non-specific/semi-specific natural’ cause of death following a full post-mortem investigation with ancillary investigations, Clinical history of heart disease and/or family history of heart disease and/or sudden death.   After applying the inclusion and exclusion criteria, 1 997 cases were identified, and medico-legal case files were retrieved. Variables pertaining to demographics, circumstances at death, known risk factors, details of post-mortem investigation, as well as medical and social histories were collected into Microsoft Excel (Table ). BMI was calculated using the conventional equation BMI = mass (kg)/height (m) 2 . For decedents < 18 years old, BMI was interpreted in relation to age and sex, based on the World Health Organization BMI-for-age-and-sex standards . For decedents ≥ 18 years old, a BMI < 18.5 was recorded as ‘underweight’, and a BMI > 24.9 was recorded as ‘overweight’. A BMI within the range of 18.5–24.9 was recorded as ‘normal’. Socioeconomic factors were obtained from routine questionnaires of next-of-kin during the post-mortem investigation, which are available in the case files. The effect of socioeconomic factors such as marital status has been associated with health and mortality in the literature . Marital status of adults was recorded where available. For minors (< 18 years of age), marital status of the minor’s mother/guardian was recorded. Highest level of education and annual household income were collected for minors, as details pertaining to these variables are routinely requested for these cases. Double entry validation was carried out on all included cases. The 10-year dataset was then cleaned to ensure consistency and uniformity before data analysis.   Descriptive statistics were carried out to summarise the data. Numerical data were assessed with the Shapiro-Wilk test for normality. Differences between numerical data were assessed using Student’s t-tests for normally distributed data and Wilcoxon rank-sum tests where data did not conform to normality. Associations between categorical data were assessed using Pearson’s Chi-squared test. Where assumptions of this test were violated Fisher’s Exact test was applied. Pairwise differences between proportions within categorical variables were assessed post-hoc with Bonferroni correction applied. A p-value of ≤ 0.05 was deemed statistically significant for all tests. Statistical analyses were performed using the Statistical Package for Social Sciences (SPSS) Ver. 24 (IBM corp., Armonk, NY). Notably, details pertaining to every variable in this study were not always available for every case. This was also noted by Tiemensma et al. , and may be either due to missing documents, absence of a response, language barriers, or the details were not specified. As a result, the denominator for each variable is different, reflecting the variability in availability of data per variable.   Study population SRM received a total of 34 601 admissions between 1 January 2010 and 31 December 2019. The total number of SUDY admissions to SRM in the 10-year study period was 1 997, thus comprising 5.77% of the 10-year caseload. This equates to approximately 200 SUDY admissions to SRM annually. A total of 52 cases were identified as potential candidates for a molecular autopsy, and of these, 47/52 (90.38%) had biological samples available for future investigations (Fig. ). Demographics and physical profile of the SUDY cases Age and sex The mean age for the overall SUDY population was 26.89 ± 10.87 years. The mean age of the male and female SUDY admissions was 27.21 ± 10.89 and 26.35 ± 10.82 years, respectively. Within the children age category, there was a significantly greater proportion of females compared to males ( p = 0.028). No significant difference between the proportion of male and female was observed in the toddler, teenager or adult age categories. Males accounted for the majority (1 250/1 997; 62.59%) of the SUDY admissions within the 10-year study period. However, the male SUDY admissions represented only 4.7% (1 250/26 596) of the total male admissions to SRM over the 10 years, whereas the female SUDY admissions represented 9.43% (747/7 925) of the total female admissions to SRM over the 10 years. There were 80 admissions to SRM over the study period with undetermined sex. Upon dividing the study population into SUDC (1–18 years) and SUD in adults (SUDA) (18–40 years) age groups, these groups accounted for 0.90% and 4.87% of the 10-year SRM caseload, respectively. With respect to the prevalence of admissions across the ages, from 1 to 40 years, one-year olds comprised the largest individual age group of SUDY admissions to SRM (6.56%), and 67.01% (132/197) of SUDY admissions within the 1–4 year age category (Fig. ). SRM received few 2–15 year old SUDY admissions. More SUDY cases were received from older age groups, peaking again between the ages 30–35 years. The 1–4 year old SUDY admissions comprised the largest proportion of SRM admissions per age category for the study period (197/603; 32.67%), based on the Office Autopsy Database. BMI The mean BMI of the SUDY admissions to SRM in the 10-year period was 23.44 ± 7.22. The ‘underweight’ group may be overrepresented as several SUDY admissions comprised decomposed remains. The BMI and weight status is presented in Fig. for males and females. The mean female and male BMI were 25.73 ± 7.22 and 22.04 ± 7.22 ( p < 0.01), respectively. A significant association was identified between sex and weight status ( p < 0.001). The male sex accounted for the majority of the underweight ( p < 0.001) and normal admissions ( p < 0.001), whereas the female sex accounted for majority of the overweight admissions ( p < 0.001). The pulmonary system ( n = 552; 30.16%) and cardiovascular system ( n = 392; 21.42%) were the two most prominent organ systems associated with death in SUDY cases. Weight status was significantly associated with involvement of the cardiovascular system ( p < 0.001) with a significantly greater proportion of individuals with cardiovascular involvement being classified as overweight ( p < 0.001). Similarly, weight status was significantly associated with involvement of the pulmonary system ( p < 0.001), however a significantly greater proportion of individuals with pulmonary involvement were classified as underweight ( p < 0.001). Profile of the SUDY admissions to SRM Geographical location of the SUDY admissions All incidents of SUD are to be reported to the nearest South African Police Services (SAPS) station . The SAPS station that received the highest number of SUDY cases in the 10-year study period was Nyanga (294/1 997; 14.72%), followed by Gugulethu (184/1 997; 9.21%) and Mitchell’s Plain (178/1 997; 8.91%). Monthly and seasonal distribution of SUDY admissions to SRM The cumulative monthly SUDY admissions to SRM in the 10-year study period peaked in June and December (Fig. ), representing a seasonal peak at the beginning of winter and summer, respectively, in a South African context. The winter season experienced the highest frequency of SUDY, followed by spring, autumn, and summer ( p = 0.0233). Circumstances surrounding death Where specified, the most frequently recorded position at death was ‘lying down’, more specifically supine (728/1 262; 57.69%), prone (179/1 262; 14.18%), and side (157/1 262; 12,44%) (Fig. a). A significant association was identified between sex and position at death ( p = 0.002). A significantly greater proportion of males were found lying prone ( p < 0.001) or supine ( p = 0.0251) at death than females. No other positions were significantly associated with sex. Position at death was significantly associated with age group ( p < 0.001), with toddlers having a greater risk of dying in a supine position or lying on their side than other age groups. Where specified, the most frequently reported locations at death were residential (897/1 979; 45.33%) and medical centre (697/1 979; 35.22%) (Fig. b). A significant association was identified between age and location at death ( p = 0.001), with more adults dying outdoors ( p < 0.001), and in residential settings ( p = 0.0214). Toddlers had a greater risk of being declared dead at a medical centre ( p < 0.001). Sex was significantly associated with location at death ( p < 0.001). A significantly greater proportion of males were found outdoors ( p < 0.001), with females having a greater risk of being declared dead at medical centres ( p < 0.001). Where specified, the most frequently reported activity at/before death was ‘sleeping’ (484/936; 51.71%), and ‘resting’ (212/936; 