Cellular components in interstitial lung tissue in sudden infant death--immunohistochemical characterization

Monoclonal antibodies against the Leucocyte Common Antigens LC and MAC-387 expressed by lymphocytes, mononuclear phagocytes and polymorphonuclears failed to mark the cells of the pulmonary interstitial connective tissue in cases of SIDS. Controls with interstitial pneumonia showed clearly marked inflammatory cells. Although focal proliferation of cells was frequently observed in the vicinity of distended lymphatics in SIDS cases, an inflammatory origin as in the cases of interstitial pneumonia could not be confirmed. A relationship between interstitial edema and a non-inflammatory proliferation of the cells is discussed.     

Morphometrical investigations into alterations of the wall thickness of small pulmonary arteries after birth and in cases of sudden infant death syndrome (SIDS)

In 1973 Naeye was the first to demonstrate that, in cases of SIDS, the small pulmonary arteries have more smooth muscle than in controls and suggested that this is a consequence of chronic alveolar hypoxia. Seventy-five cases have been investigated morphometrically in order to obtain quantitative data on the alterations of wall thickness of the small pulmonary arteries after birth and in cases of SIDS. The investigations comprise seven cases of stillbirth, 19 cases of newborn, 33 cases of SIDS and 16 controls. In each case the thickness of the media, the external diameter of the artery and the media area have been measured planimetrically for 90 arteries ranging between 50 μm and 500 μm. A media index was calculated as the ratio of the thickness of the media to the diameter of the artery. Using this index a thickening of the media of the small pulmonary arteries, corresponding to the situation in fetal and neonatal life, has been confirmed for cases of SIDS. The normal postnatal changes in the small pulmonary arteries, media thinning and enlargement of the lumen, could not be observed in SIDS cases in the first year of life.     

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.     

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.     

Incidence and forensic value of liver cell hydrops in external asphyxia and sudden infant death

A histological examination was carried out in 108 cases of asphyxia, 28 cases of SIDS, and 33 cases with other causes of death to assess the occurrence of liver-cell hydrops. In almost all cases of violent suffocation of newborns and children up to 10 years of age hydrops of the hepatocytes were found, whereas these results could be verified only exceptionally after violent suffocation of adults. Eighteen cases or 64.3% of SIDS showed a diffuse distribution of liver-cell hydrops over each liver lobule. Liver-cell hydrops seems to represent a frequent morphological equivalent of acute oxygen deficiency in asphyxia in childhood and is a common finding in SIDS.     

Toxic environmental factors in sudden infant death (SIDS)

The increasing number of discussions on the influence of toxic environmental factors, including SIDS, prompted systematic postmortem chemical-toxicological investigations to be carried out on 54 SIDS cases and 2 control cases of the same age group. Tissue levels of arsenic, lead, cadmium, mercury, and pentachlorphenol, as well as other organic noxious agents, were measured in several organs. In addition, the COHb concentrations were determined. In spite of the widely scattered values, the extreme levels measured and the arithmetic means and median averages of As, Pb, Cd, Hg, PCP, and COHb had no more range in concentrations than can be expected for toxic effects - according to present knowledge anyway. It was observed that infants from an urban environment showed no greater concentration of noxious agents than did infants from rural regions. There were also no differences between SIDS cases and the controls, nor was there a correlation between infections of the respiratory system that are often morphologically detected - including laryngitis - and higher concentrations of these agents in the organs of SIDS cases.     

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.     

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.     

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.     

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.     

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.     

Changes in the lung connective tissue framework in sudden infant death (SIDS)

Light microscopy findings are reported on the interstitial connective tissue framework of 45 lungs from babies who died within the first 2 years of life. Thirty were confirmed cases of SIDS and 15 were controls of similar age who died of known causes. The stains applied were H & E, PAS, Prussian blue, Elastica van Gieson, Trichrom (Masson-Goldner), Gomori's silver methenamine and Picro-Sirius polarization (modified). Particular attention was paid to type I and type III collagen, reticulin fibers and ground substance. All investigated cases showed evidence of chronic recurrent interstitial edema in a highly significant frequency and intensity in contrast to the controls. Areas of recent and persistent lymphedema were observed, some of them with reactive fibroplastic activity, which tended towards gradual fibrosis. These changes were irregularly distributed and frequently involved the mural interstitium. Considering the effects of such changes on expansibility, ventilation and perfusion of the lungs, as well as the impairment of gas diffusion, the findings described could be significant in the forensic evaluation of the signs of asphyxia found in most cases of 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.     

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。     

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.     

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.     

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.     

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.     

Morphometrical analysis of retinal hemorrhages in the shaken baby syndrome

A morphometrical analysis of retinal hemorrhages was performed in cases of physical child abuse including the shaken baby syndrome and in controls (severe head injury, intravital brain death, non-traumatic intracranial hemorrhage, SIDS including cardiopulmonary resuscitation). The extent of the retinal hemorrhages was significantly different between both groups. In all cases of physical child abuse, massive retinal hemorrhages in at least one eye could be found ranging between a maximum value of 19.2 and 73.2% of the entire retinal area. In contrast, only two cases of the control group (severe head injury with skull fractures and intracranial bleeding following traffic accident or fall) showed slight hemorrhages of 3.33 or 1.18% of the retinal area but only in one eye. Therefore, the results provide evidence that massive intraretinal hemorrhages indicate violent shaking — in particular in association with other signs of physical child abuse.     

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.