Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pediatric cardiomyopathy and sudden death.
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BACKGROUND: Genetic defects are being increasingly recognized in the etiology of primary cardiomyopathy (CM). Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the first step in the beta-oxidation spiral of fatty acid metabolism, the crucial pathway for cardiac energy production. METHODS AND RESULTS: We studied 37 patients with CM, nonketotic hypoglycemia and hepatic dysfunction, skeletal myopathy, or sudden death in infancy with hepatic steatosis, features suggestive of fatty acid oxidation disorders. Single-stranded conformational variance was used to screen genomic DNA. DNA sequencing and mutational analysis revealed 21 different mutations on the VLCAD gene in 18 patients. Of the mutations, 80% were associated with CM. Severe CM in infancy was recognized in most patients (67%) at presentation. Hepatic dysfunction was common (33%). RNA blot analysis and VLCAD enzyme assays showed a severe reduction in VLCAD mRNA in patients with frame-shift or splice-site mutations and absent or severe reduction in enzyme activity in all. CONCLUSIONS: Infantile CM is the most common clinical phenotype of VLCAD deficiency. Mutations in the human VLCAD gene are heterogeneous. Although mortality at presentation is high, both the metabolic disorder and cardiomyopathy are reversible. (+info)
Health effects of passive smoking-10: Summary of effects of parental smoking on the respiratory health of children and implications for research.
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BACKGROUND: Two recent reviews have assessed the effect of parental smoking on respiratory disease in children. METHODS: The results of the systematic quantitative review published as a series in Thorax are summarised and brought up to date by considering papers appearing on Embase or Medline up to June 1998. The findings are compared with those of the review published recently by the Californian Environmental Protection Agency (EPA). Areas requiring further research are identified. RESULTS: Overall there is a very consistent picture with odds ratios for respiratory illnesses and symptoms and middle ear disease of between 1.2 and 1.6 for either parent smoking, the odds usually being higher in pre-school than in school aged children. For sudden infant death syndrome the odds ratio for maternal smoking is about 2. Significant effects from paternal smoking suggest a role for postnatal exposure to environmental tobacco smoke. Recent publications do not lead us to alter the conclusions of our earlier reviews. While essentially narrative rather than systematic and quantitative, the findings of the Californian EPA review are broadly similar. In addition they have reviewed studies of the effects of environmental tobacco smoke on children with cystic fibrosis and conclude from the limited evidence that there is a strong case for a relationship between parental smoking and admissions to hospital. They also review data from adults of the effects of acute exposure to environmental tobacco smoke under laboratory conditions which suggest acute effects on spirometric parameters rather than on bronchial hyperresponsiveness. It seems likely that such effects are also present in children. CONCLUSIONS: Substantial benefits to children would arise if parents stopped smoking after birth, even if the mother smoked during pregnancy. Policies need to be developed which reduce smoking amongst parents and protect infants and young children from exposure to environmental tobacco smoke. The weight of evidence is such that new prevalence studies are no longer justified. What are needed are studies which allow comparison of the effects of critical periods of exposure to cigarette smoke, particularly in utero, early infancy, and later childhood. Where longitudinal studies are carried out they should be analysed to look at the way in which changes in exposure are related to changes in outcome. Better still would be studies demonstrating reversibility of adverse effects, especially in asthmatic subjects or children with cystic fibrosis. (+info)
The modified anaphylaxis hypothesis for cot death. Anaphylactic sensitization in guinea-pigs fed cow's milk.
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Guinea-pigs on a normal diet, but given cow's milk to drink instead of water, very soon became anaphylactically sensitive to cow's milk and may be fatally shocked following either i.v. injection or intratracheal inhalation of cow's milk. (+info)
Tobacco smoke exposure at one month of age and subsequent risk of SIDS--a prospective study.
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The aim of this investigation was to identify the sources of postnatal exposure to tobacco smoke at 1 month of age and to examine their relation to sudden infant death syndrome (SIDS). The Tasmanian Infant Health Survey was a prospective cohort study undertaken from 1988 to 1995. It involved 9,826 infants (89% of eligible infants) at higher risk of SIDS. Subsequently 53 eligible infants died of SIDS. Hospital interviews were available on 51 and home interviews on 35 SIDS infants. Urinary cotinine assays were conducted using gas-liquid chromatography (n = 100). Within a predictive model that explained 63% of urinary cotinine variance, the strongest predictor of cotinine and also of SIDS was maternal smoking, though the effects of prenatal and postnatal smoking could not be separated. However, for particular smoking-related behaviors, there was a discordance between prediction of cotinine concentration and prediction of risk of SIDS. If smoking mothers did not smoke in the room with the baby, the cotinine level in the infant's urine was reduced by a little more than a half (p = 0.009), but this was not associated with a reduction in SIDS risk (odds ratio = 1.09, 95% confidence interval 0.47-2.55). Similarly, the presence of other adult resident smokers was associated with a 63% increase in urinary cotinine (p = 0.047) but not with increased SIDS risk (odds ratio = 0.69, 95% confidence interval 0.34-1.40). However, the study lacked the power to detect modest effects, that is, those altering risk less than twofold. (+info)
Maternal placental abnormality and the risk of sudden infant death syndrome.
