Contribution of Long-QT Syndrome Genetic Variants in Sudden Infant Death Syndrome

A cohort of 52 French unrelated infant cases who died unexpectedly before they reached 12 months of age was blindly investigated to better quantify the contribution of long-QT syndrome (LQTS) genetic variants in French cases of sudden infant death syndrome (SIDS). After a standardized autopsy protocol, a blinded molecular screening of the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes was performed on each case. These postmortem investigations enabled us to reclassify 18 as non-SIDS cases, 32 as SIDS cases, and 2 as suspected SIDS cases. Among the 18 non-SIDS cases, no LQTS mutation was identified. In contrast, our results led to a possible explanation for the death of at least three infants in the SIDS cohort. Half of the LQTS gene variants identified were located on the SCN5A gene. This study confirms that LQTS mutations may represent one of the leading genetic causes of SIDS. If autopsy fails to provide an explanation for an unexplained infant death, medicolegal investigation should be extended with a molecular screening of major LQTS genes. Identification of more LQTS mutations in SIDS cases could provide new insights into the pathophysiology of SIDS and, consequently, reduce the number of unexplained sudden infant deaths.     

Travel and changes in routine do not increase the risk of sudden infant death syndrome

We investigated the relationship between travel and changes in routine and the sudden infant death syndrome (SIDS) among 485 SIDS cases compared with 1800 randomly selected control infants. There was no increased risk of SIDS with travel. Special events, such as christenings, were not associated with an increased risk of SIDS. However, visits to and by friends or relatives were associated with a significantly reduced risk of SIDS after controlling for potential confounders (odds ratios = 0.70; 95% confidence interval = 0.52, 0.96). These findings may indicate less social support in SIDS cases.     

Sudden infant death syndrome and infant mortality in Aboriginal and non-Aboriginal infants

The aim of this study was to investigate sudden infant death syndrome (SIDS) in the context of total infant mortality for Aboriginal and non-Aboriginal infants. Deaths for infants born in Western Australia from 1980 to 1988 inclusive were ascertained from a total population data base. Infant mortality rates and rates by period and cause of death were calculated for both populations. Aboriginal infants had a mortality rate three times that for non-Aboriginal infants (23.6 cf. 7.9 per 1000 live births) and both populations showed a similar rate of decline in mortality over the study period. There were differences in the proportion of deaths occurring neonatally and postneonatally in the two populations. In terms of SIDS, 21% of the deaths in Aboriginal infants occurred neonatally compared with 7% for non-Aboriginal infants. The overall cause of infant death distribution differed significantly between the two populations ( P < 0.001). During the study period, Aboriginal infants showed a significant increase in deaths due to SIDS and a significant decrease in those due to birth defects and low birthweight. These results suggest it would be useful to review the pathology and diagnosis of sudden unexplained death in infancy.     

Epidemiology of sudden infant death syndrome in Japan

An epidemiological survey was carried out to examine the present situation with respect to sudden infant death syndrome (SIDS) in Kanagawa Prefecture. Questionnaires on sudden unexpected death of infants aged < 1 year in 1990-91 were sent to the hospitals and clinics in Kanagawa Prefecture which may take care of such infants. By analysing information from 10 485 replies, 48 out of 73 reported sudden infant deaths were confirmed to be SIDS, although autopsy was not performed in 13 cases (27%). The incidence of SIDS per 1000 live births in Kanagawa Prefecture was 0.29 in 1990 and 0.31 in 1991; and if limited to autopsy cases 0.19 and 0.25, respectively. Sudden infant death syndrome cases in Japan were found to occur more frequently when infants were < 6 months old, at home and sleeping alone, but less in the winter and between midnight and early morning. There was little difference between the numbers in prone and supine sleeping positions at discovery. It was not clear whether SIDS occurred more often to babies sleeping prone than supine, because there were no controls matched with the SIDS cases. In future, continuous epidemiological surveys of SIDS in Japan should be carried out.     