22.65%) (Fig. c). A significant association was identified between age and activity at/before death ( p < 0.001), with more toddlers dying while eating, and more children and toddlers dying while at play or sleeping. A significant association between sex and activity at/before death was observed ( p < 0.001). A greater proportion of males died during physical activity, while a greater proportion of females died during domestic work. Extent of post-mortem investigation and cause of death Following a post-mortem investigation, the cause of death was deemed natural, under investigation, unnatural and undetermined in 1 460/1 931 (75.56%), 280/1 931 (14.50%), 101/1 931 (5.23%) and 91/1 931 (4.71%) of cases, respectively. Where affidavits were available, the extent of post-mortem investigation was external in 724/1 930 (37.51%) cases, partial in 134/1 930 (6.94%) cases, and full in 1 072/1 930 (55.54%) cases. Of the cases with a presumed manner of death, ancillary investigations were performed in 1 873/1 931 (97.00%) cases. The frequency of ancillary investigations performed is depicted in Table . Unnatural deaths did not undergo any further analysis as they do not meet the study criteria. Additionally, deaths with a missing cause of death outcome (65/1 997; 3.25%) were excluded to avoid misrepresentation of possible risk factors for SUDY. The organ system involved in the cause of death of natural SUDY cases was not specified in 243/1 460 (16.64%) cases. When specified, the main organ system implicated was the pulmonary system (550/1 217; 45.19%), followed by the cardiovascular system (387/1 217; 31.80%), and central nervous system (166/1 217; 13.64%) (Table ). The greatest overlap of organ systems existed between the pulmonary and cardiovascular systems (63/1 217; 5.18%). The overall leading cause of death in specified natural cases was pneumonia (142/830; 17.11%), followed by tuberculosis (TB) (117/830; 14.10%). Previous TB-exposure during lifetime was only reported in 57/117 (48.72%) SUDY cases whose cause of death was determined to be TB. The leading causes of death in specified natural deaths were assessed by organ system and age category (Table ). Notably, infectious diseases accounted for at least 396/1 220 (32.46%) of specific/semi-specific natural causes of SUDY cases. The proportion of infectious and non-infectious related deaths pertaining to the main organ systems implicated in cause of death is depicted in Fig. . Social history Majority of the SUDY admissions were that of unmarried individuals, or of minors (< 18 years) with unmarried mothers/guardians (1 243/1 593; 78.03%) (Table ). Where specified, nearly all (135/137; 98.54%) mothers of minors received some level of education, of which the majority completed a secondary level of education (117/135; 86.67%). The type of housing in which the decedents lived was fairly equally distributed between formal (528/1 015; 52.02%) and informal (468/1 015; 46.11%) (Table ). Excluding minors and students, 42.88% (671/1 565) of decedents were not economically active. The annual household income was captured for minors (< 18 years old) only and ranged from R0.00 to R780 000.00, with a mean annual income of R60 566.67. Where available (1 474/1 831; 80.50%), 805/1 474 (54.61%) SUDY cases reported that some form of substance, either alcohol, tobacco products, or illicit drugs, or a combination, was engaged with during the deceased’s lifetime (Fig. ). Of these, 29/805 (3.60%) cases did not specify which substance. Underaged substance-use was noted in seven cases, of which 3/7 engaged with tobacco products only, 2/7 engaged with alcohol only, 1/7 engaged with illicit drugs only, and 1/7 engaged with a combination of alcohol and illicit drugs. A total of 42 individuals were reported to have engaged in physical activity. The leading organ system implicated in the cause of death of these individuals was the cardiovascular system (21/42; 50%). Medical history The medical history of the SUDY victims was collected with the aim of identifying various symptoms, chronic or acute illnesses, or family history that may place one at risk for SUD. Chronic/acute illnesses or infections, and family history that contributed to > 5% of SUDY cases are depicted. Symptoms prior to death were unknown/not reported in 377/1 831 (20.59%) cases. Where specified, symptoms preceding death were experienced in at least 1 363/1 454 (93.74%) cases (Table ). The leading symptom prior to death was breathlessness, experienced in almost a third of cases (450/1 363; 33.02%). ‘Breathlessness’ was the predominant symptom experienced in the age categories 5–13 and 18–40 years and in both sexes, while ‘vomiting (no blood)’ and ‘fitting’ predominated in the 1–4 and 14–17 year age categories, respectively. ‘Vomiting’ and ‘coughing’ were divided into ‘(no blood)’ and ‘blood’ categories, as the aetiology of these symptoms differ. Significant associations between age and symptoms were observed. Adults had a greater risk of chest pains ( p < 0.001), teenagers had a greater risk of fitting prior to death ( p < 0.001), and children had a greater risk of foaming at the mouth/nose ( p = 0.001), paralysis ( p < 0.001) and weakness before death ( p < 0.001). In general, a greater proportion of toddlers experienced symptoms prior to death than other age groups. Significantly more toddlers had reported diarrhoea ( p < 0.001), vomiting (no blood), coughing (no blood) ( p < 0.001), fever ( p < 0.001), and general listlessness ( p < 0.001). Sex was significantly associated with symptoms with a significantly greater proportion of females having a history of breathlessness ( p < 0.001) abdominal pain ( p = 0.01), vomiting (no blood) ( p < 0.001), foaming at the mouth/nose ( p = 0.032), headache ( p < 0.001), paralysis ( p = 0.005), or weakness ( p = 0.011). At least 874/1 594 (54.83%) cases herein had a chronic or acute illness during their lifetime (Table ). The three main chronic or acute illnesses identified were TB-exposure (210/874; 24.03%), human immunodeficiency virus (HIV)-exposure (141/872; 16.13%) and epilepsy (139/872; 15.90%). At least 394/909 (43.34%) cases herein had a family history of disease or illness, of which asthma (147/394; 37.31%) and heart disease (119/394; 30.20%) predominated.   SRM received a total of 34 601 admissions between 1 January 2010 and 31 December 2019. The total number of SUDY admissions to SRM in the 10-year study period was 1 997, thus comprising 5.77% of the 10-year caseload. This equates to approximately 200 SUDY admissions to SRM annually. A total of 52 cases were identified as potential candidates for a molecular autopsy, and of these, 47/52 (90.38%) had biological samples available for future investigations (Fig. ).   Age and sex The mean age for the overall SUDY population was 26.89 ± 10.87 years. The mean age of the male and female SUDY admissions was 27.21 ± 10.89 and 26.35 ± 10.82 years, respectively. Within the children age category, there was a significantly greater proportion of females compared to males ( p = 0.028). No significant difference between the proportion of male and female was observed in the toddler, teenager or adult age categories. Males accounted for the majority (1 250/1 997; 62.59%) of the SUDY admissions within the 10-year study period. However, the male SUDY admissions represented only 4.7% (1 250/26 596) of the total male admissions to SRM over the 10 years, whereas the female SUDY admissions represented 9.43% (747/7 925) of the total female admissions to SRM over the 10 years. There were 80 admissions to SRM over the study period with undetermined sex. Upon dividing the study population into SUDC (1–18 years) and SUD in adults (SUDA) (18–40 years) age groups, these groups accounted for 0.90% and 4.87% of the 10-year SRM caseload, respectively. With respect to the prevalence of admissions across the ages, from 1 to 40 years, one-year olds comprised the largest individual age group of SUDY admissions to SRM (6.56%), and 67.01% (132/197) of SUDY admissions within the 1–4 year age category (Fig. ). SRM received few 2–15 year old SUDY admissions. More SUDY cases were received from older age groups, peaking again between the ages 30–35 years. The 1–4 year old SUDY admissions comprised the largest proportion of SRM admissions per age category for the study period (197/603; 32.67%), based on the Office Autopsy Database. BMI The mean BMI of the SUDY admissions to SRM in the 10-year period was 23.44 ± 7.22. The ‘underweight’ group may be overrepresented as several SUDY admissions comprised decomposed remains. The BMI and weight status is presented in Fig. for males and females. The mean female and male BMI were 25.73 ± 7.22 and 22.04 ± 7.22 ( p < 0.01), respectively. A significant association was identified between sex and weight status ( p < 0.001). The male sex accounted for the majority of the underweight ( p < 0.001) and normal admissions ( p < 0.001), whereas the female sex accounted for majority of the overweight admissions ( p < 0.001). The pulmonary system ( n = 552; 30.16%) and cardiovascular system ( n = 392; 21.42%) were the two most prominent organ systems associated with death in SUDY cases. Weight status was significantly associated with involvement of the cardiovascular system ( p < 0.001) with a significantly greater proportion of individuals with cardiovascular involvement being classified as overweight ( p < 0.001). Similarly, weight status was significantly associated with involvement of the pulmonary system ( p < 0.001), however a significantly greater proportion of individuals with pulmonary involvement were classified as underweight ( p < 0.001).   