High postmortem concentrations of hypoxanthine and urate in the vitreous humor of infants are not confined to cases of sudden infant death syndrome

OBJECTIVE: High concentrations of hypoxanthine and urate have been found in the blood of rats who died suddenly during induced respiratory alkalosis as well as in cases of sudden death in malignant hyperthermia-susceptible pigs challenged with halothane. The origin of these metabolites is the excessive hydrolysis of adenine nucleotides, which is associated with the production of free radicals. We wished to establish whether high levels of these compounds were also to be found in sudden infant death syndrome (SIDS) victims, compared with other causes of death. DESIGN: Vitreous humor samples were analysed for hypoxanthine and urate by high-performance liquid chromatography. SETTING: Forensic Laboratories, Salt River, Cape Town. PARTICIPANTS: Vitreous humor samples were collected from 91 infants presented for postmortem examination. MAIN OUTCOME AND RESULTS: From autopsy reports, cause of death was classified as: (i) SIDS (N = 50); (ii) acute sudden death (N = 5); and (iii) all other causes of death (N = 36). There were no differences in the hypoxanthine or urate levels of groups (i) and (iii) over the first 5 days of the postmortem period. Group (ii) levels were lower than those of both (i) and (iii). CONCLUSION: Adenine nucleotide hydrolysis is not only a feature of SIDS, and possibly results from antemortem hypoxia in most deaths. The lower concentrations found in cases of acute sudden death probably resulted only from postmortem hydrolysis of the nucleotides.     

Implantable hearing devices for sensorineural hearing loss: a review of the audiometric data

BACKGROUND: Child fatality review (CFR) by interagency teams can contribute to the prevention of childhood deaths. We investigated the potential usefulness of Georgia's CFR, legislated in 1990 primarily to prevent death from child maltreatment, for identifying preventable deaths from injury and sudden infant death syndrome (SIDS). METHODS: Using CFR report data and death certificate data, we examined reviewed and nonreviewed childhood deaths in Georgia in 1991 and examined data by etiology, county, risk factors, and preventability. RESULTS: Injury or SIDS caused 33.2% of childhood deaths in Georgia in 1991; CFR reviewed 29.4% of these. Child fatality review was most sensitive for investigating death from intentional injury (40.5%) and SIDS (35.3%). Review teams reassigned the cause of five deaths (2.0%) to child abuse or neglect. County participation was low (31.4%). Overall, 29.0% of deaths were judged preventable. CONCLUSIONS: Georgia's CFR has potential for identifying preventable childhood deaths. Refinements in the system can increase the number and accuracy of death investigations. By participating in the system, physicians may make meaningful contributions to preventing childhood death in their own communities.     

Genetic counseling in a case of Takayasu arteritis

Two cases affected with Takayashu arteritis are presented. The adult probanda born in 1960 after genetic counselling and appropriate prenatal care had a healthy liveborn boy. Her previous six pregnancies were terminated on the basis of forced medical reason. The infant probanda died at the age of 4 months with the features of sudden infant death syndrome (SIDS). Pathohistological examination detected her Takayashu arteritis. It seems to be the youngest published case in the international literature and Takayashu arteritis may be the rare cause of SIDS.     

Fetal hemoglobin levels in sudden infant death syndrome

OBJECTIVE: The aim of this study was to determine and compare fetal hemoglobin levels from infants dying of the sudden infant death syndrome (SIDS) with aged-matched control infants dying of other causes. Similar previous studies have reported both elevated and normal levels of fetal hemoglobin in whole blood samples from infants dying of SIDS. DESIGN: Triton-acid-urea gel electrophoresis and densitometry were used to determine fetal hemoglobin levels in postmortem whole blood samples from infants dying of SIDS and from appropriately age-matched control infants. Whole blood samples were analyzed blindly and matched for postgestational age. Infant ages at death ranged from birth to less than 1 year. MAIN OUTCOME MEASURES: Fetal hemoglobin in whole blood from infants dying of SIDS and control infants. RESULTS: During the period of postnatal development most associated with SIDS cases (2 to 6 months after birth), fetal hemoglobin levels were found to be significantly elevated in postmortem whole blood samples from SIDS infants compared with gestational age-matched control infants dying of causes other than SIDS. CONCLUSION: We conclude that levels of fetal hemoglobin are elevated in postmortem whole blood of SIDS infants compared with controls. Furthermore, the apparent conflict in the literature regarding fetal hemoglobin levels in SIDS infants and controls is most likely due to variability in the control data of some studies.     

