Sudden infant death due to neurofibromatosis type I

Sudden infant death syndrome (SIDS) is the unexpected death of an infant under the age of 1 year, where a complete autopsy, including scene investigation, fails to reveal a cause of death. Although the frequency of SIDS has decreased almost 50% over the past 10 years, it remains the leading cause of death in infants aged 1 to 6 months. SIDS is a diagnosis of exclusion and requires the elimination of a wide range of possible causes, including asphyxia, poisoning, abuse, occult heart disease, and other natural disease processes. In this report, we describe the case of an infant death initially suspected to be a SIDS death in which autopsy revealed an optic pathway glioma (optic glioma or hypothalamic glioma) and other stigmata of neurofibromatosis type I.     

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.     

Toxicologic analysis in cases of possible sudden infant death syndrome: a worthwhile exercise?

The diagnosis of sudden infant death syndrome (SIDS) is one of exclusion. At the Department of Forensic Medicine, Westmead Hospital, toxicologic analysis is performed as part of the postmortem examination of all apparent SIDS deaths. The results for the 5-year period January 1, 1994, to December 31, 1999, were audited to determine whether such routine testing was worthwhile. During this time there were 117 cases with a history consistent with SIDS. Drugs were detected in 19 (16%) of these cases. In 1 case, death was attributed to the finding of methadone. The presence of methadone was regarded as a possible contributing factor to death in a further 2 cases. The presence of possible methadone toxicity had not been expected from the history given before the examination in these 3 cases. In 114 cases there was a suitable sample for alcohol testing; in no case was alcohol detected. In 13 cases the postmortem examination revealed an anatomic cause of death (including 3 cases consistent with whiplash/shaken baby/impact head injury), which excluded a diagnosis of SIDS. In conclusion, routine toxicologic testing in all possible cases of SIDS death supplements the postmortem examination in excluding cases of non-SIDS.     

Evaluation of diagnostic tools applied in the examination of sudden unexpected deaths in infancy and early childhood

During the period between 1984 and 1999, 309 cases of sudden unexpected death in infancy and early childhood (0-3 years) were investigated at the Institute of Forensic Medicine in Oslo. In 73 cases, an explainable cause of death was found. In this non-sudden infant death syndrome (SIDS) group, 42 cases were due to disease, 14 to accidents, 7 to neglect/abuse and 10 cases were due to homicide. In 43 cases, there were pathological findings at the autopsy or suspect features in the history and/or circumstances, which were, however, insufficient to explain death ("borderline" SIDS). In the remaining 193 cases, nothing of significance was detected ("pure" SIDS).The purpose of the present study was to evaluate the importance of the different diagnostic tools used in diagnosing non-SIDS and borderline SIDS cases. The definition of SIDS requires a negative history as well as a negative autopsy result. Thus, the following variables were analysed: circumstances, medical history and autopsy, which included a gross pathological investigation, histology, neuropathology, microbiology, radiology and toxicology. In diagnosing deaths due to disease, histology, neuropathology and microbiology were the most important diagnostic tools. In contrast, information about the circumstances of death and the gross pathological findings at autopsy most often revealed the cause of death in accidents and cases of neglect/abuse and homicide.Following the drop in SIDS rate in Norway after 1989, the share of pure SIDS in proportion to the total population of sudden unexpected deaths in infancy and early childhood has decreased. The increasing proportion of non-SIDS and borderline SIDS cases presents a challenge to improve the quality of the investigation in cases of sudden death in infancy and early childhood.     

Laryngeal basement membrane thickening is not a reliable postmortem marker for SIDS: results from the Chicago Infant Mortality Study.

It has been suggested that laryngeal basement membrane (LBM) thickening is a pathognomonic postmortem marker for sudden infant death syndrome (SIDS) and is not seen in other causes of explained sudden infant death. To test this hypothesis, we evaluated longitudinal sections of the right hemilarynx taken through the midpoint of the true vocal cord from 129 SIDS cases and 77 postneonatal sudden infant death controls. Using a five-point semi-quantitative scale, maximum LBM thickness (LBMT) for SIDS cases and controls was not statistically different (mean, 2.39 + 0.69 and 2.40 + 0.77, respectively). Likewise, scores based on the average thickness along the entire basement membrane (i.e., "average" score), were not found to be different between SIDS cases and controls. Average and maximum LBMT increased with age in both SIDS cases and controls and were not different between SIDS cases and controls within each age interval. Similar trends in the distribution of maximum and average LBMTs were found between black and Hispanic SIDS and controls; the number of white/non-Hispanic infants was too low for meaningful comparisons. Maximum and average LBMTs were not different in SIDS cases and controls exposed to environmental tobacco compared with unexposed infants. The LBMTs also increased significantly with body weight and length in both SIDS cases and controls. Finally, there were no differences in LBMT in infants intubated prior to death compared with those who were not intubated. From these data, we conclude that LBMT is not pathognomonic of SIDS, is present or absent with equal frequency in SIDS and controls, increases with postnatal age, and does not correlate with passive smoke exposure. Therefore, LBMT should not be used to diagnose SIDS.     

Inadvertent clavicular fractures caused by "chiropractic" manipulations in an infant: an unusual form of pseudoabuse

A nine-month-old child was found unresponsive in his crib, five hours after his last feeding. At autopsy, there were no external or internal signs of abuse or neglect, and a few visceral pleural and epicardial petechiae were consistent with the sudden infant death syndrome (SIDS). However, postmortem total body radiographs revealed healing, symmetrical clavicular fractures and a healing left medial humeral epicondyle fracture. The parents had no explanation for these injuries and denied causing any harm to the child. The location and nature of the fractures strongly suggested abusive origin, and the case was reported to the police and the district attorney's office as child abuse. During the investigation, information from the parents indicated that the child had undergone "chiropractic" manipulations by an unlicensed therapist, between three and four weeks prior to death, to correct supposed "shoulder dislocations." This time interval correlated with the histologic age of the injuries, and the history explained their unusual bilateral location and appearance. The parents were exonerated of abuse charges, and the death was ascribed to SIDS.     