The mean age for the overall SUDY population was 26.89 ± 10.87 years. The mean age of the male and female SUDY admissions was 27.21 ± 10.89 and 26.35 ± 10.82 years, respectively. Within the children age category, there was a significantly greater proportion of females compared to males ( p = 0.028). No significant difference between the proportion of male and female was observed in the toddler, teenager or adult age categories. Males accounted for the majority (1 250/1 997; 62.59%) of the SUDY admissions within the 10-year study period. However, the male SUDY admissions represented only 4.7% (1 250/26 596) of the total male admissions to SRM over the 10 years, whereas the female SUDY admissions represented 9.43% (747/7 925) of the total female admissions to SRM over the 10 years. There were 80 admissions to SRM over the study period with undetermined sex. Upon dividing the study population into SUDC (1–18 years) and SUD in adults (SUDA) (18–40 years) age groups, these groups accounted for 0.90% and 4.87% of the 10-year SRM caseload, respectively. With respect to the prevalence of admissions across the ages, from 1 to 40 years, one-year olds comprised the largest individual age group of SUDY admissions to SRM (6.56%), and 67.01% (132/197) of SUDY admissions within the 1–4 year age category (Fig. ). SRM received few 2–15 year old SUDY admissions. More SUDY cases were received from older age groups, peaking again between the ages 30–35 years. The 1–4 year old SUDY admissions comprised the largest proportion of SRM admissions per age category for the study period (197/603; 32.67%), based on the Office Autopsy Database.   The mean BMI of the SUDY admissions to SRM in the 10-year period was 23.44 ± 7.22. The ‘underweight’ group may be overrepresented as several SUDY admissions comprised decomposed remains. The BMI and weight status is presented in Fig. for males and females. The mean female and male BMI were 25.73 ± 7.22 and 22.04 ± 7.22 ( p < 0.01), respectively. A significant association was identified between sex and weight status ( p < 0.001). The male sex accounted for the majority of the underweight ( p < 0.001) and normal admissions ( p < 0.001), whereas the female sex accounted for majority of the overweight admissions ( p < 0.001). The pulmonary system ( n = 552; 30.16%) and cardiovascular system ( n = 392; 21.42%) were the two most prominent organ systems associated with death in SUDY cases. Weight status was significantly associated with involvement of the cardiovascular system ( p < 0.001) with a significantly greater proportion of individuals with cardiovascular involvement being classified as overweight ( p < 0.001). Similarly, weight status was significantly associated with involvement of the pulmonary system ( p < 0.001), however a significantly greater proportion of individuals with pulmonary involvement were classified as underweight ( p < 0.001).   Geographical location of the SUDY admissions All incidents of SUD are to be reported to the nearest South African Police Services (SAPS) station . The SAPS station that received the highest number of SUDY cases in the 10-year study period was Nyanga (294/1 997; 14.72%), followed by Gugulethu (184/1 997; 9.21%) and Mitchell’s Plain (178/1 997; 8.91%). Monthly and seasonal distribution of SUDY admissions to SRM The cumulative monthly SUDY admissions to SRM in the 10-year study period peaked in June and December (Fig. ), representing a seasonal peak at the beginning of winter and summer, respectively, in a South African context. The winter season experienced the highest frequency of SUDY, followed by spring, autumn, and summer ( p = 0.0233). Circumstances surrounding death Where specified, the most frequently recorded position at death was ‘lying down’, more specifically supine (728/1 262; 57.69%), prone (179/1 262; 14.18%), and side (157/1 262; 12,44%) (Fig. a). A significant association was identified between sex and position at death ( p = 0.002). A significantly greater proportion of males were found lying prone ( p < 0.001) or supine ( p = 0.0251) at death than females. No other positions were significantly associated with sex. Position at death was significantly associated with age group ( p < 0.001), with toddlers having a greater risk of dying in a supine position or lying on their side than other age groups. Where specified, the most frequently reported locations at death were residential (897/1 979; 45.33%) and medical centre (697/1 979; 35.22%) (Fig. b). A significant association was identified between age and location at death ( p = 0.001), with more adults dying outdoors ( p < 0.001), and in residential settings ( p = 0.0214). Toddlers had a greater risk of being declared dead at a medical centre ( p < 0.001). Sex was significantly associated with location at death ( p < 0.001). A significantly greater proportion of males were found outdoors ( p < 0.001), with females having a greater risk of being declared dead at medical centres ( p < 0.001). Where specified, the most frequently reported activity at/before death was ‘sleeping’ (484/936; 51.71%), and ‘resting’ (212/936; 22.65%) (Fig. c). A significant association was identified between age and activity at/before death ( p < 0.001), with more toddlers dying while eating, and more children and toddlers dying while at play or sleeping. A significant association between sex and activity at/before death was observed ( p < 0.001). A greater proportion of males died during physical activity, while a greater proportion of females died during domestic work.   All incidents of SUD are to be reported to the nearest South African Police Services (SAPS) station . The SAPS station that received the highest number of SUDY cases in the 10-year study period was Nyanga (294/1 997; 14.72%), followed by Gugulethu (184/1 997; 9.21%) and Mitchell’s Plain (178/1 997; 8.91%).   The cumulative monthly SUDY admissions to SRM in the 10-year study period peaked in June and December (Fig. ), representing a seasonal peak at the beginning of winter and summer, respectively, in a South African context. The winter season experienced the highest frequency of SUDY, followed by spring, autumn, and summer ( p = 0.0233).   Where specified, the most frequently recorded position at death was ‘lying down’, more specifically supine (728/1 262; 57.69%), prone (179/1 262; 14.18%), and side (157/1 262; 12,44%) (Fig. a). A significant association was identified between sex and position at death ( p = 0.002). A significantly greater proportion of males were found lying prone ( p < 0.001) or supine ( p = 0.0251) at death than females. No other positions were significantly associated with sex. Position at death was significantly associated with age group ( p < 0.001), with toddlers having a greater risk of dying in a supine position or lying on their side than other age groups. Where specified, the most frequently reported locations at death were residential (897/1 979; 45.33%) and medical centre (697/1 979; 35.22%) (Fig. b). A significant association was identified between age and location at death ( p = 0.001), with more adults dying outdoors ( p < 0.001), and in residential settings ( p = 0.0214). Toddlers had a greater risk of being declared dead at a medical centre ( p < 0.001). Sex was significantly associated with location at death ( p < 0.001). A significantly greater proportion of males were found outdoors ( p < 0.001), with females having a greater risk of being declared dead at medical centres ( p < 0.001). Where specified, the most frequently reported activity at/before death was ‘sleeping’ (484/936; 51.71%), and ‘resting’ (212/936; 22.65%) (Fig. c). A significant association was identified between age and activity at/before death ( p < 0.001), with more toddlers dying while eating, and more children and toddlers dying while at play or sleeping. A significant association between sex and activity at/before death was observed ( p < 0.001). A greater proportion of males died during physical activity, while a greater proportion of females died during domestic work.   