Myocarditis and sudden infant death syndrome

This is a retrospective survey of findings of myocarditis in 437 infants under the age of 1 year who died suddenly and unexpectedly between 1982 and 1999, and were investigated at the Department of Forensic Medicine in Stockholm, Sweden. Myocarditis was diagnosed in 69/410 infants who died naturally (16.8%) and in 2/27 violent deaths (7.4%). In 43/410 natural deaths (10.5%) the myocarditis was an isolated finding and the only explanation for cause of death and in 26 (6.3%) there were additional possible causes of death. The myocarditis was acute in 45/69 and chronic in 24/69 natural deaths, and was found to occur as early as at a few weeks of age. No specific risk factors were found when reviewing critical time of year, age, gender, previous symptoms, sleeping position, aspiration of gastric contents and environmental factors in infant deaths with finding of myocarditis compared to 313 deaths due to sudden infant death syndrome. Myocarditis was found in 13 of 37 deaths where cultures for cytomegalovirus were positive. More than 50% of the foci of the isolated myocarditis were located in the upper part of the interventricular septum and the adjacent part of the right atrium, areas including parts of the conduction system. This localisation is significant for the cause of death when comparing deaths with myocarditis as an isolated finding to deaths with other possible causes.     

Intrauterine hypoxia and sudden infant death syndrome

Sudden infant death syndrome (SIDS) or crib or cot death are synonyms for the sudden, unexpected and unexplained death of an infant. The incidence of SIDS has been estimated to be from 1-2% to 3%. Protracted intrauterine hypoxia or recurrent hypoxic insults during fetal life undoubtedly influence the development of the central nervous structures as a tissue most susceptible to hypoxia, although well developed mechanisms of defense against hypoxia exist during the fetal life. The mechanisms underlying SIDS include neurologically compromised infants who are deprived of compensatory mechanisms during sleep, sustaining a hypoxic insult with alterations in neurotransmitter receptors within the regions involved in chemoreception and cardiovascular control. Changes in the brain result from perinatal prolonged hypoxia (persistent reticular pathways in the pons and medulla, astroglia in the brainstem, gliosis of brain nerve nuclei, defects in neurotransmitter receptors, neuronal apoptosis, microthrombosis, and hypoxic ischemic lesion). Hypoxic perinatal risk factors for SIDS included passive and active exposure to cigarette smoking in pregnancy, abuse of drugs, alcohol, coffee and medication in pregnancy, intrauterine growth retardation, perinatal hypoxia with or without resuscitation, preeclampsia, anemia in pregnancy, prematurity, multiparity, multiple pregnancy, pregnant women aged < 20 years and > 35 years, cardiocirculatory, pulmonary and endocrine diseases in pregnancy, and short time interval between two pregnancies. As cigarette smoking has been demonstrated to lead to fetoplacental insufficiency, which result in fetal hypoxia, it is concluded that hypoxia is a precondition for the occurrence of SIDS. Prenatal exposure to cigarette smoke decreases maternal red blood cell count, and concentrations of tyrosine and selenium, reduces fetal and neonatal cerebral blood flow, and increases maternal MCV, leukocytosis, especially neutrophils, monocytes and lymphocytes, maternal and fetal heart rate, systolic and diastolic blood pressure, resistance index in umbilical artery, fetal hemoglobin, cytokine, serotonine, dopamine, catecholamine, hypoxanthine, endorphin and interleukin-6. Pregnancy at a risk of hypoxia, especially in heavy smokers, is a major risk factor for SIDS, and such pregnancy requires close and intensive antenatal monitoring.     

Staphylococcal toxins and sudden infant death syndrome.

AIMS: To investigate the hypothesis that commonly occurring bacterial toxins cause sudden infant death syndrome (SIDS) by (1), determining in which tissues bacterial toxins are concentrated after intravenous injection in rats; and (2), seeing if the same tissues contain detectable toxins in cases of SIDS. METHODS: The tissue distribution of intravenously injected staphylococcal enterotoxin A (SEA), enterotoxin B (SEB), enterotoxin C (SEC), enterotoxin D (SED), toxic shock syndrome toxin (TSST-1), and alpha-haemolysin was studied in rats using immunohistology and polyacrylamide gel electrophoresis with immunoblotting. Immunostaining was also carried out on formalin fixed kidneys from cases of SIDS and a comparison series of necropsy cases using anti-SEA, anti-SEB, anti-SEC2 and anti-SED. RESULTS: Immunohistology showed that SEB, SEC, SED and TSST-1 were all concentrated in the proximal convoluted tubular cells of the kidney. The presence of these toxins was confirmed in kidney homogenates using electrophoresis and immunoblotting. There was positive granular staining in the proximal convoluted tubular cells of the kidney in 36% of SIDS cases and 12% of the comparison series with anti SEC2 (chi 2 = 6; p < 0.025). CONCLUSION: SEC, or a bacterial toxin with epitopes in common, could have a pathogenic role in SIDS.     

