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.     

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.     

婴儿急死综合征(SIDS)颈动脉体的超微结构

作者利用透射电镜对8例婴儿急死综合征死亡及4例其他原因死亡的婴儿的颈动脉体进行观察。发现婴儿急死综合征与非婴儿急死综合征死亡的婴儿,其颈动脉体的主细胞形态结构相似。两组检材的主细胞内均含大量致密颗粒,其大小及数量无明显不同。认为有必要进一步应用生化技术对婴儿急死综合征颈动脉体主细胞中致密颗粒物质进行定性和定量研究。     

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.     

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.     

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.     

Alcohol and drug consumption among sexual offenders

Purpose

To evaluate the role of alcohol and drug consumption between sexual offenders against boys and girls.

Method

It was an observational, retrospective and cross-sectional study carried out by the Ambulatory for the treatment of sexual disorders of ABC Medical College, Santo André, São Paulo, Brazil (ABSex). The sample comprised 104 convicts, over 18 years old, sentenced only for sexual crimes against children (below 11 years old). Alcohol and drug consumption, sexual abuse history, sexual impulsivity, and risk of recidivism were evaluated.

Results

The sexual offenders against boys showed higher alcohol consumption problems than sexual offenders against girls (χ² = 19.76, 1 d.f., p < 0.01). The severity of alcohol consumption was also significantly higher in the sexual offenders against non-related boys than in the sexual offenders against non-related girls (p = 0.037, ANOVA). After adjustment for other variables, such as monthly income before the penalty and alcohol consumption at the moment of the crime, the alcohol consumption severity in sexual offenders against boys was significantly higher than in sexual offenders against girls (OR = 1.05, CI 1.01–1.08, p < 0.01).

Conclusions

Alcohol use or abuse is associated with the perpetration of sexual aggression. The role of alcohol consumption seems to be greater in sexual offenders against boys than in girls and this can contribute to criminal recidivism.     

Differential diagnosis SIDS/non-SIDS on the basis of histological findings of petechial thymus hemorrhages

Petechial thymus hemorrhages are found most frequently in SIDS (87%), and very much more rarely in fetuses after abortion and stillbirths (55%) as well as in perinatal deaths (40%). In these groups, there was a uniform histological bleeding pattern with emphasis on the cortical zone. In non-SIDS deaths of natural causes or extrinsic suffocation in babies and infants, it could be demonstrated in 39%. In extrinsic suffocation, the thymus hemorrhages were mostly less pronounced in quantitative terms than in SIDS. In non-SIDS (without extrinsic suffocation), a hemorrhage pattern different from SIDS could be detected with hemorrhagias of different sizes and irregularly distributed over the cortex and medulla.     

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.     

Histologic findings in the esophagus in infancy. A contribution to the question of gastroesophageal reflux in sudden infant death

In 53 mortalities (1 stillbirth, 2 neonates, 7 cases up to 5 years of age and 43 SIDS cases), systematic histological investigations were carried out on the esophagus. The results comprised a topography of epithelial defects and inflammatory wall changes. In the SIDS cases, focal epithelial defects could be detected in 14% and fresh inflammatory infiltrates in 7% without preferential localization. There were also lymphocytic reactions of varying extent (62%), but mainly in the upper one-third of the esophagus. Similar findings were found in the 10 non-SIDS cases. The results pattern is discussed with regard to its pathological relevance. It appears to be doubtful that the inflammatory changes are the result of reflux, as reflected in morphological terms.     

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 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.     

Forensic analysis of carbohydrate-deficient transferrin (CDT) by HPLC--statistics and extreme CDT values

Background

Carbohydrate-deficient transferrin (CDT) is the most specific serum marker of chronic alcohol abuse so far. There is little knowledge about extreme CDT values of >20% and the more >30% CDT.

Methods

Serum CDT/transferrin ratios from 19,236 serum samples sent to our laboratory for routine CDT analysis were determined by HPLC. About 75% of these serum samples were from traffic or employment medicine investigations. A CDT value frequency histogram was computed and extreme CDT values were clinically validated.

Results

Fourteen thousand four hundred and sixty-one CDT results were normal (≤1.7%) and 4775 increased (1.8–36.9% CDT). Most frequent normal and increased results were 0.9% CDT (n = 1964) and 1.8% CDT (n = 356). CA. 70% of the pathological results were between 1.8% and 5.0% CDT, ca. 88% between 1.8% and 10.0% CDT, and 98% between 1.8% and 20.0%. CDT values >20.0% appeared in 79 cases and results >30.0% in two cases (33.8% and 36.9%). In each case of CDT values >20%, chronic alcohol abuse was the underlying cause as confirmed by anamnestic exploration.

Conclusions

CDT/transferrin ratios are usually <20%. Higher values can appear in rare cases. CDT results >30% can be due to alcohol abuse but should be considered as remarkable single observations. Visualization of the transferrin isoform patterns by HPLC allows the detection of pathological transferrin isoform patterns and of genetic transferrin variants. This is essential for a reliable interpretation of (extreme) CDT values. CDT analysis by immunoassays without physico-chemical confirmatory analysis is no longer acceptable.     

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.     

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.     

Melatonin concentrations in the sudden infant death syndrome

To examine a possible relationship between pineal function and the sudden infant death syndrome (SIDS), samples of whole blood, ventricular cerebrospinal fluid (CSF) and/or vitreous humor (VH) were obtained at autopsy from 68 infants (45 male, 23 female) whose deaths were attributed to either SIDS (n = 32, 0.5-5.0 months of age; mean +/- S.E.M., 2.6 +/- 0.2 months) or other causes (non-SIDS, n = 36, 0.3-8.0 months of age 4.3 +/- 0.3 months). The melatonin concentrations were measured by radioimmunoassay. A significant correlation was observed for melatonin levels in different body fluids from the same individual. After adjusting for age differences, CSF melatonin levels were significantly lower among the SIDS infants (91 +/- 29 pmol/l; n = 32) than among those dying of other causes (180 +/- 27; n = 35, P less than 0.05). A similar, but non-significant trend was also noted in blood (97 +/- 23, n = 30 vs. 144 +/- 22 pmol/l, n = 33) and vitreous humor (68 +/- 21, n = 10 vs. 81 +/- 17 pmol/l, n = 15). These differences do not appear to be explainable in terms of the interval between death and autopsy, gender, premortem infection or therapeutic measures instituted prior to death. Diminished melatonin production may be characteristic of SIDS and could represent an impairment in the maturation of physiologic circadian organization.     

Positional Asphyxia in Opioid-Related Deaths: Is It Being Overlooked?

The contribution of positional asphyxia in opioid-related deaths is currently unknown. Diagnostic criteria for positional asphyxia include finding the decedent in a position that does not allow for adequate respiration and an inability to extricate themselves from the position due to various conditions. Our primary objective was to assess whether positional asphyxia and the resulting airway compromise were a contributing factor to death due to the toxic effects of opioids. We evaluated 225 deaths where the death scene investigation contained adequate information to evaluate for positional asphyxia and performed a Pearson chi-square test to determine if the proportion of deaths found in an airway compromising position was higher when opioid(s) caused the death. The proportion of decedents found in a potential airway compromising position was greater when the death was related to opioid use (p < 0.0001). Further, narrowing the dataset to decedents who were definitely in an airway compromising position [Yes (24.49%) vs. No (11.02%)] showed a statistically significant association between positional asphyxia and deaths related to opioid use (p = 0.0021). Carefully documenting the position in which the decedent was initially found may be a significant factor in accurate reporting and in harm reduction efforts to decrease the opioid mortality rate.     

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.