Effects of nicotine on bacterial toxins associated with cot death.

Toxins produced by staphylococci and enterobacteria isolated from the nasopharynx of cases of sudden infant death syndrome (SIDS) have a lethal effect when injected into chick embryos. If the toxins are progressively diluted the lethal effect disappears, but certain combinations of toxins show synergy so that if sublethal doses are mixed a highly lethal effect is produced. In this paper it is shown that nicotine at very low concentrations (less than that produced in man by 0.05 cigarettes) potentiates the lethal action of certain SIDS associated bacterial toxins and markedly potentiates the lethal action of synergistic combinations of bacterial toxins. These results could explain, at least in part, why parental smoking increases the risk of SIDS. They also provide further support for the common bacterial toxin hypothesis of cot death.     

Evolution and significance of the triple risk model in sudden infant death syndrome

Sudden infant death syndrome (SIDS) is a leading cause of death in infants, although the mechanisms leading to death remain unclear. Multiple theories have emerged over time, with one of the most influential hypotheses being the triple risk model. This model, first devised in 1972 and later revised in 1994 by Filiano and Kinney, is still widely used in assisting with conceptualising and understanding sudden death in infancy. This model has evolved over time, with each version stressing that SIDS is likely to occur when certain risk factors coincide, suggesting that the lethal mechanisms in SIDS are likely to be multifactorial. All versions of the triple risk model from 1972 to the present have emphasised the complexity of SIDS and serve as useful guides for current and future research into the enigma of sudden and unexpected death in infancy.     

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.     

The sudden infant death syndrome gene: does it exist?

BACKGROUND: Sudden infant death syndrome (SIDS) is in a difficult position between the legal and medical systems. In the United Kingdom, prosecutors have for years applied the simple rule that 1 unexpected death in a family is a tragedy, 2 are suspicious, and 3 are murder. However, it seems that the pendulum has now swung to the opposite extreme; mutations or polymorphisms with unclear biological significance are accepted in court as possible causes of death. This development makes research on genetic predisposing factors for SIDS increasingly important, from the standpoint of the legal protection of infants. The genetic component of sudden infant death can be divided into 2 categories, ie (1) mutations that give rise to genetic disorders that constitute the cause of death by themselves and (2) polymorphisms that might predispose infants to death in critical situations. Distinguishing between these 2 categories is essential, and cases in which a mutation causing a lethal genetic disorder is identified should be diagnosed not as SIDS but as explained death. GENETIC ALTERATIONS THAT MAY CAUSE SUDDEN INFANT DEATH: Deficiencies in fatty acid metabolism have been extensively studied in cases of SIDS, and by far the most well-investigated mutation is the A985G mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene, which is the most prevalent mutation causing MCAD deficiency. However, <1% of sudden infant death cases investigated have this mutation, and findings of biochemical profiles seen in specific fatty acid oxidation disorders in a number of such cases emphasize the importance of investigating fatty acid oxidation disorders other than MCAD deficiency. Severe acute hypoglycemia may cause sudden death among infants, but only rare novel polymorphisms have been found when key proteins involved in the regulation of blood glucose levels are investigated in cases of SIDS. The long QT syndrome (LQTS) is another inherited condition proposed as the cause of death in some cases of sudden infant death. The LQTS is caused by mutations in genes encoding cardiac ion channels, and mutations in the genes KVLQT1 and SCNA5 have been identified in cases initially diagnosed as SIDS, in addition to several polymorphisms in these 2 genes and in the HERG gene. In addition, genetic risk factors for thrombosis were investigated in a small number of SIDS cases; the study concluded that venous thrombosis is not a major cause of sudden infant death. GENE POLYMORPHISMS THAT MAY PREDISPOSE INFANTS TO SUDDEN INFANT DEATH UNDER CERTAIN CIRCUMSTANCES: Many SIDS victims have an activated immune system, which may indicate that they are vulnerable to simple infections. One reason for such vulnerability may be partial deletions of the complement component 4 gene. In cases of SIDS, an association between slight infections before death and partial deletions of the complement component 4 gene has been identified, which may indicate that this combination represents increased risk of sudden infant death. There have been a few studies investigating HLA-DR genotypes and SIDS, but no association has been demonstrated. The most common polymorphisms in the interleukin-10 (IL-10) gene promoter have been investigated in SIDS cases, and the ATA/ATA genotype has been reported to be associated with both SIDS and infectious death. The findings may indicate that, in a given situation, an infant with an unfavorable IL-10 genotype may exhibit aberrant IL-10 production, and they confirm the assumption that genes involved in the immune system are of importance with respect to sudden unexpected infant death. Another gene that has been investigated is the serotonin transporter gene, and an association between the long alleles of this gene and SIDS has been demonstrated. Serotonin influences a broad range of physiologic systems, as well as the interactions between the immune and nervous systems, and findings of decreased serotonergic binding in parts of the brainstem, together with the findings in the serotonin transporter gene, may indicate that serotonin plays a regulatory role in SIDS. It has also been speculated that inadequate thermal regulation is involved in SIDS, but investigations of genes encoding heat-shock proteins and genes encoding proteins involved in lipolysis from brown adipose tissue have not found evidence of linkages between common polymorphisms in these genes and SIDS. A number of human diseases are attributable to mutations in mitochondrial DNA (mtDNA), and there are several reasons to think that mtDNA mutations also are involved in SIDS. Both a higher substitution frequency and a different substitution pattern in the HVR-I region of mtDNA have been reported in SIDS cases, compared with control cases. A number of coding region mtDNA mutations have also been reported, but many are found only in 1 or a few SIDS cases, and, to date, no predominant mtDNA mutation has been found to be associated with SIDS. CONCLUSIONS: All mutations giving rise to metabolic disorders known to be associated with life-threatening events are possible candidates for genes involved in cases of sudden infant death, either as a cause of death or as a predisposing factor. It is necessary to distinguish between lethal mutations leading to diseases such as MCAD and LQTS, and polymorphisms (for instance, in the IL-10 gene and mtDNA) that are normal gene variants but might be suboptimal in critical situations and thus predispose infants to sudden infant death. It is unlikely that one mutation or polymorphism is the predisposing factor in all SIDS cases. However, it is likely that there are "SIDS genes" operating as a polygenic inheritance predisposing infants to sudden infant death, in combination with environmental risk factors. For genetically predisposed infants, a combination of, for instance, a slight infection, a prone sleeping position, and a warm environment may trigger a vicious circle with a death mechanism, including hyperthermia, irregular breathing, hypoxemia, and defective autoresuscitation, eventually leading to severe hypoxia, coma, and death.     