Following a post-mortem investigation, the cause of death was deemed natural, under investigation, unnatural and undetermined in 1 460/1 931 (75.56%), 280/1 931 (14.50%), 101/1 931 (5.23%) and 91/1 931 (4.71%) of cases, respectively. Where affidavits were available, the extent of post-mortem investigation was external in 724/1 930 (37.51%) cases, partial in 134/1 930 (6.94%) cases, and full in 1 072/1 930 (55.54%) cases. Of the cases with a presumed manner of death, ancillary investigations were performed in 1 873/1 931 (97.00%) cases. The frequency of ancillary investigations performed is depicted in Table . Unnatural deaths did not undergo any further analysis as they do not meet the study criteria. Additionally, deaths with a missing cause of death outcome (65/1 997; 3.25%) were excluded to avoid misrepresentation of possible risk factors for SUDY. The organ system involved in the cause of death of natural SUDY cases was not specified in 243/1 460 (16.64%) cases. When specified, the main organ system implicated was the pulmonary system (550/1 217; 45.19%), followed by the cardiovascular system (387/1 217; 31.80%), and central nervous system (166/1 217; 13.64%) (Table ). The greatest overlap of organ systems existed between the pulmonary and cardiovascular systems (63/1 217; 5.18%). The overall leading cause of death in specified natural cases was pneumonia (142/830; 17.11%), followed by tuberculosis (TB) (117/830; 14.10%). Previous TB-exposure during lifetime was only reported in 57/117 (48.72%) SUDY cases whose cause of death was determined to be TB. The leading causes of death in specified natural deaths were assessed by organ system and age category (Table ). Notably, infectious diseases accounted for at least 396/1 220 (32.46%) of specific/semi-specific natural causes of SUDY cases. The proportion of infectious and non-infectious related deaths pertaining to the main organ systems implicated in cause of death is depicted in Fig. .   Majority of the SUDY admissions were that of unmarried individuals, or of minors (< 18 years) with unmarried mothers/guardians (1 243/1 593; 78.03%) (Table ). Where specified, nearly all (135/137; 98.54%) mothers of minors received some level of education, of which the majority completed a secondary level of education (117/135; 86.67%). The type of housing in which the decedents lived was fairly equally distributed between formal (528/1 015; 52.02%) and informal (468/1 015; 46.11%) (Table ). Excluding minors and students, 42.88% (671/1 565) of decedents were not economically active. The annual household income was captured for minors (< 18 years old) only and ranged from R0.00 to R780 000.00, with a mean annual income of R60 566.67. Where available (1 474/1 831; 80.50%), 805/1 474 (54.61%) SUDY cases reported that some form of substance, either alcohol, tobacco products, or illicit drugs, or a combination, was engaged with during the deceased’s lifetime (Fig. ). Of these, 29/805 (3.60%) cases did not specify which substance. Underaged substance-use was noted in seven cases, of which 3/7 engaged with tobacco products only, 2/7 engaged with alcohol only, 1/7 engaged with illicit drugs only, and 1/7 engaged with a combination of alcohol and illicit drugs. A total of 42 individuals were reported to have engaged in physical activity. The leading organ system implicated in the cause of death of these individuals was the cardiovascular system (21/42; 50%).   The medical history of the SUDY victims was collected with the aim of identifying various symptoms, chronic or acute illnesses, or family history that may place one at risk for SUD. Chronic/acute illnesses or infections, and family history that contributed to > 5% of SUDY cases are depicted. Symptoms prior to death were unknown/not reported in 377/1 831 (20.59%) cases. Where specified, symptoms preceding death were experienced in at least 1 363/1 454 (93.74%) cases (Table ). The leading symptom prior to death was breathlessness, experienced in almost a third of cases (450/1 363; 33.02%). ‘Breathlessness’ was the predominant symptom experienced in the age categories 5–13 and 18–40 years and in both sexes, while ‘vomiting (no blood)’ and ‘fitting’ predominated in the 1–4 and 14–17 year age categories, respectively. ‘Vomiting’ and ‘coughing’ were divided into ‘(no blood)’ and ‘blood’ categories, as the aetiology of these symptoms differ. Significant associations between age and symptoms were observed. Adults had a greater risk of chest pains ( p < 0.001), teenagers had a greater risk of fitting prior to death ( p < 0.001), and children had a greater risk of foaming at the mouth/nose ( p = 0.001), paralysis ( p < 0.001) and weakness before death ( p < 0.001). In general, a greater proportion of toddlers experienced symptoms prior to death than other age groups. Significantly more toddlers had reported diarrhoea ( p < 0.001), vomiting (no blood), coughing (no blood) ( p < 0.001), fever ( p < 0.001), and general listlessness ( p < 0.001). Sex was significantly associated with symptoms with a significantly greater proportion of females having a history of breathlessness ( p < 0.001) abdominal pain ( p = 0.01), vomiting (no blood) ( p < 0.001), foaming at the mouth/nose ( p = 0.032), headache ( p < 0.001), paralysis ( p = 0.005), or weakness ( p = 0.011). At least 874/1 594 (54.83%) cases herein had a chronic or acute illness during their lifetime (Table ). The three main chronic or acute illnesses identified were TB-exposure (210/874; 24.03%), human immunodeficiency virus (HIV)-exposure (141/872; 16.13%) and epilepsy (139/872; 15.90%). At least 394/909 (43.34%) cases herein had a family history of disease or illness, of which asthma (147/394; 37.31%) and heart disease (119/394; 30.20%) predominated.   This is the first study to investigate and document the profile and risk factors of SUDY victims in a South African setting. International research has been conducted on this population, and other forensic mortuaries in South Africa have investigated the SUDA (≥ 18 years) and SUDC (1–18 years) populations, respectively . Although both populations overlap with SUDY, it is critical to investigate this markedly understudied population as a whole. Considering the novel nature of this study, the findings herein cannot be fully compared in a South African context. Nevertheless, this study adds to the growing body of literature on SUD. Incidence of SUDY admitted to SRM SUDY accounted for 5.77% of the 10-year caseload at SRM (Fig. ). This is similar to a report from Australia over a 9-year study period . Although the proportion of these deaths may appear small, the sudden and unexpected nature of these deaths can have an immense impact on loved ones. It is also probable that the proportion of these deaths may be understated as a result of the large homicide burden experienced by SRM . Two local studies found that SUDA and SUDC accounted for 6.10% and 0.86% of their respective mortuaries’ caseloads . Similarly, upon dividing the SUDY population of the present study into SUDA and SUDC groups, these groups accounted for 4.87% and 0.90% of the SRM caseload, respectively. Demographics and physical profile of the SUDY admissions Males accounted for nearly two thirds of the SUDY population (62.59%), which is in agreement with local and international literature . The mean age of the SUDY population herein was similar to that found by other researchers , although further comparison was hindered due to varying age inclusion criteria between studies. Accounting for the total SRM intake data per age category over the 10 years, toddlers (1–4 years) comprised the largest proportion of SUD admissions, suggesting that the risk for SUD is heightened during the earlier years of life (Fig. a). A substantial body of data indicates that obesity and an overweight status increase the risk of cardiovascular diseases, including heart failure, coronary heart disease, and atrial fibrillation . However, data pertaining to the association between adiposity and sudden cardiac death (SCD) is limited and