Tyrosine Hydroxylase TH01 9.3 Allele in the Occurrence of Sudden Infant Death Syndrome in Swiss Caucasians

Catecholamines, especially noradrenalin, are essential in the control of respiration and arousal. Thus, an impaired production of these neurotransmitters may contribute to the occurrence of sudden infant death syndrome (SIDS). The first step of the noradrenergic synthesis pathway is catalyzed by the enzyme tyrosine hydroxylase (TH). The TH‐encoding gene contains a tetrameric short tandem repeat in intron 1 (TH01), with allele 9.3 reported to be associated with SIDS in German infants. We investigated the allelic frequency of the TH01 marker in 171 Swiss SIDS infants and 500 healthy and gender‐matched Caucasian adults. In our study population, the allelic frequency of the 9.3 allele is similarly distributed in SIDS cases and controls (27.2% vs. 25.6%; p‐value = 0.562). Nevertheless, the TH‐encoding gene is only one of several genes involved in the noradrenergic biosynthesis pathway. Therefore, further genetic investigations are required with focus on the whole noradrenergic signaling system.     

No association of IL-10 promoter SNP −592 and −1082 and SIDS

Sudden infant death syndrome (SIDS) constitutes a considerable percentage of infant death of unknown etiology. The genetically controlled pathway of cytokine mediated response to inflammation is presumed to play a role in SIDS. The A allele of SNP ?592 of the promoter region of the anti-inflammatory cytokine IL-10 has been suggested to be associated with SIDS. Herein we investigated whether we could confirm this finding by SNP genotyping a series of 123 cases of SIDS and 406 control cases. We did not find a correlation between the A allele or an A allele containing genotype of IL-10 promoter SNP ?592 and SIDS which is in contrast to previous studies. Also, in concordance with previous work, no association of the A allele or A allele containing genotypes of IL-10 promoter SNP ?1082 and SIDS was found.     

The Institution of a Standardized Investigation Protocol for Sudden Infant Death in the Eastern Metropole,Cape Town,South Africa,,

The rate for the sudden infant death syndrome (SIDS) in Cape Town, South Africa, is estimated to be among the highest in the world (3.41/1000 live births). In several of these areas, including those of extreme poverty, only sporadic, nonstandardized infant autopsy, and death scene investigation (DSI) occurred. In this report, we detail a feasibility project comprising 18 autopsied infants with sudden and unexpected death whose causes of death were adjudicated according to the 1991 NICHD definitions (SIDS, n = 7; known cause of death, n = 7; and unclassified, n = 4). We instituted a standardized autopsy and infant DSI through a collaborative effort of local forensic pathology officers and clinical providers. The high standard of forensic investigation met international standards, identified preventable disease, and allowed for incorporation of research. We conclude that an effective infant autopsy and DSI protocol can be established in areas with both high sudden unexpected infant death, and elsewhere. (SUID)/SIDS risk and infrastructure challenges.     

Differentiating cause-of-death terminology for deaths coded as sudden infant death syndrome, accidental suffocation, and unknown cause: an investigation using US death certificates, 2003-2004

We compared written text on infant death certificates for deaths coded as sudden infant death syndrome (R95), unknown cause (R99), and accidental suffocation (W75). Using US mortality files supplemented with the death certifiers' written text for all infant deaths with International Classification of Diseases (ICD)-10 assigned codes R95, R99, and W75, we formed cause-of-death subcategories from common themes identified from the written text. Among all infant deaths in 2003-2004, the underlying cause of death was listed as R99 for 2128 deaths, R95 for 4408 deaths, and W75 for 931 deaths. Among the postneonatal deaths, the differences in subcategories varied between assigned ICD-10 codes: for R99-coded deaths, 45.8% were categorized as "Unknown" and 48.6% as "Pending"; for R95-coded deaths, 67.7% were categorized as "sudden infant death syndrome (SIDS)"; and for W75-coded deaths, 76.4% were categorized as "Suffocation." Examination of the written text on the death certificates demonstrates variability in the assigned ICD-10 codes which could have an important effect on the estimates of SIDS cases in the United States.     

