Ma Weber

Infection and sudden unexpected death in infancy: a systematic retrospective case review

BACKGROUND The cause and mechanism of most cases of sudden unexpected death in infancy (SUDI) remain unknown, despite specialist autopsy examination. We reviewed autopsy results to determine whether infection was a cause of SUDI. METHODS We did a systematic retrospective case review of autopsies, done at one specialist centre between 1996 and 2005, of 546 infants (aged 7-365 days) who died suddenly and unexpectedly. Cases of SUDI were categorised as unexplained, explained with histological evidence of bacterial infection, or explained by non-infective causes. Microbial isolates gathered at autopsy were classified as non-pathogens, group 1 pathogens (organisms usually associated with an identifiable focus of infection), or group 2 pathogens (organisms known to cause septicaemia without an obvious focus of infection). FINDINGS Of 546 SUDI cases, 39 autopsies were excluded because of viral or pneumocystis infection or secondary bacterial infection after initial collapse and resuscitation. Bacteriological sampling was done in 470 (93%) of the remaining 507 autopsies. 2079 bacteriological samples were taken, of which 571 (27%) were sterile. Positive cultures yielded 2871 separate isolates, 484 (32%) of which showed pure growth and 1024 (68%) mixed growth. Significantly more isolates from infants whose deaths were explained by bacterial infection (78/322, 24%) and from those whose death was unexplained (440/2306, 19%) contained group 2 pathogens than did those from infants whose death was explained by a non-infective cause (27/243, 11%; difference 13.1%, 95% CI 6.9-19.2, p<0.0001 vs bacterial infection; and 8.0%, 3.2-11.8, p=0.001 vs unexplained). Significantly more cultures from infants whose deaths were unexplained contained Staphylococcus aureus (262/1628, 16%) or Escherichia coli (93/1628; 6%) than did those from infants whose deaths were of non-infective cause (S aureus: 19/211, 9%; difference 7.1%, 95% CI 2.2-10.8, p=0.005; E coli: 3/211, 1%, difference 4.3%, 1.5-5.9, p=0.003). INTERPRETATION Although many post-mortem bacteriological cultures in SUDI yield organisms, most seem to be unrelated to the cause of death. The high rate of detection of group 2 pathogens, particularly S aureus and E coli, in otherwise unexplained cases of SUDI suggests that these bacteria could be associated with this condition.

The role of post-mortem investigations in determining the cause of sudden unexpected death in infancy

Introduction: Several autopsy protocols have been suggested for investigating sudden unexpected deaths in infancy (SUDI). The aim of this study is to provide data on the utility of such post-mortem investigations from a large paediatric autopsy series to inform future policy. Methods: Retrospective analysis of >1500 consecutive post-mortem examinations carried out by specialist paediatric pathologists at a single centre during a 10-year period according to a common autopsy protocol that included the use of detailed ancillary investigations. SUDI was defined as the sudden unexpected death of an infant aged from 7 to 365 days. All data capture and cause of death classification were carried out according to defined criteria. Results: Of 1516 paediatric post-mortem examinations, 546 presented as SUDI. In 202 infants (37%), death was explained by the autopsy findings. The other 344 cases (63%) remained unexplained. Of the explained deaths, over half (58%) were infective, most commonly due to pneumonia (22%). The component of the post-mortem examination that primarily determined the final cause of death was histological examination in 92 infants (46%), macroscopic examination in 61 (30%), microbiological investigations in 38 (19%) and clinical history in 10 (5%). Conclusion: This constitutes the largest single-institution autopsy study of SUDI. Ten years on from the Confidential Enquiry into Stillbirths and Deaths in Infancy (CESDI) SUDI studies, the ascertainment of a cause of death at autopsy has improved. However, with almost two thirds of SUDI remaining unexplained, alternative and/or additional diagnostic techniques are required to improve detection rates of identifiable causes of death at autopsy.

Minimally invasive perinatal autopsies using magnetic resonance imaging and endoscopic postmortem examination ("keyhole autopsy"): feasibility and initial experience

Objective: Perinatal autopsy provides additional diagnostic information in a significant proportion of cases but parents and relatives frequently decline traditional postmortem (PM) examination, partly due to the unacceptability of the cosmetic effects of large incisions and concerns regarding organ retention. We present a novel minimally invasive autopsy method for fetal and neonatal PMexaminations, which includes PM magnetic resonance imaging (MRI) for assessment of anatomy and endoscopic internal examination to allow direct organ visualization and targeted tissue biopsy. Methods: Descriptive retrospective feasibility report of the first 10 perinatal cases undergoing endoscopic minimally invasive autopsy. Results: A minimally invasive autopsy (MIA) approach based on postmortem MRI (PM MRI) and endoscopic autopsy with tissue biopsy is feasible and effective with minimal cosmetic consequences compared to traditional PM examination. Endoscopic examination with tissue biopsy provided additional diagnostic information to PM MRI alone in the majority of cases. Conclusions: Endoscopic MIA is a feasible and potentially more acceptable approach to perinatal autopsy and provides an additional option for parents who do not agree to a traditional PM examination. This approach could result in increased utilization of investigations after death in this group of patients.

