Simultaneous sudden unexpected death in infancy of twins: case report

Simultaneous sudden infant death syndrome (SIDS) in twins is an extremely rare event. Some believe these are natural deaths, whereas others suggest they are unnatural. We report monozygotic twins dying at 12 weeks of age. Extensive investigation concluded that the cause of death was natural. Our case fulfilled the criteria of simultaneous SIDS in twins. However, thermal stress due to excessive thermal insulation, use of a pillow and placing twins in the same cot all represent a potentially unsafe sleeping environment. We recommend the term “simultaneous sudden unexpected death in infancy of twins” to describe such cases.     

Sudden infant death while awake

Epidemiologic data suggest that SIDS is related to the sleep state, but exiguous literature has addressed infants who had been awake at the time of sudden catastrophic deterioration and subsequent death. The aims of this study are to: (1) Report five infants who were awake at the onset of the lethal event, and (2) Discuss potential lethal pathophysiological events that may lead to these circumstances. The demographic and pathologic profiles of these cases are similar to SIDS. Altered responses to severe hypotension, bradycardia, and apnea, perhaps elicited by aspiration and mediated by cerebellar and vestibular structures, might be involved in the pathogenesis of these deaths. Comprehensive medical history review, investigation of the circumstances of death, thorough postmortem examination with ancillary studies, and preservation of tissues for gene testing, are crucial to explaining these deaths. Careful attention should be given to the awake or sleep state immediately prior to the sudden clinical collapse, and death of infants; those who were awake should be reported to enhance understanding of this phenomenon.     

Is SIDS associated with sleep?

Epidemiological studies suggest an important association of sudden infant death syndrome (SIDS) with sleep. Because these deaths are very rarely observed, this association is difficult to confirm. When nearby caretakers hear noises suggesting that some infants are awake before their deaths from SIDS, this determination may be even more difficult. We report six cases illustrating the difficulty in determining the sleep status of SIDS infants immediately prior to their deaths. A retrospective analysis was undertaken of the San Diego SIDS/SUDC Research Project database and the new SIDS definition proposed at the January 2004 conference in San Diego, California was applied. The circumstances surrounding the deaths of six infants led nearby caretakers to speculate that all were awake before dying. However, careful analyses suggest that all but one infant were actually sleeping before their deaths. This study strengthens the association of SIDS with sleep and emphasizes the importance of very detailed evaluation of the circumstances of death in all cases of sudden infant death. The use of the recently stratified definition for SIDS as well as the new category of unclassified sudden infant death (USID) is recommended.     

Sudden twin infant death on the same day: a case report and review of the literature

Sudden infant death syndrome (SIDS) is a major contributor to infant mortality. The cause of death is unknown: suggested possibilities include cardiovascular disease, anaphylactic shock, and suffocation. The occurrence of simultaneous sudden infant death syndrome is uncommon, such cases being extremely rare in forensic pathologic practice. We report two 10-week-old male twins who appeared well at the time of their evening feeding, yet died while sleeping on their backs. Both infants had petechial hemorrhages on the visceral pleura, epicardial surface of the heart, and thymus gland. Microscopic examination revealed pulmonary edema, intra-alveolar hemorrhage, and minor lymphocytic infiltration, again in both infants. In this report, we discuss the risk factors for SIDS, which should be considered individually or in combination as possible causes of death.     

The medico-legal investigation of sudden, unexpected and/or unexplained infant deaths in South Africa: where are we—and where are we going?