Effect of maternal cigarette smoking on pregnancy complications and sudden infant death syndrome

BACKGROUND: The purpose of this study was to estimate the annual morbidity and mortality among fetuses and infants that can be attributed to the use of tobacco products by pregnant women. METHODS: Published research reports identified by literature review were combined in a series of meta-analyses to compute pooled risk ratios, which, in turn, were used to determine the population attributable risk. RESULTS: Each year, use of tobacco products is responsible for an estimated 19,000 to 141,000 tobacco-induced abortions, 32,000 to 61,000 infants born with low birthweight, and 14,000 to 26,000 infants who require admission to neonatal intensive care units. Tobacco use is also annually responsible for an estimated 1900 to 4800 infant deaths resulting from perinatal disorders, and 1200 to 2200 deaths from sudden infant death syndrome (SIDS). CONCLUSIONS: Tobacco use is an important preventable cause of abortions, low birthweight, and deaths from perinatal disorders and SIDS. All pregnant women should be advised that smoking places their unborn children in danger. The low success rate of smoking cessation among pregnant women suggests that efforts to reduce the complications of pregnancy attributable to tobacco use by pregnant women should focus on preventing nicotine addiction among teenaged girls.     

Neurons as well as astrocytes express proteoglycan-type protein tyrosine phosphatase zeta/RPTPbeta: analysis of mice in which the PTPzeta/RPTPbeta gene was replaced with the LacZ gene

Mannan binding lectin (MBL) may be important for innate immunity and some cases of sudden infant death syndrome (SIDS) may be preceded by bacterial infection. Therefore, relative MBL deficiency might be associated with susceptibility to SIDS. We measured MBL concentrations in 46 SIDS infants and 26 controls. The proportion of subjects with low MBL values was similar in the two groups. However, the mean for the SIDS group (3 micrograms/ml) was higher than that of the controls (2.2 micrograms/ml; P < 0.05). We interpret this difference as due to acute phase responses and suggest these findings are consistent with the view that some cot deaths are preceded by bacterial infections.     

Ethnic differences in the sudden infant death syndrome: what we can learn from immigrants to the UK

AIMS: To compare the effect of potential maternal and birth factors on rates of sudden infant death syndrome (SIDS) within and between infants born to mothers of different ethnic groups. METHODS: Routinely collected obstetric, child health data relating to 39,101 residents of three East London Districts born in 1989-1990 were obtained. These were matched with 312 death registration records to validate death and add registered cause of death. Mortality rates were calculated in the usual way, and using life-table methods. RESULTS: These related to six ethnic groups, the largest of which were Anglo-European and Bangladeshi. Low birth-weight was the only factor associated with a greater risk of SIDS in all ethnic groups. Maternal smoking was uncommon amongst all Asian groups and African mothers, and rates of SIDS were uniformly low amongst non-smokers in all ethnic groups except Pakistanis. Adjustment for maternal age, parity, gestational age and birthweight would widen the differences between risk of SIDS observed between Anglo-Europeans and Bangladeshi infants. CONCLUSIONS: The study has demonstrated that local data is more timely and of greater detail than that available nationally. Of the risk factors considered, smoking reported during pregnancy is the most commonly encountered and is particularly associated with deaths attributed to SIDS.     