Sudden Death in an Infant with Central Nervous System Abnormalities

Some deaths during the first year of life are classified as sudden infant death syndrome (SIDS), the diagnosis of which requires a complete autopsy without adequate explanation for the death. We report a 1-month-old infant whose clinical history was fairly typical for SIDS. Postmortem examination was remarkable in revealing clinically unsuspected central nervous system (CNS) abnormalities, including lobar holoprosencephaly, absence of the olfactory tracts and grooves (arhinencephaly), subependymal gray matter heterotopias, and delayed myelination. Although the CNS findings do not adequately explain the patient's sudden death, this case illustrates the need for a complete autopsy to include careful CNS evaluation, especially in any presumed SIDS death.     

Has changing diagnostic preference been responsible for the recent fall in incidence of sudden infant death syndrome in South Australia?

Objective: An apparent decrease in deaths attributed to sudden infant death syndrome (SIDS) has been noted in a number of diverse geographical areas during the past several years. At the same time the definition of SIDS has been in a state of flux and some observers have raised the possibility that the fall in SIDS deaths is due to diagnostic transfer rather than to a genuine decrease in numbers. The present study was undertaken to investigate this possibility.
Methodology: All sudden and unexpected deaths in infants under 1 year of age in South Australia during a 10 year period from 1984 to 1993 were reviewed.
Results: The number of deaths due to SIDS fell from 40 in 1984 to 17 in 1993, with a maximum of 52 cases per year in 1987. In contrast, the number of cases of sudden death not due to SIDS remained under 10 per year. The overall infant death rate also fell, while the total number of births per year remained relatively unchanged.
Conclusions: The lack of major change in sudden infant death rates from other causes, combined with the fall in SIDS deaths, is not supportive of diagnostic transfer being a major determinant of the declining SIDS death rate. Therefore, other factors are likely to be responsible for the falling SIDS rate in this population.     

The airway occlusion test as a screening for sudden infant death syndrome (SIDS)

The airway occlusion test was carried out as a screening test for sudden infant death syndrome (SIDS). To obtain the normal values for use as control values, the relationship of the airway occlusion test with various variables was determined in 234 infants. The result shows that the best correlation was seen between percentage prolongation and the corrected gestational age. Percentage prolongation increased with the progression of age up to about the 40th week of corrected gestational age. Subsequently, there was no remarkable change in percentage prolongation. In six out of eight cases with apparent life threatening events, percentage prolongation was reduced. These results indicate that the determination of percentage prolongation can be used for screening of high risk babies for SIDS.     

Increased number of substitutions in the D-loop of mitochondrial DNA in the sudden infant death syndrome

The purpose of the present study was to investigate substitutions in the D-loop of mitochondrial DNA (mtDNA) in sudden infant death syndrome (SIDS) and controls, since several observations indicate the involvement of mtDNA mutations in SIDS. These include elevated levels of vitreous humour hypoxanthine in SIDS victims, familial clustering without mendelian traits, and observations of increased sleepiness and a lower activity score in infants who later succumbed to SIDS. Eighty-two cases of SIDS and 133 controls were investigated and the D-loop sequences were recorded in the base-pair range 16 055-16 500 in the mtDNA sequence. The sequencing was carried out using the Applied Biosystems Sequenase dye terminator method and a ABD373A sequencer. The recorded D-loop sequences were compared with the Cambridge sequence and differences were recorded as substitutions. The SIDS cases had a tendency towards a higher substitution rate in the D-loop than the controls ( p = 0.088). This observation makes it interesting to search for deleterious mutations in other locations in the mtDNA.     