Sudden Infant Death Syndrome (SIDS) has been reported to be the leading cause of death in infants under 1 year of age in many countries. Unfortunately, a paucity of published research data exists in South Africa, with regard to the incidence of and investigation into the circumstances surrounding Sudden Unexplained Deaths in Infants (SUDI) and/or SIDS. Currently, even though most academic centers conform to a protocol consistent with internationally accepted standards, there exists no nationally accepted infant death investigation protocol in South Africa. It is the aim of this study to review the current practice of infant death investigation in two representative but geographically and demographically distinct centers. Retrospective case audit over a five-year period (2000–2004) was conducted at two large medico-legal mortuaries in Pretoria (Gauteng) and Tygerberg (Cape Town). Case files on all infants younger than 1 year of age were reviewed. The outcome measures included number of deaths, demographic details and the nature and final outcome of the post mortem examinations. A total of 512 cases were identified as possible SIDS cases and of these, 171 was classified as SIDS. The study showed marked inter-case and inter-divisional variation in terms of the investigation of infant deaths at the two institutions. It is envisaged that this study will focus attention on the current lack of usable data regarding sudden/unexplained/unexpected infant deaths in South Africa, and aid in the formulation and implementation of a practical (yet internationally accountable) infant death investigation protocol, which could facilitate comparisons with other countries and initiate further structured research in this field.     

Pulmonary intra-alveolar hemorrhage in SIDS and suffocation

The differentiation of SIDS from accidental or inflicted suffocation may be impossible in some cases. Severe pulmonary intra-alveolar hemorrhage has been suggested as a potential marker for such differentiation. Our aims are to: (1) Compare pulmonary hemorrhage in SIDS and a control group comprised of infants whose deaths were attributed to accidental or inflicted suffocation. (2) Review individual cases with the most severe pulmonary hemorrhage regardless of the cause of death, and (3) Assess the effect of age, bedsharing, cardiopulmonary resuscitation, and postmortem interval, with regard to the severity of pulmonary hemorrhage in 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 444 cases of sudden infant death caused by SIDS (405), accidental suffocation (36), and inflicted suffocation (3) from the San Diego SIDS/SUDC Research Project database were compared using a semiquantitative measure of pulmonary intra-alveolar hemorrhage [absent (0) to severe (4)]. Grades 3 or 4 pulmonary hemorrhage occurred in 33% of deaths attributed to suffocation, but in only 11% of the SIDS cases, however, all grades of pulmonary hemorrhage occurred in both groups. Therefore, our results indicate that the severity of pulmonary hemorrhage cannot be used in isolation to determine the cause or manner of sudden infant death. Among SIDS cases, those with a higher pulmonary hemorrhage grade (3 or 4) were more likely to bedshare, and with more than one co-sleeper, than those with a lower pulmonary hemorrhage grade (0 or 1). We conclude that each case must be evaluated on its own merits after thorough review of the medical history, circumstances of death, and postmortem findings.     

Toward a standardized investigation protocol in sudden unexpected deaths in infancy in South Africa: a multicenter study of medico-legal investigation procedures and outcomes

Introduction

South Africa manifests a socio-economic dichotomy that shows features of both a developed and developing country. As a result of this, areas exist where a lack of resources and expertise prevents the implementation of a highly standardized protocol for the investigation of sudden and unexpected deaths in infants (SUDI). Although the medico-legal mortuaries attached to academic centers have the capacity to implement standardized protocols, a previous study conducted at two large medico-legal mortuaries indicated otherwise. This study also revealed that the exact number and incidence of sudden infant death syndrome (SIDS) cases was unknown. These findings prompted a multicenter study of the medico-legal investigation procedures and outcomes in five academic centers in South Africa.

Methods

A retrospective case audit was conducted for a 5-year period (2005–2009) at medico-legal laboratories attached to universities in Bloemfontein, Cape Town—Tygerberg, Durban, Johannesburg, and Pretoria. The total case load as well as the total number of infants younger than 1 year of age admitted to these mortuaries was documented. The case files on all infants younger than 1 year of age who were admitted as sudden and unexpected or unexplained deaths were included in the study population. Data collected on the target population included demographic details, the nature and scope of the post-mortem examinations, as well as the final outcome (cause of death).

