A contribution to a possible differentiation between SIDS and asphyxiation

The singular and combined appearance of conjunctival petechiae, of acute pulmonary emphysema and of signs of aspiration was evaluated in resuscitated and non-resuscitated children dying of SIDS (n=115), of other causes of natural death (n=17), of severe head injury (n=10) and of asphyxiation/strangulation (n=7). Conjunctival petechiae occurred in all of the asphyxiated victims and in five out of 10 children dying of severe head injury, but were exclusively found in four resuscitated babies and one baby with questionable resuscitation trials of the SIDS-group (4%), furthermore in one resuscitated child dying of a congenital heart defect. Acute pulmonary emphysema was detected in six out of the seven children of the asphyxiation/strangulation group, in two resuscitated children with head injury and in five resuscitated babies dying of SIDS. Both parameters were observed exclusively in the asphyxiation/strangulation group (71% of the cases) but not in the control cases. Therefore, it can be concluded that the simultaneous appearance of conjunctival petechiae and of acute pulmonary emphysema strongly indicates death by asphyxiation.     

Sudden infant death and liver phosphoenolpyruvate carboxykinase analysis

In an effort to substantiate the impaired gluconeogenesis-terminal hypoglycemia hypothesis of sudden infant death syndrome (SIDS), 52 infants ranging from 3 weeks to 7 months of age which had been brought to autopsy were studied. The stomach contents, vitreous humor glucose concentrations, hepatic glycogen content and hepatic phospho-enolpyruvate carboxykinase (PEPCK) activity were measured as part of the laboratory component of the postmortem investigation. The stomach contents, vitreous humor glucose concentrations and liver glycogen content were similar in SIDS/and non-SIDS victims. PEPCK activity was, however, significantly lower in SIDS (p < 0.001) victims and in SIDS with other findings (p < 0.01) victims when compared to non-SIDS victims. Despite the fact that SIDS victims had lower hepatic PEPCK activity and hence potentially lower gluconeogenic capacity, terminal hypoglycemia could not be demonstrated in this group as compared to the SIDS with other findings and the non-SIDS infants. The impaired gluconeogenesis-terminal hypoglycemia hypothesis thus could not be substantiated.     

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.     

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.     

Homicidal asphyxia

Homicides due to asphyxia are relatively uncommon. To better understand the presentation of such cases, the files of the Bexar County Medical Examiner's Office were reviewed from January 1, 1985, through December 31, 1998, for all such homicides. A total of 133 cases were found. The largest category was ligature strangulation with 48 deaths (21 male, 27 female). Petechiae were present in the conjunctivae and/or sclerae in 86% of the cases; fractures of the hyoid and/or thyroid cartilage were present in 12.5%. There were a total of 41 deaths from manual strangulation (27 female, 14 male). Petechiae were present in 89% of the cases. In cases of manual strangulation, fractures of the hyoid, thyroid, or cricoid cartilage were found in all the male victims and slightly more than one half of the female victims. Twenty-six cases of suffocation were found; 20 of the victims were < or =2 years of age. Only 1 of these children had petechiae and/or scleral hemorrhage. Five deaths were due to choking. Three of the deaths involved adults who were gagged; 2 deaths involved infants with foreign material pushed into the mouth. Other categories of asphyxia were as follows: 9 deaths due to more than one form of asphyxia; 1 death due to hanging, and 3 deaths due to drowning. Rape was the motive in 66% of the female victims of ligature strangulation and 52% of those due to manual strangulation.     

Histological Changes in the Thyroid Gland in Cases of Infant and Early Childhood Asphyxia—A Preliminary Study

A retrospective blinded study of thyroid gland histology was undertaken in 50 infants and young children aged from 1 to 24 months. Deaths were due to (i) suffocation (N = 7), hanging (4), wedging (3), and chest and/or neck compression (4), and (ii) SIDS (20), noncervical trauma (7), organic disease, (4) and drug toxicity (1). In the asphyxia group (N = 18), thyroid gland congestion ranged from 0 to 3+ with 39% of cases (7/18) having moderate/marked congestion. In three cases, focal aggregates of red blood cells (blood islands) were observed within the intrafollicular colloid. These deaths involved chest compression, chest and/or neck compression, and crush asphyxia in a vehicle accident, and all had facial petechiae. Only 22% of the 32 control cases (7/32) had moderate/marked congestion with no blood islands being identified (p < 0.05). Blood islands within the thyroid gland may be caused by congestion associated with crushing or compression and may provide supportive evidence for this diagnosis.     

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.     

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.     

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.     

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.     

Failure to detect elevated levels of carboxyhemoglobin in infants dying from SIDS

Carboxyhemoglobin (COHb) levels were determined in stored blood samples from 91 infants diagnosed to have died from the sudden infant death syndrome (SIDS) (0.59+/-0.41%, excluding one outlying value of 10.83%); 48 age-matched controls (0.53+/-0.38%); and three individuals who died from fire related causes (41+/-20%). No statistical differences in COHb levels were detected between blood from SIDS and control infants (p = 0.43).     

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.     

