Sudden infant death syndrome and lipoproteins.

Lipoprotein secretion and vitamin E transport depend on an adequate supply of inositol which functions synergistically with choline. Feeding rats a choline deficient diet was associated with decreased linoleic and arachidonic acids and increased docosapentenoic and docosahexenoic acids in liver phosphatidylethanolamine. Lipoprotein secretion by the liver is impaired by long chain omega 3 fatty acids and by the high carbohydrate diet of Kwashiorkor. Pulmonary surfactant is a lipoprotein which functions in preventing alveolar collapse in the lung. Inositol supplements to premature infants altered the composition of surfactant phospholipids and reduced the need for oxygen therapy. Oxygen free radicals, generated in oxygen therapy, convert low density lipoproteins (LDL) into potent toxins, without adequate antioxidants and free radical scavengers to block free radical generation. Vitamin E deficiency predisposes humans to increased susceptability to oxygen toxicity leading to Bronchopulmonary dysplasia (BPD), a form of chronic pulmonary insufficiency.

Lung immunoglobulins in the sudden infant death syndrome.

The incidence of the sudden infant death syndrome parallels that of respiratory tract infections in the paediatric community. On the basis that the aetiology of the sudden infant death syndrome may lie in an unusual response to a trivial intercurrent respiratory infection a necropsy study was carried out investigating pulmonary immunoglobulins in 16 victims of the syndrome and a series of infants (controls) who had died of non-pulmonary causes. Compared with the controls victims of the sudden infant death syndrome had grossly raised concentrations of IgG, IgM, and to a less extent IgA in lung lavage samples. In addition, pulmonary interstitial and terminal airway cells expressing these immunoglobulins were identified far more often in victims than controls. The study failed to determine whether the increased immunoglobulin concentrations were a consequence of an unusual response to a trivial infection or an expression of otherwise altered immunological control in the respiratory tract. Epidemiological evidence and the findings of this study suggest that the respiratory tract is the prime target organ in the sudden infant death syndrome.

Beta-endorphin in the brainstem, pituitary, and spinal fluid of infants at autopsy: relation to sudden infant death syndrome.

Immunohistochemical localization of beta-endorphin was studied in the pituitaries and medullas of forty human infants at autopsy. beta-Endorphin immunoreactivity was found in anterior pituitary cells in all cases. In the medulla, beta-endorphin immunoreactivity was found in the neurons of the medial and lateral cuneate nuclei in ten out of the forty cases. In eight of these ten cases, the infants died of causes other than sudden infant death syndrome (SIDS). Only two of 25 SIDS cases had demonstrable beta-endorphin in the brainstem nuclei. Beta-endorphin levels in the spinal fluids of all the cases showed no correlation to cause of death, age or gender.

Pulmonary surfactant. II. In sudden infant death syndrome.

The lung surfactant phospholipid composition of lavage samples from 102 babies dying from Sudden Infant Death Syndrome (SIDS) (one-third with minor signs of inflammation) was compared with that of: 34 babies dying from Hyaline Membrane Disease (HMD), 15 mature babies dying soon after birth, 16 mature babies dying in the same age range as the sudden infant death syndrome cases, 13 babies dying from pneumonia and 6 from septicaemia. The surfactant of the two groups of babies dying from SIDS was identical and approximated that obtained from babies dying from HMD, pneumonia or septicaemia. Compared to that obtained from mature babies, the surfactant of babies dying from SIDS contained significantly lower proportions of phosphatidylcholine (PC) and significantly higher proportions of lyso-PC and sphingomyelin. The proportion of disaturated PC was similar to that of the surfactant of the age-matched mature babies. The surfactant composition of the babies dying from SIDS did not change appreciably after death nor vary with age at death. The surfactant phospholipid composition of postmortem samples from mature babies was similar to that of aspirates from living babies and infants and to that of bronchoalveolar lavage samples from living adults.

Acylcoenzyme A dehydrogenase deficiency in heart tissue from infants who died unexpectedly with fatty change in the liver.

Heart muscle from infants who died unexpectedly and who showed fatty changes in the liver at necropsy was analysed for long chain and medium chain acylcoenzyme A dehydrogenase activities by using the natural electron acceptor. In two of the seven cases investigated a deficiency in acylcoenzyme A dehydrogenase activity was found. In one case the deficiency was in medium chain acylcoenzyme A dehydrogenase activity and in the other long chain acylcoenzyme A dehydrogenase activity. These findings emphasise the importance of investigating fatty acid oxidation in infants who have died unexpectedly.

Abnormal myocardial lipid composition in an infant with type II glutaric aciduria.