Axonal injury in young pediatric head trauma: a comparison study of β-amyloid precursor protein (β-APP) immunohistochemical staining in traumatic and nontraumatic deaths

We tested the independent utility of β-amyloid precursor protein (β-APP) immunohistochemical staining as evidence of brain trauma in the deaths of young children. Blinded reviewers retrospectively reviewed immunostained brain tissues from homicidal deaths, age-matched control cases without evidence of trauma, as well as cases of sudden infant death syndrome (SIDS). The reviewers correctly identified five of the seven cases with documented inflicted head trauma. However, one of seven age-matched control cases and one of 10 SIDS/sudden unexplained death in infancy (SUDI) cases demonstrated staining patterns similar to those seen in cases of inflicted trauma. We discuss these cases and the circumstances surrounding them with the intent to explain the difficulties associated with immunohistological interpretation of axonal injury. Although the utility of β-APP is quite powerful if not confounded by global hypoxic-ischemic injury, ultimately, β-APP studies should be only one piece of information in the determination of cause and manner of death.     

Oronasal blood in sudden infant death.

Oronasal secretions are observed frequently in sudden infant death syndrome (SIDS), but overt blood is uncommonly reported. The literature on oronasal blood in sudden infant death is limited. The goal of this study was to determine the frequency of oronasal blood in sudden infant deaths and to examine possible causative factors. Oronasal blood was described in 28 (7%) of 406 cases of sudden infant death. Oronasal blood could not be attributed to cardiopulmonary resuscitation in 14 cases, including 10 (3%) of 300 cases of SIDS, 2 (14%) of 14 accidental suffocation cases, and 2 (15%) of 13 undetermined cases. Eight of the 10 infants in cases of sudden infant death were bedsharing: 5 with both parents, 2 between both parents. The infant in 1 SIDS case was from a family that had had three referrals to Child Protective Services. Oronasal blood not attributable to cardiopulmonary resuscitation occurs rarely in SIDS when the infant is sleeping supine in a safe environment. Bedsharing may place infants at risk of suffocation from overlaying. Oronasal blood observed before cardiopulmonary resuscitation is given is probably of oronasal skin or mucous membrane origin and may be a sign of accidental or inflicted suffocation. Sanguineous secretions that are mucoid or frothy are likely of remote origin, such as lung alveoli. The use of an otoscope to establish the origin of oronasal blood in cases of sudden infant death is recommended.     

Sarcomeric gene mutations in sudden infant death syndrome (SIDS)

In developed countries, sudden infant death syndrome (SIDS) represents the most prevalent cause of death in children between 1 month and 1 year of age. SIDS is a diagnosis of exclusion, a negative autopsy which requires the absence of structural organ disease. Although investigators have confirmed that a significant percentage of SIDS cases are actually channelopathies, no data have been made available as to whether other sudden cardiac death-associated diseases, such as hypertrophic cardiomyopathy (HCM), could be responsible for some cases of SIDS. The presence of a genetic mutation in the sarcomeric protein usually affects the force of contraction of the myocyte, whose weakness is compensated with progressive hypertrophy and disarray. However, it is unclear whether in the most incipient forms, that is, first years of life, the lack of these phenotypes still confers a risk of arrhythmogenesis. The main goal of the present study is to wonder whether genetic defects in the sarcomeric proteins, previously associated with HCM, could be responsible for SIDS. We have analysed 286 SIDS cases for the most common genes implicated in HCM in adults. A total of 680 mutations localised in 16 genes were analysed by semi-automated matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDITOF-MS) using the Sequenom MassARRAY(?) System. Ten subjects with completely normal hearts showed mutated alleles at nine of the genetic variants analysed, and one additional novel mutation was detected by conventional sequencing. Therefore, a genetic mutation associated with HCM may cause sudden cardiac death in the absence of an identifiable phenotype.     

Comparative analysis of differences by gender in sudden infant death syndrome in Hungary and Japan

We examined the sex ratio in sudden infant death syndrome (SIDS) cases in Hungary, in Tokyo and Japan between 1985 and 1996. From all the infant death cases in Hungary 395 (240 male, 155 female) were SIDS (odds ratio (OR)=1.179, with 95% confidence interval (CI)=0.961, 1.446), in Japan 4348 (2550 male, 1798 female) were SIDS (OR=1.145, with 95% CI=1.076, 1.218) and in Tokyo 307 (178 male, 129 female) were SIDS (OR=1.128, with 95% CI=0.894, 1.423). Male infants showed a significantly higher birth rate than females. The male infants are more vulnerable (p<0.005), however, higher mortality among male infants should not be considered a characteristic feature for SIDS.     