Budd-Chiari syndrome presenting as sudden infant death

Budd-Chiari syndrome rarely occurs in infants. We report a case of a 1-month-old female infant who presented as a sudden infant death and was found at autopsy to have thrombi occluding both hepatic veins. Microscopically the liver showed perivenular fibrosis extending into the lobule and central venous congestion consistent with Budd-Chiari syndrome.     

Allergy and the risk of sudden infant death syndrome

Background and Objective There are several sources that suggest that there is a link between allergy and sudden infant death syndrome. We endevavoured to look for evidence of an association between allergic disease and the risk of sudden infant death syndrome (SIDS). Methods A nationwide case-control study covering a region with 78% of all births in New Zealand during 1987–90. Interviews were completed with the parents of 393 (81.0% of total) infants who died from the sudden infant death syndrome (SIDS), and 1592 (88.4% of total) control families who were a representative sample of all hospital births in the study region. Results Eczema was reported in 13.9% control infants compared with only 8.0% of the SIDS infants, univariate odds ratio for this in terms of risk for SIDS was 0.56 (95% confidence interval 0.37, 0.84) for infants with eczema compared with those without. This lesser risk for SIDS was unchanged when adjusted for potential confounding factors. The risk of SIDS was not associated with reported cow's milk reactions or a family history of allergic symptoms once adjustments were made for possible confounding factors. Conclusion Infants with skin disorders identified by their parents as eczema had a low risk for SIDS. Families can be reassured that atopy is not a risk factor for SIDS.     

Noncardiac genetic predisposition in sudden infant death syndrome

PurposeSudden infant death syndrome (SIDS) is the commonest cause of sudden death of an infant; however, the genetic basis remains poorly understood. We aimed to identify noncardiac genes underpinning SIDS and determine their prevalence compared with ethnically matched controls.MethodsUsing exome sequencing we assessed the yield of ultrarare nonsynonymous variants (minor allele frequency [MAF] ≤0.00005, dominant model; MAF ≤0.01, recessive model) in 278 European SIDS cases (62% male; average age =2.7 ± 2 months) versus 973 European controls across 61 noncardiac SIDS-susceptibility genes. The variants were classified according to American College of Medical Genetics and Genomics criteria. Case-control, gene-collapsing analysis was performed in eight candidate biological pathways previously implicated in SIDS pathogenesis.ResultsOverall 43/278 SIDS cases harbored an ultrarare single-nucleotide variant compared with 114/973 controls (15.5 vs. 11.7%, p=0.10). Only 2/61 noncardiac genes were significantly overrepresented in cases compared with controls (ECE1, 3/278 [1%] vs. 1/973 [0.1%] p=0.036; SLC6A4, 2/278 [0.7%] vs. 1/973 [0.1%] p=0.049). There was no difference in yield of pathogenic or likely pathogenic variants between cases and controls (1/278 [0.36%] vs. 4/973 [0.41%]; p=1.0). Gene-collapsing analysis did not identify any specific biological pathways to be significantly associated with SIDS.ConclusionsA monogenic basis for SIDS amongst the previously implicated noncardiac genes and their encoded biological pathways is negligible.     

Type IV Ehlers-Danlos syndrome presenting as sudden infant death

A previously healthy 5-month-old female infant presented with sudden death due to spontaneous subarachnoid hemorrhage associated with minor multifocal visceral hemorrhages. The clinical diagnosis had been sudden infant death syndrome. Although the family history was noncontributory and other features of type IV Ehlers-Danlos syndrome (EDS) were absent, the pattern of hemorrhage was consistent with this type of connective tissue disorder. The diagnosis was confirmed after postmortem analysis of skin and aorta showed less than 5% type III collagen (normal greater than 15%). Extensive literature review failed to find any other reported cases of sudden death in infancy due to intracranial hemorrhage in patients with previously unsuspected type IV EDS. The authors suggest that collagen analysis should be performed in cases of unexplained multifocal spontaneous hemorrhage in infancy so that this rare diagnosis will not be missed.     

Elevated fetal hemoglobin levels in sudden infant death syndrome

The cause of sudden infant death syndrome (SIDS) is unknown, although deficits in cardiopulmonary function and central respiratory control have been suggested as possible mechanisms of the disorder. In this study, we tested the hypothesis that SIDS is associated with a delay in the maturation of hematopoiesis. Prolonged elevation in the levels of fetal hemoglobin (hemoglobin F) in infants with SIDS could denote a compromised delivery of oxygen to sensitive tissue sites. Normally, hemoglobin F (alpha 2 gamma 2) is largely replaced by adult hemoglobin, hemoglobin A (alpha 2 beta 2), during the first six months after birth. Using an isoelectric-focusing procedure for measuring stable hemoglobin subunits, we quantitated the levels of hemoglobin F in blood samples from 59 patients with SIDS and 40 controls (32 living and 8 dead) matched for postconceptional age. The level of hemoglobin F in the population with SIDS was significantly higher than that in the controls in the age range tested (39 to 75 weeks); the mean (+/- SEM) proportion of hemoglobin F was 63.2 +/- 3.6 percent in the group with SIDS, as compared with 48.1 +/- 5.0 percent in the controls (P less than 0.025). The difference in hemoglobin F levels was most pronounced 50 weeks after conception: the proportion of hemoglobin F in the 37 patients with SIDS with a postconceptional age of more than 50 weeks was 47.4 +/- 3.6 percent, as compared with 18.8 +/- 3.1 percent in the 19 controls of that age (P less than 0.0005). We conclude that hemoglobin F is a useful postmortem marker for the population with SIDS that we studied and that it may have value as a prospective marker for some infants at risk for SIDS.     