inconsistent . The significant association between being overweight and the cardiovascular system involvement in the cause of death herein suggests that being overweight is a risk factor for SCD in young people. It is of major public health importance to investigate the link between excess BMI and an increased risk for SCD in light of the increased prevalence of overweight and obesity on a global scale, as this could contribute towards the development of prevention guidelines . Almirall et al.  identified that being underweight is a risk factor for community-acquired pneumonia which corroborates the significant association identified between the underweight status and pulmonary system herein. This finding may be explained by nutritional deficiency or underlying immune-related diseases . SUDY admission profiles A variety of socioeconomic levels are represented in the west metropole of the City of Cape Town . Within the lower socioeconomic suburbs, restricted access to medical centres and resources has been reported . This may explain why the low socioeconomic, densely populated neighbouring regions of Nyanga, Gugulethu and Mitchell’s Plain were distinguished SUDY hotspots in this study . Seasonal variation in SUD has been documented in several publications suggesting that SUD may be linked to external factors such as climatic conditions . The seasonal peak of SUDY in winter aligns with Katz et al.  in the Negev Desert region of Israel. This phenomenon may be explained by the cold winter spells, which exacerbate cardiovascular and pulmonary diseases . Indeed, Ryti et al.  has identified an elevated risk of SCD with preceding cold spells. The majority of SUDY victims being found in a ‘lying down’ position (Fig. a) corresponds with the literature , however, contrast to other research, majority of our SUDY victims were found in a supine position. Majority of deaths occurred during sleep (Fig. c), which is consistent with majority of deaths occurring in residential settings (Fig. b). Indeed, there is a consistent pattern for residential locations in the literature , which may indicate that most victims were unaware of a prevailing disease or condition, refused to seek or simply could not afford the necessary medical attention . Therefore, initiatives should be implemented to help educate all members of society regarding the importance of recognising the warning signs and symptoms of various medical conditions, as well as the importance of seeking medical attention promptly . Cause of death and medical history SUDs have been found to follow a similar pattern to the disease pattern prevalent in any given geographical region, and thus vary globally . It is well established that the cardiovascular, pulmonary, and central nervous systems constitute the most prevalent organ systems implicated in SUD , which is corroborated by this study (Table ). Moreover, breathlessness and chest pain were two of the leading symptoms experienced prior to death (Table ), which are cardinal symptoms of cardiovascular and pulmonary diseases . In contrast to numerous international studies where cardiovascular disease was the leading cause of SUD , this study found that the majority of the deaths were of pulmonary origin (Table ). This is likely related to the TB epidemic in South Africa, as South Africa is one of 30 high TB incidence countries that accounted for 87% of global estimated incidence TB cases in 2022 . The fact that only 48.72% cases with TB implicated in cause of death had documented prior TB-exposure during the deceased’s lifetime indicates that a large proportion of SUDY due to TB were undiagnosed prior to death. A study investigating the burden of diagnosed and undiagnosed TB in SUDC and SUDA at Tygerberg Mortuary in Cape Town found that active TB identified at autopsy was undiagnosed prior to death in an alarming 91.70% of cases . The leading cause of death herein was pneumonia, accounting for 17.11% specified natural SUDY cases. This aligns with the research from developing countries  . Nonetheless, multiple studies have identified pneumonia as one of the leading causes of death in non-cardiac SUD . In 2019, pneumonia and other lower respiratory tract infections were classified as the most fatal group of infectious diseases, and together ranked as the fourth cause of death globally . Deaths from pneumonia comprised a larger proportion of the 1–4 year age category (25.30%) than any other age category in the present study (Table ). It is widely known that children < 5 years of age are at greater risk for contracting pneumonia, and this may be related to their under-developed immune systems . Indeed, in 2019, pneumonia comprised 22% of all deaths in children aged 1–5 years according to the World Health Organization, thus supporting our observation . The main cause of death involving the cardiovascular system was ischaemic heart disease (Table ), which aligns with other literature . Although central nervous system causes of death were identified to a lower extent in the present study and appear to be less prevalent in causes of SUD in local studies , SUD due to epilepsy (SUDEP) is an important, well-documented cause of SUD in international literature . Communicable disease-related deaths represented at least 32.46% of SUDY, which is concerning considering communicable diseases are not only preventable but can also be treated if antibiotics are administered appropriately and timeously . In the present study, post-mortem microbiology testing had only been performed in 8.60% of cases (Table ). In light of this, it is evident that microbiological investigations should be conducted more routinely in SUD cases at post-mortem, especially when a cause of death of an infectious nature is suspected. TB- and HIV-exposure were the two leading medical histories identified (Table ). This is not surprising since South Africa has the world’s largest antiretroviral therapy (ART) program and has made the World Health Organization’s three global lists of high-incidence countries for TB, HIV-associated TB, and multidrug-resistant/rifampicin-resistant TB . This may explain a considerable portion of deaths, given that HIV is known to compromise the immune system, rendering affected individuals more vulnerable to other diseases. A positive family history was reported in 43.34% of cases, which may indicate that many of these victims failed to seek medical attention or adhere to preventative measures, or lacked the resources to do so. Although participation in physical activity was only reported in few cases, 50% of these SUDY cases were of cardiovascular origin. This is supported by Maron et al.  investigating SUDY in competitive athletes in the United States. However, Corrado et al.  found that the increased mortality associated with physical activity in adolescents and young adults was not directly caused by the physical activity, but rather from the exercise provoking a pre-existing cardiovascular disease. Nonetheless, physical activity could not be fully investigated as the questionnaires did not specifically refer to the physical activity of the deceased, and thus, minimal cases had reported on this variable. Social history Several studies have investigated and identified associations between socioeconomic status and SUD . However, the literature is more abundant on SUD in infants (SUDI) in this regard, which hinders comparison of our study population. These studies consistently demonstrate an increased risk for SUDI with lower socioeconomic status . The effects of socioeconomic status are likely to be mediated by other factors, such as occupation, education, and housing, rather than being directly causal. Health outcomes have been shown to be affected by socioeconomic status . More specifically, individuals from lower socioeconomic backgrounds have a greater degree of risk factors for cardiovascular disease  and demonstrate longer delays when seeking medical treatment than those from higher socioeconomic backgrounds . Although the majority of SUDY victims in the present study resided in formal housing, a large proportion resided in informal housing (46.11%) (Table ). It has been demonstrated that residents of informal settlements face a substantial health burden, as they are exposed to unsafe water, unsanitary conditions, and overcrowding, which ultimately heightens the risk for contracting infectious diseases . This may also explain the large proportion of infectious-related deaths in our study. Although marital status does not exclusively reflect socioeconomic status, it has been consistently associated with