Reappraisal of the SIDS enigma: An epidemiological and clinicopathological approach

Abstract The possibility that most cases of sudden infant death syndrome (SIDS) are caused by a transmissible agent is explored. A hypothesis of causation is developed using pathological and epidemiological data and our microbiological findings. The nature and distribution of vascular damage together with the consistent finding of liquid blood, in addition to the epidemiological features of SIDS, form the basis of the hypothesis that a bacterial toxin is a likely single cause of most cases of the syndrome. Future research ideas and a new definition of SIDS are proposed.     

Current controversies in the pathophysiology and prevention of sudden infant death syndrome

PURPOSE OF REVIEW: To examine recent research relevant to sudden infant death syndrome (SIDS) to determine whether there is a place for home monitoring in the care of children believed to be at risk. RECENT FINDINGS: Current SIDS research has focused on the genetics of SIDS, brainstem abnormalities and arousal failures, the effects of tobacco smoke and other environmental agents, the role of infectious diseases, and prenatal factors that may contribute to SIDS. Investigations have suggested that there are infants who appear to respond less effectively when challenged by certain environmental or infectious agents. These infants have blunted responses to stress and diminished arousal to hypoxemia, in part because of failures in genetically determined brainstem function. It is unclear at this time whether home monitoring would offer protection in all circumstances, but it may be helpful in certain patients. SUMMARY: There appears to be progress in understanding the causes of SIDS. As additional studies emerge, the optimal approaches to care will become more apparent, with home monitoring one of the possible interventions.     

Redefinition of the Sudden Infant Death Syndrome: the Disadvantages

For many years the definition of SIDS has been the sudden death of an infant that was unexpected by history and in which a thorough postmortem examination failed to demonstrate an adequate cause of death. In 1991 a report was published in this journal from a panel convened by the NICHD which recommended that the diagnosis of SIDS not be made unless a death scene investigation has been conducted. The panel recommended further exclusions from the diagnosis of SIDS of certain “unresolved” cases. We believe the changes recommended by the NICHD panel are impractical and may have a serious negative impact on SIDS research and on the surviving family members of the SIDS victims.     

