Medial Smooth Muscle Thickness in Small Pulmonary Arteries in Sudden Infant Death Syndrome Revisited

Increased relative medial thickness (RMT) of smooth muscle in small pulmonary arteries, peripheral extension of smooth muscle into the alveolar wall arteries, and right ventricular hypertrophy (RVH), in response to purported prolonged hypoxia, have been reported in sudden infant death syndrome (SIDS). Prone sleep position, an important risk factor for SIDS, predisposes infants to hypoxia from airway obstruction or rebreathing. Since publication of the earlier pulmonary artery studies, the SIDS definition has been expanded, and sudden infant death investigational protocols have been implemented. Our aims in this study were to (1) compare RMT in preacinar arteries (PA), intra-acinar arteries accompanying small airways (SIA), and alveolar wall arteries (AW) in SIDS infants and controls; (2) correlate RMT with postmortem variables; (3) determine if peripheral extension occurred more often in SIDS infants than in controls; and (4) determine if RVH occurred in SIDS. Movat-stained sections from standardized tissue blocks taken prospectively from the apex of the right upper lobe from 88 SIDS cases and 17 controls were evaluated using a computer-assisted digitizing system with images obtained from a microscope with an attached video camera. When adjusted for age, the RMT values for the SIA arteries were significantly greater in controls, while the PA and AW arteries were not statistically different between the SIDS cases and controls. Peripheral medial smooth muscle extension did not differ between the groups, and RVH was not seen in SIDS cases. Given the recent identification of brain stem abnormalities interfering with protective cardiorespiratory responses against acute life-threatening hypoxia perhaps precipitated by prone sleeping, our data suggest that SIDS is an acute event not preceded by recurrent or prolonged apnea and hypoxia.     

Development of peripheral chemoreceptor function in infants with chronic lung disease and initially lacking hyperoxic response.

Ten preterm infants with chronic lung disease (CLD) and undeveloped peripheral chemoreceptor function, described as ventilatory response to hyperoxia, were investigated, according to an individual protocol. Each infant was followed up until the response to hyperoxic inhalation had been observed on two occasions. Each examination consisted of overnight recording of saturation, testing of lung compliance and airway resistance, and the hyperoxic test. The hyperoxic response appeared at a mean postnatal age of 14 weeks (range 9-33 weeks). This response, which was independent of the infant's lung mechanics, appeared much later in infants with the severe form of CLD. As undeveloped peripheral chemoreceptor function has been suggested to be a key factor in sudden infant death syndrome (SIDS), the delayed development of their chemosensitivity leaves some infants with CLD unprotected against hypoxia at the age at which the risk for SIDS is highest.     

Abnormal patterns of pulmonary neuroendocrine cells in victims of sudden infant death syndrome

Ventilatory dysfunction has become the main focus of current research in sudden infant death syndrome (SIDS). This has been correlated with structural abnormalities in the carotid body and respiratory nuclei of the brainstem. In recent studies, the denervating effect of asphyxial brainstem dysfunction on the pulmonary neuroendocrine cells, which probably function as chemoreceptors, was demonstrated and prompted the following study. The pulmonary neuroendocrine system was evaluated in 25 victims of SIDS and 20 control infants, ranging in age from 3 weeks to 7 months and 1 to 12 months, respectively. The pulmonary neuroendocrine cells were stained by the Churukian-Schenk method and the neuroendocrine cell-positive airway values expressed as a percentage of the total number of airways. The range of positive airway values for victims of SIDS was 2% to 97% with a median of 73%. In contrast, the range for the control infants was 1% to 44% with a median of 25.5%. The SIDS victims' percentage was significantly greater than the control infants' percentage (P less than .0001). The number of pulmonary neuroendocrine cells in positive airway was also increased among SIDS victims compared with control infants. The altered pulmonary neuroendocrine cell pattern could be attributable to either brainstem dysfunction or chronic hypoxia. These explanations are not, however, mutually exclusive of one another; in fact, it is possible that both mechanisms may be operative.     

