How Useful is Postmortem Examination in Sudden Infant Death Syndrome?

There exists great variability in the literature as to the percentage of cases of sudden and unexpected infant death in which definable causes can be identified. Review was undertaken of the clinical and family histories, death scene features including parental interviews, and pathological and microbiological features of 361 consecutive cases presenting as sudden and unexpected infant death with minimal preceding symptoms and signs to the Adelaide Children's Hospital over a 10-year period from 1983 to 1992. Three hundred and twenty-nine cases of SIDS were identified. Nine cases (2.5%) were attributed to accidental asphyxia based partly on death scene examination. This left only 23 cases (6.4%), which were due to a variety of other diverse entities including sepsis, volvulus with sepsis, congenital cardiac disease, probable metabolic disorders, heat stroke, and unclassifiable disorders. This relatively low figure lends support to definitions of SIDS that emphasize the importance of death scene investigation and clinical history review prior to postmortem examination.     

Inherited metabolic diseases in the sudden infant death syndrome.

All sudden, unexpected infant deaths presenting during a two year period within a defined geographical area in Avon and north Somerset were investigated for inherited metabolic disease. Of 95 deaths, 88 were classified as cases of sudden infant death syndrome (SIDS). In addition to the normal postmortem investigations, samples of cerebrospinal fluid, urine, vitreous humour, and skin were collected for metabolic studies. No abnormal organic acid metabolites were found in the fluids from the 88 cases of SIDS. Fatty acid oxidation was assessed in skin fibroblasts from 70 cases of SIDS, but no examples of medium chain acyl CoA dehydrogenase (MCAD) deficiency were found. One case with abundant glycogen in the liver was subsequently diagnosed as having glycogen storage disease type 1c. These findings suggest that the incidence of MCAD deficiency and other metabolic diseases in SIDS is much lower than previously claimed.     

Contribution of Long-QT Syndrome Genetic Variants in Sudden Infant Death Syndrome

A cohort of 52 French unrelated infant cases who died unexpectedly before they reached 12 months of age was blindly investigated to better quantify the contribution of long-QT syndrome (LQTS) genetic variants in French cases of sudden infant death syndrome (SIDS). After a standardized autopsy protocol, a blinded molecular screening of the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes was performed on each case. These postmortem investigations enabled us to reclassify 18 as non-SIDS cases, 32 as SIDS cases, and 2 as suspected SIDS cases. Among the 18 non-SIDS cases, no LQTS mutation was identified. In contrast, our results led to a possible explanation for the death of at least three infants in the SIDS cohort. Half of the LQTS gene variants identified were located on the SCN5A gene. This study confirms that LQTS mutations may represent one of the leading genetic causes of SIDS. If autopsy fails to provide an explanation for an unexplained infant death, medicolegal investigation should be extended with a molecular screening of major LQTS genes. Identification of more LQTS mutations in SIDS cases could provide new insights into the pathophysiology of SIDS and, consequently, reduce the number of unexplained sudden infant deaths.     

Sudden death of twins: botulism because of contamination by pap vegetables

Botulism is caused by the blockage of the neural transmission in the cholinergic synapses by botulinum neurotoxin (BoNT) which is produced by Clostridium botulinum or other Clostridia. The classic form of botulism occurs after the ingestion of food contaminated by BoNT. The course of the infection can be asymptomatic, mild with subtle paralysis ("failure to thrive") oder severe with generalized paralysis ("floppy infant"). Infected infants can also die sudden and unexpectedly. These deaths often are attributed to Sudden Infant Death Syndrome (SIDS), unless a thorough postmortem examination reveals Botulism. The rate of fatal Botulism falsely attributed to SIDS is not known, because it is difficult in most cases to show the causal relationship between contamination, disease and death. We report the sudden and unexpected simultaneous death of twins of 22 months which could be attributed to Botulism. Contamination of food, colonization of the gut by Clostridia and infection with specific pathomorphological changes could be proven. The initial suspicion of infanticide could be excluded. lt could be shown, that Botulism is a potential cause of simultaneous unexpected deaths in twins.     

Has changing diagnostic preference been responsible for the recent fall in incidence of sudden infant death syndrome in South Australia?