Interactions between maternal smoking and other prenatal risk factors for sudden infant death syndrome (SIDS)

Abstract In numerous investigations, maternal smoking increases the risk of sudden infant death syndrome (SIDS). In the present study we investigated whether prenatal risk factors for SIDS modify the effect of maternal smoking on SIDS mortality. We analysed data from a population-based cohort study (222 cases, 260,604 infants at risk) within the Westphalian Perinatal Inquiry in Germany between 1990 and 1994. In the stratified analysis, smoking was classified into non-smoking, moderate (1–10 cigarettes/d) and heavy smoking (> 10 cigarettes/d). Multiplicative interactions between smoking and other prenatal risk factors were assessed in a logistic regression model. The relative risk (RR) for maternal smoking was 2.4 (95% confidence interval 1.7-5.4) for moderate and 7.2 (5.3, 9.7) for heavy smokers. Previous established risk factors for SIDS, such as preterm birth, low birthweight, and number of prenatal visits did not increase the risk of SIDS among non-smokers, but became important risk factors among smokers. In preterm infants (< 37 weeks) of heavy smokers, the RR was 19.6 (10.4, 36.8) compared to term infants of non-smokers. Low birthweight infants (< 2500 g) of heavy smokers had a RR of 16.3 (8.4, 31.2) compared to normal weighted infants of non-smokers. Adjustment for occupational status did not change the crude estimates. The RR of < 6 prenatal visits in the heavy smoking subgroup was 14.8 (7.2, 29.6) compared to > 9 prenatal visits in the nonsmoking strata. Heavy smoking potentiates other prenatal risk factors for SIDS suggesting an increased susceptibility towards the adverse effects of tobacco smoke in utero. In infants born to non-smoking mothers, prenatal risk factors are absent and postnatal factors may be of major importance.     

Clinical implications of sudden infant death syndrome epidemiology

The diagnosis of sudden infant death syndrome (SIDS) is less than 100% certain in any given instance. Approximately 90% of all SIDS have occurred by age 6 months. A visual aid consisting of 1,000 dots helps in communicating numerical information such as 'rates' to parents (and others as well). The annual and seasonal occurrence patterns are independent of so-called SIDS risk factors. A single, major gene defect cannot account for SIDS but the root cause may be genetic (polygenic). Recent estimates of sibling risk to SIDS indicate that earlier estimates were inflated. Use of apnea monitors to prevent SIDS has no basis in fact but may provide emotional support. DTP immunization does not cause SIDS.     