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To determine whether placental abnormality (placental abruption or placental previa) during pregnancy predisposes an infant to a high risk of sudden infant death syndrome (SIDS), the authors conducted a population-based case-control study using 1989-1991 California linked birth and death certificate data. They identified 2,107 SIDS cases, 96% of whom were diagnosed through autopsy. Ten controls were randomly selected for each case from the same linked birth-death certificate data, matched to the case on year of birth. About 1.4% of mothers of cases and 0.7% of mothers of controls had either placental abruption or placenta previa during the index pregnancy. After adjustment for potential confounders, placental abnormality during pregnancy was associated with a twofold increase in the risk of SIDS in offspring (odds ratio = 2.1, 95% confidence interval 1.3-3.1). The individual effects of placental abruption and placenta previa on the risk of SIDS did not differ significantly. An impaired fetal development due to placental abnormality may predispose an infant to a high risk of SIDS. (+info)
Case-control study of current validity of previously described risk factors for SIDS in The Netherlands.
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This study aimed to assess whether previously established risk factors for sudden infant death syndrome (SIDS) are still valid now that the incidence in the Netherlands has dropped to 0.26 per 1000 liveborn infants. A distinction was made between immutable and mutable risk factors. This case-control study (part of the European Concerted Action on SIDS) comprised 73 SIDS cases and 146 controls and lasted from March 1995 to September 1996. Adjustments were made for sleeping position and bedding factors by treating them as covariables. Apart from these factors, well known risk factors that remain of importance in the Netherlands are: male sex, young maternal age, twins, and low socioeconomic status. These factors are largely immutable. Other well known risk factors which might reflect attitudes to child care and could possibly be mutable are: smoking, alcohol consumption by the mother, bottle feeding, and change of babycare routine. Intervention strategies should focus on early signalling, thereby assisting parents in changing these unfavourable parenting attitudes. Information on optimal child care and extra support by public health nurses specifically aimed at families at risk could help to decrease further the incidence of SIDS in the Netherlands. (+info)
Decrease in infant mortality and sudden infant death syndrome among Northwest American Indians and Alaskan Natives--Pacific Northwest, 1985-1996.
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Although the infant mortality rate (IMR) has steadily declined in the United States since the early 1900s, the rate varies among racial/ethnic populations. A goal of the national health objectives for 2010 is to eliminate racial/ethnic health disparities (U.S. Department of Health and Human Services, unpublished data, 1999). Historically, IMRs among American Indians and Alaskan Natives (AI/AN) have been high. In addition, IMRs have varied among AI/AN populations. To determine recent trends in infant mortality among Northwest AI/AN, the Northwest Portland Area Indian Health Board (NPAIHB) analyzed annual IMRs among AI/AN in Idaho, Oregon, and Washington. In addition, because sudden infant death syndrome (SIDS) is the major contributor to excess infant mortality in Northwest AI/AN, NPAIHB analyzed SIDS rates to determine whether the decline in SIDS rates in the United States also was occurring among Northwest AI/AN. This report summarizes the results of this analysis and documents dramatic decreases in both SIDS and non-SIDS infant mortality. (+info)
Living at high altitude and risk of sudden infant death syndrome.
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OBJECTIVE: To investigate the association between altitude of residence and risk of sudden infant death syndrome (SIDS). METHODS: A retrospective, case control study in the Tyrol, Austria enrolled 99 infants with SIDS occurring between 1984 and 1994, and 136 randomly selected control cases. Data on pregnancy, delivery, child care practice, and socio-demographic characteristics including altitude of residence were collected with a standardised questionnaire. RESULTS: The risk of SIDS increased gradually with increasing altitude of residence. This relation remained independently significant when the analysis was adjusted for gestational age, birth weight, prenatal care, mother's age at delivery, educational level of parents, and cigarette smoking during pregnancy. The prone sleeping position emerged as an obligatory cofactor in this association. In the whole of Austria, a similar trend of association emerged between the average altitudes in the 99 political counties and the rates of SIDS. CONCLUSIONS: This study identified altitude of residence as a significant risk predictor of SIDS, primarily in combination with the prone sleeping position. Respiratory disturbances, reduced oxygen saturation, and lower temperatures at high altitude might explain this association. (+info)