J Pryce

Histological examination in sudden unexpected death in infancy: evidence base for histological sampling

Aim Pathologists currently follow the ‘Kennedy guidelines’ when performing autopsies for sudden unexpected death in infancy (SUDI); these include extensive histological sampling. This study establishes the frequency with which histological examination of visceral organs determines cause of death and examines associations between clinical, macroscopic and microscopic findings. Methods Retrospective review of 546 SUDI autopsies performed for a 10-year period (1996–2005) at a single centre. The proportion of cases in which non-neuropathological histological examination directly determined the cause of death was identified, and clinical, macroscopic and histological findings at autopsy were compared. Results Of 510 SUDIs included, 166 cases were explained SUDI, and of these, 54% (89/166) were identified solely on microscopic examination, based on histology of the lungs in 71 (43%), heart in 13 (8%), liver in 4 (2%) and kidneys in 1 (<1%). The proportions of macroscopically normal organs with significant histological findings were 26% lungs, 2% heart and 1% each of liver and kidneys, but none of spleen, thymus, pancreas or adrenals. Macroscopically abnormal organs were more likely to yield significant histological features. Symptoms preceding death were more common in cases with significant histological findings in lungs, heart, liver and adrenals. Conclusion A non-neuropathological cause of death in explained SUDI can be established from histological examination of lungs, heart, liver and kidneys. Significant histological abnormalities may be detected in selected organs with macroscopically normal appearances. Routine histological sampling of other organs in the absence of specific clinical history or macroscopic abnormalities has a low yield for establishing cause of death.

Difficulties in interpretation of post-mortem microbiology results in unexpected infant death: evidence from a multidisciplinary survey

Background Post-mortem (PM) microbiological investigations are recommended in cases of sudden unexpected death in infancy (SUDI), and infection is a recognised cause of such deaths, but no current evidence-based guidelines exist for the appropriate interpretation of results. Aim To assess interpretive difficulties using a targeted cross-specialty questionnaire. Methods 109 consultant specialists involved in infant death management were given a questionnaire providing information on five hypothetical standardised SUDI cases, which differed only in their PM microbiology findings. Participants classified each case into categories: definite bacterial infection, probable bacterial infection, bacterial growth of uncertain significance and PM contamination. Results 63 (57%) specialists responded. There was no clinical scenario in which complete concordance in interpretation of PM microbiology results was established among participants. In cases with pure growth of Group 2 pathogens such as Group B β-haemolytic Streptococcus, 96% of respondents agreed upon probable or definite bacterial infection. With mixed growth of Group 2 pathogens, 83% reported probable or definite bacterial infection. Growth of organisms such as Staphylococcus aureus caused the most difficulty, with almost equal numbers of participants interpreting the finding as significant or non-significant. There were no consistent differences in interpretation between different specialist groups. Conclusions While there is general agreement in interpretation of PM microbiology findings in some SUDI scenarios, no consensus was achieved for any clinical setting, and variation in the presumed significance between specialists was apparent. In the absence of appropriate evidence-based guidelines, this has practical implications for the management of such deaths in a multidisciplinary setting.

Fatal Aspiration of Foreign Bodies in Infants and Children

Purpose: To investigate the frequency, circumstances, demographics and autopsy findings of infants and children dying as a result of foreign body aspiration. Methods: Retrospective review of autopsy cases in children aged between seven days and 18 years, at one specialist centre over a 16-year period, in which death was the result of aspiration of a foreign body. Results: Ten cases were identified out of a total autopsy population of 2165. Only one individual had an underlying diagnosis potentially contributing to aspiration. All but one case involved aspiration of food, with grapes being a feature of four cases. In cases with a prolonged survival interval, autopsy demonstrated bronchopneumonia and hypoxic-ischaemic encephalopathy. In the remaining cases autopsy findings were non-specific. Conclusions: Fatal aspiration of a foreign body is rare in this population. The cases involve normal children who aspirate food, particularly grapes. There are typically minimal, non-specific findings at autopsy.