Results

A total case load of 80,399 cases were admitted to the mortuaries over the 5 year period with a total of 3,295 (6.5 %) infants. In the infant group, 591 (0.7 %) died from non-natural causes and 2,704 (3.3 %) cases of sudden, unexpected and/or unexplained deaths in infants were admitted and included in the detailed case analysis study. One hundred and ninety-nine babies were between 0 and 7 days of age and 210 babies between 8 and 30 days. The remaining 2,295 infants were between 1 month and 12 months of age. Death scene investigation was done in a total of 14 (0.5 %) cases. Discrepancies were present in the extent of the macroscopic post-mortem examinations, as well as the type and extent of the ancillary investigations performed. The investigations were completed in 2,583 of the cases. The majority of these infants died from natural disease processes [1,976 infants (76.5 %)]. Bronchopneumonia was the leading cause of natural deaths at all the mortuaries [674 cases (26.1 %)]. SIDS was diagnosed in only 224 cases (8.7 %) and in 383 (14.8 %) cases, where a full post-mortem examination with ancillary investigations was conducted; the cause of death was recorded as “unascertained.”

Conclusions

This study indicated that the admission criteria (to medico-legal mortuaries) and the investigative process/protocols in cases of SUDI differ greatly among 5 of the largest academic medical institutions in South Africa. Establishing and implementing standardized admission criteria (to medico-legal mortuaries) and implementing uniform investigative and autopsy protocols would appear to be an essential prerequisite to gain better understanding of the mystery of SIDS in South Africa.     

The San Diego definition of SIDS: practical application and comparison with the GeSID classification

The new definition of the term sudden infant death syndrome (SIDS) and the criteria introduced in San Diego for the subclassification of cases have been used to re-classify the first 100 consecutive cases of sudden and unexpected infant deaths that were registered with the German SIDS study (GeSID). Although there are 30 different variables that have to be considered in the general and stratified sections of the San Diego definition, it is practical, in particular, as an international standard to perform scientific studies. The comparison of the San Diego definition and the classification used for GeSID shows similarities in the methods but differences in the criteria used. Nevertheless, the numbers of cases classified as SIDS and borderline SIDS are similar (San Diego n=69, GeSID n=74). The SIDS IA criteria of the San Diego definition were not fulfilled by any case because metabolic screening and vitreous chemistry were not included in the GeSID investigation scheme. An important advantage of the San Diego definition is the introduction of the category of unclassified sudden infant death, which includes cases for which no autopsy was performed. This demonstrates that such cases cannot be classified as SIDS. In conclusion, we recommend the universal acceptance and use of the San Diego SIDS definition.     

A practical classification schema incorporating consideration of possible asphyxia in cases of sudden unexpected infant death

Although the rate of the sudden infant death syndrome (SIDS) has decreased over the last two decades, medical examiners and coroners are increasingly unwilling to use the SIDS diagnosis, particularly when there is an unsafe sleeping environment that might pose a risk for asphyxia. In order to reliably classify the infant deaths studied in a research setting in the mixed ancestory population in Cape Town, South Africa, we tested a classification system devised by us that incorporates the uncertainty of asphyxial risks at an infant death scene. We classified sudden infant deaths as: A) SIDS (where only a trivial potential for an overt asphyxial event existed); B) Unclassified—Possibly Asphyxial-Related (when any potential for an asphyxial death existed); C) Unclassified—Non-Asphyxial-Related (e.g., hyperthermia); D) Unclassified—No autopsy and/or death scene investigation; and E) Known Cause of Death. Ten infant deaths were classified according to the proposed schema as: SIDS, n = 2; Unclassified—Possibly Asphyxial-Related, n = 4; and Known Cause, n = 4. A conventional schema categorized the deaths as 6 cases, SIDS, and 4 cases, Known Cause, indicating that 4/6 (67%) of deaths previously classified as SIDS are considered related importantly to asphyxia and warrant their own subgroup. This new classification schema applies a simpler, more qualitative approach to asphyxial risk in infant deaths. It also allows us to test hypotheses about the role of asphyxia in sudden infant deaths, such as in brainstem defects in a range of asphyxial challenges.     

Sudden infant death syndrome: deletions of glutathione-S-transferase genes M1 and T1 and tobacco smoke exposure

International Journal of Legal Medicine - In developed countries, sudden infant death syndrome (SIDS) is the leading cause of death in infants in their first year of life. The risk of SIDS is...     