Investigation of the Sudden Death of Infants: A Multicenter Analysis

The investigation of sudden death of infants varies, and death rates may depend on local practices of death certification. We studied the extent of the investigation and the final cause of death (COD) in 3 regions: New York, New York, USA (NY); King County, Washington, USA (KC); and Montevideo, Uruguay (MU). We conducted a retrospective review of 543 cases (NY 258, KC 56, MU 229) of previously healthy babies who died suddenly without obvious trauma, at ages 0 to 12 months, over a 3-year period (1998 to 2001). All cases included a complete autopsy and histologic examination. Cases were assessed for completion of special studies (including radiographs, photos, toxicology and metabolic sampling, cultures, and vitreous humor chemistry), measurements, and scene investigation. Specialized pediatric measurements and testing were done less often than routine procedures, and were done less often in cases overall compared with cases certified as sudden infant death syndrome (SIDS). Fifty-five percent of SIDS cases in NYC and 12% of SIDS cases in KC had no scene investigation. Manhattan had a complete workup in 42% of SIDS cases, whereas the remaining sites had fewer that 15% of cases completely worked up. The most common non-natural COD was suffocation at all 3 sites. The overall most common COD were respiratory infection in MU (22%) and SIDS in NY (45%) and KC (86%). We conclude that the sudden death of infants requires special consideration and still lacks consistency. SIDS investigations are not done completely in all cases and rates may depend on regional differences in certifying infant deaths. This work was presented in part at the annual meeting of the Society for Pediatric Pathology; Washington, DC; March 22-23, 2003.     

Sinus tachycardia in term infants preceding sudden infant death

The quantities of sinus tachycardia in 24-h recordings of the electrocardiogram from 16 full-term infants (37 weeks gestation) who were subsequently victims of the sudden infant death syndrome (SIDS), from 230 randomly selected age-matched full-term survivors and from 64 full-term survivors matched for age and birth weight were measured by computer and manual analysis techniques. Of 16 infants dying of SIDS, 7 had elevated levels of sinus tachycardia (>95th centile in controls) (P<0.01). Although high levels of sinus tachycardia might be of value in identifying infants at high risk of SIDS, these encouraging findings must first be validated by further prospective studies.Abbreviations IHR instantaneous heart rate - SIDS sudden infant death syndrome - ECG electrocardiogram     

What else do SIDS risk prediction scores predict?

Various aspects of the medical and social history of 12 743 children examined at the age of 5 years were related to two risk scores for the sudden infant death syndrome (SIDS) computed from data collected in the neonatal period. Children at high risk of SIDS were also at high risk of pneumonia, non-accidental injury and repeated or prolonged hospital admissions. There were stronger associations, however, with factors indicating social disruption and environmental disadvantage.     

Clinical and Genetic Analysis of Long QT Syndrome in Children from Six Families in Saudi Arabia: Are They Different?

Congenital long QT syndrome (LQTS) is an inherited cardiac arrhythmia disorder characterized by prolongation of the QT interval; patients are predisposed to ventricular tachyarrhythmias and fibrillation leading to recurrent syncope or sudden cardiac death. We performed clinical and genetic studies in six Saudi Arabian families with a history of sudden unexplained death of children. Clinical symptoms, ECG phenotypes, and genetic findings led to the diagnosis of LQT1 in two families (recessive) and LQT2 in four families (three recessive and one dominant). Onset of arrhythmia was more severe in the recessive carriers and occurred during early childhood in all recessive LQT1 patients. Arrhythmia originated at the intrauterine stages of life in the recessive LQT2 patients. LQT1, causing mutation c.387-5 T > A in the KCNQ1 gene, and LQT2, causing mutation c.3208 C > T in the KCNH2 gene, are presumably founder mutations in the Assir province of Saudi Arabia. Further, all LQTS causing mutations detected in this study are novel and have not been reported in other populations.     

Autopsy findings of co-sleeping-associated sudden unexpected deaths in infancy: relationship between pathological features and asphyxial mode of death