Tandem mass spectrometry findings at autopsy for detection of metabolic disease in infant deaths: postmortem changes and confounding factors

Aim Tandem mass spectrometry (MS/MS) is a recommended investigation for sudden unexpected death in infancy (SUDI), but there are limited data regarding yield and potential influencing factors. This study investigates postmortem acylcarnitine profiles in a large cohort of infant deaths from a single centre, including those with metabolic disease. Methods Acylcarnitine results obtained by MS/MS from routine blood/bile spot samples during the standard autopsy investigation were identified from infant deaths over a 14-year period. Results were categorised as normal or abnormal according to the clinical report by a specialist paediatric biochemist. Possible interdependent variables were assessed, multiple linear regression models were constructed and residual comparison was undertaken. Results 397 blood and 268 bile MS/MS results were identified from infant cases, including 255 matched blood–bile pairs. There was significant association between blood acylcarnitine findings and postmortem interval (PMI), body mass index and liver weight. A probable cause of death was identified in 40% of sudden death cases, including 18 (2%) with a definite or highly likely cause of death as underlying metabolic disease; this represented 12 (12%) unexpected deaths in the first week of life and six (<1%) aged 7–365 days. Fatty acid oxidation disorders identified included very long chain acyl-CoA dehydrogenase deficiency, medium chain acyl-CoA dehydrogenase deficiency and carnitine transporter defects. Conclusion Postmortem blood and bile acylcarnitine profiles are influenced by several variables, and PMI can influence MS/MS acylcarnitine results. Metabolic disease may present as SUDI and may be identified from postmortem samples.

Microbiological findings in sudden unexpected death in infancy: comparison of immediate postmortem sampling in casualty departments and at autopsy

Aim Sudden unexpected death in infancy (SUDI) represents the commonest presentation of post-neonatal infant death in the UK. This audit reviews current practice in the investigation of SUDI deaths, with particular regard to the practice of microbiological sampling in emergency departments (ED) compared with samples obtained at the time of autopsy for establishing the cause of death, as suggested by current guidelines. Methods Coronial autopsies performed for the indication of SUDI over a 4-year period at a single specialist centre were reviewed with particular regard to the findings of microbiological investigations performed in ED compared with those performed at the time of autopsy. Results Of 229 SUDI postmortems performed during the period, there were 136 cases in which both bacteriological samples taken in ED and at autopsy were available, including 109 with blood cultures taken at both time points. 66 cases had sterile blood cultures in ED of which 37 (56%) showed positive microbiological growth from autopsy samples including nine (14%) cases with group II pathogens. Group II pathogens were identified from ED samples in six (6%) of the total cases; all but two cases of Staphylococcus aureus were not detected at autopsy. Conclusion Blood cultures obtained at autopsy are associated with a significantly higher rate of positive microbial cultures compared with blood samples taken in life. Most represent easily identified postmortem translocation or overgrowth rather than infection as the cause of death. No cases with a final infective cause of death would have been missed if ED sampling had not been performed.

Use of the complement inhibitor Coversin to treat HSCT-associated TMA

Finding an inherited complement abnormality in HSCT-associated TMA provides a rationale for the use of a complement inhibitor.Alternative complement inhibitors such as Coversin should be considered in patients who are resistant to eculizumab.

Role of routine neuropathological examination for determining cause of death in sudden unexpected deaths in infancy (SUDI)

Background Current guidelines for the investigation of sudden unexpected death in infancy (SUDI) include full neuropathological examination with recommendations for brain fixation for 1–2 weeks. Little evidence is available regarding the yield of such examination in determining cause of death in clinical practice. This study examines the frequency of neuropathological findings determining cause of death at postmortem examination in SUDI in relation to clinical and macroscopic features. Methods All postmortem examinations performed for the indication of SUDI at a single specialist centre over a 14-year period were reviewed, including clinical history, macroscopic and neuropathological findings. Results 6% of postmortem examinations performed for cases of SUDI demonstrated a neuropathological cause of death; in almost all (>90%) the clinical history and/or macroscopic examination suggested the cause of death. In 2% of all cases the cause of death was determined by histological neuropathological examination, but there were no cases in which histological neuropathological examination of a macroscopically normal brain revealed the cause of death in the absence of a ‘neurological history’. Macroscopic brain abnormalities and the presence of a ‘neurological history’ were significantly more likely to yield histological brain abnormalities (11-fold and fourfold, respectively). Conclusions Histological neuropathological examination rarely determines the cause of death in SUDI in the absence of macroscopic abnormalities or neurological clinical history. A macroscopically abnormal brain and the presence of a clinical history of possible neurological disease or of inflicted injury are significantly more likely to be associated with significant histological brain abnormalities.

