Overview of sudden infant death syndrome in Japan

In spite of rapid medical advancement in the care of infants and children, not only the general public but also many medical personnel have remained unaware of sudden infant death syndrome (SIDS) until very recently in Japan. In 1981, a research project team on SIDS financed by the Ministry of Health and Welfare was founded. Current incidence of SIDS is estimated to be about 0.5 per 1000 live births. The SIDS Family Association was organized in 1993 in Japan and began to publicize the social importance of SIDS and to support SIDS families by training befrienders. A series of articles on current achievements from SIDS research projects and from the SIDS Family Association are submitted to this issue. The present paper summarizes the status of SIDS in Japan by overviewing the activities of the research team and the SIDS Family Association.     

Annotation Accidental death or sudden infant death syndrome?

Objective: To describe the reasons why it is difficult to decide whether to attribute some infant deaths to accidents or to SIDS.
Methodology To extract from infant deaths data in South Australia those where the cause of death is debatable.
Results The risks associated with rocking cradles, bed sharing, bedclothes, couch sleeping, unsafe cots or beds and the prone position are presented.
Conclusions : Uniform worldwide death scene investigations for all infant deaths should help identify unsafe sleeping conditions for infants.     

Cytokine gene polymorphisms and sudden infant death syndrome

Aim: Several studies indicate that the mucosal immune system is stimulated in cases of sudden infant death syndrome (SIDS), and our hypothesis is that this immune reaction is because of an unfavourable combination of functional polymorphisms in the cytokine genes. Methods: Thus, in this study, single nucleotide polymorphisms (SNPs) in the genes encoding IL‐6, IL‐8, IL‐12, IL‐13, IL‐16, IL‐18 and IFNγ were investigated in 148 SIDS cases, 56 borderline SIDS cases, 41 cases of infectious death and 131 controls. Results: Regarding genotype distribution, no differences between the investigated groups were found. However, in the SIDS group, the genotypes IL‐8 ?251AA/AT and IL‐8 ?781CT/TT were significantly more frequent in the SIDS cases found dead in a prone sleeping position, compared with SIDS cases found dead in other sleeping positions. In addition, there was an association between fever prior to death and the genotype IL‐13 +4464GG in the cases of infectious death. Conclusion: This study indicates that specific interleukin genotypes are a part of a genetic make up that make infants sleeping prone at risk for SIDS.     

Analysis of the mitochondrial genome in sudden infant death syndrome

AIM: To investigate the mitochondrial genome and its association with sudden infant death syndrome (SIDS). METHODS: Twenty SIDS infants were screened for previously reported mitochondrial DNA mutations using direct sequencing. The whole mitochondrial genome was also sequenced for six of the infants. RESULTS: Three substitutions, A11467G, A12308G and G12372A, comprising a haplogroup were present in four infants diagnosed as pure SIDS. This haplogroup was also common in a control group. CONCLUSIONS: No specific mutation or polymorphism was found in association with SIDS.     

Mitochondrial tRNA genes and flanking regions in sudden infant death syndrome

AIM: Mitochondrial DNA (mtDNA) mutations have been proposed as a genetic risk factor for sudden infant death syndrome (SIDS). The aim of this study was to further investigate this issue, by sequencing the mitochondrial tRNA genes with flanking regions in SIDS cases and controls. METHOD: The selected genes were investigated in 24 cases of SIDS and 10 controls, the method used were direct sequencing. In addition, the A10398G mutation in the ND3 gene was investigated in 220 SIDS cases, 26 cases of infectious death and 93 controls, using allele-specific PCR. RESULTS: Mutations, recorded as differences from the revised Cambridge sequence, were found in 32 different sites in the coding regions investigated. There was no difference in mutation frequency between SIDS cases and controls, and no single mutation was found associated with SIDS. CONCLUSION: The present study does not indicate an association between a specific mitochondrial tRNA gene mutation and SIDS, nor a higher mtDNA tRNA mutation frequency in SIDS cases than in controls.     

Impact of home monitoring for sudden infant death syndrome on family life

As home monitoring has been advocated for the prevention of sudden infant death (SIDS) we investigated the influence of such a monitoring programme on family life. Twenty European middle and lower-class families with a child monitored at home after a near miss for SIDS event were investigated. Some psychological and social findings were compared with a group of 20 matched control families. It appears that home monitoring induces severe stress, mainly in the mothers. Fathers and siblings also manifested significant emotional stress. Poor schooling of the parents and previous marital discord seem to be predictors of bad adaptation to home monitoring.     