Genetics and developmental pathology of twinning

Twin pregnancy is associated with a high risk of congenital malformations. This review covers the risk of such anomalies in both dizygotic and monozygotic twin pregnancies, and discusses current insights into the associations relating to zygosity, chorionicity and genetic factors. The pathological basis of specific malformations unique to the monochorionic twinning process, including conjoined twinning and twin reversed arterial perfusion (TRAP) sequence, is discussed in more detail, and factors contributing to the higher perinatal mortality rate in multiple pregnancies are addressed.

Clinicopathological features of paediatric deaths due to myocarditis: an autopsy series

Introduction: Myocarditis is a recognised cause of cardiac failure in childhood but the frequency of myocarditis as a cause of sudden unexpected death across the paediatric age range is uncertain. Methods: A structured review of the results of all autopsies carried out in a single paediatric centre over a 10-year period, including the results of all investigations performed as part of the centre’s policy for the post-mortem investigation of paediatric deaths. Results: During the study period there were 1516 autopsies of children aged 0–18 years. Histologically proven myocarditis was present in 28 cases (1.8%, age range 10 days to 16 years, median age 10 months), of which 16 (57%) presented as sudden death. More than half of all cases (54%) occurred in infants less than 1 year of age, accounting for 2% of infant deaths referred for autopsy, compared with around 5% of childhood deaths over the age of 5 years. In almost 40% of cases there were no macroscopic cardiac abnormalities, the diagnosis being entirely dependent on routine histological examination of the heart, and post-mortem heart weight was normal in the majority of cases. Virus was detected in nine (36%) of the 25 cases in whom virological analyses were performed. The histological features were similar in all cases, with an interstitial inflammatory cell infiltrate, predominantly lymphocytic, with focal myocyte necrosis and interstitial oedema. Conclusions: Myocarditis is a rare cause of death in infancy and childhood, and the majority of cases present as sudden unexpected deaths, which require routine histological sampling of the heart for its detection.

Sudden unexpected neonatal death in the first week of life: Autopsy findings from a specialist centre

Objective. Sudden unexpected early neonatal death (SUEND) in the first week of life shares features with sudden unexpected death in infancy (SUDI) but is not included as SUDI, which is limited to post-perinatal deaths. The aim of this study was to review SUEND autopsies performed in a single specialist centre over a 10-year period, (1996–2005). Methods. Retrospective analysis of >1500 consecutively performed paediatric autopsies performed by paediatric pathologists at one centre conducted according to a standard protocol including ancillary investigations. SUENDs were identified and autopsy findings reviewed. Results. Of 1516 post-mortem examinations, 180 were first-week neonatal deaths, 55 (31%) presenting as SUEND. Thirty-two (58%) were explained following autopsy, whilst the remainder were unexplained; most deaths during sleep were associated with adult co-sleeping. Around 40% of explained deaths were associated with undiagnosed congenital abnormalities, mainly congenital heart disease. In addition, there were nine infection-related deaths and three deaths from unsuspected metabolic disease (fatty acid oxidation defects). Conclusion. There are distinct differences between SUEND and SUDI, with significantly more explained deaths in the former and a much greater proportion due to congenital abnormalities and metabolic disease.

Prospective parental consent for autopsy research following sudden unexpected childhood deaths: a successful model

Background: Organ retention issues, recent changes in the Coroners’ (Amendment) Rules 2005 and the Human Tissue Act have resulted in pessimism regarding prospective consent for paediatric autopsy research in the UK. Objectives: To examine the feasibility and acceptability of a prospective telephone consenting model for post-mortem magnetic resonance (MR) imaging research in HM Coroners’ cases. Design: Following each autopsy referral from the HM Coroner, permission to contact the family for research was requested. A family liaison sister, with experience in dealing with bereaved families, then contacted the parents by telephone, explained the study and obtained oral, and then written consent for post-mortem imaging. Setting: London and an area south of London. Results: Of 76 eligible HM Coroners’ cases referred during the study period, permission to contact parents (provided by the HM Coroners’ Office) was obtained for only 32 cases (42%). The research sister contacted 32 parents during the study period of whom 31 (96.8%) gave oral research consent. “Helping other parents in the future” and “the importance of post-mortem research” were the main reasons for parents wanting to participate in research. Conclusions: Prospective consenting for HM Coroners’ cases for research is feasible in children, and can be done ethically by parental consenting via telephone contact before autopsy by appropriately trained staff. However, close co-ordination between mortuary staff, HM Coroners, research staff and medical staff is required. This model may be useful in performing post-mortem research in HM Coroners’ cases and in developing paediatric tissue and brain banks in the UK.

