Histologic thyroid gland findings in the newborn infant and infant, with special reference to sudden infant death

The morphological picture of the thyroid gland, the only endocrine organ with a follicle structure, allows a limited conclusion to be drawn with respect to the functional state in spite of any physiological variability. The thyroid of the newborn shows total colloid release and collapse of the follicles. The regular structure of the thyroid will be rebuilt within several weeks after birth. Total colloid absorption can be found in cases of stress-activated thyroids as well as in cases of death due to freezing. A histological examination was done on 88 thyroids of fetuses, newborns and infants. About 70% of the results on 27 cases of sudden infant death syndrome (SIDS) may be interpreted as a morphological correlate of a premortal chronic or recurrent stress reaction. The value of these results is discussed.     

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.     

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.     

Cytomegalic inclusion disease of the salivary glands in sudden infant death syndrome

The parotid gland and/or the submandibular gland in SIDS cases (180 from Berlin und 75 cases from Hamburg) were examined by means of HE staining, immunohistochemical analysis, in situ hybridization and electron microscopy. The SIDS cases were taken from the last 10 years; the age of the children ranged from 2 weeks to 1 year. Typical cytomegaly inclusion bodies were recognized in 10% (18 cases from Berlin; more girls than boys) and 7% (6 cases from Hamburg; more boys than girls). Our files indicate that the frequency of CMV infection was not age-dependent within the first 12 months of life. Using immunohistochemical analysis and in situ hybridization, virus substances were detected in cytomegal cells as well as in morphologically uninfected cells. The literature on the clinical and epidemiological aspects of cytomegaly indicates that a localized CMV infection of the salivary glands does not sufficiently explain the sudden death of these infants; however, it should be emphasized that cytomegaly can influence the immunological status of the organism.     

Epidemiology of sudden infant death (sudden infant death syndrome, SIDS) in the Lübeck area. Catamnestic studies of 155 observed cases from 1971 to 1981

The 155 cases of SIDS investigated at the Institut für Rechtsmedizin of the Medizinische Hochschule in Lübeck (northern part of the Federal Republic of Germany) between 1971 and 1981 have been analysed retrospectively under epidemiological aspects. The incidence was 2.17 cases of SIDS/1,000 live-born babies, 63.9% were male, 79.3% of the infants died during the first 6 months of life with a clear peak in the 2nd month. There was no seasonal accumulation; 68.4% of the infants died between 8.00 p.m. and 8.00 a.m., in 75% the socio-economic factors were inconspicuous, but we observed a significantly higher incidence of infants from mothers younger than 25 years. In 58% of our cases no signs of illness or changed behaviour had been observed during the 48 h before death. The results of our study are compared with the literature and discussed with special regard to a possible prevention.     

Neck extension as a cause of SIDS

The intradural sagittal diameter at the second cervical vertebra (SD/C2) of 62 SIDS cases was measured myelographically. This SD/C2 proved to be dependent on body size, body weight, and age. A clear, age-dependent difference is to be found in the primarily narrow spinal canal. This parameter (SD/C2), which is more precisely defined in adults on the basis of clinical, radiological, and autopsical findings is assumed to have the value of 0.5 cm in the first 2 months, 0.6 cm in the third month, and 0.65 cm in the fourth month. The resulting potential danger to infants is dependent upon their position. The SD/C2, was significantly decreased in extension as compared to a neutral posture. With consideration of the primarily narrow spinal canal in the infant, there is, according to our measurements, a potential hazard for the infant in any further, significant shortening of the SD/C2. This is independent of the width of the spinal canal under maximal extension. We found individual cases in which the SD/C2 was decreased by almost 50% from the normal value in neutral position. No correlation was found between the primary width of the spinal canal and the degree of luminal reduction upon extension.     

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.     

Sarcomeric gene mutations in sudden infant death syndrome (SIDS)

In developed countries, sudden infant death syndrome (SIDS) represents the most prevalent cause of death in children between 1 month and 1 year of age. SIDS is a diagnosis of exclusion, a negative autopsy which requires the absence of structural organ disease. Although investigators have confirmed that a significant percentage of SIDS cases are actually channelopathies, no data have been made available as to whether other sudden cardiac death-associated diseases, such as hypertrophic cardiomyopathy (HCM), could be responsible for some cases of SIDS. The presence of a genetic mutation in the sarcomeric protein usually affects the force of contraction of the myocyte, whose weakness is compensated with progressive hypertrophy and disarray. However, it is unclear whether in the most incipient forms, that is, first years of life, the lack of these phenotypes still confers a risk of arrhythmogenesis. The main goal of the present study is to wonder whether genetic defects in the sarcomeric proteins, previously associated with HCM, could be responsible for SIDS. We have analysed 286 SIDS cases for the most common genes implicated in HCM in adults. A total of 680 mutations localised in 16 genes were analysed by semi-automated matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDITOF-MS) using the Sequenom MassARRAY(?) System. Ten subjects with completely normal hearts showed mutated alleles at nine of the genetic variants analysed, and one additional novel mutation was detected by conventional sequencing. Therefore, a genetic mutation associated with HCM may cause sudden cardiac death in the absence of an identifiable phenotype.     