Objective: An apparent decrease in deaths attributed to sudden infant death syndrome (SIDS) has been noted in a number of diverse geographical areas during the past several years. At the same time the definition of SIDS has been in a state of flux and some observers have raised the possibility that the fall in SIDS deaths is due to diagnostic transfer rather than to a genuine decrease in numbers. The present study was undertaken to investigate this possibility.
Methodology: All sudden and unexpected deaths in infants under 1 year of age in South Australia during a 10 year period from 1984 to 1993 were reviewed.
Results: The number of deaths due to SIDS fell from 40 in 1984 to 17 in 1993, with a maximum of 52 cases per year in 1987. In contrast, the number of cases of sudden death not due to SIDS remained under 10 per year. The overall infant death rate also fell, while the total number of births per year remained relatively unchanged.
Conclusions: The lack of major change in sudden infant death rates from other causes, combined with the fall in SIDS deaths, is not supportive of diagnostic transfer being a major determinant of the declining SIDS death rate. Therefore, other factors are likely to be responsible for the falling SIDS rate in this population.     

A Comparison of the Incidence of Cytomegalovirus Inclusion Bodies in Submandibular and Tracheobronchial Glands in SIDS and non-SIDS Autopsies

Submandibular salivary glands and tracheobronchial glands from postmortem examinations of 89 cases of sudden infant death syndrome (SIDS) and 67 age-matched control cases in which death was not due to SIDS were examined for the presence of intranuclear and intracytoplasmic inclusions characteristic of cytomegalovirus (CMV). Inclusions were identified by light microscopy and confirmed by immunohistochemistry in submandibular glands of 5 of 89 (5.6%) SIDS and 6 of 67 (8.9%) non-SIDS patients. No inclusions were found in tracheobronchial glands. No further cases were detected following immunoperoxidase studies and examination of multiple levels of inflamed submandibular glands. Brain stem glial knots were found in only one case with CMV inclusions, which was a non-SIDS case with death due to congenital immunodeficiency. We have found no difference in the incidence of CMV inclusions in the submandibular gland between SIDS and age-matched non-SIDS infants. No strong association between CMV inclusions in salivary gland and brain stem glial knots was present.     

Routine microbiological testing in sudden and unexpected infant death

Objective : To evaluate the significance of microbiological test results in a series of infants who had died suddenly and unexpectedly.
Methodology : Following a review of all cases of sudden natural death in infants presenting to the Adelaide Children's Hospital (ACH) division of the Women's and Children's Hospital (WCH) over the 10 year period between 1983 and 1992, specific evaluation of microbiological test results was undertaken.
Results : There were 329 cases of sudden infant death syndrome (SIDS) and 23 cases in which sudden infant death was either attributed to other conditions or was unclassifiable. Positive microbiological results were recorded in the majority of cases, most being considered to be due to postmortem overgrowth or to contamination at autopsy. Of the remaining cases, microbiological results were essential to the establishment of the diagnosis in three cases, and were a useful adjunct to the diagnosis in a further six cases.
Conclusions : Routine microbiological testing in cases presenting as SIDS did not reveal occult sepsis in most instances. Such testing did, however, add support to the diagnosis of SIDS where no pathogens were isolated and, if not undertaken, would have resulted in a small percentage of cases of sudden infant death due to infections remaining undiagnosed.     

Sudden unexpected death in infancy: epidemiologically determined risk factors related to pathological classification

Infants that died suddenly and unexpectedly were studied as part of the European Concerted Action on sudden infant death syndrome (SIDS). Three paediatric pathologists, first independently of each other and later in a consensus meeting, classified 63 cases into 3 groups: SIDS (19 cases), borderline SIDS (30 cases) and non-SIDS (14 cases). The interobserver agreement among the pathologists before the consensus meeting was moderate (Kappa = 0.41) and jointly it was higher (Kappa = 0.83). The distribution of epidemiologically determined risk factors was studied over these three groups. Maternal smoking after birth, low socioeconomic status and thumb sucking were found more often in SIDS than in the other cases. Inexperienced prone sleeping was a determinant for SIDS, but not for non-SIDS. Previous hospital admission, low birthweight and/or short gestation were associated with borderline SIDS. Non-SIDS cases received more breastfeeding, the parents hardly smoked during pregnancy and after birth, a firm mattress had been used, and more often signs of illness had been reported by the parents, compared with the SIDS and borderline SIDS cases. Bedding factors and both primary and secondary prone sleeping were equally distributed over the three groups which supports the hypothesis that, in SIDS and borderline SIDS, as well as in non-SIDS cases, some similar external and preventable factors might influence the events leading to death. Research should therefore focus on all sudden unexpected deaths, after which subgroups such as SIDS cases can be separately analysed. The postmortem is an essential part of the whole work-up of each case and the results should be interpreted with all other available data to arrive at a sound evaluation of cases and thus form the basis for the prevention of all sudden unexpected infant death.     