Hippocampal asymmetry and sudden unexpected death in infancy: a case report

The differential diagnosis of known entities associated with sudden unexpected death in infancy is ever expanding. Here we report the case of a 10-month-old infant boy whose clinical presentation mimicked that of the sudden infant death syndrome (SIDS). This presentation included the typical features of SIDS: sleep-related death; prone position upon discovery; and minor illness within 2?days of death. Nevertheless, neuropathologic examination revealed striking hippocampal asymmetry and microdysgenesis similar to that reported previously by us in toddlers with sleep-related sudden death. Hippocampal maldevelopment in the setting of sudden death in infants and toddlers is analogous to sudden unexpected death in epilepsy associated with temporal lobe pathology, and suggests a possible role for seizures in the terminal events leading to sudden death. This report serves to alert pediatric and forensic pathologists to hippocampal asymmetry and microdysgenesis in the differential diagnosis of sudden infant death mimicking SIDS.     

German study on sudden infant death (GeSID): design,epidemiological and pathological profile

The German study on sudden infant death (GeSID) is a multi-centre case-control study aiming at the assessment of etiological factors and risk factors of SIDS. This report describes the study design and the methods applied and presents some general findings. Between 1998 and 2001, 455 cases of sudden and unexpected death of infants aged between 8 and 365 days were recruited into the study. The study comprised at least 11 out of the 16 German states with 18 centres involved. In 1999 and 2000, 75% of all SIDS cases registered with the Federal Office of Statistics (ICD 10/R95, n=384) in the study area were recruited into the study (n=286). A standardised autopsy including extended histology, microbiology, virology, toxicology and neuropathology investigations was carried out. Of the parents 82% (n=373) agreed to fill in an extensive questionnaire containing 120 questions reflecting all important aspects of the infants development. For each SIDS case, the parents of three living control infants were interviewed. These controls were matched for age, gender and region (n=1,118). The response rate of the controls was 58.7%. Data were linked with medical records obtained from obstetrics departments, the childrens hospitals, and general practitioners. Death scene investigation was performed in 4 study areas (cases: n=64, controls: n=191). All cases were classified into one of 4 categories using defined criteria: 7.3% of the children were assigned to category 1 (no pathological findings: SIDS), 61.1% to category 2 (minor findings: SIDS+), 20.4% to category 3 (severe findings: SIDS+) and 11.2% to category 4 (findings which explained the death: non-SIDS). In case conferences the previous history and circumstantial factors were included and an extended category (E-cat.) was defined. The consideration of these factors for the final classification is of great importance in the causal explanation of some cases. An analysis of 18 main variables in cases of categories 1–3 (SIDS) compared to the cases of category 4 (non-SIDS) showed significant differences for the sleeping position, coughing the day before death and breast-feeding indicating that the cases of both groups should be separated for further analyses.Electronic Supplementary Material Supplementary material is available in the online version of this article at A list of the collaborating authors and institutes is given in the appendix.     

Esophageal dysmotility and the sudden infant death syndrome: clinical experience

Symptoms equated with "threatened" or "near-miss" sudden infant death syndrome (SIDS) were noted during feedings in 4 infants. In each case, barium esophagrams revealed dysmotility. Acute "near-miss" symptoms required cardiopulmonary resuscitation during esophagography in 2 infants. The authors suggest that esophageal dysmotility is a cause of "near-miss" SIDS and most likely is responsible for more fatalities than commonly realized. The cause-and-effect relationship is explained by a vagovagal reaction. Etiologies of esophageal dysmotility and possible prophylactic measures are discussed.     

Does β-APP staining of the brain in infant bed-sharing deaths differentiate these cases from sudden infant death syndrome?