We have analyzed the myocardial lipids of an infant with glutaric aciduria type II (GAII) who died from sudden cardiac failure and of five infants who died suddenly from indeterminate causes (sudden infant death syndrome, SIDS). Histology of the SIDS hearts was normal, but there was marked fatty deposition in the GAII heart. Fatty acid composition of myocardial lipids was determined by thin-layer chromatography-gas-liquid chromatography. Total lipid was elevated 20-fold in the GAII heart. Of total fatty acids, 75% was derived from phospholipids in SIDS heart and 89% from neutral lipids in GAII heart. Increased levels of free oleic acid and a 6-fold elevation in the (n-6)/(n-3) fatty acid ratio in phospholipid were noted in GAII heart compared to SIDS hearts.

Lipids in airway secretions.

Lipids form a significant portion of airway mucus yet they have not received the same attention that epithelial glycoproteins have. We have analyzed, by thin layer chromatography, lipids present in airway mucus under "normal" and hypersecretory (pathological) conditions. The 'normals' included (1) bronchial lavage obtained from healthy human volunteers and from dogs and (2) secretions produced "in vitro" by human (bronchial) and canine (tracheal) explants. Hypersecretory mucus samples included (1) lavage from dogs made bronchitic by exposure to SO2, (2) bronchial aspirates from acute and chronic tracheostomy patients, (3) sputum from patients with cystic fibrosis and chronic bronchitis and (4) postmortem secretions from patients who died from sudden infant death syndrome (SIDS) or from status asthmaticus. Cholesterol was found to be the predominant lipid in 'normal' mucus with lesser amounts of phospholipids. No glycolipids were detected. In the hypersecretory mucus, in addition to neutral and phospholipids, glycolipids were present in appreciable amounts, often the predominant species, suggesting that these may be useful as markers of disease. Radioactive precursors 14C acetate and 14C palmitate were incorporated into lipids secreted "in vitro" by canine tracheal explants indicating that they are synthesised by the airway.

An hepatic metabolic profile in sudden infant death (SIDS).

Levels of 18 enzymes and metabolites were measured in liver obtained at autopsy from 41 infants, 28 of whom were found unexpectedly dead at home. Four infants had meningitis, 11 had pathologic findings not clearly sufficient to explain death (SUD), and 13 were considered totally unexplained pathologically (SIDS). The possible contributions of postmortem interval, age and diet to the results are reviewed. No characteristic metabolic profile was recognized amongst SUD and SIDS groups. It is speculated that the amount of glycogen found in liver may provide insight into premortal events and reflect the rapidity of the death mechanism. Five individuals (20%) were suspected of having major metabolic abnormality including glycogenosis (1), urea cycle defect (1), and possibly abnormal levels of carnitine palmityl transferase (3).

Carotid bodies in sudden infant death syndrome: a combined light microscopic, ultrastructural, and biochemical study.

Carotid bodies (CBs) are peripheral chemoreceptors that can undergo compensatory hypertrophy and hyperplasia in some patients with chronic hypoxemia. At the Children's Hospital morphometric and biochemical analyses were done on CBs obtained at autopsy from 89 infants in the first year of life to determine if there were statistically significant differences in sudden infant death syndrome (SIDS, n = 38) compared with an age-matched control population (n = 51). Mean combined weights of CBs from SIDS victims were greater than controls in the 1- to 4-month age interval (mean = 3.4 mg, p less than 0.075) and the 4- to 8-month interval (mean = 5.0 mg, p less than 0.098) but the differences were not statistically significant (t-test, p less than 0.05). Computerized planimetry of total surface area and area occupied by "functional" parenchyma revealed no statistically significant differences. Both groups showed an equally intense degree of cytoplasmic argyrophilia of chief cells, and electron microscopy of CBs from 5 SIDS victims was indistinguishable from controls, including overall content of dense-core neurosecretory granules. There were also no significant differences in catecholamine content using liquid chromatography with electrochemical detection (SIDS n = 29, controls n = 21). These morphometric, ultrastructural, and biochemical data are not supportive for CBs having a significant role in the pathogenesis or etiology of SIDS.

Defects of metabolism of fatty acids in the sudden infant death syndrome.

Two hundred consecutive cases of the sudden infant death syndrome were reviewed for the presence of fat in the liver; 14 showed diffuse panlobular microvesicular fatty change indistinguishable from that found in Reye's syndrome. Samples of frozen liver were available in five of the 14 cases; histochemical analysis showed well preserved cytochrome oxidase and succinate dehydrogenase activity in all five, uncharacteristic of Reye's syndrome. Fatty acyl-coenzyme A dehydrogenase activity in the liver was assayed biochemically in two of the same five cases with severe hepatic fatty infiltration; both showed a defect in medium chain acyl-coenzyme A dehydrogenase activity using the substrate octanoyl-coenzyme A. Both cases also showed cerebral oedema in association with fatty infiltration of renal tubules, myocardium, and skeletal muscle, characteristic of Reye's syndrome. It is concluded that diffuse panlobular microvesicular fatty change of the liver in victims of the sudden infant death syndrome, although essentially non-specific, indicates that the state of mitochondrial enzymes should be investigated.