Immunohistochemical expression of inflammatory markers in sudden infant death; ancillary tests for identification of infection.

Aims Sudden unexpected death in infancy (SUDI) investigation requires extensive ancillary investigations, the results of which, such as postmortem microbiology, can be difficult to interpret. Markers of an inflammatory response, including interleukin 6 (IL-6), c-reactive protein (CRP) and cellular adhesion molecules are elevated in infections, yet little attention has been paid to their assessment after death. This study investigates the role of inflammatory markers in SUDI autopsies for determining cause of death. Methods Cases of SUDI over a 14 year period were identified from an autopsy database and 100 cases were selected for immunohistochemical staining of heart and liver for IL-6, CRP, P-selectin, VCAM-1 and ICAM-1 (CD54), with staining patterns compared between five groups, including infectious and unexplained SUDI. Results There were significant differences between groups. Cases of histological infection demonstrated strongly positive hepatocyte CRP and ICAM-1 expression and increased myocardial staining for CRP. Half of trauma-related deaths demonstrated diffuse hepatic CRP expression but without myocardial CRP staining. Staining of unexplained SUDI cases were predominantly negative, apart from a subgroup in whom Escherichia Coli was identified, who had increased expression of hepatic IL-6. Conclusions There were distinct patterns of organ-specific CRP and ICAM-1 expression in SUDI by cause of death. These markers of inflammation were rarely present in unexplained SUDI suggesting either a non-inflammatory cause of death or a failure to mount an effective acute phase response. Immunohistochemical staining offers potential to identify infection-related deaths and provides insight into SUDI mechanisms.

Clinicopathological features of fatal cardiomyopathy in childhood: An autopsy series

Aim:  Cardiomyopathy, a group of primary myocardial disorders, is an uncommon, but important, cause of death in childhood. This study examines the demographic, clinical and pathological features of fatal cardiomyopathy in childhood with particular reference to its classification and autopsy findings.

Changing patterns of infant death over the last 100 years: autopsy experience from a specialist children's hospital

Objectives Infant mortality has undergone a dramatic reduction in the UK over the past century because of improvements in public health policy and medical advances. Postmortem examinations have been performed at Great Ormond Street Hospital for over 100 years, and analysis of cases across this period has been performed to assess changing patterns of infant deaths undergoing autopsy. Design Autopsy reports from 1909 and 2009 were examined. Age, major pathology and cause of death was reviewed from these cases and entered into an anonymized database. A subsequent comparative analysis was performed. Setting All postmortems performed and reported at Great Ormond Street Hospital in 1909 and 2009. Participants Infant deaths, aged 0–365 days, were identified and subsequently analysed for the two years. Main outcome measures Comparative proportional analysis of postmortem findings from the two time periods. Results Three-hundred and fifty-seven and 347 autopsy reports were identified from 1909 and 2009 including 178 and 128 infant deaths, respectively. The commonest cause of death in 1909 was infection (74%) compared to 20% of deaths in 2009. The most frequent final ‘diagnosis’ in 2009 was ‘unexplained sudden unexpected infant death (SUDI)’, despite a full postmortem including ancillary investigations. In contrast, there were no such cases recorded in 1909, but there were frequent deaths due to gastroenteritis and malnutrition together accounting for 16% of cases, compared to one case of gastroenteritis in 2009. Fifteen percent of 1909 cases had infections which are almost never fatal with appropriate treatment in 2009, including tuberculosis, diphtheria and syphilis. Congenital anomalies were detected with similar frequencies at both time points, (21% and 19% in 1909 and 2009, respectively). Conclusion In the UK, significant changes in patterns of pathology have occurred in paediatric autopsy cases performed at a single specialist centre. Fatal infections and malnutrition (both poverty-related) have reduced yet the incidence of congenital anomalies has remained similar.