Increase of pulmonary density of macrophages in sudden infant death syndrome

A 1996 cytodensitometric study found increased cellular density in the pulmonary parenchyma of infants who died of sudden infant death syndrome (SIDS). The present study clarifies these results in quantifying the density of immunohistochemical subtyped inflammatory cells. Histomorphometry was used to compare the density of macrophages, granulocytes and T and B lymphocytes in the lungs of two groups of infants. From the post-mortem records of infant deaths between 1983 and 1995, 29 (mean age = 5 months) were randomly selected including 16 cases of SIDS and 13 who died of other non-pulmonary causes. Densities of immunoreactive cells were measured under blind conditions in the parenchyma. The mean density of macrophages was significantly higher in cases of SIDS compared with the controls (P = 0.0318), but there were no differences for the lymphocytes and the granulocytes. These morphometrical results must be interpreted within the methodological limits of this study, especially the non-uniform level of lung inflation between selected subjects. However, the differences in level of inflation are not sufficient to explain the observed increase of macrophage density. Indeed, the mean values of alveolar surface area, which represent an indirect measure of lung inflation, are not significantly different between the two groups. Increase of pulmonary macrophage density in SIDS agrees with three non-exclusive hypotheses: (1) an abnormal inflammatory reaction by expression of Th1 helper cell phenotype activation; (2) consequence of passive smoking; and (3) post-agonal mechanisms. Bacterial superantigens produced by toxigenic bacteria in the respiratory tract could play a role as a trigger factor that initiates a fatal cascade with overproduction of cytokines leading to death. The significant increase of pulmonary macrophage density would be the morphological expression of this potential mechanism of death.     

Thyreoglobulin and violent asphyxia

The concentration of thyreoglobulin (tg) was determined for death caused by hanging, strangulation by ligature, and throttling. Cases of sudden death (traumatic aortic rupture, penetrating wounds of the heart) were used for comparison. The mean values in cases of hanging (149.9±202.3 ng/ml), strangulation by ligature (193.1±173.3), manual strangulation (561.6±173.9) are distinguishable from violent acute deaths (23.3±27.6) and living healthy individuals (17.3±16.1). By means of statistical comparisons, significant differences were found between throttling and strangulation by ligature and between throttling and hanging (adjusted P<0.001). In connection with examination of the bodies high tg values can be regarded as a vital reaction in obstructive asphyxia.     

An hepatic metabolic profile in sudden infant death (SIDS)

Levels of 18 enzymes and metabolites were measured in liver obtained at autopsy from 41 infants, 28 of whom were found unexpectedly dead at home. Four infants had meningitis, 11 had pathologic findings not clearly sufficient to explain death (SUD), and 13 were considered totally unexplained pathologically (SIDS). The possible contributions of postmortem interval, age and diet to the results are reviewed. No characteristic metabolic profile was recognized amongst SUD and SIDS groups. It is speculated that the amount of glycogen found in liver may provide insight into premortal events and reflect the rapidity of the death mechanism. Five individuals (20%) were suspected of having major metabolic abnormality including glycogenosis (1), urea cycle defect (1), and possibly abnormal levels of carnitine palmityl transferase (3).     

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.     

Cardiovascular malformations and sudden death in infancy

BACKGROUND: We survey the postmortem findings of cardiovascular malformations in infants under the age of 1 year who died suddenly and unexpectedly, in a way that mimicked sudden infant death syndrome (SIDS), and evaluate the importance of the malformation for the fatal outcome. METHODS: Four hundred fifty-seven infants under the age of 1 year, who died between 1982 and 2001, were investigated at the Department of Forensic Medicine in Stockholm, Sweden. RESULTS: Cardiovascular malformations were found in 18 infants (3.9%). Only 6 of 18 malformations, mostly severe, were clinically diagnosed before death. In the other 12 infants, cardiovascular malformations were found, such as atrial or ventricular septal defects, coarctation of aorta, stenosis of the aortic or pulmonary artery orifice, and aneurysm of the membranous portion of the interventricular septum. In all instances, the heart weight was increased. CONCLUSIONS: The observation of undiagnosed cardiovascular malformations as the only explanation for the cause of sudden and unexpected death in apparently healthy infants may advocate more examinations of the infant during early life. It is also important to enlarge the debate of the cause of death in infants with cardiovascular malformations. Should they be included in borderline SIDS?     

Comparative histologic studies of the origin of petechial thymus hemorrhage

Systematic histological investigations were carried out on the thymus with regard to the incidence and genesis of petechial thymus hemorrhages in 145 cases of death (fetuses from pregnancy terminations and stillbirth, mature and immature neonates, SIDS cases, other baby deaths, deaths during infancy and childhood). Petechial thymus hemorrhages were most frequently found in SIDS cases (87%). Even though distinguishable, a distribution pattern similar to that of thymus hemorrhages in SIDS cases (including hemorrhages mainly in the cortical zone of the lobes) could be detected in the group of fetuses from pregnancy terminations and stillbirth, as well as in mature and immature neonates. Histologically, deaths in babies and infants without extrinsic suffocation showed a different histological bleeding pattern (irregular hemorrhages of varying size in the cortex and medulla of the lobes). In violent extrinsic suffocation of babies and infants, thymus hemorrhages were much rarer and less pronounced in quantitative terms. Acute and subacute or chronic forms of asphyxia, the cause of death and the duration of the death struggle are discussed as pathogenetic factors to explain the different patterns of the findings.     

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.