Rib fractures identified at post-mortem examination in sudden unexpected deaths in infancy (SUDI).

Rib fractures may be associated with non-accidental injury (NAI) in infancy, but the possible significance of fresh rib fractures in relation to resuscitation remains undetermined. Consequently, it is important to detect and confirm the presence of rib fractures when performing a post-mortem examination, particularly in the context of sudden unexpected death in infancy (SUDI). At our centre, it has been local policy to perform routine radiological skeletal surveys and detailed post-mortem examination of the ribs in all SUDI autopsies. The aim of this study is to establish the characteristics of all rib fractures identified at autopsy in the setting of SUDI from a large series of cases examined at a single specialist centre. As part of a larger review of paediatric post-mortem examinations performed at a single specialist institution over a 10-year period (1996-2005), all cases presenting as SUDI (aged 7-365 days) were identified and their anonymised records searched to identify all cases in which rib fractures were recorded. Over the 10-year period, 546 post-mortem examinations were performed for the indication of SUDI, including 94 forensic autopsies. Rib fractures were identified in 24 cases (4%). 15 infants (3% of SUDI) demonstrated healing rib fractures, of which 10 infants (67%) showed additional features suggestive of NAI. The other 9 infants (2% of SUDI) demonstrated fresh rib fractures only with no surrounding tissue reaction histologically; in 7 (78%) of these there were no other injuries and the fresh fractures were interpreted to have been caused by resuscitation-related trauma. All of the resuscitation-related fractures were situated in the anterolateral chest, in contrast to NAI-associated fractures, which were located in the anterolateral and/or posterior chest. Anterior costochondral junction fractures were also seen in a minority of NAI-associated cases, but such fractures were not seen in apparent resuscitation-related cases. Compared to healing rib fractures, which were detected on skeletal survey in 93%, fresh rib fractures were only detected in 22% of skeletal surveys. Rib fractures are uncommon in infancy and may indicate NAI, particularly when healed or healing, posterior or involving the costochondral junction. Fresh rib fractures may be missed on skeletal survey, but can be reliably detected at post-mortem examination following stripping of the pleura and detailed examination of each rib. Fresh anterolateral fractures, which may be multiple, contiguous and even bilateral, are highly likely to be related to resuscitation if there are no other associated injuries.

Co-occurrence of massive perivillous fibrin deposition and chronic intervillositis: case report.

Chronic intervillositis (CI) and massive perivillous fibrin deposition (MFD), together with its related entity, maternal floor infarction (MFI), are rare and poorly understood placental lesions. Both MFD/MFI and CI are associated with poor fetal outcome and high risk of recurrence. We report a patient who was found to have both MFD and CI in the same placenta, resulting in severe intrauterine fetal growth restriction and intrauterine fetal death at 37 weeks of gestation. Characteristic histological findings included both very extensive perivillous deposition of fibrinoid material and a heavy infiltrate of CD68-positive macrophages/monocytes in the maternal intervillous space. To our knowledge, this is the first time the co-occurrence of MFD and CI is reported in the literature.

Virological investigations in sudden unexpected deaths in infancy (SUDI)

Previous studies have implicated viral infections in the pathogenesis of sudden unexpected death in infancy (SUDI), and routine virological investigations are recommended by current SUDI autopsy protocols. The aim of this study is to determine the role of post-mortem virology in establishing a cause of death. A retrospective review of 546 SUDI autopsies was carried out as part of a larger series of >1,500 consecutive paediatric autopsies performed over a 10-year period, 1996–2005, in a single specialist centre. Virological tests were performed as part of the post-mortem examination in 490 (90%) of the 546 SUDI autopsies, comprising 4,639 individual virological tests, of which 79% were performed on lung tissue samples. Diagnostic methods included immunofluorescence assays (using a routine respiratory virus panel; 98% of cases), cell culture (61%), rapid culture techniques such as the DEAFF test for CMV (55%), PCR (13%), electron microscopy (10%), and others. Virus was identified in only 18 cases (4%), viz. five cases of enterovirus, four of RSV, three of HSV and CMV, and one each of adenovirus, influenza virus and HIV. In seven of the 18 cases the death was classified as due to viral infection, whilst of the remaining 11 cases, death was due to bacterial infection in five, a non-infective cause in one and unexplained in five. Virus was identified in 33% of deaths due to probable viral infections, but also in 6% of SUDI due to bacterial infections, and in 2% of SUDI due to known non-infective causes and unexplained SUDI. When predominantly using immunofluorescence, virus is identified in only a small proportion of SUDI autopsies, resulting in a contribution to the final cause of death in <2% of SUDI post-mortem examinations. Routine post-mortem virological analysis by means of an immunofluorescence respiratory virus panel appears to be of limited benefit in SUDI for the purposes of determining cause of death. Application of a broader panel using more sensitive detection techniques may reveal more viruses, although their contribution to the final cause of death requires further exploration.