Suffocation,shaking or sudden infant death syndrome: Can we tell the difference?

Given that the diagnosis of sudden infant death syndrome (SIDS) remains one of exclusion, problems still exist in distinguishing possible cases from those where the deaths were due to accidental or inflicted suffocation. The term 'SIDS' cannot be used unless a complete autopsy examination has been performed, augmented by review of the clinical history and examination of the death scene. In the absence of a cause of death, a more suitable designation in the presence of inflicted injury is 'undetermined' rather than 'SIDS'. Use of standard autopsy and death scene protocols that have been endorsed by professional bodies will improve the investigation of unexpected infant death and will increase the likelihood of diagnosing subtle disorders that may be confused with SIDS.     

Pulmonary intra-alveolar siderophages in SIDS and suffocation: a San Diego SIDS/SUDC Research Project report.

Pulmonary intra-alveolar siderophages (PS) have been suggested as a marker of previous attempts at imposed suffocation in infants dying suddenly and unexpectedly. The aims of this study were to (1) compare PS counts between cases of sudden infant death syndrome (SIDS) and a control group comprised of infants whose deaths were attributed to accidental or inflicted suffocation, (2) compare clinical variables in SIDS and control suffocation cases, and (3) review individual cases irrespective of the cause and manner of death with an average PS count greater than 200 per 20 high-power fields (hpf) per lung lobe. Retrospective assessment of siderophages in available iron-stained lung sections was undertaken in 91 SIDS cases and 29 cases of death due to suffocation (27 accidents and 2 homicides) from the San Diego SIDS and Sudden Unexplained Death in Childhood (SUDC) Research Project (SDSSRP) database. Neither the means of the log-transformed PS counts nor the medians of the raw PS counts were significantly different between the SIDS and control suffocation groups. The distributions of the PS data were different, however-the range was wider in the SIDS group. Only 6% of each group had a history of prior apparent life-threatening events. Approximately three fourths of the families from both groups had no prior referral to Child Protective Services. The number of PS varies widely in cases of sudden infant death caused by SIDS and accidental or inflicted suffocation and cannot be used as an independent variable to ascertain past attempts at suffocation.     

Sudden infant death in France during the winter of 1986

From the statistics of the medical causes of deaths and the results of a retrospective survey carried out among the physicians who certified the deaths, an analysis of post-neonatal mortality during winter of 1986 was undertaken in order to know if the relative part of the sudden infant death syndrome (SIDS) had increased during that winter. It appeared that the deaths attributed to SIDS can be distinguished from deaths of other causes for several factors (place of death, former status of the baby). However, the low number of post mortem examinations performed does not allow in all the declared cases to assess SIDS as internationally defined. However, it is shown that sudden mortality was not higher during this special winter and that immunizations were not more frequently related to this cause than to other causes of death.     

Sudden Death in an Infant with Central Nervous System Abnormalities

Some deaths during the first year of life are classified as sudden infant death syndrome (SIDS), the diagnosis of which requires a complete autopsy without adequate explanation for the death. We report a 1-month-old infant whose clinical history was fairly typical for SIDS. Postmortem examination was remarkable in revealing clinically unsuspected central nervous system (CNS) abnormalities, including lobar holoprosencephaly, absence of the olfactory tracts and grooves (arhinencephaly), subependymal gray matter heterotopias, and delayed myelination. Although the CNS findings do not adequately explain the patient's sudden death, this case illustrates the need for a complete autopsy to include careful CNS evaluation, especially in any presumed SIDS death.     

Autopsies of sudden infant death syndrome—classification and epidemiology

An enquiry into sudden infant death syndrome (SIDS) in 1987 furnished us with detailed epidemiological data for 281 cases that underwent a thorough post-mortem examination. This analysis uses these data to evaluate the role the autopsy plays in explaining sudden death. The cases were classified into three diagnostic groups: explained causes of death (group 1), unexplained deaths with anomalies (group 2), and no anomaly (group 3). These 281 cases show the three essential features that characterize SIDS: over-representation of males, increased deaths during the second and third months of life, and increased deaths during winter. The autopsy examination revealed that many of these deaths had a medical explanation. Almost half were assigned to group 1. At the time of autopsy, no precise pathology could be diagnosed for 147 deaths; of these, 140 showed histological anomalies. There were only seven sudden deaths for which no abnormal sign was evident at the autopsy. These results are compared with those of similar studies and discussed in connection with three factors: the initial selection of cases, the nature and degree of the investigations, and the possible interpretations of the symptoms uncovered.     

