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.     

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.     

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.     

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.     

Significant association of TH01 allele 9.3 and SIDS

Sudden infant death syndrome (SIDS) constitutes a considerable percentage of infant death of unknown etiology. Individual catecholamine response variation is suspected to play a role in SIDS. TH01 is a tetrameric short tandem repeat marker in the tyrosine hydroxylase gene, which regulates gene expression and catecholamine production with allele 9.3 exerting a particularly strong effect on noradrenaline production. We investigated in an age-controlled study the TH01 allele frequencies in 127 cases of SIDS and 406 control cases to assess whether in SIDS cases a distinct TH01 allele distribution could be determined as has been reported by a previous study. We found that genotypes containing one or two 9.3 alleles were significantly more frequent in SIDS patients (58.2%) than in control subjects (48.4%, p=0.038), whereas all other alleles were more frequent in the control subjects. Our findings support the notion that there exists a significant association between TH01 gene configuration and SIDS.     

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.     

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.     

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.     

Ocular findings in pediatric deaths under 2 years of age (1994-2004)

Abstract:  Our purpose is to highlight novel ocular findings of 102 forensic pediatric cases under 2 years of age who die suddenly. Forensic information, grossing, and microscopic eye protocol was followed. The most common diagnosis was Sudden Infant Death Syndrome (SIDS) (57/102). Novel cytoid bodies were present in the retina of 72/102 cases and they were located predominantly 90% (65/72) at the anterior part of the retina ( p  < 0.001). Of the SIDS cases, 85% (47/57) showed the presence of cytoid bodies, and among all diagnosis, SIDS was the most associated with cytoid bodies ( p  = 0.003). A second observation was extramedullary hematopoiesis (EMH) identified in 35/102 cases and 22 of the 57 SIDS cases. The most frequent EMH location was the choroids (29/35). This study is the first to demonstrate the presence of cytoid bodies and extramedullary hematopoiesis in the retinas of SIDS cases and children who die suddenly from other causes.     

Lactic acid concentrations in vitreous humor: their use in asphyxial deaths in children

Lactic acid concentrations in brain tissue of humans have been shown to increase with an extended agonal period. Infants and children dying from various causes are undergoing different stress conditions terminally and the postulate of this study is that natural death cases and traumatic asphyxia cases are characterized by varying agonal periods, the former being somewhat prolonged with the latter being rather brief. One-hundred-and-two cases of infants and children were examined for vitreous humor lactic acid concentrations. They were divided into two major categories, Sudden Infant Death Syndrome (SIDS) and non-SIDS cases. SIDS was further divided into SIDS without additional findings and SIDS with secondary findings which contributed to death. The non-SIDS category included traumatic asphyxia cases as well as those dying from blunt trauma, known respiratory diseases, and other causes. Categorical mean values and standard deviations were calculated. The vitreous humor lactic acid mean value for traumatic asphyxia was significantly lower than the mean value for SIDS. Also the mean value for known respiratory diseases was statistically lower than the mean value for SIDS with secondary findings. These findings are probably suggestive of agonal time differences and may be a reflection of the various mechanisms of death.     

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.     

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 histologic and hormonal studies of the thyroid gland with special reference to sudden infant death (SIDS)

In 53 cases of death - including 12 cases of sudden infant death syndrome (SIDS) - where blood samples could be taken within 18 h postmortem, the thyroxines T4, FT4, T3 and FT3 were determined (ELISA and RIA). These hormone values were compared with the corresponding histological thyroid findings in 43 cases (11 SIDS, 32 controls). Nearly identical T4 and FT4 mean values were found in both groups which were within the norms. In contrast to the average values of the control group, the T3 and FT3 concentrations of the SIDS group showed an increase of 3.7-fold and 1.9-fold. Accordingly, histological examination of the SIDS group showed highly activated and extensively released follicles whereas normal colloidal-containing follicle structures were observed in nearly all control cases. The present findings indicate that neither postmortem T4 T3 conversion nor intensified agonal hormone secretion is likely to be the only cause of the increasing T3 and FT3 values. In SIDS cases chronic or recurring chronic stress situations are supposed to be the cause for the hormonal and histological thyroid findings. Some differential diagnoses are discussed. Within 18 h after death, increased concentrations of T3 and FT3, together with simultaneous colloid release, represent a diagnosis of SIDS.     

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.     

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.     

婴幼儿猝死综合征心传导系统的免疫组化研究

作者应用ＰＧＰ９．５与抗Ｓ１００抗体和高压消毒蒸锅抗原复活技术对４例婴幼儿猝死综合征（ＳＩＤＳ）和３例非心源性死亡对照婴儿心传导系统的神经组织总量进行免疫组化研究。结果：在正常婴儿心传导系统，ＰＧＰ９．５与Ｓ１００阳性的神经纤维里不均匀分布，以窦房结最多，房室结次之，希氏束最少；４例ＳＩＤＳ心传导系统的神经组织分布同对照组无明显差异。     

Sudden infant death syndrome (SIDS): a burgeoning medicolegal problem.

This Article presents a summary analysis of the administrative and statutory bases for the documented, prevalent mismanagement of Suddern Infant Death Syndrome (SIDS) cases by a majority of local death investigation agencies in the United States. Herein, Alan P. Cleveland, J.D. advances the theory that the unsatisfactory handling of cases of SIDS by the medicolegal community is the inevitable outgrowth of state laws that expressly require investigative agencies to approach a sudden, unexplained death from the direction of determining first whether or not a criminal act has occurred. In so doing, most statutorily mandated autopsy procedures are socially counterproductive since, in ignoring an acute medical need for supportive family counselling, they often constitute an insuperable obstacle to the effective management of SIDS as a public health problem. The author recommends that a requisite first step in implementing an SIDS management program at the state level is to insulate surviving family members form criminal investigative procedures by appropriate amendment of state laws governing local death investigation systems.     

Investigation of sudden infant deaths in the State of Maryland (1990-2000)

The Office of the Chief Medical Examiner (OCME) has recorded a significant decline in the deaths of sudden infant death syndrome (SIDS) in the state of Maryland since 1994. However, infants who died of accidental or non-accidental injuries remained consistent during the same time period. This report focuses on the epidemiological characteristics and scene investigation findings of infant victims who died suddenly and unexpectedly in Maryland between 1990 and 2000. A retrospective study of OCME cases between 1990 and 2000 yielded a total of 1619 infant fatalities. 802 infant deaths were determined to be SIDS, which represented 50% of the total infant deaths in our study population. Five hundred and twenty-three (31.8%) deaths were due to natural diseases, 128 (7.9%) deaths were accidents, and 74 (4.6%) were homicides. The manner of death could not be determined after a thorough scene investigation, review of history and a complete postmortem examination in 92 (5.7%) infants. SIDS deaths most often involved infants who were male and black. The peak incidence of SIDS was between 2 and 4 months of age. The majority of SIDS infants (60%) were found unresponsive on their stomach. Among SIDS infants, 269 (33.4%) were found in bed with another person or persons (bed sharing). Of the bed-sharing SIDS cases, 182 (68%) were African-American. In the past 11 years, 52 infants died of asphyxia due to unsafe sleeping environment, such as defective cribs, ill-fitting mattresses, inappropriate bedding materials. Of the 74 homicide victims, 53 (70%) involved infants less than 6 months of age. Twenty (27%) exhibited the classical abuse syndrome characterized by repeated acts of trauma to the infants.