Hypoxanthine in vitreous humor and cerebrospinal fluid--a marker of postmortem interval and prolonged (vital) hypoxia? Remarks also on hypoxanthine in SIDS

Hypoxanthine (Hx) is a degradation product of adenosine. Increased concentrations were reported in cases of hypoxia as well as with prolonged postmortem interval (PMI). Hx is recommended as an indicator of prolonged (cerebral) hypoxia, for example in vitamins of sudden infant death as well as a new biochemical method for estimation of postmortem time. The correlation of vitreous Hx values with the time since death was reported to be even higher than the vitreous potassium (K+) values. The authors' investigations on 92 bodies with known time since death gave a completely opposite result: a much higher correlation between vitreous K+ and time since death than vitreous Hx. The possible discrepancies between these different results will be discussed (disturbing of intra-ocular fluid dynamics by repeated sample-taking in the study of Rognum et al. The results published so far on vitreous Hx values in sudden infant death syndrome (SIDS) cases as an indicator for a prolonged cerebral hypoxia are also not convincing. When vitreous concentrations of newborn infants or infants of age < 6 months are compared to those of older infants or adults the vitreous diameter must be taken into consideration (diffusion gradient; Fick's law of diffusion). The discrepant results on vitreous Hx as a measure of vital hypoxia and PMI will be discussed. The authors' results on Hx determinations on cerebrospinal fluid in comparison to cerebrospinal spinal (CSF) potassium will also be briefly addressed.     

Activation of p70 S6 protein kinase is necessary for angiotensin II-induced hypertrophy in neonatal rat cardiac myocytes

Infants with mandibular hypoplasia are at risk of sudden death from cardiorespiratory arrest secondary to upper airway obstruction. To evaluate diagnostic difficulties that may occur at autopsy in such infants, the autopsy files at the Adelaide Children's Hospital (ACH) for 36 years, 1959 to 1994, were reviewed. Eight cases were identified (age range, 2 days to 10 months; mean age, 2.2 months; male/female ratio, 5:3). In all cases, death was considered most likely due to airway obstruction related to mandibular hypoplasia or its treatment. Although death occurred in the hospital in five cases, one infant suddenly collapsed at home while feeding and died, and two infants were unexpectedly found dead in their cribs at home. Three infants had defined genetic syndromes. Although all the infants had histories of antemortem airway obstruction, one infant had normal oxygen saturation studies before hospital discharge, and one infant had a tracheostomy. Acute bronchopneumonia was an exacerbating factor in one case. Assessment of mandibular size is important in any infant who dies unexpectedly; and if hypoplasia is found, careful review of the clinical details for evidence of airway obstruction is necessary to help distinguish these cases from sudden infant death syndrome (SIDS). Sudden death may, however, occur in infants with mandibular hypoplasia in spite of apparent clinical stability before death with no significant recent episodes of oxygen desaturation.     

A record-linkage study on risk factors for cause-specific infant mortality

Infant death certificates were linked with birth certificates for infants born to residents of Tohoku, Tokai and Kyushu regions in 1989 (n = 409, 679, or about one-third of all births in Japan), to examine the effects of variables, as reported on birth certificates, on cause-specific infant mortality. "Certain conditions originating in the perinatal period" and "congenital anomalies" accounted for nearly 90 percent of neonatal deaths, while "congenital anomalies", "injuries and poisoning" and "sudden infant death" were responsible for about 65 percent of postneonatal deaths. Mortality rates for almost all causes of infant deaths, except injuries and poisonings, increased as birth weight decreased not only in the neonatal period but also in the postneonatal period. This suggests that low birth weight places some infants at higher risk of death, and conditions that lead to low birth weight independently contribute to the risk of infant death. Cox's proportional hazards linear model was used to assess the effects of variables on infant mortalities by causes of death. An extremely strong birth weight effect was noted for "certain conditions originating in the perinatal period" and "congenital anomalies". Being a male infant and late order of birth in multiparity were other risk factors for deaths from "congenital anomalies", while being a male infant, resident of Tohoku region and maternal stillbirth experience related to deaths from "certain conditions originating in the perinatal period". Elevated risks of sudden infant death syndrome (SIDS), of which mortality rate in Japan was considerably lower than those in most developed Western countries, i.e. 0.23 per 1,000 live births in 1989, were associated with low birth weight, being a male infant, low maternal age, late order of birth in multiparity and illegitimacy. Low maternal age, late order of birth in multiparity and illegitimacy, also, related significantly to increased risk of infant deaths for "injuries and poisoning". These results suggest the independent contributions of socioeconomic factors to infant mortality, especially postneonatal mortality, from SIDS, "injuries and poisonings".     

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.     