The triple risk hypotheses in sudden infant death syndrome

Sudden infant death syndrome (SIDS) victims were regarded as normal as a matter of definition (Beckwith 1970) until 1952 when Kinney and colleagues argued for elimination of the clause, "unexpected by history." They argued that "not all SIDS victims were normal," and referred to their hypothesis that SIDS results from brain abnormalities, which they postulated "to originate in utero and lead to sudden death during a vulnerable postnatal period." Bergman (1970) argued that SIDS did not depend on any "single characteristic that ordains a infant for death," but on an interaction of risk factors with variable probabilities. Wedgwood (1972) agreed and grouped risk factors into the first "triple risk hypothesis" consisting of general vulnerability, age-specific risks, and precipitating factors. Raring (1975), based on a bell-shaped curve of age of death (log-transformed), concluded that SIDS was a random process with multifactorial causation. Rognum and Saugstad (1993) developed a "fatal triangle" in 1993, with groupings similar to those of Wedgwood, but included mucosal immunity under a vulnerable developmental stage of the infant. Filiano and Kinney (1994) presented the best known triple risk hypothesis and emphasized prenatal injury of the brainstem. They added a qualifier, "in at least a subset of SIDS," but, the National Institute of Child Health and Development SIDS Strategic Plan 2000, quoting Kinney's work, states unequivocally that "SIDS is a developmental disorder. Its origins are during fetal development." Except for the emphasis on prenatal origin, all 3 triple risk hypotheses are similar. Interest in the brainstem of SIDS victims began with Naeye's 1976 report of astrogliosis in 50% of all victims. He concluded that these changes were caused by hypoxia and were not the cause of SIDS. He noted an absence of astrogliosis in some older SIDS victims, compatible with a single, terminal episode of hypoxia without previous hypoxic episodes, prenatal or postnatal. Kinney and colleagues (1983) reported gliosis in 22% of their SIDS victims. Subsequently, they instituted studies of neurotransmitter systems in the brainstem, particularly the muscarinic (1995) and serotenergic systems (2001). The major issue is when did the brainstem abnormalities, astrogliosis, or neurotransmitter changes occur and whether either is specific to SIDS. There is no published method known to us of determining the time of origin of these markers except that the injury causing astrogliosis must have occurred at least 4 days before death (Del Bigio and Becker, 1994). Because the changes in neurotransmitter systems found in the arcuate nucleus in SIDS victims were also found in the chronic controls with known hypoxia, specificity of these markers for SIDS has not been established. It seems likely that the "acute control" group of Kinney et al (1995) died too quickly to develop gliosis or severe depletion of the neurotransmitter systems. We can conclude that the acute controls had no previous episodes of severe hypoxia, unlike SIDS or their "chronic controls." Although the average muscarinic cholinergic receptor level in the SIDS victim was significantly less than in the acute controls, the difference was only 27%, and only 21 of 41 SIDS victims had values below the mean of the acute controls. The study of the medullary serotonergic network by Kinney et al (2001) revealed greater reductions in the SIDS victims than in acute controls, but the questions of cause versus effect of the abnormalities, and whether they occurred prenatally or postnatally, remain unanswered. Hypoplasia of the arcuate nucleus was stated to occur in 5% of their SIDS cases by Kinney et al (2001), but this is a "primary developmental defect" according to Matturri et al (2002) with a larger series, many of whom were stillbirths. These cases should not be included under the rubric of SIDS, by definition. There are difficulties with Filiano and Kinney's (1994) explanation of the age at death distribution of SIDS. They postulate that the period between 1 and 6 months represents an unstable time for virtually all physiologic systems. However, this period demonstrates much less instability than does the neonatal period, when most deaths from congenital defects and severe maternal anemia occur. We present data for infants born to mothers who were likely to have suffered severe anemia as a consequence of placenta previa, abruptio placentae, and excessive bleeding during pregnancy; these infants presumably are at increased risk of hypoxia and brainstem injury. The total neonatal mortality rate in these 3 groups of infants is 4 times greater than the respective postneonatal mortality, and in the postneonatal period the non-SIDS mortality rate is between 14 and 22 times greater than the postneonatal SIDS rate in these 3 groups. A preponderance of deaths in the neonatal period is also found for congenital anomalies, a category that logically should include infants who experienced prenatal hypoxia or ischemia; this distribution of age of death is very different from that for SIDS, which mostly spares the first month and peaks between 2 and 3 months of age. Finally, evidence inconsistent with prenatal injury as a frequent cause of SIDS comes from prospective studies of ventilatory control in neonates who subsequently died of SIDS; no significant respiratory abnormalities in these infants have been found (Waggener et al 1990; Schectman et al 1991). We conclude that none of the triple risk hypotheses presented so far have significantly improved our understanding of the cause of SIDS. Bergman's and Raring's concepts of multifactorial causation with interaction of risk factors with variable probabilities is less restrictive and more in keeping with the large number of demonstrated risk factors and their varying prevalence. If prenatal hypoxic damage of the brainstem occurred, it seems likely that the infant so afflicted would be at risk for SIDS, but it is even more likely that their death would occur in the neonatal period, as we have demonstrated in infants who have known maternal risk factors that involve severe anemia. This is in contrast to the delay until the postneonatal period of most SIDS deaths. A categorical statement that the origin of SIDS is prenatal is unwarranted by the evidence. Brainstem abnormalities have not been shown to cause SIDS, but are more likely a nonspecific effect of hypoxia.     

The epidemiology of sudden infant death syndrome

Background: Twins compared to singletons are at increased risk of sudden infant death syndrome (SIDS). Aims: To compare the epidemiology of SIDS in twins and singletons and to test the hypothesis that monozygous (MZ) were at greater risk of SIDS than dizygous (DZ) twins. Methods: Data from the Office for National Statistics on all registered live births and infant deaths with registered cause of death "sudden unexpected death in infancy" in England and Wales from 1993 to 1998 were obtained, together with the registered birth weight and, for twins, whether they were of like or unlike sex. Results: The crude relative risk of SIDS in twins is twice that in singletons. There has been a significant temporal decline in SIDS mortality. There is also a significant increase in risk with decreasing birth weight for both twins and singletons. The birth weight specific risk of SIDS in all except for those ≥3000 g is greater in singletons than in twins. There is no significant difference in risk of SIDS in like compared with unlike sex twins. Conclusions: In spite of a lower risk of SIDS in twins compared with singletons for each birth weight group <3000 g, one component of the higher crude relative risk of SIDS in twins is attributable to the higher proportion of twins that are of low birth weight. A second component is the higher risk in twins compared with singletons for those of birth weight ≥3000 g. Like sex are at no greater risk than unlike sex twins, which suggests that zygosity is not a significant factor in SIDS.     