Hyperplasia of Bombesin-Immunoreactive Pulmonary Neuroendocrine Cells and Neuroepithelial Bodies in Sudden Infant Death Syndrome

The distribution and frequency of bombesin immunoreactive neuroendocrine (NE) cells including neuroepithelial bodies (NEB) was analyzed morphometrically in lung sections from 25 infants who died of sudden infant death syndrome (SIDS) and 25 control infants. The control group included infants age-matched to those with SIDS, as well as subjects ranging in age from early to late infancy, to define the postnatal development of pulmonary NE-cell system. Quantitative analysis was performed on lung sections immunostained with monoclonal antibody against bombesin and the contents of bombesin-like peptide in lung extracts were measured by a specific radioimmunoassay (RIA). In control infants, the frequency of NE cells was high at birth but decreased dramatically during the first year of life. In SIDS infants, the frequency of NE cells, the size of NEB, and the mean concentration of bombesin-like peptide detected by RIA were significantly increased compared to those values for age-matched controls. These findings suggest hyperplasia of bombesin-immunoreactive NE-cell system in the lungs of SIDS infants. Since NEB are thought to function as hypoxia-sensitive airway chemoreceptors and since these cells are prominent in the neonates but decline postnatally, we speculate that chronic hypoxia and/or developmental delay may be responsible for this alteration in the lungs of SIDS victims. Potential dysfunction of pulmonary NE-cell system, compounded by other abnormalities in the autonomic regulation of respiration may be of importance in the pathogenesis of SIDS.     

Multiple causes of asphyxia in infants at high risk for sudden infant death.

A wide range of clinical findings was present in 58 near-miss sudden infant death syndrome (SIDS) infants and 6 surviving twins of SIDS siblings. Specific investigations included: studies of gastro-oesophageal reflux and aspiration (24-hour oesophageal pH recordings, barium swallow, radionuclide ''milk-scan''); polygraphic studies of breathing, reflux, and sleep state; studies of upper airways disease (lateral airways radiography and endoscopy); detection of seizure activity by electroencephalography; evaluation of thiamine status by erythrocyte transketolase activity of venous blood. Thiamine deficiency was found in 12 of 43 tested infants; 5 of the deficient infants had a familial history of SIDS. Many potential mechanisms for asphyxia were found: idiopathic central apnoea (7 infants), tracheal obstruction from minimal tracheomalacia or aberrant innominate artery (4 infants), temporal lobe or generalised seizures (6 infants), gastro-oesophageal reflux (55 infants) with intrapulmonary aspiration (11 infants). The high incidence, severity, and timing of reflux were new findings. Reflux occurred in active and indeterminate sleep, but not in quiet sleep. The depression of respiratory reflexes by active sleep stresses the vulnerability to asphyxia. Two factors suggest that near-miss episodes are related to SIDS: the similar age distribution but earlier occurrence of near-miss episodes compared with age at death of SIDS infants, and the subsequent sudden death of 2 infants whose necropsies were consistent with SIDS.     

Pulmonary intra-alveolar siderophages in SIDS and suffocation: a San Diego SIDS/SUDC Research Project report.

Pulmonary intra-alveolar siderophages (PS) have been suggested as a marker of previous attempts at imposed suffocation in infants dying suddenly and unexpectedly. The aims of this study were to (1) compare PS counts between cases of sudden infant death syndrome (SIDS) and a control group comprised of infants whose deaths were attributed to accidental or inflicted suffocation, (2) compare clinical variables in SIDS and control suffocation cases, and (3) review individual cases irrespective of the cause and manner of death with an average PS count greater than 200 per 20 high-power fields (hpf) per lung lobe. Retrospective assessment of siderophages in available iron-stained lung sections was undertaken in 91 SIDS cases and 29 cases of death due to suffocation (27 accidents and 2 homicides) from the San Diego SIDS and Sudden Unexplained Death in Childhood (SUDC) Research Project (SDSSRP) database. Neither the means of the log-transformed PS counts nor the medians of the raw PS counts were significantly different between the SIDS and control suffocation groups. The distributions of the PS data were different, however-the range was wider in the SIDS group. Only 6% of each group had a history of prior apparent life-threatening events. Approximately three fourths of the families from both groups had no prior referral to Child Protective Services. The number of PS varies widely in cases of sudden infant death caused by SIDS and accidental or inflicted suffocation and cannot be used as an independent variable to ascertain past attempts at suffocation.     