Archival cerebral tissue from infants whose deaths were attributed to sudden infant death syndrome (SIDS) from South Australia and Western Denmark were stained for β-amyloid precursor protein (β-APP) and graded according to a simple scoring chart. The resulting APP scores were correlated with sleeping situation (shared vs. alone) showing a significantly higher amount of β-APP staining in the non-bed-sharing, than in the bed-sharing infants (Mann–Whitney, Australia: p = 0.0128, Denmark: p = 0.0014, Combined: p = 0.0031). There was also a marked but non-significant difference in sex distribution between bed-sharers and non-bed-sharers with a male to female ratio of 1:1 in the first group and 2:1 in the latter. Of 48 Australian and 76 Danish SIDS infants, β-APP staining was present in 116 (94%) cases. The eight negative cases were all from the Danish cohort. This study has shown that the amount of β-APP staining was significantly higher in infants who were sleeping alone compared to those who were bed-sharing with one or more adults, in both an Australian and Danish cohort of SIDS infants. Whether this results from differences in the speed with which these infants die, differences in lethal mechanisms involving possible accidental asphyxiation in shared sleepers, or differences in the number of previous hypoxic-ischemic events, remains to be clarified.     

Sudden infant death syndrome and long QT syndrome: an epidemiological and genetic study

Sudden infant death syndrome (SIDS) is a frequent cause of death among infants. The etiology of SIDS is unknown and several theories, including fatal ventricular arrhythmias, have been suggested. We performed an epidemiological and genetic investigation of SIDS victims to estimate the presence of inherited long QT syndrome (LQTS) as a contributor for SIDS. Forty-one consecutively collected and unrelated SIDS cases were characterized by clinical and epidemiological criteria. We performed a comprehensive gene mutation screening with single-strand conformation polymorphism analysis and sequencing techniques of the most relevant LQTS genes to assess mutation frequencies. In vitro characterization of identified mutants was subsequently performed by heterologous expression experiments in Chinese hamster ovary cells and in Xenopus laevis oocytes. A positive family history for LQTS was suspected by mild prolonged Q-T interval in family members in 2 of the 41 SIDS cases (5%). In neither case, a family history of sudden cardiac death was present nor a mutation could be identified after thorough investigation. In another SIDS case, a heterozygous missense mutation (H105L) was identified in the N-terminal region of the KCNQ1 (LQTS 1) gene. Despite absence of this mutation in the general population and a high conservational degree of the residue H105 during evolution, electrophysiological investigations failed to show a significant difference between wild-type and KCNQ1_H105L/minK-mediated I_Ks currents. Our data suggest that a molecular diagnosis of SIDS related to LQTS genes is rare and that, even when an ion channel mutation is identified, this should be regarded with caution unless a pathophysiological relationship between SIDS and the electrophysiological characterization of the mutated ion channel has been demonstrated.H. Wedekind, T. Bajanowski and P. Friederich contributed equally to this study.     

Sleeping environments as risk factors of sudden infant death syndrome in Japan

For the purpose of assessing the risk factors of the sleeping environment in SIDS, we performed a population-based, case-control study. Index cases comprised 56 SIDS cases which were diagnosed on the basis of autopsies during a period of 11 years at the Department of Legal Medicine, Faculty of Medicine, University of the Ryukyus. Control cases comprised infants who were examined at regional health centers for Infant Health Screening. The incidence of SIDS obtained was 0.25 per 1000 live births, which was comparable to that obtained in other districts having the established medical examiner's system. The proportion of prone sleeping was 81.0% and 38.3% in the SIDS and control groups, respectively, and an odds ratio was calculated as 10.4 (99% confidence interval, 3.9 to 37.6). This indicates that prone sleeping is a risk factor of SIDS, in Japan, as reported in various countries. Various kinds of bedclothes were used in this country, and our survey of bedclothes in the control revealed their improper use for infants to sleep, particularly with the prone position. In addition, the co-sleeping habit, which was not uncommon in Japan, seems to contribute to certain deaths of infants whose causes of death were controversial. In the investigation of SIDS, therefore, the sleeping environments, such as bedclothes and the co-sleeping habit, as well as the sleeping position should be taken into consideration as risk factors.     