Aim: Co‐sleeping is associated with increased risk of sudden unexpected death in infancy (SUDI)/sudden infant death syndrome (SIDS). The aim of this study is to examine autopsy findings from a single UK specialist centre to determine the relationship between co‐sleeping and cause of death. Methods: Retrospective analysis of >1500 paediatric autopsies carried out by paediatric pathologists over a 10‐year period. SUDI was defined as sudden unexpected death of an infant aged 7–365 days; deaths were categorised into explained SUDI (cause of death was determined) and unexplained SUDI (equivalent to SIDS). Results: There were 546 SUDI; sleeping arrangements were specifically recorded in 314; of these, 174 (55%) were co‐sleeping‐associated deaths. Almost two thirds (59%) of unexplained SUDI were co‐sleeping compared to 44% explained SUDI (95% confidence interval (CI) 1.0–27.2%, P= 0.03); however, this difference remained statistically significant only for the first 5 months of life (95% CI 3.5–33.2%, P= 0.01). In unexplained SUDI aged < 6 months, there were no significant differences between co‐sleeping and non‐co‐sleeping deaths with respect to ante‐mortem symptoms, intrathoracic petechiae, macroscopic lung appearances, pulmonary haemosiderin‐laden macrophages, and isolation of specific bacterial pathogens; however, fresh intra‐alveolar haemorrhage was reported more commonly in co‐sleeping (54%) than in those that were not (38%; 95% CI 1.4–30.5%, P= 0.03). Conclusions: Co‐sleeping is associated with unexplained SUDI/SIDS in infants aged < 6 months, suggesting that co‐sleeping is related to the pathogenesis of death in younger infants. The finding that intra‐alveolar haemorrhage is more common in co‐sleeping suggests that a minority of co‐sleeping‐associated deaths may be related to an asphyxial process.     

Can home monitoring reduce mortality in infants at increased risk of sudden infant death syndrome? A systematic review

Aim: To conduct a systematic review to evaluate the effectiveness of home monitoring devices in the prevention of sudden infant death syndrome (SIDS). Methods: Systematic literature review to June 30, 2010. Results: Eleven unique studies were identified. Only one of these studies involved a comparison of home monitoring with a control intervention and so could be deemed level I evidence. The remaining studies constituted level III evidence. Conclusions: There is no high‐level evidence that home monitoring may be of use in preventing SIDS; further research is needed.     

Sudden unexpected death in infancy: epidemiologically determined risk factors related to pathological classification

Infants that died suddenly and unexpectedly were studied as part of the European Concerted Action on sudden infant death syndrome (SIDS). Three paediatric pathologists, first independently of each other and later in a consensus meeting, classified 63 cases into 3 groups: SIDS (19 cases), borderline SIDS (30 cases) and non-SIDS (14 cases). The interobserver agreement among the pathologists before the consensus meeting was moderate (Kappa = 0.41) and jointly it was higher (Kappa = 0.83). The distribution of epidemiologically determined risk factors was studied over these three groups. Maternal smoking after birth, low socioeconomic status and thumb sucking were found more often in SIDS than in the other cases. Inexperienced prone sleeping was a determinant for SIDS, but not for non-SIDS. Previous hospital admission, low birthweight and/or short gestation were associated with borderline SIDS. Non-SIDS cases received more breastfeeding, the parents hardly smoked during pregnancy and after birth, a firm mattress had been used, and more often signs of illness had been reported by the parents, compared with the SIDS and borderline SIDS cases. Bedding factors and both primary and secondary prone sleeping were equally distributed over the three groups which supports the hypothesis that, in SIDS and borderline SIDS, as well as in non-SIDS cases, some similar external and preventable factors might influence the events leading to death. Research should therefore focus on all sudden unexpected deaths, after which subgroups such as SIDS cases can be separately analysed. The postmortem is an essential part of the whole work-up of each case and the results should be interpreted with all other available data to arrive at a sound evaluation of cases and thus form the basis for the prevention of all sudden unexpected infant death.     

Sudden unexpected death in infancy: A historical perspective

Epidemiological, developmental and pathological research over the last 40 years has done much to unravel the enigma of sudden unexpected death in infancy (SUDI) and sudden infant death syndrome (SIDS) that has afflicted the human condition for millennia. Modifications in infant care practices based on the avoidance of risk factors identified from a consistent epidemiological profile across time and multiple locations have resulted in dramatic reductions in the incidence of SUDI and SIDS in particular. The definition of SIDS (or unexplained SUDI) has been continually refined allowing enhanced multidisciplinary research, results of which can be more reliably compared between investigators. These latter expanded definitions mandating death scene investigations, evaluation of the circumstances of death and more comprehensive autopsies including additional ancillary testing have illuminated the importance of life‐threatening sleep environments. The triple‐risk hypothesis for SIDS has been increasingly validated and formulates an inextricable relationship between an infant's state of development, underlying pathological vulnerability and an unsafe sleep environment for sudden infant death to occur. Today, the major risk factors for SUDI are maternal smoking and bed sharing, and the challenge is to implement effective strategies that will reduce the exposure to such risks as was done with prone sleeping position. The challenges ahead include development of clinical methods and/or laboratory testing that will accurately identify which infants are at particularly high risk of SIDS but also means by which their deaths can be prevented.     