Retrospective biochemical screening of fatty acid oxidation disorders in postmortem livers of 418 cases of sudden death in the first year of life

OBJECTIVE: Fatty acid oxidation (FAO) disorders are frequently reported as the cause of sudden and unexpected death, but their postmortem recognition remains difficult. We have devised a biochemical protocol in which informative findings in liver tissue are microvesicular steatosis, elevated concentrations of C8-C16 fatty acids, glucose depletion, and low carnitine concentration. STUDY DESIGN: We analyzed 27 cases representing five FAO disorders and compared the results with those obtained in a retrospective blinded analysis of 418 cases of sudden infant death (313 SIDS, 45 infections, and 34 accidents and abuse). RESULTS: All cases of accidents and abuse correctly tested negative. Among the others, 25 (6%) showed at least two abnormal findings. Of these, 14 closely matched the biochemical profiles seen in specific FAO disorders. These included 2 cases with medium-chain acyl-CoA dehydrogenase deficiency, 4 cases consistent with glutaric acidemia type 2, 4 cases with either very long-chain acylcoenzyme A dehydrogenase deficiency or long-chain 3-hydroxy-acyl-coenzyme A dehydrogenase deficiency, and 4 cases predicted to be affected with carnitine uptake defect. CONCLUSION: The results of this study support the view that approximately 5% of all cases of sudden infant death are likely caused by an FAO disorder.     

Housing and sudden infant death syndrome. The New Zealand Cot Death Study Group

AIMS: This paper examined factors relating to the infants' place of domicile to see whether they increased the risk of sudden infant death syndrome (SIDS) beyond social and environmental effects previously published. METHODS: A case control study was undertaken in New Zealand between the years 1987-90. From all sudden infant death syndrome diagnoses over this time, parents of 393 (81%) sudden infant death syndrome infants consented to participate and these derive the cases. Controls were ascertained by randomly sampling 1800 infants from all babies born over 78% of the country. Parents of 1592 (88%) control infants consented to participate in the study. RESULTS: The relative risk of sudden infant death for infants usually residing in houses rented from the government (State houses) was 1.73 (95% CI: 1.13, 2.66) times that of infants with parents owning their house, after adjusting for likely social, economic and environmental confounding factors. However, the type of housing, construction of housing, heating and age of housing was not associated with sudden infant death syndrome. Although house size, measured in terms of bedroom numbers, was similar for sudden infant death syndrome and control infants (chi 2 = 0.40, df = 2, p = 0.82), the number of people normally residing within these houses was different. Sudden infant death syndrome infants' houses were less likely to have two adults and more likely to have more children normally resident. Density calculations (derived by calculating the children and/or adult numbers divided by bedroom numbers) revealed a non significant increase in relative risk, suggesting that housing overcrowding was not associated with sudden infant death syndrome in New Zealand. CONCLUSIONS: Infants domiciled in State houses are more likely to experience sudden infant death syndrome. However, this increased relative risk for sudden infant death syndrome appears to have little to do with the house per se and, perhaps, more to do with socioeconomic characteristics.     

Tritiated-naloxone binding to brainstem opioid receptors in the sudden infant death syndrome

The sudden infant death syndrome (SIDS) is defined as the sudden death of an infant under 1 year of age that remains unexplained after a thorough case investigation, including a complete autopsy. We hypothesized that SIDS is associated with altered 3H - naloxone binding to opioid receptors in brainstem nuclei related to respiratory and autonomic control. We analyzed 3H - naloxone binding in 21 regions in SIDS and control brainstems using quantitative tissue receptor autoradiography. Three groups were analyzed: SIDS (n = 45); acute controls (n = 14); and a chronic group with oxygenation disorders (n = 15). Opioid binding was heavily concentrated in the caudal nucleus of the solitary tract, nucleus parabrachialis medialis, spinal trigeminal nucleus, inferior olive, and interpeduncular nucleus in all cases analyzed (n = 74). The arcuate nucleus on the ventral medullary surface contained negligible binding in all cases (n = 74), and therefore binding was not measurable at this site. We found no significant differences among the three groups in the age-adjusted mean 3H - naloxone binding in 21 brainstem sites analyzed. The only differences we have found to date between SIDS and acute controls are decreases in 3H - quinuclidinyl benzilate binding to muscarinic cholinergic receptors and in 3H - kainate binding to kainate receptors in the arcuate nucleus in alternate sections of this same data set. The present study suggests that there is not a defect in opioid receptor binding in cardiorespiratory nuclei in SIDS brainstems.     