The epidemiological study on registered cases of sudden infant death syndrome (SIDS) in Tokyo: examination of the effect of autopsy on diagnosis of SIDS and the mortality statistics in Japan

In the United States and most of European countries, a diagnosis of sudden infant death syndrome (SIDS) may be given only after an autopsy has been performed. Under the new definition of SIDS in Japan, an autopsy is now mandatory for the diagnosis of SIDS. However, according to the official records on autopsies, the proportion of autopsy for sudden infant death in Japan is still low (less than 30%). If a physician suspects SIDS from a review of the patient's medical history and medical findings, he can write 'suspected SIDS' as the cause of death on the death certificate without performing an autopsy. Such a clinical diagnosis is entered in the Vital Statistics section by the Japanese Ministry of Health and Welfare. In this report, a comparative epidemiological survey of registered cases of SIDS--after autopsy and with no autopsy--was carried out by examining the data from the death certificates registered by the Japanese Ministry of Health and Welfare (vital statistics in Tokyo from January 1979 to December 1996). There were 369 cases of SIDS registered in Tokyo. We found 247 diagnosed after autopsy (66.9%) and 122 with no autopsy (33.1%). The following epidemiological variables were used: address of the deceased (a specific area in Tokyo), sex, year of death, time of death, month of death, age at death, occupation of householders, and place of death. There were epidemiological differences at the 0.05 significance level between registered cases diagnosed after autopsy and those diagnosed without autopsies, as follows: year (P=0.016) and place of death (P=0.037). In addition, there were slight epidemiological differences at the 0.10 significance level between registered cases diagnosed after autopsy and with no autopsy, as follows: month of death (P=0.076) and age at death (P=0.082). This suggests that the quality of diagnosis of SIDS is not completely guaranteed. With respect to the area of residence, the incidence of SIDS is high in those areas where autopsy is performed frequently. In Tokyo, the medical examiner system is enforced only in the urban area and there is a possibility that SIDS is being underdiagnosed in the rural area of the Metropolitan Tokyo. It is likely that the diagnosis of SIDS without autopsy will influence the quality of SIDS diagnoses. The administrative inadequacy in the autopsy system in Japan should be corrected to improve the accuracy of SIDS diagnosis.     

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 syndrome: a subject of medicolegal research

During the last decade, much attention has been paid to the risk factors of sudden infant death syndrome (SIDS). Many researchers have demonstrated that infant-care practices are linked to the risk of SIDS. Prone sleeping, bed sharing, maternal substance abuse, and cigarette smoking have been reported to be significant potentially modifiable risk factors for SIDS. Despite the reports that the incidence of SIDS has decreased by 38% in the United States, it remains the leading cause of death in the first year of life. Deaths resulting from child abuse or neglect inflicted or permitted by their caretakers being second only to SIDS in infant mortalities and some recommendations regarding the differentiation of SIDS and child abuse have generated speculation that some cases of infanticide were misdiagnosed as SIDS. To reach a proper conclusion as to the cause and manner of death of an infant who died suddenly and unexpectedly, investigation must be thorough and professional.     

Post-mortem radiological examination in infants:: Evidence of child abuse?

We examined the value of post-mortem radiological examination of infants who were brought in for medico–legal autopsy. Twenty children between the age of 1 month and 15 months died under the picture of SIDS. No radiological or other signs of previous child abuse were seen in our autopsy material. A fatal case of child abuse with several metaphyseal fractures is reported. Some fractures were not visible on gross examination, but could be demonstrated by radiography and histology. In our material no association between SIDS and child abuse was found. In suspected cases of child abuse, particularly rib fractures and metaphyseal fractures should be sought. We recommend that post-mortem radiography is performed in such cases. If fractures are demonstrated, they should be verified by histologic examination.     

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 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.     

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.     

Natural death as viewed by the medical examiner: a review of 1000 consecutive autopsies of individuals dying of natural disease

A study of 1000 consecutive autopsies of individuals dying of natural disease was conducted. Cardiovascular disease was responsible for 60.9% of all deaths with coronary artery disease--not only the main cause of cardiovascular death but also the main cause of all natural deaths--accounting for 45.1% of such cases. Diseases of the central nervous and respiratory systems accounted for 8.7 and 8.6%, respectively, of the natural deaths. Seizure disorders and pneumonia were the main causes of death in these organ systems. There were 124 deaths of children less than one year in age, 91 of which were due to sudden infant death syndrome (SIDS). All of the SIDS deaths were in children less than 10 months old.     

尸体甲状腺球蛋白降解及其与死亡时间的关系

目的探讨尸体甲状腺球蛋白降解程度与死亡时间(PM I)的关系。方法死后21d内尸体的甲状腺组织,经免疫组化(EPOS)法染色,观察甲状腺球蛋白的染色反应;对63例阳性染色的甲状腺组织(PM I≤5d)进行计算机图像分析,并对所得图像参数的数据进行统计学分析。结果PM I≤5d的甲状腺组织,甲状腺腺泡上皮细胞胞浆及甲状腺胶质中均显示了不同程度的免疫反应阳性;PM I超过12d,免疫反应阴性;经图像分析及统计学处理,其积分光密度、分布密度和目标面积与PM I之间的确定系数(R2)分别达0.9794,0.9732及0.9884。结论尸体甲状腺组织的甲状腺球蛋白降解程度随PM I不同而变化,二者呈现较强的相关性。     

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.     

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.