The epidemiology of sudden infant death syndrome.

BACKGROUND: Twins compared to singletons are at increased risk of sudden infant death syndrome (SIDS). AIMS: To compare the epidemiology of SIDS in twins and singletons and to test the hypothesis that monozygous (MZ) were at greater risk of SIDS than dizygous (DZ) twins. METHODS: Data from the Office for National Statistics on all registered live births and infant deaths with registered cause of death "sudden unexpected death in infancy" in England and Wales from 1993 to 1998 were obtained, together with the registered birth weight and, for twins, whether they were of like or unlike sex. RESULTS: The crude relative risk of SIDS in twins is twice that in singletons. There has been a significant temporal decline in SIDS mortality. There is also a significant increase in risk with decreasing birth weight for both twins and singletons. The birth weight specific risk of SIDS in all except for those > or =3000 g is greater in singletons than in twins. There is no significant difference in risk of SIDS in like compared with unlike sex twins. CONCLUSIONS: In spite of a lower risk of SIDS in twins compared with singletons for each birth weight group <3000 g, one component of the higher crude relative risk of SIDS in twins is attributable to the higher proportion of twins that are of low birth weight. A second component is the higher risk in twins compared with singletons for those of birth weight > or =3000 g. Like sex are at no greater risk than unlike sex twins, which suggests that zygosity is not a significant factor in SIDS.     

Sudden infant death syndrome

Over the last 20 years, the sudden infant death syndrome has become the leading cause of death in infants aged one month to one year in developed countries. The SIDS Referral Centers set up in France have been assigned the task of performing thorough clinical, metabolic, infectious and histologic studies. This post-mortem evaluation, whose results are difficult to interpret, is undertaken in an attempt to discriminate between the multiple causes of conditions present at the time of death. This classification task will improve the definition of a number of risk factors. Among these factors, prematurity, perinatal distress requiring resuscitation, and an unfavorable sociocultural environment are often mentioned. Other factors, including intrauterine growth retardation, dysmorphic disorders, impaired regulation of ventilation, heart rhythm anomalies, and inherited defects in fatty acid metabolism are still under study since they are all infrequent. Various combinations of these factors may result in increased vulnerability to stress during the first months of life, the period when SIDS is most common. This ongoing research is indispensable for providing advice and support of the family and developing appropriate individual preventive measures for newborn SIDS siblings.     

Sibling grief in reaction to sudden infant death syndrome

Much of the literature that exists regarding psychologic outcomes of sudden infant death syndrome (SIDS) has focused on parental grief or family response; at least two studies suggest that a SIDS death also affected siblings. It is believed that children who experience the death of a sibling due to SIDS do grieve. Factors related to bereavement are the child's age at the time of the sibling's death, special circumstances of the SIDS death, and explanations and grieving response of the parents. However, no information currently exists that characterizes the course of the grief response of these children. Studies have indicated that about 1 year is a normal grieving period for adults. This study was conducted to evaluate the time frame of children's grief response to the death of a sibling from SIDS. A questionnaire was designed that incorporated child grieving behaviors from several sources; 151 questionnaires were distributed to families in which a SIDS death had occurred in the past 16 years in Iowa and Illinois. Information was obtained from 43 families for 50 children who were older than 2 years of age at the time of the sibling's death. With respect to the length of children's grief response, 54% were reported to have grieved longer than 1 year and only 40% were reported to have grieved less than 6 months. Thus, it appears that the length of the grieving response for these children is similar to that described for adults.     

Changing infants' sleep position increases risk of sudden infant death syndrome. New Zealand Cot Death Study.