Delayed death in sudden infant death syndrome: a San Diego SIDS/SUDC Research Project 15-year population-based report

A fraction of SIDS cases have death delayed by successful CPR, yet they have not been compared to SIDS cases which were found dead or not successfully resuscitated. Our aims were to: (1) determine the percent of SIDS cases in the San Diego SIDS Research Project database for whom death was delayed by CPR and subsequent life support; (2) compare demographics, circumstances of death and autopsy findings of delayed death SIDS cases (delayed SIDS) with those whose deaths were not delayed (non-delayed SIDS); (3) examine the evolution of pathologic changes in delayed SIDS as a function of survival interval. A retrospective 15-year population-based study of 454 infant deaths attributed to SIDS revealed 29 delayed SIDS cases (Group I) and 425 non-delayed SIDS cases (Group II). Group I cases were significantly older than Group II cases (mean age 132 days vs. 102 days and p<0.0001). Eighty-nine percent of the Group I cases were discovered between 08.00 and 19.59 h; none were found between 00.00 and 07.59 h, compared to 38% of the Group II cases. Group I infants were found significantly more often away from home (at daycare, or at the home of a relative, friend, or baby sitter) than Group II infants (45% vs. 25%, p<0.05). There were no differences between groups with regard to gender, gestational age, type of delivery, bed sharing, URI within 48 h of death, ALTEs, a history of referral to child protective services, body position when placed or found, or face position when found. Pathologic changes were semiquantitatively evaluated; findings were characteristic of anoxic-ischemic injury that generally became more severe with increasing survival intervals. Anoxic-ischemic brain injury was the immediate cause of death in all delayed SIDS cases. Aspiration of gastric contents was identified in Group I cases surviving less than 48 h and was the likely etiology of acute bronchopneumonia occurring in 83% of the Group I cases. We did not identify factors that would reliably predict which SIDS cases might be discovered soon enough to allow earlier and more effective CPR and survival without permanent brain injury.     

Sudden infant death syndrome: diagnostic practices and investigative policies, 2004

Using a 2004 population-based survey of all US medical examiner and coroner offices, we examined the characteristics of offices accepting an infant death case and calculated the percentage of offices that had death scene investigation or autopsy policies for the investigation of sudden unexpected infant death (SUID). We also calculated the percentage of offices that used and did not use sudden infant death syndrome (SIDS) as a cause of death, and we compared differences in characteristics among those offices.Of medical examiner and coroner offices, 52% did not report an infant death in 2004. Of the 7957 infant deaths reported, 43% occurred in jurisdictions that experienced 1 or 2 infant deaths. Of the offices that used SIDS as a classification, 34% did not have policies for conducting death scene investigations and autopsies for SUID. At least 5% of offices that reported an infant death did not use SIDS as a cause of death classification. These findings have important implications for understanding recent trends in SIDS and SUID. Supporting the implementation of national standards for investigating and certifying infant deaths could provide guidelines for consistent practices in medical examiner and coroner offices.     

A comparison of respiratory symptoms and inflammation in sudden infant death syndrome and in accidental or inflicted infant death

Upper respiratory infection and pulmonary inflammation are common in sudden infant death syndrome, but their role in the cause of death remains controversial. Controlled studies comparing clinical upper respiratory infection and inflammation in sudden infant death syndrome with sudden infant deaths caused by accidents and inflicted injuries (controls) are unavailable. Our aim was to compare respiratory inflammation and upper respiratory infection within 48 hours of death and postmortem culture results in these two groups. A retrospective analysis of upper respiratory infection and pathologic variables in the trachea and lung of 155 infants dying of sudden infant death syndrome and 33 control infants was undertaken. Upper respiratory infection was present in 39% of sudden infant death syndrome cases and 40% of control cases. Upper respiratory infection was more likely to have occurred in association with more severe lymphocytic interstitial pneumonitis when sudden infant death syndrome cases and control cases were combined ( P=.04). Proximal and distal tracheal lymphocytic infiltration was more severe in control cases than in sudden infant death syndrome cases ( P=.01 and.01, respectively). Lymphocytic infiltrations of the bronchi, bronchioles, and pulmonary interstitium were similar between groups. Bronchial associated lymphoid tissue was more prominent in control cases ( P=.04). Cultures were positive in 80% of sudden infant death syndrome cases, 78% of which were polymicrobial. Among control cases, 89% were positive, with 94% being polymicrobial. This study confirms that microscopic inflammatory infiltrates in sudden infant death syndrome are not lethal.     