Problems on the diagnosis of sudden infant death syndrome

Various autopsy cases of sudden unexpected death (SUD) in infancy were examined at the Tokyo Medical Examiner's Office between 1985 and 1994. More than half of the SUD were diagnosed as sudden infant death syndrome (SIDS), but a number of other causes, such as mechanical asphyxia, were also diagnosed. SIDS is diagnosed by autopsy, but there are no clear diagnostic criteria differentiating SIDS from other causes of SUD. SUD is diagnosed as SIDS when other causes are excluded, but it is difficult to distinguish between SIDS and mechanical asphyxia. There was not a large difference in autopsy findings, or in death scene or statistical data, between SIDS and non-SIDS cases. In their estimation of the diagnostic ratio of SIDS to other causes of death, medical examiners might be divided into three groups: ‘SIDS tolerationist’ examiners think that SUD should be positively diagnosed as SIDS, insofar as another cause of death is not proved clearly. A second group of examiners might be regarded as ‘SIDS exclusionist’; these consider microscopic findings or peculiar death scenes as important contributing factors leading to death. The third group represents a middle stance somewhere between these two. We thought that (forensic) pathologists as well as medical examiners in Japan might have differing stances on SIDS diagnosis. The statistical analysis of SIDS in certain research areas may be affected by the diagnostic ‘preference’ of pathologists belonging to a certain institute.     

Research and sudden infant death syndrome: definitions, diagnostic difficulties and discrepancies

The diagnosis of causes of sudden infant death is an often complex and difficult process. Variable standards of autopsy practice and the use of different definitions for entities such as sudden infant death syndrome (SIDS) have also contributed to confusion and discrepancies. For example, the term SIDS has been used when the requirements of standard definitions have not been fulfilled. In an attempt to correct this situation recent initiatives have been undertaken to stratify cases of unexpected infant death and to institute protocols that provide frameworks for investigations. However, if research is to be meaningful, researchers must be scrupulous in assessing how extensively cases have been investigated and how closely cases fit with internationally recognized definitions and standards. Unless this approach is adopted, evaluation of research findings in SIDS will be difficult and the literature will continue to be beset by contradictions and unsubstantiated conclusions.     

Heart weight in infants--a comparison between sudden infant death syndrome and other causes of death

Heart and body weights were compared with regard to heart pathology and cause of death in well-defined groups of infants under 1 y of age. In the period 1980 to 1998, out of 468 infants autopsied at the Department of Forensic Medicine in Stockholm, Sweden, 331 died of sudden infant death syndrome (SIDS), while 137 died of other causes. Physical violence was the known cause of death in 30 infants and cardiovascular malformations in another 19. Inflammatory alterations of the myocardium were found in 74 cases (16%): in 17 cases (3.6%) myocarditis was interpreted as the main cause of death; in 45 (10%) it was interpreted as contributing to SIDS and in 12 cases (2.5%) it was observed but judged not to be a contributory cause of death in non-SIDS victims. Two of these infants died as a result of physical violence. Body weight was the best predictor for heart weight as analysed by multiple regression, including age, sex, body weight, length, BMI and birth weight. An equation for estimating heart weight from body weight gave an accuracy within the range 0.75-1.25 in 89.2% and 85.0% of the SIDS and non-SIDS groups, respectively. CONCLUSION: Body weight is the best predictor for estimating heart weight. No evidence supported the notion that heart weight, body weight or birth weight of SIDS victims differs from non-SIDS, although heart weight in infants with cardiovascular malformations deviated from observations in the other groups.     

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.     

Vitamin A and sudden infant death syndrome in Scandinavia 1992-1995

Aim: To assess the effect of vitamin supplementation on the risk of sudden infant death syndrome (SIDS). Methods: The analyses are based on data from the Nordic Epidemiological SIDS Study, a case-control study in which parents of SIDS victims in the Scandinavian countries were invited to participate together with parents of four matched controls between 1 September 1992 and 31 August 1995. The odds ratios presented are computed by conditional logistic regression analysis. Results: The crude odds ratio in Scandinavia for not giving vitamin substitution was 2.8 (95% CI (1.9, 4.3)). This effect was statistically significant in Norway and Sweden, which use A and D vitamin supplementation, but not in Denmark, where only vitamin D supplementation is given. The odds ratios remained significant in Sweden when an adjustment was made for confounding factors (OR 28.4, 95% CI (4.7, 171.3)). Conclusion: We found an association between increased risk of sudden infant death syndrome and infants not being given vitamin supplementation during their first year of life. This was highly significant in Sweden, and the effect is possibly connected with vitamin A deficiency. This effect persisted when an adjustment was made for potential confounders, including socioeconomic factors.     

Bedsharing, roomsharing, and sudden infant death syndrome in Scotland: a case-control study

OBJECTIVE: To examine the hypothesis that bedsharing with an infant is associated with an increased risk of sudden infant death syndrome (SIDS). STUDY DESIGN: A 1:2, case:control study in Scotland UK, population 5.1 million, including 123 infants who died of SIDS between January 1, 1996 and May 31, 2000, and 263 controls. The main outcome measure was sharing a sleep surface during last sleep. RESULTS: Sharing a sleep surface was associated with SIDS (multivariate OR 2.89, 95% CI 1.40, 5.97). The largest risk was associated with couch sharing (OR 66.9, 95% CI 2.8, 1597). Of 46 SIDS infants who bedshared during their last sleep, 40 (87%) were found in the parents' bed. Sharing a bed when <11 weeks (OR 10.20, 95% CI 2.99, 34.8) was associated with a greater risk, P = .010, compared with sharing when older (OR 1.07, 95% CI 0.32, 3.56). The association remained if mother did not smoke (OR 8.01, 95% CI 1.20, 53.3) or the infant was breastfed (OR 13.10, 95% CI 1.29, 133). CONCLUSIONS: Bedsharing is associated with an increased risk of SIDS for infants <11 weeks of age. Sharing a couch for sleep should be strongly discouraged at any age.     