measures of social status, particularly in studies examining infant outcomes . Studies have described marriage to have positive effects on the health of unemployed women by providing a source of financial and social support . Moreover, marriage between two working individuals implies that there are two sources of income. Thus, married individuals may be less hesitant to seek medical attention than unmarried individuals. It is therefore unsurprising that 78.03% of SUDY victims were unmarried or were minors with unmarried parents/guardians (Table ). Research by Chaudhari and Mohite  found that workers in industries, mills and shops constituted the highest number of SUD cases and attributed this to low socioeconomic status, neglect of warning signs of illness, unaffordable medical assistance, as well as physical and mental stress associated with these occupations . This low affordability to medical care may be particularly relevant in the present study as 42.88% victims were unemployed (Table ). A key aspect of an individual’s social history is substance use. Worldwide, illicit drug use for recreational purposes remains a major problem and has been associated with a heightened risk for SUD compared with the general population . In more than half the SUDY cases (54.61%), some form of substance was engaged with during the deceased’s lifetime, of which alcohol was the most prevalent (Fig. ). Due to the ease of access to alcohol and the presence of numerous lower socioeconomic residences in the west metropole of Cape Town, individuals often have access to unlicensed alcohol-serving establishments . Interestingly, underaged substance-use was noted in seven cases. This finding was unsurprising given that nationally, 49.60%, 29.50%, and 12.70% of learners had engaged with alcohol, tobacco products, and dagga in their lifetime, respectively, based on the results of a South African survey conducted in 2008 . Moreover, there was a significantly higher prevalence of each of these substances in the Western Cape province when compared to the national average. As only 32.31% of the cases had toxicology performed post-mortem (Table ), it is likely that the prevalence of substance-use reported herein is an underestimate, thus motivating for the implementation of routine toxicology in all cases of SUD. Molecular autopsy candidates Currently, molecular autopsies are being developed in a local setting to facilitate the identification of cause of death, particularly when undetermined after a thorough post-mortem investigation. Studies have documented varying resolution rates of previously unexplained SUD cases of up to 44% . Thus, molecular autopsies present an appealing option for grieving relatives seeking answers . The results from the molecular autopsy may bring closure to relatives and encourage them to take the necessary next steps. This may include seeking genetic counselling and testing themselves, should they be at-risk . Since unresolved SUDs may have heritable origins, cardiological and genetic assessment of surviving relatives of SUD victims is recommended as this may expose a possible underlying condition and unveil presymptomatic or asymptomatic carriers . The results from a molecular autopsy may also be beneficial for the family in that it may provide a more definitive family medical history and assist with family planning in cases of SUDI. Candidates for molecular autopsies must be meticulously selected. Currently, there is a high caseload associated with forensic laboratories in South Africa which can delay ancillary investigations. Thus, molecular autopsies have the potential to alleviate this burden for both the laboratories and grieving families. For this reason, cases that are under investigation (pending ancillary testing results) are also assessed for their potential as molecular autopsy candidates. Additionally, non-specific (i.e. ‘natural causes’) and semi-specific natural deaths (i.e. ‘lung pathology’ or ‘cardiorespiratory causes’) are also assessed in the hopes of identifying a more specific cause of death, perhaps with an underlying genetic mechanism. This is important for the prevention of future SUD, particularly in genetically predisposed relatives. The retention of biological samples at autopsy is currently at the discretion of the forensic pathologist. Although majority of the molecular autopsy candidates identified had biological samples available (90.38%) (Fig. ), it is unfortunate that some did not. This study advocates for the mandatory retention of biological samples in undetermined cases or in ill-defined causes of death, to allow for future investigations. Limitations The retrospective nature of this study meant engaging with medico-legal case files, where there is inevitable incompleteness and inherent difficulties in ensuring accuracy. Missing forms and details on forms were frequently encountered, however this could not be avoided. Several factors may have contributed to these issues, such as the extensive caseload experienced by SRM, the lengthy questionnaires, the emotional and delicate nature of interviews, the inadequate training of forensic and police officers due to resource restrictions, poor access to transportation for relatives to attend an interview at the mortuary, as well as language barriers . Language barriers may be a particularly significant factor as South Africa is a highly diverse, multi-lingual country . Additionally, the deceased may have been unidentified when found and thus only minimal details could be captured for these decedents. Although it is preferable to utilise more descriptive criteria when evaluating SUDY (such as time between onset of symptoms and death), the authors were limited in this regard as the National Health Act (61 of 2003) of South Africa does not specify time from symptom onset until death for inclusion in the SUD category, and this data is not always available from the case files. Conclusion SUD has an important place in all medicolegal autopsies, and identifying the risk factors and lifestyle contributors to SUDY may contribute greatly to the public health sector. In addition, the diverse population of South Africa warrants investigation into the socioeconomic standing and demographics of SUDY. Being overweight was significantly associated with cardiovascular-linked SUD, while being underweight was significantly associated with pulmonary-linked SUD. Therefore, making the necessary lifestyle and dietary modifications may improve the health of those most vulnerable, and mitigate the risk for these fatalities. A large proportion of SUDY admissions had a reported acute/chronic illness and/or family history, indicating a missed opportunity to diagnose or treat, and ultimately prevent the death. If family history of illness is present, SUDY could be prevented by early screening of risk factors and familial diseases. The leading symptoms experienced prior to death were breathlessness, vomiting (no blood), and chest pain. This finding urges public awareness, especially among healthcare workers, to recognise these early symptoms of SUD and to encourage medical intervention as soon as possible. Furthermore, this study demonstrates the importance of post-mortem ancillary investigations in identifying cause of death in SUDY, especially in a country with a large burden of substance abuse and infectious disease. Accordingly, ancillary investigations should become routine components of post-mortem examinations of SUD. Our findings warrant that the retention of biological samples at autopsy becomes a statutory requirement in unresolved and non-specific natural SUD cases. This may assist in identifying cause of death on a molecular basis through further genetic investigations. The results of a molecular autopsy are invaluable to the surviving family as well as to the public health sectors.   SUDY accounted for 5.77% of the 10-year caseload at SRM (Fig. ). This is similar to a report from Australia over a 9-year study period . Although the proportion of these deaths may appear small, the sudden and unexpected nature of these deaths can have an immense impact on loved ones. It is also probable that the proportion of these deaths may be understated as a result of the large homicide burden experienced by SRM . Two local studies found that SUDA and SUDC accounted for 6.10% and 0.86% of their respective mortuaries’ caseloads . Similarly, upon dividing the SUDY population of the present study into SUDA and SUDC groups, these groups accounted for 4.87% and 0.90% of the SRM caseload, respectively.   