Unexpected perinatal death and sudden infant death syndrome (SIDS): anatomopathologic and legal aspects

This work intends to be a review of the recent histopathological findings elicited by research into sudden and unexpected perinatal death and sudden infant death syndrome (SIDS) that have dictated a novel approach to the inherent problems by pathologists, especially those entrusted with forensic medical authority. The new approach stems from the recent advances made in the understanding of neuro- and/or cardiac-conduction-system diseases present in unexpected perinatal death and SIDS. These demand that an accurate morphologic examination be performed of these structures, which modulate respiratory, cardiovascular, digestive, and arousal activities, in all victims of sudden death. A histopathologic study of an ample register of cases of victims of sudden death, either perinatally or in early infancy, has demonstrated frequent alterations both of the autonomic nervous system (especially hypoplasia of the arcuate nucleus) and of the cardiac conduction system (accessory atrioventricular pathways). The present research provides an in-depth study of the many still-controversial aspects underlying perinatal unexpected death and SIDS and is recommended for professionals working in the forensic field, whose greater insight into this problem will allow more complete medicolegal documentation.     

Sudden infant death syndrome and hypertrophy of the palatine tonsil: reports on two cases.

Two cases of sudden infant death syndrome (SIDS) with hypertrophy of the palatine tonsil were reported. The pathogenesis of the SIDS has been clarified (Guilleminault et al., Pediatrics, 68 (1981) 354-360). According to this theory, it is due to a central impairment of the breathing control during sleep, which is particularly pronounced in predisposed subjects. The present cases suggest that the hypertrophied palatine tonsil might contribute as a predisposing factor to the emergence of a SIDS by mechanical impediment to breathing by narrowing of the upper airway.     

A deadly anti-SIDS device

The diagnosis of sudden infant death syndrome (SIDS) has been an enigma to medical examiners and coroners for decades. The recent drastic decrease in the number of SIDS cases has been associated with infants sleeping supine instead of prone. The apparent relation between sleeping position and SIDS has led to the marketing of several positioning sleep aids. We report a case of the improper use of one such device which resulted in the death of an infant.     

婴儿猝死综合征的研究现状及其法医学检验

婴儿猝死综合征(dudden infant death s yndrome,SIDS)一直是法医学和儿科学领域的研究热点。相对于北美、欧洲、澳洲以及日本等地对SIDS广泛深入的研究,来自中国的报道相对较少。本文通过总结文献,介绍SIDS的发展历史、研究现状和新的发展趋势,并结合2004年各国学者在美国圣地亚哥公布的SIDS分型,讨论实际检案中需注意的问题以及推进其调查研究的可行性。     

Virological analysis in the diagnosis of sudden children death: a medico-legal approach

Infections are considered to be an important cause of unexpected death in children. It has also been assumed that respiratory viruses are involved in the genesis of sudden infant death syndrome (SIDS). The Spanish National Institute of Toxicology and Forensic Sciences act as the forensic reference centre for Spain. We analyse the experience of this centre in the virological study of 64 cases of sudden children death where viral serology, virological cultures, herpesviruses polymerase chain reaction (PCR) and electron microscopy were performed. According to pathological findings, death could only be attributed to an adenovirus infection in one amygdalitis with upper airways stenosis and asphyxia. Human herpes virus 6 (HHV-6) was detected by PCR in one case with pathological findings characteristic of SIDS. Recent infection by respiratory syncytial virus (RSV), Epstein-Barr virus (EBV) and cytomegalovirus (CMV) were also detected. Meanwhile, 85.9% of the cases yielded negative viral results. Twenty-eight infants were finally categorised as SIDS. Pathological findings of infection were detected in 12 patients despite the negativity of viral analyses. Although viral infection is an uncommon cause of sudden children death, a complete microbiological investigation will help to solve the puzzle of SIDS. Definitive guidelines for microbiological analyses need to be updated whilst new pathogens are discovered or new techniques are implemented in order to clarify unsolved cases.     