Gender and the sudden infant death syndrome

Abstract A nationwide case-control study compared the prevalence and magnitude of risk factors for sudden infant death syndrome (SIDS) in male and female infants. The risk factors of SIDS and their magnitude for males and females are very similar. After adjustment for potential confounders male infants had a 1.42-fold (95% CI = 1.04, 1.94) increased risk of SIDS compared with females. Risk factors identified in most epidemiological studies are not the reason for the increased SIDS mortality seen in male infants.     

An analysis of trends in the incidence of sudden infant death in The Netherlands 1969–89

There is considerable interest in the relationship between sleeping position and the occurrence of sudden infant death syndrome (SIDS). As changes have been reported in The Netherlands in the position infants have been placed to sleep, the national Dutch sudden infant death rates were analyzed over the time that such changes have taken place. The overall post-perinatal death rate (1 week less than 1 year) was around 4-4.5 per 1000 live births from 1969 until 1985. From 1985 until 1989 the rate fell from 4.1 to 2.9 per 1000 live births. During the same period the cot death/SIDS rate rose from 0.44 per 1000 in 1969 to between 1.08 and 1.31 per 1000 in 1977-87, and subsequently fell to 0.7 per 1000 in 1989. These trends coincided with changes in prone sleeping position demonstrated in national surveys. The problems of interpreting such national data, with only 50-60% of infant deaths being autopsied and with the possibilities of misclassification over time, are fully discussed. The data are supportive of the relationship between prone sleeping position and cot death.     

Study of the conduction system in a population of patients with sudden infant death syndrome

Summary The conduction system of 23 infant hearts, 15 of sudden infant death syndrome (SIDS) and eight of those dying from known cause, was serially sectioned. A left-sided His bundle was found more commonly in (SIDS) (eight of 15) than in the controls (two of eight). Taking into account a previous study in which a left-sided His bundle was found in only four of 32 hearts from all age groups, this is statistically significant and may be a factor promoting SIDS.This research was aided by grant HL-30558-02 from the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.     

Sudden infant death syndrome in Indigenous and non-Indigenous infants in north Queensland, 1990-1998

OBJECTIVE: To compare the epidemiology of sudden infant death syndrome (SIDS) in Indigenous and non-Indigenous infants in north Queensland, and to assess the quality of data recorded for SIDS deaths. METHODS: Records were obtained for SIDS cases from all coronial courts in north Queensland from 1990 to 1998. Demographic characteristics, ethnicity, age at death, sleeping and feeding patterns, smoking incidences and autopsy findings were compared. Incidences, medians and univariate associations were generated where appropriate. RESULTS: There were 83 248 live births for the 9-year period; 71 389 non-Indigenous and 11 859 Indigenous births. There were 69 SIDS deaths (0.83 per 1000 live births). Overall, recording of demographic and death scene data was poor. Thirty-eight autopsies (55%) were performed by specialist pathologists. There were 22 (32%) non-Indigenous and 22 (32%) Indigenous SIDS deaths (25 ethnicity unknown), giving an estimated relative risk of 2.82 (95% CI 2, 4). Median age at death was 13.1 weeks (range 1-83 weeks) with 14% of deaths occurring in the neonatal period for both groups. Sleeping position was not recorded in 42% of cases and co-sleeping was not recorded in 27% of cases. Bed sharing was more common amongst Indigenous infants. Fifty-two per cent of SIDS cases occurred in the wet season and 48% in the dry season. CONCLUSIONS: Data recorded for SIDS deaths in north Queensland are poor, preventing specific conclusions concerning SIDS risk factors. However, SIDS rates may be up to three-fold higher in the Indigenous population. A uniform system of post-mortem and death scene data reporting is needed urgently.