OBJECTIVE: To examine whether the prone sleeping position may increase the risk for sudden infant death syndrome (SIDS), particularly in infants unused to prone sleep. DESIGN: A 3-year (1987-1990) case-control study. SETTING: Nationwide study in New Zealand. SUBJECTS: Four hundred eighty-five infants who died of SIDS and 1800 controls. MAIN OUTCOME MEASURES: Infants were classified as unaccustomed to prone if their usual sleep position was nonprone and they were placed prone for the last sleep. Secondary prone was used to describe infants placed nonprone but found prone. RESULTS: Infants usually and last placed nonprone were at the lowest risk for SIDS (odds ratio [OR], 1.0); those usually and last placed prone were at increased risk (adjusted OR, 4.6; 95% confidence interval, 3.4-6.3). Risk was greatly increased among infants unaccustomed to the prone position (adjusted OR, 19.3; 95% confidence interval, 8.2-44.8). These infants accounted for 8% (31/ 386) of all SIDS deaths. Ninety percent (28/ 31) of infants in this group were found prone, and 71% (20/28) of those found prone were found with their faces turned down into bedding-a position in which asphyxia has been implicated as a mechanism of death. In addition, 138 infants who died of SIDS were last placed nonprone. Forty-seven infants (34%) in this group were found prone (secondary prone), and 60% (28/47) of those found prone were found with their faces turned down into the bedding. This group accounted for 12% of all SIDS deaths. Most of these infants (91% [43/47]) were usually placed nonprone. CONCLUSIONS: Infants placed supine to sleep were at the lowest risk of SIDS, which supports the recommendation that this is the preferred sleeping position for healthy infants. In New Zealand, 20% of SIDS deaths involved lack of experience with the prone sleeping position. Our findings suggest the possibility that an infant's competence in escaping from potentially lethal situations during prone sleep (eg, the face-down position) may be impaired by inexperience in prone sleeping. Great caution should be exercised in placing infants unaccustomed to the prone sleeping position in the prone position.     

Investigation of unexplained infant deaths in Jerusalem, Israel 1996-2003.

BACKGROUND: Sudden infant death syndrome (SIDS) is a diagnosis of exclusion that may be assigned only after investigations including a forensic autopsy are performed to exclude possible organic and environmental causes of death. Israeli society is influenced by the Jewish and Islamic faiths, which permit autopsy only under selected circumstances. Against this background, we carried out a study to determine what examinations are performed to investigate unexplained infant deaths in Jerusalem, Israel. METHODS: We examined hospital, Ministry of Health and Ministry of Interior records of unexplained infant deaths in the Jerusalem district from the years 1996-2003. RESULTS: Ninety six cases were identified from all sources. Forty nine (51%) infants were brought to a hospital at or near the time of death. Studies to determine the cause of death were performed in 54% of cases for which medical records were available for review. These studies included bacterial cultures (44%), skeletal surveys (12%), computerised tomography (3%) and metabolic studies (3%). Only one forensic autopsy was performed, and in no instance was the death site examined by medical personnel. There was a high rate of retrospective review by district health physicians. The most frequently assigned cause of death was SIDS. CONCLUSIONS: : The capacity of public health officials and forensic pathologists to investigate unexplained infant deaths is strongly affected by the legal, religious and political milieu in which they work. Efforts should be made to develop socially acceptable methods of improving the quality of infant death investigations in Jerusalem.     

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.     

Peut-on expliquer la mort inattendue du nourrisson ? Réflexions à partir d’une série de 80 cas autopsiés au CHU de Rennes entre 1994 et 2007

Sudden infant death syndrome (SIDS) is a huge hardship for parents, but also for health professionals. In 2007, 210 cases occurred in France, corresponding to a crude rate of 31.8 for 100,000 births. Between 1994 and 2007, 140 children of less than 2 years old were examined in the reference centre for SIDS in Rennes, France. We included in our study the children who were aged more than 28 days at death date, did not have a known lethal disease and were autopsied. A total of 80 children fulfilled those criteria. Post-mortem investigation included an autopsy, clinical and paraclinical exams (blood test, radiography, CT-scan…), and investigation of the circumstances of the death. Most of the cases were boys and were 2- to 5-month old. Ventral decubitus and gastrointestinal symptoms were often present. Autopsy gave elements about the causes of death in 23 cases and the other exams performed frequently showed an infectious viral context. Thanks to prevention and information campaigns about childcare done in the 1990s, SIDS incidence has largely decreased in France, but it is still too frequent. In our opinion, advices need to be given again and again, especially concerning safe sleep practices, in order to increase adherence to these recommendations. Moreover, research should be continued to better understand this unexplained syndrome.     

Sudden unexpected death in infants of narcotic-dependent mothers

During the study years 1972--1974, 8 of 383 infants born to mothers with known narcotic dependency during pregnancy died unexpectedly within the first 4 mth of life; autopsies were compatible with the diagnosis of SIDS. This incidence of SIDS was 5.5 times that in our hospital populations (P < 0.001) and 8.7 times that of our borough within New York City (P < 0.001). Similar factors, such as sex ratio, age at time of death, and diurnal and seasonal variations suggest that narcotic-associated sudden death may be a relevant study model for sudden unexpected death in the general population. Intrauterine exposure to narcotics and its subsequent effect on central control of respiration in the young infant may be the underlying mechanism of drug related SIDS.