Sudden death in the first 2 years of life following immunization in the Republic of Korea

Background: Because the peak age for incidence of sudden deaths in infancy temporally coincides with the age of infant primary immunization, some have raised the question as to whether immunization is a risk factor for sudden death in infancy. Recent occurrence of two sudden deaths in infants in Korea has renewed concerns about the causal association between immunization and sudden deaths in infants. Methods: We carried out a retrospective review of data from the Korea Centers for Disease Control and Prevention Adverse Events Following Immunization Surveillance System and Vaccine Compensation programs. Results: From 1994 to 2011, a total of 45 cases of sudden deaths in the first 2 years of life following immunization were reported in Korea. The causes of death were classified as follows: infectious diseases (n= 13); accidental injuries (n= 7); congenital abnormalities (n= 2); and malignancy (n= 1). Of 20 sudden deaths in infancy, nine deaths met Brighton Collaboration case definition level I and II, and therefore were classified as possible sudden infant death syndrome cases. Hepatitis B vaccine (n= 13) was the most frequent vaccine with temporal association with sudden deaths in the first 2 years of life. Conclusion: Few sudden deaths in the first 2 years of life following immunization have been reported, despite the use of universal immunization in Korea. The majority of deaths in infancy did not meet case definition for sudden infant death syndrome. Encouraging investigators to perform thorough investigation, including postmortem autopsy and death scene examination, may promote data comparability and provide guidance on decision‐making in the vaccine‐safety monitoring and response system in Korea.     

Investigation of the Sudden Death of Infants: A Multicenter Analysis

The investigation of sudden death of infants varies, and death rates may depend on local practices of death certification. We studied the extent of the investigation and the final cause of death (COD) in 3 regions: New York, New York, USA (NY); King County, Washington, USA (KC); and Montevideo, Uruguay (MU). We conducted a retrospective review of 543 cases (NY 258, KC 56, MU 229) of previously healthy babies who died suddenly without obvious trauma, at ages 0 to 12 months, over a 3-year period (1998 to 2001). All cases included a complete autopsy and histologic examination. Cases were assessed for completion of special studies (including radiographs, photos, toxicology and metabolic sampling, cultures, and vitreous humor chemistry), measurements, and scene investigation. Specialized pediatric measurements and testing were done less often than routine procedures, and were done less often in cases overall compared with cases certified as sudden infant death syndrome (SIDS). Fifty-five percent of SIDS cases in NYC and 12% of SIDS cases in KC had no scene investigation. Manhattan had a complete workup in 42% of SIDS cases, whereas the remaining sites had fewer that 15% of cases completely worked up. The most common non-natural COD was suffocation at all 3 sites. The overall most common COD were respiratory infection in MU (22%) and SIDS in NY (45%) and KC (86%). We conclude that the sudden death of infants requires special consideration and still lacks consistency. SIDS investigations are not done completely in all cases and rates may depend on regional differences in certifying infant deaths. This work was presented in part at the annual meeting of the Society for Pediatric Pathology; Washington, DC; March 22-23, 2003.     

Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach

The definition of sudden infant death syndrome (SIDS) originally appeared in 1969 and was modified 2 decades later. During the following 15 years, an enormous amount of additional information has emerged, justifying additional refinement of the definition of SIDS to incorporate epidemiologic features, risk factors, pathologic features, and ancillary test findings. An expert panel of pediatric and forensic pathologists and pediatricians considered these issues and developed a new general definition of SIDS for administrative and vital statistics purposes. The new definition was then stratified to facilitate research into sudden infant death. Another category, defined as unclassified sudden infant deaths, was introduced for cases that do not meet the criteria for a diagnosis of SIDS and for which alternative diagnoses of natural or unnatural conditions were equivocal. It is anticipated that these new definitions will be modified in the future to accommodate new understanding of SIDS and sudden infant death.     