Pulmonary aspiration of gastric contents and the sudden infant death syndrome

OBJECTIVE: To determine ante-mortem and post-mortem risk factors for the finding of gastric contents in pulmonary airways (aspiration of gastric contents) at post-mortem examination in the sudden infant death syndrome (SIDS). METHODS: There were 217 post-neonatal deaths in the Auckland region of the New Zealand Cot Death Study. No deaths were certified as due to aspiration of gastric contents. There were 138 SIDS cases. The parents of 110 (80%) of these cases were interviewed. Histological sections from the periphery of the lungs in 99 of the 110 cases were reviewed for evidence of aspiration of gastric contents. A wide range of variables were analysed in SIDS cases with and without aspiration to determine risk factors. RESULTS: Aspiration of gastric contents was identified in 37 (37%) of SIDS cases. Aspiration was of mild-to-moderate degree and in no case was severe and a potential cause of death. Finding infants on their backs at death (P = 0.024) and conducting the post-mortem on the day after the death or subsequently (P = 0.033) were statistically significant variables linked to identification of aspiration. Position placed to sleep, symptoms of gastro-oesophageal reflux and other variables were not related to aspiration. CONCLUSIONS: The only determinants for aspiration of gastric contents identified were agonal or post-mortem events, supporting the contention that aspiration has limited relevance to the mechanism of SIDS.     

ASSESSMENT OF PULMONARY AND INTRATHYMIC HEMOSIDERIN DEPOSITION IN SUDDEN INFANT DEATH SYNDROME

The aim of this study was to stain lung and thymus gland sections that had been taken from infants who had died of sudden infant death syndrome SIDS for interstitial hemosiderin and to compare the results with those obtained for controls. There were two groups of SIDS infants, one with, and a second group without, histories of apparent life-threatening events ALTEs . No significant difference in numbers of cases with interstitial hemosiderin deposition was found between SIDS infants with histories of ALTEs n 4 of 12, 33.3 , SIDS infants without histories of ALTEs n 4 of 22, 18.2 , and controls n 4 of 24, 16.7 . However, if four of the control cases with histories of previous chest trauma were excluded, there was a significantly greater number of cases with pulmonary interstitial hemosiderin in the SIDS infants with histories of ALTEs compared with the subgroup of control infants with no previous chest trauma n 1 of 20, 5 P .05 . No relationship could be established between the timing of the ALTEs, the type of resuscitation or age of the infant at death, and the presence of hemosiderin. None of the sections of thymus gland stained positively for hemosiderin. Positive staining for pulmonary interstitial hemosiderin, therefore, differentiated a group of SIDS infants with histories of previous ALTEs from a subgroup of control infants with no histories of previous chest trauma. However, pulmonary interstitial hemosiderin staining could not be used with certainty to confirm or exclude previous ALTEs in individual SIDS cases as not every SIDS case with a history of an ALTE stained for pulmonary interstitial hemosiderin. In addition, positive staining occurred for SIDS infants without histories of ALTEs and also for control infants who died of other causes.     

Identification of Pneumocystis carinii in the lungs of infants dying of sudden infant death syndrome

BACKGROUND: Recently Pneumocystis carinii has been identified in a significant number of infants diagnosed as having died from sudden infant death syndrome (SIDS) in South America and Europe. METHODS: We examined lung sections of 79 infants who died with a diagnosis of SIDS in Rochester, NY, and Connecticut for the presence of P. carinii. RESULTS: Organisms with a characteristic silver stain appearance for P. carinii were identified in 14% of the lung sections. CONCLUSIONS: These data suggest that a possible link between some cases of SIDS and infection with P. carinii should be further evaluated and that infection of young infants may serve as an important reservoir for human P. carinii.     