SIDS cases have increased levels of interleukin-6 in cerebrospinal fluid

Cerebrospinal fluid (CSF) from 20 infants who died of sudden infant death syndrome (SIDS), 7 cases of infectious death and 5 cases of violent death were examined with respect to concentrations of interleukin-6 (IL-6). The measurements were performed by ELISA. IL-6 levels in SIDS were significantly lower than in infectious death (p < 0.02), but significantly higher than in violent death (p < 0.02). Since IL-6 plays an important role in immune responses and may induce fever, the findings may suggest that immune activation plays a role in SIDS. The presence of cytokines in the central nervous system (CNS) may cause respiratory depression, especially in vulnerable infants.     

Sudden infant death syndrome: risk factor profiles for distinct subgroups

The authors investigated risk profiles of sudden infant death syndrome (SIDS) as a function of age at death. A case-control study carried out in the Tyrol region of Austria enrolled 99 infants who died of SIDS between 1984 and 1994 and 136 randomly selected controls. Early and late SIDS (< 120 days of age vs. > or = 120 days) were defined according to the clear-cut bimodal age-at-death distribution. Inadequate antenatal care, low parental social and educational level, and the prone sleeping position were risk conditions that applied to both early and late SIDS. A marked seasonal variation (winter preponderance) was the most outstanding feature of late SIDS. A gestational age of < 37 weeks (odds ratio (OR) = 8.4, 95% confidence interval (CI) 2.6-26.0), repeated episodes of apnea (OR = 5.7, 95% CI 1.2-27.0), low birth weight (< 2,500 g) (OR = 3.4, 95% CI 1.1-11.0), a family history of sudden infant death (OR = 2.9, 95% CI 1.1-7.5), and maternal smoking during pregnancy (OR = 2.2, 95% CI 1.0-4.5) were associated with early SIDS. This study identified two distinct subgroups of SIDS infants characterized by different risk conditions and ages at death. These results underline a multiple-cause hypothesis for SIDS etiology which involves a genetic predisposition, immaturity in the first months of life, and environmental factors acting at various ages.     

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 16055-16500 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.     

Pathological fear of cot death

Cot death (sudden infant death syndrome) is one of the most common causes of death in the first year of life. Four cases with a pathological fear of cot death are presented. All the patients were depressed and in 2 cases the fear of cot death had an obsessional quality. In all cases there were complications during pregnancy (miscarriage, threatened abortion, recurrent vomiting in last trimester). In 1 case, the patient knew 3 mothers who had suffered cot deaths; in another, the infant was gravely ill in the neonatal period. Pathological fear of cot death can be recognised by the presence of two central features - overvigilance and excessive nocturnal checking of the baby's breathing. Therapeutic interventions are discussed.     

Relationship of passive cigarette-smoking to sudden infant death syndrome

The smoking habits of 56 families who lost babies to the sudden infant death syndrome (SIDS) were compared to those of 86 control families. A higher proportion of SIDS mothers smoked both during pregnancy (61% vs. 42%) and after their babies were born (59% vs. 37%). SIDS mother also smoked a significantly greater number of cigarettes than controls. Exposure to cigarette smoke ("passive smoking") appears to enhance the risk of SIDS for reasons not known.     

Sudden infant death syndrome. A prospective study

One hundred twenty-five sudden infant death syndrome (SIDS) victims followed up since birth from a large prospective study were compared with matched controls. Some of the future SIDS victims showed evidences of neonatal brain dysfunction including abnormalities in respiration, feeding, temperature regulation, and specific neurologic tests. These abnormalities could not be ralated to events in labor or delivery. A greater proportion of the future victims were mildly underweight for gestational age. The gestations that produced the SIDS victims were characterized by a greater frequency of mothers who smoked cigarettes and had anemia. The demographic profile of SIDS families proved to be indentical to the profile for families with excessive perinatal mortality. Many of the SIDS victims showed a retardation in postnatal growth prior to death.