Males accounted for nearly two thirds of the SUDY population (62.59%), which is in agreement with local and international literature . The mean age of the SUDY population herein was similar to that found by other researchers , although further comparison was hindered due to varying age inclusion criteria between studies. Accounting for the total SRM intake data per age category over the 10 years, toddlers (1–4 years) comprised the largest proportion of SUD admissions, suggesting that the risk for SUD is heightened during the earlier years of life (Fig. a). A substantial body of data indicates that obesity and an overweight status increase the risk of cardiovascular diseases, including heart failure, coronary heart disease, and atrial fibrillation . However, data pertaining to the association between adiposity and sudden cardiac death (SCD) is limited and inconsistent . The significant association between being overweight and the cardiovascular system involvement in the cause of death herein suggests that being overweight is a risk factor for SCD in young people. It is of major public health importance to investigate the link between excess BMI and an increased risk for SCD in light of the increased prevalence of overweight and obesity on a global scale, as this could contribute towards the development of prevention guidelines . Almirall et al.  identified that being underweight is a risk factor for community-acquired pneumonia which corroborates the significant association identified between the underweight status and pulmonary system herein. This finding may be explained by nutritional deficiency or underlying immune-related diseases .   A variety of socioeconomic levels are represented in the west metropole of the City of Cape Town . Within the lower socioeconomic suburbs, restricted access to medical centres and resources has been reported . This may explain why the low socioeconomic, densely populated neighbouring regions of Nyanga, Gugulethu and Mitchell’s Plain were distinguished SUDY hotspots in this study . Seasonal variation in SUD has been documented in several publications suggesting that SUD may be linked to external factors such as climatic conditions . The seasonal peak of SUDY in winter aligns with Katz et al.  in the Negev Desert region of Israel. This phenomenon may be explained by the cold winter spells, which exacerbate cardiovascular and pulmonary diseases . Indeed, Ryti et al.  has identified an elevated risk of SCD with preceding cold spells. The majority of SUDY victims being found in a ‘lying down’ position (Fig. a) corresponds with the literature , however, contrast to other research, majority of our SUDY victims were found in a supine position. Majority of deaths occurred during sleep (Fig. c), which is consistent with majority of deaths occurring in residential settings (Fig. b). Indeed, there is a consistent pattern for residential locations in the literature , which may indicate that most victims were unaware of a prevailing disease or condition, refused to seek or simply could not afford the necessary medical attention . Therefore, initiatives should be implemented to help educate all members of society regarding the importance of recognising the warning signs and symptoms of various medical conditions, as well as the importance of seeking medical attention promptly .   SUDs have been found to follow a similar pattern to the disease pattern prevalent in any given geographical region, and thus vary globally . It is well established that the cardiovascular, pulmonary, and central nervous systems constitute the most prevalent organ systems implicated in SUD , which is corroborated by this study (Table ). Moreover, breathlessness and chest pain were two of the leading symptoms experienced prior to death (Table ), which are cardinal symptoms of cardiovascular and pulmonary diseases . In contrast to numerous international studies where cardiovascular disease was the leading cause of SUD , this study found that the majority of the deaths were of pulmonary origin (Table ). This is likely related to the TB epidemic in South Africa, as South Africa is one of 30 high TB incidence countries that accounted for 87% of global estimated incidence TB cases in 2022 . The fact that only 48.72% cases with TB implicated in cause of death had documented prior TB-exposure during the deceased’s lifetime indicates that a large proportion of SUDY due to TB were undiagnosed prior to death. A study investigating the burden of diagnosed and undiagnosed TB in SUDC and SUDA at Tygerberg Mortuary in Cape Town found that active TB identified at autopsy was undiagnosed prior to death in an alarming 91.70% of cases . The leading cause of death herein was pneumonia, accounting for 17.11% specified natural SUDY cases. This aligns with the research from developing countries  . Nonetheless, multiple studies have identified pneumonia as one of the leading causes of death in non-cardiac SUD . In 2019, pneumonia and other lower respiratory tract infections were classified as the most fatal group of infectious diseases, and together ranked as the fourth cause of death globally . Deaths from pneumonia comprised a larger proportion of the 1–4 year age category (25.30%) than any other age category in the present study (Table ). It is widely known that children < 5 years of age are at greater risk for contracting pneumonia, and this may be related to their under-developed immune systems . Indeed, in 2019, pneumonia comprised 22% of all deaths in children aged 1–5 years according to the World Health Organization, thus supporting our observation . The main cause of death involving the cardiovascular system was ischaemic heart disease (Table ), which aligns with other literature . Although central nervous system causes of death were identified to a lower extent in the present study and appear to be less prevalent in causes of SUD in local studies , SUD due to epilepsy (SUDEP) is an important, well-documented cause of SUD in international literature . Communicable disease-related deaths represented at least 32.46% of SUDY, which is concerning considering communicable diseases are not only preventable but can also be treated if antibiotics are administered appropriately and timeously . In the present study, post-mortem microbiology testing had only been performed in 8.60% of cases (Table ). In light of this, it is evident that microbiological investigations should be conducted more routinely in SUD cases at post-mortem, especially when a cause of death of an infectious nature is suspected. TB- and HIV-exposure were the two leading medical histories identified (Table ). This is not surprising since South Africa has the world’s largest antiretroviral therapy (ART) program and has made the World Health Organization’s three global lists of high-incidence countries for TB, HIV-associated TB, and multidrug-resistant/rifampicin-resistant TB . This may explain a considerable portion of deaths, given that HIV is known to compromise the immune system, rendering affected individuals more vulnerable to other diseases. A positive family history was reported in 43.34% of cases, which may indicate that many of these victims failed to seek medical attention or adhere to preventative measures, or lacked the resources to do so. Although participation in physical activity was only reported in few cases, 50% of these SUDY cases were of cardiovascular origin. This is supported by Maron et al.  investigating SUDY in competitive athletes in the United States. However, Corrado et al.  found that the increased mortality associated with physical activity in adolescents and young adults was not directly caused by the physical activity, but rather from the exercise provoking a pre-existing cardiovascular disease. Nonetheless, physical activity could not be fully investigated as the questionnaires did not specifically refer to the physical activity of the deceased, and thus, minimal cases had reported on this variable.   