Pulmonary neuroendocrine cells and neuroepithelial bodies in sudden infant death syndrome: potential markers of airway chemoreceptor dysfunction.

Pulmonary neuroendocrine cells (PNEC), including neuroepithelial bodies (NEB), are amine- and peptide (for example, bombesin)-producing cells that function as hypoxia/hypercapnia-sensitive chemoreceptors that could be involved in the pathophysiology of sudden infant death syndrome (SIDS). We assessed morphometrically the frequency and size of PNEC/NEB in lungs of infants who died of SIDS (n = 21) and compared them to an equal number PNEC/NEB in lungs of age-matched control infants who died of accidental death or homicide, with all cases obtained from the San Diego SIDS/SUDC Research Project database. As a marker for PNEC/NEB we used an antibody against chromogranin A (CGA), and computer-assisted morphometric analysis was employed to determine the relative frequency of PNEC per airway epithelial area (% immunostained area, %IMS), the size of NEB, the number of nuclei/NEB, and the size of the NEB cells. The lungs of SIDS infants showed significantly greater %IMS of airway epithelium (2.72 +/- 0.28 [standard error of the mean, SEM] versus 1.88 +/- 0.24; P < 0.05) and larger NEB (1557 +/- 153 microm(2) versus 1151 +/- 106 microm(2); P < 0.05) compared to control infants. The size of NEB cells was also significantly increased in SIDS cases compared to the controls (180 +/- 6.39 microm(2) versus 157 +/- 8.0 microm(2); P < 0.05), indicating the presence of hypertrophy in addition to hyperplasia. Our findings support previous studies demonstrating hyperplasia of PNEC/NEB in lungs of infants who died of SIDS. These changes could be secondary to chronic hypoxia and/or could be attributable to maturational delay. Morphometric assessment and/or measurement of the secretory products of these cells (for example, CGA, bombesin) could provide a potential biological marker for SIDS.     

Tissue mineral levels in victims of sudden infant death syndrome II. Essential minerals: copper, zinc, calcium, and magnesium

Deficiencies of various vitamin and minerals per se have been suggested as possible causes of sudden infant death syndrome (SIDS). Further, a deficiency of essential minerals may lead to enhanced toxicity of toxic elements, in particular, lead and cadmium to explore the possibility of mineral deficiencies or interactions with the toxic metals, lead and cadmium, lung, liver, kidney, and rib specimens were obtained at autopsy from 66 SIDS infants and 23 infants who died suddenly from other cases. Tissue copper, zinc, calcium, and magnesium were measured by atomic absorption spectroscopy. No differences were found between SIDS and non-SIDS for any element in any tissue except for more magnesium in the liver (P less than 0.0001) and less copper in the lungs (P less than 0.02) in the SIDS group. Only sporadic interactions between toxic and essential elements could be found. We found no evidence of any essential mineral deficiencies per se or significant interactions of essential and toxic minerals that might potentiate the effects of toxic metals. The physiologic significance, if any, of the higher liver magnesium and lower lung copper found in SIDS is unclear.     

The airway occlusion test as a screening for sudden infant death syndrome (SIDS)

The airway occlusion test was carried out as a screening test for sudden infant death syndrome (SIDS). To obtain the normal values for use as control values, the relationship of the airway occlusion test with various variables was determined in 234 infants. The result shows that the best correlation was seen between percentage prolongation and the corrected gestational age. Percentage prolongation increased with the progression of age up to about the 40th week of corrected gestational age. Subsequently, there was no remarkable change in percentage prolongation. In six out of eight cases with apparent life threatening events, percentage prolongation was reduced. These results indicate that the determination of percentage prolongation can be used for screening of high risk babies for SIDS.     