Serum testosterone and estradiol in sudden infant death

OBJECTIVE: To test the hypothesis that among infants who die unexpectedly, testosterone and/or estradiol levels are elevated in those diagnosed with SIDS versus those with known causes of death (controls). STUDY DESIGN: Postmortem blood was collected and coded from infant autopsies, and serum was prepared and frozen until assayed for total testosterone and estradiol by fluoroimmunoassay. Subject information was then collected from the medical examiner's report. RESULTS: Testosterone, but not estradiol, was significantly higher in 127 SIDS cases versus 42 controls for both males (4.8 +/- 0.4 vs 2.2 +/- 0.4 nmol, respectively; P < .005) and females (2.4 +/- 0.2 vs 1.6 +/- 0.2 nmol, respectively; P < 0.03). CONCLUSIONS: Higher testosterone levels in infant victims of unexpected, unexplained death may indicate a role for testosterone or related steroids in SIDS. Further research is needed to understand the potential utility of testosterone as an indicator of SIDS risk.     

Birth order and risk of sudden infant death syndrome: Is the true relationship negative?

Abstract The risk of SIDS has been reported consistently as being positively related to parity or birth order. However the reports in question have failed to take into account the possible confounding effects of sibship size. In the present study it was reasoned that if this were done the relationship would be negative, not positive. In an analysis of births stratified by sibship size occurring in the years 1975–84 in the state of Oregon, it was found that the risk of SIDS in the age range 7–364 days did indeed tend to decrease with increasing birth order when sibship size was held constant. An expected tendency for SIDS rates to increase with increasing sibship size when birth order was held constant was also confirmed. This tendency is probably explained by a negative correlation between family size and socio-economic status. Non-SIDS rates behaved in a similar manner to SIDS rates. The tendency for the risk of SIDS to decrease with increasing birth order was more evident when births following a pregnancy interval of less than 12 months were excluded.     

A mitochondrial DNA polymorphism associated with cardiac arrhythmia investigated in sudden infant death syndrome

AIM: Long QT syndrome (LQTS) has been shown to be the cause of death in some cases originally diagnosed as sudden infant death syndrome (SIDS). Such cardiac arrhythmias have also been noted in families with mitochondrial disease, and studies indicate that mitochondrial disease could be involved in SIDS. This makes the mtDNA polymorphism T3394C interesting, as a previous study has shown it to be associated with electrocardiographic (ECG) changes after exercise in a family with LQTS, where some members harboured a KCNH2 mutation. SUBJECTS: A total of 245 SIDS cases and 176 control cases. METHODS: DNA was prepared from blood/tissue samples. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to search for the mtDNA polymorphism and KCNH2 mutation. Differences were confirmed by sequencing. RESULTS: The T3394C polymorphism was found in 3 pure SIDS cases (1.5%), 2 borderline SIDS cases (4.4%), 1 case of explained death (1.6%) and 2 living control cases (1.8%) (p = 0.62). The KCNH2 mutation was not found in cases or controls. CONCLUSION: The mtDNA polymorphism studied was found in a small number of SIDS cases and the frequency did not differ statistically from control subjects, making an association with increased SIDS risk unlikely.     

Maternal smoking: an increasing unique risk factor for sudden infant death syndrome in Sweden

Aim: To assess the change of risk factors that are specific to sudden infant death syndrome (SIDS) after the initialization of a campaign to reduce the risk (RTR) of SIDS compared to non-SIDS postneonatal deaths. Methods: Data were extracted from the Swedish Medical Birth Registry, 1982-1991 and 1993-1998. 1105 infants died from SIDS during the postneonatal period, 2115 postneonatal deaths were from other causes and 11 050 live birth controls were selected. Risk factors previously identified to be related to SIDS were defined as high parity, prematurity, young maternal age, low Apgar score, birth during the night, single motherhood, multiple births, maternal smoking, male gender, short length standard deviation score (SDS) and small weight-to-length SDS. Results: Non-SIDS deaths were more significantly related to a low 5-min Apgar score, smaller weight-to-length SDS, and/or short length SDS values; while SIDS deaths were more closely related to mothers with higher parity or multiple births, mothers who smoked during pregnancy and single-parent (mother) families. Maternal smoking was even more prominent among SIDS deaths in the post-campaign period. The adjusted odds ratios, compared with non-SIDS deaths, increased from 1.84 (95% CI: 1.48, 2.28) in the pre-campaign period to 4.11 (95% CI: 2.72, 6.21) in the post-campaign period.

Conclusions: Maternal smoking during pregnancy remains the most important modifiable risk factor for SIDS in the post-campaign period in comparison with non-SIDS postneonatal deaths. Other than putting babies in a supine sleeping position, maternal smoking should be the next most important issue to be considered, if there is to be a second campaign.