The role of infection and inflammation in sudden infant death syndrome

Sudden Infant Death Syndrome (SIDS) is the most common cause of post-neonatal mortality in the developed world. The exact cause of SIDS is likely to be multifactorial involving a critical developmental period, a vulnerable infant, and one or more triggers. Many SIDS infants have a history of viral illness preceding death. Prone sleep position, one of the leading risk factors, can increase airway temperature, as well as stimulate bacterial colonization and bacterial toxin production. Markers of infection and inflammation are often found on autopsy along with microbial isolates. Although the causal link between infection and SIDS is not conclusive, there is evidence that an infectious insult could be a likely trigger of SIDS in some infants.     

Cardiac and other abnormalities in the sudden infant death syndrome.

Many victims of the sudden infant death syndrome (SIDS) have abnormally heavy cardiac right ventricles. The degree of this abnormality is directly proportional to: a) the mass of muscle about small pulmonary arteries, b) the amount of brown fat retention about adrenal glands, and c) the presence of hepatic erythropoiesis. The pulmonary arterial abnormality is probably the result of chronic alveolar hypoventilation, while brown fat retention and hepatic erythropoiesis are likely consequences of chronic hypoxemia. These abnormalities are found in both SIDS victims who die with and those who die without mild respiratory tract infections. However, there are some differences between the two SIDS groups. Infected victims die at an older age and have smaller thymus glands and larger spleens; there is a greater proportion of males in the infected victims than in the noninfected victims.     

Hypovitaminosis A: A model for sudden infant death syndrome

The cause of sudden infant death syndrome (SIDS) is unknown. It is the leading cause of death from age one month to one year in North America. The purpose of this essay is to generate some testable hypotheses as to the cause of SIDS by drawing attention to distinct epidemiological parallels between SIDS and a newly recognized form of enamel hypoplasia, termed localized hypoplasia of the primary canine tooth (LHPC), which has been attributed to vitamin A deficiency. LHPC and SIDS share a common epidemiological profile: winter seasonality, occurrence at 3–5 months, and affecting apparently healthy children, but with increased incidence in socio economically disadvantaged families particularly racial/ethnic minorities (except Hispanics who show a reduced incidence), previously compromised infant health, less prenatal counselling, and less breastfeeding. Vitamin A has pervasive functions throughout the body including bone growth and maintenance of epithelial membranes. It is proposed that SIDS is due in part to hypovitaminosis A through one of several mechanisms: imbalanced basicranial growth producing mechanical constriction on the respiratory nerves passing through the jugular foramen; or through compromised myelination and/or maturation of the brain stem and cranial nerves involved in respiration; or through pharyngeal collapse due to mandibular undergrowth; or dysfunction of hypoxia-sensitive epithelial cells in the trachea. It is recommended that assay of hypoxia-sensitive epithelial cells in the trachea. It is recommended that assay of the retinyl ester content of the liver of SIDS victims be included in autopsy protocol. © 1995 Wiley-Liss, Inc.     

Normal fetal hemoglobin levels in the sudden infant death syndrome

It has been reported that infants who die of the sudden infant death syndrome (SIDS) have elevated fetal hemoglobin levels. To test this hypothesis, we determined the level of fetal hemoglobin in dead and living infants in three different laboratories by three methods: high-performance liquid chromatography, polyacrylamide-gel electrophoresis, and cell-based immunofluorescence assays for fetal hemoglobin-containing red cells (F cells). Our infant study population consisted of 67 infants who had died of SIDS, 22 control infants examined at autopsy, and 80 living infants. The fetal hemoglobin level was not higher in the infants who had died of SIDS than in the control infants for any age group analyzed. Immunofluorescence assays for F cells were also performed in blood samples from 105 mothers of infants who had died of SIDS, 55 adult female controls, 52 fathers of infants who had died of SIDS, and 67 adult male controls. The percentage of fetal hemoglobin-containing red cells in the parents of infants who had died of SIDS was not statistically different from that in sex-matched adults in the control groups. We conclude that elevated fetal hemoglobin levels in infants or their parents are not suitable for use as indicators of the risk of SIDS in the infants. Furthermore, the fetal hemoglobin level is not useful as a postmortem marker of an infant's having died of SIDS.