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.     

Viruses and sudden infant death

Viral respiratory infections are the most likely trigger for sudden infant death syndrome (SIDS). SIDS cases commonly have evidence of respiratory tract inflammation, a preceding history of symptoms of minor illness and occur in winter peaks coinciding with respiratory viral epidemics. Respiratory infections are a common cause for infants presenting with sudden events, involving apnoea and hypoxaemia and there are physiological mechanisms by which infants may develop sudden and severe, potentially life-threatening hypoxaemia. The rate of SIDS has fallen in the last 15 years. This is probably more to do with the reasons for the fall in deaths from respiratory causes rather than changes in sleeping position. Further falls in SIDS death rates may occur with reductions in cigarette smoking, encouragement of breastfeeding and minimising the potential for young infants to acquire respiratory infections. Early identification and recognition of life-threatening features of infections may further minimise the risks of sudden death.     

The epidemiology of sudden infant death syndrome and attacks of lifelessness in Sweden

Infants who died showing the syndrome of sudden infant death (SIDS) and infants who survived attacks of lifelessness (AL) were examined in a prospective epidemiological multicentre study over 24 months covering close to 40% of all births in Sweden. Seventy SIDS cases and 34 cases of AL were observed, giving an incidence for SIDS of 0.94/1000 and for AL of 0.46/1000. This SIDS incidence is higher than that observed during the seventies. The boy/girl ratio was 1.4:1 for SIDS and 1.6:1 for AL. The age distribution for AL resembled that for SIDS. Similarities were also seen with regard to place of occurrence. Sixty per cent of the SIDS cases occurred during the daytime/evening. Twenty-nine per cent of the infants with AL had more than one apneic spell during the three-day-period around the attack, indicating a period of respiratory instability, but only 12% had such spells later on. None of the infants who had had AL died from SIDS. The possible relationship between AL and SIDS is discussed.     

SIDS, illness, and acute medical care. New Zealand Cot Death Study Group

One component of the Back to Sleep campaign to reduce the risk of sudden infant death syndrome (SIDS) is the recommendation that parents seek medical attention if their infant is unwell. The aim of this study was to investigate of SIDS could in part be explained by sick infants not getting appropriate medical care. Data on symptoms of illness and on acute medical contacts made for infants dying from SIDS (n = 390) within two weeks of their death were compared with those from a randomly selected group of control infants (n = 1592). SIDS cases had more severe illness than controls (odds ratio (OR) = 3.43; 95% confidence interval (CI) = 1.69 to 5.38), and were more likely to have seen a general practitioner (OR = 1.37; 95% CI = 1.09 to 1.73) or attended hospital (OR = 3.43, 95% CI = 1.09 to 1.73). Only 1.3% of all SIDS cases had symptoms suggesting severe illness and had not seen a general practitioner. A lack of medical contacts in the two weeks before death does not contribute to the risk of SIDS.     

Surfactant abnormality and the sudden infant death syndrome--a primary or secondary phenomenon?

A prospective study of 46 infant deaths occurring between 3 and 100 weeks of age was performed and comprised a structured necropsy followed by collection of lung washings for surfactant phospholipid analysis and samples for microbiological examination. Of the 46 infants studied, 23 died from sudden infant death syndrome (SIDS) alone; SIDS was the cause of death in a further 12 but there were additional clinical or pathological findings insufficient in themselves to account for the death (''SIDS-plus''). In 11 there were other causes of death (''non-SIDS''). The lung washings from infants dying from SIDS had significantly lower concentrations of phosphatidylcholine and a significantly lower palmitate content in the phosphatidylcholine. There was no association between surfactant phospholipid abnormality and the presence of recognised pathogens, histological evidence of pulmonary inflammation, aspiration of stomach contents, age at death, sex, and death-postmortem interval. There were, however, lower concentrations of phosphatidylcholine and phosphatidylcholine palmitate content in infants colonised by organisms with reported phospholipase A2 activity.     