Redefinition of the Sudden Infant Death Syndrome: the Disadvantages

For many years the definition of SIDS has been the sudden death of an infant that was unexpected by history and in which a thorough postmortem examination failed to demonstrate an adequate cause of death. In 1991 a report was published in this journal from a panel convened by the NICHD which recommended that the diagnosis of SIDS not be made unless a death scene investigation has been conducted. The panel recommended further exclusions from the diagnosis of SIDS of certain “unresolved” cases. We believe the changes recommended by the NICHD panel are impractical and may have a serious negative impact on SIDS research and on the surviving family members of the SIDS victims.     

Sudden Unexpected Death in Childhood:A Report of 50 Cases

Sudden unexplained death in childhood (SUDC) is rare, with a reported incidence in the United States of 1.5 deaths per 100,000 live births compared with 56 deaths per 100,000 live births for sudden infant death syndrome in 2001. The objectives of this study include a proposal for a general definition for SUDC and presentation of 36 cases of SUDC and 14 cases of sudden unexpected death in childhood. Cases were accrued through referrals or unsolicited via our Web page (). Our analyses tentatively suggest a SUDC profile characterized by cases being 1 to 3 years in age, predominantly male, and frequently having a personal and family history of seizures that are often associated with a fever. A history of recent minor head trauma is not uncommon. They are usually born at term as singletons and occasionally have a family history of sudden infant death syndrome or SUDC. Most are found prone, often with their face straight down into the sleep surface. Minor findings are commonly seen at postmortem examination but do not explain their deaths. Comprehensive review of the medical history and circumstances of death and performance of a complete postmortem examination including ancillary studies and extensive histologic sampling of the brain are critical in determining the cause of death in these cases of sudden unexpected childhood death. Legislation enabling research and formation of a multicenter research team is recommended to unravel the mystery of SUDC.     

Sudden unexpected child deaths: forensic autopsy results in cases of sudden deaths during a 5-year period

The aim of the present study was to determine the incidence of various causes of sudden unexpected child deaths (SUCD) and to assess the importance of an autopsy in predicting the likelihood of finding a cause of death. A retrospective analysis of autopsy findings in 97 cases of SUCD between the ages of 0--11 years was undertaken at the Council of Forensic Medicine, Ankara during a 5-year period (1995--2000). Cases were classified as explained causes (80.42 per cent) and sudden infant death syndrome (SIDS) (19.58 per cent). A total of 25.77 per cent of the deaths occurred in the neonatal period, 45.31 per cent of them in the first year of life and the remaining 28.86 per cent after 1 year of life. The causes of neonatal deaths were respiratory pathology (five cases), birth complications (four cases), gastrointestinal pathology (one case), homicide (10 cases), and SIDS (five cases). The incidence of SIDS in the newborn period was 33 per cent. The incidence of unexplained causes of deaths in the postneonatal period was 31 per cent and the causes of deaths were respiratory pathology (15 cases), aspiration (five cases), gastrointestinal pathology (four cases), SIDS (14 cases), and other causes (four cases). The study of an entire population provides more reliable data regarding causes of sudden unexpected child deaths than does the study of small groups and it is also recommended that in addition to a through evaluation, a detailed autopsy must be performed for each case in experienced centers.     

Pulmonary aspiration of gastric contents and the sudden infant death syndrome

OBJECTIVE: To determine ante-mortem and post-mortem risk factors for the finding of gastric contents in pulmonary airways (aspiration of gastric contents) at post-mortem examination in the sudden infant death syndrome (SIDS). METHODS: There were 217 post-neonatal deaths in the Auckland region of the New Zealand Cot Death Study. No deaths were certified as due to aspiration of gastric contents. There were 138 SIDS cases. The parents of 110 (80%) of these cases were interviewed. Histological sections from the periphery of the lungs in 99 of the 110 cases were reviewed for evidence of aspiration of gastric contents. A wide range of variables were analysed in SIDS cases with and without aspiration to determine risk factors. RESULTS: Aspiration of gastric contents was identified in 37 (37%) of SIDS cases. Aspiration was of mild-to-moderate degree and in no case was severe and a potential cause of death. Finding infants on their backs at death (P = 0.024) and conducting the post-mortem on the day after the death or subsequently (P = 0.033) were statistically significant variables linked to identification of aspiration. Position placed to sleep, symptoms of gastro-oesophageal reflux and other variables were not related to aspiration. CONCLUSIONS: The only determinants for aspiration of gastric contents identified were agonal or post-mortem events, supporting the contention that aspiration has limited relevance to the mechanism of SIDS.