Sudden infant death syndrome: increased carotid-body dopamine and noradrenaline content.

Carotid bodies from infants dying of sudden infant death syndrome contained significantly higher concentrations of dopamine (10-fold) and noradrenaline (3-fold) than those from age-matched control infants. Administration of dopamine inhibits respiration by direct action on the carotid body, and it is suggested that the elevated levels of endogenous catecholamines found in victims of sudden infant death syndrome may compromise the normal function of the carotid body, particularly the ventilatory response to hypoxia.

Metal content of the liver in sudden infant death syndrome.

The metals zinc, iron, copper, manganese, calcium, magnesium, potassium and sodium were analysed in the livers of 67 Australian infants who had died from Sudden Infant Death Syndrome (SIDS) and 29 infants who had died from other causes (non-SIDS). The results were evaluated in relation to medical data and fatty acid composition of the livers. In infants less than 6 months old the liver potassium levels were significantly lower in SIDS than in non-SIDS infants. No other significant differences in metals between the SIDS and non-SIDS livers were found. Zinc, iron and copper levels in infant liver fell with age during the first year.

Liver fatty acids and the sudden infant death syndrome.

Fatty acid analyses were performed on samples of liver from 325 human infants less than 1 yr old, 275 of whom had died of sudden infant death syndrome (SIDS), and 50 of other causes (non-SIDS). Data for fatty acid composition were analyzed in relation to cause of death, age of infant, liver biotin, liver metals, and other variables by a variety of statistical methods. There were significant differences in the levels of liver fatty acids between SIDS and non-SIDS infants in the age group 1 to 6 months, notably in that the fatty acids of the SIDS infants appeared to have lower levels of dihomo-gamma-linolenic acid, which is the precursor of the "1-series" prostaglandins. Statistically significant relationships were observed between various fatty acids, and there were also significant relationships involving docosapentaenoic acid and infant age, and docosahexaenoic acid and liver iron content.

Lactic acid concentrations in vitreous humor: their use in asphyxial deaths in children.

Lactic acid concentrations in brain tissue of humans have been shown to increase with an extended agonal period. Infants and children dying from various causes are undergoing different stress conditions terminally and the postulate of this study is that natural death cases and traumatic asphyxia cases are characterized by varying agonal periods, the former being somewhat prolonged with the latter being rather brief. One-hundred-and-two cases of infants and children were examined for vitreous humor lactic acid concentrations. They were divided into two major categories, Sudden Infant Death Syndrome (SIDS) and non-SIDS cases. SIDS was further divided into SIDS without additional findings and SIDS with secondary findings which contributed to death. The non-SIDS category included traumatic asphyxia cases as well as those dying from blunt trauma, known respiratory diseases, and other causes. Categorical mean values and standard deviations were calculated. The vitreous humor lactic acid mean value for traumatic asphyxia was significantly lower than the mean value for SIDS. Also the mean value for known respiratory diseases was statistically lower than the mean value for SIDS with secondary findings. These findings are probably suggestive of agonal time differences and may be a reflection of the various mechanisms of death.

Endogenous alcohol production by intestinal fermentation in sudden infant death.

In some cases of sudden infant death syndrome (SIDS) the intestinal flora was found to be dominated by Candida albicans. Microbiologic investigations of the various organs showed the occasional presence of different Candida species, but not in the form of massive growth as in sepsis. There is no basis to assume that the activity of yeasts, first of all of Candida albicans, is a contributory factor in the occurrence of SIDS. Candida albicans was shown to produce alcohol from glucose at a rate of maximally 1 mg of alcohol per gram of intestinal content per hour. It is concluded that the intestinal production of alcohol in vivo from cases showing a Candida albicans dominated intestinal flora will not be able to surpass the normal alcohol metabolizing capacity of the liver. Thus, measurable concentrations of alcohol in the blood from such cases cannot be expected.

Toxicology and sudden infant death.

One hundred thirty cases of sudden infant death occurring in Wayne County, Michigan, (population 2.7 million) were analyzed for possible drugs. The toxicological protocol has been outlined. Six cases were found to be positive, and in five of these the drugs found had been prescribed for a variety of illnesses. In one case methadone was found in the blood of an infant whose mother was undergoing methadone treatment for drug addiction, the drug being transmitted through breast milk. In none of the 102 cases of sudden infant death syndrome (SIDS) included in the study did the toxicological results affect the diagnosis. In our study, toxicological analyses never contradicted an initial diagnosis of SIDS, and, therefore, we feel that this diagnosis should be made promptly based on investigative and autopsy findings.