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.     

Cardiac lesions in sudden infant death syndrome

Sequential morphological changes as found in the hearts of 250 sudden infant death syndrome (SIDS) infants are described. Detailed examination of macroscopic and microscopic lesions reveal that all SIDS infants had identifiable lesions at the time of their death. The lesions can best be described as selective focal anoxic muscle fibre necrosis at chronologically different developmental stages. The extent of these lesions vary markedly from case to case, from a minimal muscle fibre eosinophilia through contraction band formation, myocytolysis, stromal condensation to scar formation. The morphological variations in the lesions amongst individual cases can be interpreted as relating to the time interval of the development of the lesions. The intramural and coronary arteries in some cases are also affected showing intimal hyperplasia. Although these sequential morphological aberrations are not specific and typical to SIDS infants only, they were present in all SIDS infants in this series.     

Serum tryptase levels in sudden infant death syndrome in forensic autopsy cases

An elevated serum tryptase concentration is considered to be a specific marker for systemic mast-cell activation, a central feature of anaphylaxis, which has been observed in some cases of sudden infant death syndrome (SIDS). However, it is still unclear whether anaphylaxis is involved in the etiology for SIDS. In the present study, we measured serum tryptase levels in 21 infants with SIDS, and 14 control infants from forensic autopsy cases by Uni-CAP TRYPTASE Fluoroenzyme immunoassay system, which detects both alpha- and beta-tryptase. The assay did not show any significant elevation of tryptase levels in the SIDS group compared with controls. Additionally, increased concentrations of tryptase were not observed in any SIDS case. Our results indicated that anaphylaxis does not seem to be involved in the etiology of SIDS.     

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.     

The epidemiology of sudden infant death syndrome in Finland in 1969-1980

SIDS cases were defined by examining all death certificates, in which sudden deaths were expected to be found from the years 1969-80 from the Central Statistical Office of Finland. The age limits were 28-364 days. If the death certificate did not give enough information as to whether the cause of death was explained or unexplained, autopsy records and microscopic specimens were examined. If the death was sudden, but no autopsy was done, no microscopic specimens were taken, or there were some slight findings which could have partly explained the death were classified as borderline cases. The mean annual incidence of SIDS in Finland was 0.41/1000 livebirths in 1969-80. In 1969-74 and 1975-80 the incidences were 0.31 and 0.51, respectively. The increasing tendency of SIDS was partly due to more borderline cases in the first period and partly due to more twins, and infants with small birth weight, dying of SIDS in the second period. Deaths at weekends and sleeping with parents in the second period were more common than in the first study period. In the SIDs group the young maternal age, low social class, family type unmarried couple or single mother, maternal anemia during pregnancy were more common than in the control group. Mothers of SIDS infants had more previous children and fewer visits and later first visit to prenatal clinics than control mothers. The duration of gestation was shorter and the mean birth weight and length were smaller in the SIDS case than in the control group. Twins were more common among SIDS infants than in the common population. The most important risk factor of SIDS was maternal smoking during pregnancy. The epidemiological results conform with the hypoxia hypotheses.     

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.     

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.     

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.     

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.     

Dicyclomine in the sudden infant death syndrome (SIDS)--a cause of death or an incidental finding?

We report a case of a small infant apparently dying of the Sudden Infant Death Syndrome (SIDS) with a postmortem blood dicyclomine level of 200 ng/mL. Review of the literature and the comparison with blood dicyclomine values from four rabbits given equivalent doses suggests that a blood dicyclomine value of 200 ng/mL probably is in the therapeutic range for infants. Although safely used for years for infantile colic, recently, the administration of dicyclomine has been related to acute episodes of apnea, seizures, and coma. In the absence of those acute reactions, we feel that a 200-ng/mL blood dicyclomine level in a child dying of apparent SIDS should not prevent categorization of the death as SIDS.     

Sudden infant death syndrome: a subject of medicolegal research

During the last decade, much attention has been paid to the risk factors of sudden infant death syndrome (SIDS). Many researchers have demonstrated that infant-care practices are linked to the risk of SIDS. Prone sleeping, bed sharing, maternal substance abuse, and cigarette smoking have been reported to be significant potentially modifiable risk factors for SIDS. Despite the reports that the incidence of SIDS has decreased by 38% in the United States, it remains the leading cause of death in the first year of life. Deaths resulting from child abuse or neglect inflicted or permitted by their caretakers being second only to SIDS in infant mortalities and some recommendations regarding the differentiation of SIDS and child abuse have generated speculation that some cases of infanticide were misdiagnosed as SIDS. To reach a proper conclusion as to the cause and manner of death of an infant who died suddenly and unexpectedly, investigation must be thorough and professional.     

Cardiac rhabdomyoma presenting as sudden infant death syndrome

A case of cardiac rhabdomyoma presenting as sudden infant death in a four-and-one-half month-old infant is reported. The child was the product of an essentially uncomplicated pregnancy and enjoyed good health before his unexpected, sudden death. Autopsy examination revealed the presence of multiple cardiac lesions which histologically were diagnosed as rhabdomyomas. Death was attributed to fatal cardiac arrhythmia caused by the tumor. To the authors' knowledge this represents the first reported case in the forensic science literature of death as a result of cardiac rhabdomyoma presenting as sudden infant death syndrome (SIDS).     

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.     

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.