Several studies have investigated and identified associations between socioeconomic status and SUD . However, the literature is more abundant on SUD in infants (SUDI) in this regard, which hinders comparison of our study population. These studies consistently demonstrate an increased risk for SUDI with lower socioeconomic status . The effects of socioeconomic status are likely to be mediated by other factors, such as occupation, education, and housing, rather than being directly causal. Health outcomes have been shown to be affected by socioeconomic status . More specifically, individuals from lower socioeconomic backgrounds have a greater degree of risk factors for cardiovascular disease  and demonstrate longer delays when seeking medical treatment than those from higher socioeconomic backgrounds . Although the majority of SUDY victims in the present study resided in formal housing, a large proportion resided in informal housing (46.11%) (Table ). It has been demonstrated that residents of informal settlements face a substantial health burden, as they are exposed to unsafe water, unsanitary conditions, and overcrowding, which ultimately heightens the risk for contracting infectious diseases . This may also explain the large proportion of infectious-related deaths in our study. Although marital status does not exclusively reflect socioeconomic status, it has been consistently associated with measures of social status, particularly in studies examining infant outcomes . Studies have described marriage to have positive effects on the health of unemployed women by providing a source of financial and social support . Moreover, marriage between two working individuals implies that there are two sources of income. Thus, married individuals may be less hesitant to seek medical attention than unmarried individuals. It is therefore unsurprising that 78.03% of SUDY victims were unmarried or were minors with unmarried parents/guardians (Table ). Research by Chaudhari and Mohite  found that workers in industries, mills and shops constituted the highest number of SUD cases and attributed this to low socioeconomic status, neglect of warning signs of illness, unaffordable medical assistance, as well as physical and mental stress associated with these occupations . This low affordability to medical care may be particularly relevant in the present study as 42.88% victims were unemployed (Table ). A key aspect of an individual’s social history is substance use. Worldwide, illicit drug use for recreational purposes remains a major problem and has been associated with a heightened risk for SUD compared with the general population . In more than half the SUDY cases (54.61%), some form of substance was engaged with during the deceased’s lifetime, of which alcohol was the most prevalent (Fig. ). Due to the ease of access to alcohol and the presence of numerous lower socioeconomic residences in the west metropole of Cape Town, individuals often have access to unlicensed alcohol-serving establishments . Interestingly, underaged substance-use was noted in seven cases. This finding was unsurprising given that nationally, 49.60%, 29.50%, and 12.70% of learners had engaged with alcohol, tobacco products, and dagga in their lifetime, respectively, based on the results of a South African survey conducted in 2008 . Moreover, there was a significantly higher prevalence of each of these substances in the Western Cape province when compared to the national average. As only 32.31% of the cases had toxicology performed post-mortem (Table ), it is likely that the prevalence of substance-use reported herein is an underestimate, thus motivating for the implementation of routine toxicology in all cases of SUD.   Currently, molecular autopsies are being developed in a local setting to facilitate the identification of cause of death, particularly when undetermined after a thorough post-mortem investigation. Studies have documented varying resolution rates of previously unexplained SUD cases of up to 44% . Thus, molecular autopsies present an appealing option for grieving relatives seeking answers . The results from the molecular autopsy may bring closure to relatives and encourage them to take the necessary next steps. This may include seeking genetic counselling and testing themselves, should they be at-risk . Since unresolved SUDs may have heritable origins, cardiological and genetic assessment of surviving relatives of SUD victims is recommended as this may expose a possible underlying condition and unveil presymptomatic or asymptomatic carriers . The results from a molecular autopsy may also be beneficial for the family in that it may provide a more definitive family medical history and assist with family planning in cases of SUDI. Candidates for molecular autopsies must be meticulously selected. Currently, there is a high caseload associated with forensic laboratories in South Africa which can delay ancillary investigations. Thus, molecular autopsies have the potential to alleviate this burden for both the laboratories and grieving families. For this reason, cases that are under investigation (pending ancillary testing results) are also assessed for their potential as molecular autopsy candidates. Additionally, non-specific (i.e. ‘natural causes’) and semi-specific natural deaths (i.e. ‘lung pathology’ or ‘cardiorespiratory causes’) are also assessed in the hopes of identifying a more specific cause of death, perhaps with an underlying genetic mechanism. This is important for the prevention of future SUD, particularly in genetically predisposed relatives. The retention of biological samples at autopsy is currently at the discretion of the forensic pathologist. Although majority of the molecular autopsy candidates identified had biological samples available (90.38%) (Fig. ), it is unfortunate that some did not. This study advocates for the mandatory retention of biological samples in undetermined cases or in ill-defined causes of death, to allow for future investigations.   The retrospective nature of this study meant engaging with medico-legal case files, where there is inevitable incompleteness and inherent difficulties in ensuring accuracy. Missing forms and details on forms were frequently encountered, however this could not be avoided. Several factors may have contributed to these issues, such as the extensive caseload experienced by SRM, the lengthy questionnaires, the emotional and delicate nature of interviews, the inadequate training of forensic and police officers due to resource restrictions, poor access to transportation for relatives to attend an interview at the mortuary, as well as language barriers . Language barriers may be a particularly significant factor as South Africa is a highly diverse, multi-lingual country . Additionally, the deceased may have been unidentified when found and thus only minimal details could be captured for these decedents. Although it is preferable to utilise more descriptive criteria when evaluating SUDY (such as time between onset of symptoms and death), the authors were limited in this regard as the National Health Act (61 of 2003) of South Africa does not specify time from symptom onset until death for inclusion in the SUD category, and this data is not always available from the case files.   SUD has an important place in all medicolegal autopsies, and identifying the risk factors and lifestyle contributors to SUDY may contribute greatly to the public health sector. In addition, the diverse population of South Africa warrants investigation into the socioeconomic standing and demographics of SUDY. Being overweight was significantly associated with cardiovascular-linked SUD, while being underweight was significantly associated with pulmonary-linked SUD. Therefore, making the necessary lifestyle and dietary modifications may improve the health of those most vulnerable, and mitigate the risk for these fatalities. A large proportion of SUDY admissions had a reported acute/chronic illness and/or family history, indicating a missed opportunity to diagnose or treat, and ultimately prevent the death. If family history of illness is present, SUDY could be prevented by early screening of risk factors and familial diseases. The leading symptoms experienced prior to death were breathlessness, vomiting (no blood), and chest pain. This finding urges public awareness, especially among healthcare workers, to recognise these early symptoms of SUD and to encourage medical intervention as soon as possible. Furthermore, this study demonstrates the importance of post-mortem ancillary investigations in identifying cause of death in SUDY, especially in a country with a large burden of substance abuse and infectious disease. Accordingly, ancillary investigations should become routine components of post-mortem examinations of SUD. Our findings warrant that the retention of biological samples at autopsy becomes a statutory requirement in unresolved and non-specific natural SUD cases. This may assist in identifying cause of death on a molecular basis through further genetic investigations. The results of a molecular autopsy are invaluable to the surviving family as well as to the public health sectors.   