Intrathoracic and subconjunctival petechiae in sudden infant death syndrome (SIDS)

The frequency and density of intrathoracic and subconjunctival petechiae was studied in 250 cases of SIDS and 69 controls. The control group included 37 infants with natural and 32 infants with traumatic causes of death. Intrathoracic petechiae were found significantly more frequently in the SIDS group (91.2% SIDS; 42% controls; p < 0.001) and were present at a higher density (p < 0.001). Subepicardial and thymic petechiae were detected at high density in older SIDS infants. Subconjunctival petechiae were low in density and found only in 2.4% of the SIDS group but they were detected in 8.1% of the natural death group and 21.9% (p < 0.05) of the lethal trauma group. Subconjunctival petechiae were found at highest density in strangulation. Intrathoracic petechiae are commonly found in SIDS but are not specific for SIDS. Subconjunctival petechiae are typical but not specific for strangulation. In SIDS, subconjunctival petechiae are rare and appear at low density.     

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 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.     

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.     

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?     

Beta-endorphin in the brainstem, pituitary, and spinal fluid of infants at autopsy: relation to sudden infant death syndrome

Immunohistochemical localization of beta-endorphin was studied in the pituitaries and medullas of forty human infants at autopsy. beta-Endorphin immunoreactivity was found in anterior pituitary cells in all cases. In the medulla, beta-endorphin immunoreactivity was found in the neurons of the medial and lateral cuneate nuclei in ten out of the forty cases. In eight of these ten cases, the infants died of causes other than sudden infant death syndrome (SIDS). Only two of 25 SIDS cases had demonstrable beta-endorphin in the brainstem nuclei. Beta-endorphin levels in the spinal fluids of all the cases showed no correlation to cause of death, age or gender.     

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.     

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.     

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.     

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.     

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.     

Frequency of pulmonary hemosiderosis in Eastern North Carolina

Pulmonary hemosiderosis has been attributed to airborne fungi in water-damaged homes in studies of a cluster of cases in infants and children in Cleveland, Ohio, in 1997. We have searched for such emerging infectious agents in the Coastal Plain of North Carolina, which is subject to intermittent flooding. Pulmonary tissue from 206 infants and young children whose deaths had been investigated from October 1978 to September 1996 was retained at East Carolina University School of Medicine. Ages ranged from premature newborns to 49-months. One hundred and ten deaths were attributed to sudden infant death syndrome (SIDS). New sections were cut and analyzed using hematoxylin and eosin, Prussian blue for iron, and Gomori methenamine silver for fungal organisms. Twenty-three infants and children had iron-containing macrophages. Sixteen of these had underlying illnesses, but 4 were originally diagnosed as SIDS. Only one of these had sufficient hemosiderosis to be considered as having pulmonary hemosiderosis and no fungi were present. One case without iron had fungi and was not originally diagnosed as SIDS. The single case of pulmonary hemosiderosis found in this rural area is not similar to the cluster in Cleveland. The study identifies no fungal organisms as emerging infectious diseases in this area.     

Digoxin-like immunoreactive substance in postmortem blood of infants and children

A digoxin-like immunoreactive substance (DLIS) has been reported in the serum of infants not receiving digoxin. This study was undertaken to determine if DLIS is present in the postmortem blood and tissues of infants or children and whether the endogenous substance could interfere with forensic toxicological analysis in suspected overdose. Ninety blood specimens taken from the heart at autopsy of children or infants were screened for DLIS using commercial radioimmunoassay kits. The average age at death in these cases was 8.6 months, the median age was 2 months. DLIS equivalent to 0.25 to 2.0 ng/mL digoxin was found in one third of the cases. The incidence of positive findings was 5/6 stillborns, 10/45 Sudden Infant Death Syndrome (SIDS), 10/15 deaths as a result of infection, 4/7 homicides, 1/8 deaths caused by congenital defects, and 0/9 accidental deaths. The body distribution of DLIS was investigated and highest levels were found in the liver. Findings of DLIS in blood were correlated with renal failure, (elevated vitreous urea nitrogen), electrolyte imbalance, and liver trauma. Apparent concentrations were in the equivalent therapeutic range of digoxin and would not be confused with accidental or intentional overdose with digoxin.     

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.     

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.     

Diagnosis of sudden death in infants due to acute dehydration

When infants die suddenly of acute dehydration, clinical signs and autopsy findings may be equivocal or absent, and microbiologic cultures often are not helpful. Vitreous humor electrolyte and urea nitrogen concentrations were measured in 53 infants dying of gastrointestinal infections, sudden infant death syndrome (SIDS), other infectious diseases, and miscellaneous causes to determine whether these parameters would assist in the recognition and confirmation of deaths resulting from dehydration. Significant differences were found when comparing the mean sodium and urea nitrogen levels of infants dying of gastrointestinal infections with those succumbing to SIDS or other causes. We recommend that these determinations be routinely performed whenever the gross autopsy findings are insufficient to explain the death.     

Hemosiderin findings in the liver, spleen and lung in newborn infants and infants

The content and distribution of hemosiderin in the liver, spleen and lungs of stillborn children, newborns and infants were determined histologically by Perl's method (Prussian blue reaction). We describe a study of 59 deaths up to the age of 2 years. The hemosiderin content depends on age and decreases with increasing age. No relevant differences were found in cases of sudden infant death syndrome (SIDS). In the liver hemosiderin is localized preponderantly in the periphery of the lobules. The spleen shows a diffuse siderosis of the red pulp. Minimal intrapleural, septal and perivasal depositions of hemosiderin can be found in the lung tissue. The significance of these findings is discussed.     

Sudden unexplained death among persons 1-35 years old

Sudden unexplained death (SUD) on children and young people is unusual, although the real magnitude is unknown. The clinical and physiopathological characteristics are poorly defined. The aim of this work is to analyse the epidemiological, clinical and pathological characteristics of SUD on children and young people. In this population observational study, all sudden non-violent deaths between 1 and 35 years occurred in Bizkaia (north Spain) from 1991 to 1998 were investigated, analysing those diagnosed as SUD. Pathological records, circumstances of death and autopsy findings were obtained. Out of 107 cases of sudden death (SD), 19 were SUD. The mortality rate of SUD was 0.43/100,000 persons per year. Five had pathological antecedents: syncopal episodes in three cases and tachycardia and ventricular extrasystoles one each. The initial symptom was sudden collapse (N=13). In four cases, a precipitating factor was identified (two physical exercise and two emotional stress). Six cases died during sleep. Minimal pathological findings in coronary arteries, myocardium or conduction system was found in nine cases. Heart weight increased (under interval of confidence of 95%) was present in 12 cases. In conclusion, the SUD is very infrequent in children and young people. However, it has great clinical significance because it affects people in good health and occurs without warning symptoms. Some of these cases can be due to cardiac arrhythmias. In deaths in bed there is a high frequency of SUD. In the future, it may be possible that abnormalities at a molecular level will be detected in some of the cases identified today as SUD.     

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.