Decreased lung surfactant disaturated phosphatidylcholine in sudden infant death syndrome

The lipid composition of lung surfactant obtained by lung lavage at autopsy in 40 infants dying from the sudden infant death syndrome (SIDS), was compared to that obtained from 12 infants dying from other causes (control group). Analysis of the lipids from the two groups showed no major difference in the proportions of the various phospholipid classes particularly the predominant component, phosphatidylcholine (PC), which was present at 60.7 +/- 0.9% (mean +/- S.E.) of the total phospholipids in the SIDS group and 57.9 +/- 2.9% in the control group. However the proportion of the PC present as the disaturated form (DSPC), was significantly (P less than 0.01) reduced in the SIDS group (65.8 +/- 1.6%) in comparison to the control group (77.4 +/- 3.5%). The proportion of DSPC present in the PC fraction of SIDS infants in the high-risk age range of 1-26 weeks (63.9 +/- 1.9%) was also significantly reduced (P less than 0.01) in comparison to the total control group of infants. For infants older than 26 weeks, significant differences in the proportion of DSPC in PC were not observed between SIDS and control groups. A functional consequence of the observed reduction in the DSPC content of lung surfactant of SIDS infants could be a greater degree of fluidity of the surfactant, particularly at exhalation. Such a biophysical change in surfactant properties could have a profound influence on lung function and be a causative factor in sudden infant death.     

Decreased lung surfactant disaturated phosphatidylcholine in sudden infant death syndrome

The lipid composition of lung surfactant obtained by lung lavage at autopsy in 40 infants dying from the sudden infant death syndrome (SIDS), was compared to that obtained from 12 infants dying from other causes (control group). Analysis of the lipids from the two groups showed no major difference in the proportions of the various phospholipid classes particularly the predominant component, phosphatidylcholine (PC), which was present at 60.7 ± 0.9% (mean ± S.E.) of the total phospholipids in the SIDS group and 57.9 ± 2.9% in the control group. However the proportion of the PC present as the disaturated form (DSPC), was significantly (P < 0.01) reduced in the SIDS group (65.8 ± 1.6%) in comparison to the control group (77.4 ± 3.5%). The proportion of DSPC present in the PC fraction of SIDS infants in the high-risk age range of 1–26 weeks (63.9 ± 1.9%) was also significantly reduced (P < 0.01) in comparison to the total control group of infants. For infants older than 26 weeks, significant differences in the proportion of DSPC in PC were not observed between SIDS and control groups. A functional consequence of the observed reduction in the DSPC content of lung surfactant of SIDS infants could be a greater degree of fluidity of the surfactant, particularly at exhalation. Such a biophysical change in surfactant properties could have a profound influence on lung function and be a causative factor in sudden infant death.     

Enlargement of the tongue in sudden infant death syndrome.

Anatomic details of the infantile oropharynx and relationships to possible airway obstruction in sudden infant death syndrome (SIDS) are understood incompletely. Tonkin recognized this in 1975, suggesting that enlargement of the tongue might be important in SIDS, within the context of other anatomic and physiologic factors unique to early life. We therefore conducted a morphometric study of the tongue in 100 victims of SIDS and 36 control infants; the latter group consisted of infants with the same range in age and body size who had grown normally and died acutely. Highly significant differences in tongue weight, width, and thickness were demonstrated between the two groups by linear regression and analysis of covariance. Two multivariate techniques, stepwise discriminant analysis and factor analysis, identified marked discordance between somatic and lingual size in SIDS and a statistical uniqueness in tongue thickness. Certain explanations for lingual enlargement in SIDS were ruled out: redistribution of fluid and other effects of death, postmortem interval, duration and mode of feeding, and smallness of control tongues. At present, the functional significance of these observations is unclear. The effects of both normal and increased tongue size on airway patency are, however, widely recognized. Further studies of the enlarged tongue, addressing such topics as in situ anatomy and developmental mechanisms, are necessary to establish the potential for pathophysiologic consequences in SIDS.