The epidemiological study on registered cases of sudden infant death syndrome (SIDS) in Tokyo: examination of the effect of autopsy on diagnosis of SIDS and the mortality statistics in Japan

In the United States and most of European countries, a diagnosis of sudden infant death syndrome (SIDS) may be given only after an autopsy has been performed. Under the new definition of SIDS in Japan, an autopsy is now mandatory for the diagnosis of SIDS. However, according to the official records on autopsies, the proportion of autopsy for sudden infant death in Japan is still low (less than 30%). If a physician suspects SIDS from a review of the patient's medical history and medical findings, he can write 'suspected SIDS' as the cause of death on the death certificate without performing an autopsy. Such a clinical diagnosis is entered in the Vital Statistics section by the Japanese Ministry of Health and Welfare. In this report, a comparative epidemiological survey of registered cases of SIDS--after autopsy and with no autopsy--was carried out by examining the data from the death certificates registered by the Japanese Ministry of Health and Welfare (vital statistics in Tokyo from January 1979 to December 1996). There were 369 cases of SIDS registered in Tokyo. We found 247 diagnosed after autopsy (66.9%) and 122 with no autopsy (33.1%). The following epidemiological variables were used: address of the deceased (a specific area in Tokyo), sex, year of death, time of death, month of death, age at death, occupation of householders, and place of death. There were epidemiological differences at the 0.05 significance level between registered cases diagnosed after autopsy and those diagnosed without autopsies, as follows: year (P=0.016) and place of death (P=0.037). In addition, there were slight epidemiological differences at the 0.10 significance level between registered cases diagnosed after autopsy and with no autopsy, as follows: month of death (P=0.076) and age at death (P=0.082). This suggests that the quality of diagnosis of SIDS is not completely guaranteed. With respect to the area of residence, the incidence of SIDS is high in those areas where autopsy is performed frequently. In Tokyo, the medical examiner system is enforced only in the urban area and there is a possibility that SIDS is being underdiagnosed in the rural area of the Metropolitan Tokyo. It is likely that the diagnosis of SIDS without autopsy will influence the quality of SIDS diagnoses. The administrative inadequacy in the autopsy system in Japan should be corrected to improve the accuracy of SIDS diagnosis.     

A comparison of pulmonary intra-alveolar hemorrhage in cases of sudden infant death due to SIDS in a safe sleep environment or to suffocation

The differentiation of SIDS from accidental or inflicted suffocation may be impossible without corroborating findings from the death scene or autopsy or in the absence of a confession from a perpetrator. Pulmonary intra-alveolar hemorrhage (PH) has been proposed as a potential clue to suffocation, but none of the previous studies on this topic have limited SIDS cases to those who were in a safe sleep environment, in which all were found supine and alone on a firm surface with their heads uncovered. Our aims are to: (1) compare PH in SIDS cases found in a safe sleep environment to a control group comprised of infants whose deaths were attributed to accidental or inflicted suffocation and (2) assess the effect of age, CPR, and postmortem interval (PMI), with regard to the severity of PH in this subset of safe-sleeping SIDS cases. We conducted a retrospective study of all postneonatal cases accessioned by the Office of the Medical Examiner in San Diego County, California who died of SIDS or suffocation between 1999 and 2004. A total of 74 cases of sudden infant death caused by SIDS (34 cases as defined above, comprising 8% of the total SIDS cases), accidental suffocation (37), and inflicted suffocation (3) from the San Diego SIDS/SUDC Research Project database were compared using a semiquantitative measure of pulmonary intra-alveolar hemorrhage. The most severe (grade 3 or 4) PH occurred in 35% of deaths attributed to suffocation, but in only 9% of the SIDS cases. Age, duration of CPR attempts and PMI had no effect on the severity of PH in SIDS. Our results indicate that the severity of PH cannot be used independently to differentiate SIDS from suffocation deaths. Each case must be evaluated on its own merits after thorough review of the medical history, circumstances of death, and postmortem findings.     

An analysis of the usefulness of specific stages in the pathologic investigation of sudden infant death

Retrospective analysis of autopsy findings in 60 infants who had been found unexpectedly dead in their cribs or beds in South Australia from 1994 to 1998 was undertaken to determine the diagnostic usefulness of individual stages in the postmortem investigation. Positive findings occurred in 2 of 43 scene examinations (3%), 2 of 60 external examinations (3%), 2 of 11 radiologic examinations (18%), 8 of 60 internal examinations (13%), 7 of 60 histologic examinations (12%), and 3 of 58 microbiologic examinations (5%). No positive findings were detected on toxicologic screening. Not every case underwent each diagnostic step. This gave alternative diagnoses to sudden infant death syndrome (SIDS) in 15 cases (25%). This study demonstrates an increase in the percentage of cases of unexpected infant death due to causes other than SIDS; it also shows the diagnostic yield of individual stages in the postmortem evaluation of such cases. Negative findings were important in giving validity to the diagnosis in the 45 cases that were ultimately designated as SIDS.