Intrathoracic petechiae in SIDS: a retrospective population-based 15-year study

Intrathoracic petechiae (IP), the most common gross finding in sudden infant death syndrome (SIDS) cases at autopsy, suggest upper airway obstruction (UAO) occurs during the terminal event. If true, IP would be expected more frequently among SIDS cases found face down compared to other face positions. We compare the rates of IP in SIDS cases found face down versus other face positions. A retrospective 15-year review of IP among all cases of SIDS occurring from 1991 through 2005 accessioned by the San Diego County Medical Examiner’s Office was conducted. The presence or absence of IP was based on both gross and microscopic observations of the thoracic organs. The severity of thymic petechiae was scored semiquantitatively from microscopic observations. There were 489 SIDS cases during the study period. Sixteen of these were excluded because their deaths had been delayed by initially successful cardiopulmonary resuscitation. Among the remaining 473 SIDS cases, face position when found was specifically described for 332 (70%). Of 122 cases found face down, 112 (92%) had IP, compared to 85% (179) of 210 infants found with the face up or to the side (P = 0.06). The groups were not different with respect to age or gender, but the racial distribution was significantly different (P = 0.004). African-American infants comprised 28% of the found face down group compared to only 12% of the face up or side group. Our data do not support a role for external UAO caused by face positioning directly into the sleep surface in SIDS, but are consistent with internal UAO associated with apnea or gasping before dying of SIDS.     

Inconsistent classification of unexplained sudden deaths in infants and children hinders surveillance,prevention and research: recommendations from The 3rd International Congress on Sudden Infant and Child Death

This report details the proceedings and conclusions from the 3rd International Congress on Unexplained Deaths in Infants and Children, held November 26–27, 2018 at the Radcliffe Institute at Harvard University. The Congress was motivated by the increasing rejection of the diagnosis Sudden Infant Death Syndrome (SIDS) in the medical examiner community, leading to falsely depressed reported SIDS rates and undermining the validity and reliability of the diagnosis, which remains a leading cause of infant and child mortality. We describe the diagnostic shift away from SIDS and the practical issues contributing to it. The Congress was attended by major figures and opinion leaders in this area from countries significantly engaged in this problem. Four categories (International Classification of Diseases (ICD)-11 categories of MH11, MH12, MH14, PB00-PB0Z) were recommended for classification, and explicit definitions and guidance were provided for death certifiers. SIDS was reframed as unexplained sudden death in infancy or SIDS/MH11 to emphasize that either term signifies the lack of explanation following a rigorous investigation. A distinct category for children over the age of 1 was recommended (MH12). Definitions and exclusions were provided for the alternative categories of accidental asphyxia and undetermined. As recommended, unexplained sudden death in infancy or SIDS on a death certificate will code a unique, trackable entity, accurately reflecting the inability to determine a definitive explanation, while satisfying surveillance needs and reliable identification for research efforts. The conclusions will be submitted to the World Health Organization for inclusion in the upcoming ICD-11.

     

PHOX2B polyalanine repeat length is associated with sudden infant death syndrome and unclassified sudden infant death in the Dutch population

Unclassified sudden infant death (USID) is the sudden and unexpected death of an infant that remains unexplained after thorough case investigation including performance of a complete autopsy and review of the circumstances of death and the clinical history. When the infant is below 1 year of age and with onset of the fatal episode apparently occurring during sleep, this is referred to as sudden infant death syndrome (SIDS). USID and SIDS remain poorly understood despite the identification of several environmental and some genetic risk factors. In this study, we investigated genetic risk factors involved in the autonomous nervous system in 195 Dutch USID/SIDS cases and 846 Dutch, age-matched healthy controls. Twenty-five DNA variants from 11 genes previously implicated in the serotonin household or in the congenital central hypoventilation syndrome, of which some have been associated with SIDS before, were tested. Of all DNA variants considered, only the length variation of the polyalanine repeat in exon 3 of the PHOX2B gene was found to be statistically significantly associated with USID/SIDS in the Dutch population after multiple test correction. Interestingly, our data suggest that contraction of the PHOX2B exon 3 polyalanine repeat that we found in six of 160 SIDS and USID cases and in six of 814 controls serves as a probable genetic risk factor for USID/SIDS at least in the Dutch population. Future studies are needed to confirm this finding and to understand the functional effect of the polyalanine repeat length variation, in particular contraction, in exon 3 of the PHOX2B gene.