Symptoms, sweating and reactivity of infants who die of SIDS compared with community controls

Objective : To describe the symptoms of illness reported by the parents of infants who have died of sudden infant death syndrome (SIDS) compared with those reported by community controls. Methodology : A nationwide case—control study involving regions of New Zealand with 78% of all births between 1987 and 1990. Home interviews were completed with parents of 393 (81% of total) infants who died from SIDS in the post neonatal age group, and 1592 (88.4% of total) controls who were a representative sample of all hospital births in the study region. Results : Symptoms of infection were common in both cases and controls, but were not significantly different. Infants dying of SIDS, however, were likely to have symptoms suggestive of more severe illness in the 2 days before death (odds ratio [OR] = 3.02, 95% confidence interval [CI] 1.69-5.38). After adjusting for potential confounding this was still statistically significant (adjusted OR 2.36, 95% Cl 1.14-4.90). Also, babies dying of SIDS were more likely to have been less reactive to their environment in the 2 weeks before death compared with the controls (univariate OR 0.88, 95% Cl 0.55-1.39, adjusted OR 0.55, 95% Cl 0.59-0.88). ‘Drenching’ sweats at least weekly were reported for 15.6% of case infants compared with 5.9% of control infants (adjusted OR 2.12, 95% Cl 1.53-3.39). Forty per cent of these infants had this symptom in the first 4 weeks of life when it was also associated with a significantly raised risk of SIDS. Apnoea lasting more than 20 s was reported for 13.2% of case infants compared with 5.3% of control infants (adjusted OR 1.93, 95% Cl 1.17-3.17). Similarly, 71.8% of case infants' faces were reported to never turn red while awake compared to 49.8% of control infants (adjusted OR 2.98, 95% Cl 2.19-4.07). Conclusions : Only a small number (6.4%) of babies who die of SIDS have symptoms of serious illness in the 2 days before death. There is support for the hypothesis that there is a group of babies dying of SIDS who have subtle abnormalities in autonomic control or arousal ability.     

Why do ALTE infants not die in SIDS?

Aim: To compare known risk factors for sudden infant death syndrome (SIDS) amongst infants with apparent life threatening events (ALTE) with their matched controls, and ALTE infants who subsequently died of SIDS with infants surviving an ALTE.
Methods: Questionnaires with replies were obtained from 58 ALTE infants and 56 sex and age matched ALTE control infants. 244 SIDS cases and 868 SIDS controls were used as comparison.
Results: The incidence of ALTE was found to be 1.9% among SIDS controls, but 7.4% among infants who later on died of SIDS. The parents sought medical advice in 0.9% vs 3.7%. ALTE infants did not differ from their matched controls. In the ALTE group 13.3% of the survivors had the combination of prone sleeping and maternal smoking compared with 33.3% of those who became SIDS victims.
Conclusions: Our results show some major differences between the ALTE infants and SIDS victims not supporting that these conditions belong to the same entity. However, we cannot exclude the possibility that there is a subpopulation of ALTE infants who did not die in SIDS due to that they were sleeping on the back and not exposed to nicotine.     

Pneumocystis is not a direct cause of sudden infant death syndrome

We compared the frequency of Pneumocystis in 126 sudden infant death syndrome (SIDS) cases with a control group of 24 infants from the San Diego SIDS/SUDC Research Project who died of accidental or inflicted injuries. Cysts were identified in 33% of SIDS cases and 29% of controls. We conclude that Pneumocystis is not a direct cause of SIDS.     

Concentrations of antimony in infants dying from SIDS and infants dying from other causes.

OBJECTIVES: Raised concentrations of antimony have been found in infants dying of sudden infant death syndrome (SIDS). The presumed source of this antimony is toxic gases generated from fire retardants that are present in cot mattresses. The aim of this study was to determine the role of antimony in SIDS. DESIGN: Samples of liver, brain, serum, and urine were collected from all patients dying from SIDS and a group of aged matched control infants who had died of other causes. SETTING: Nationwide study in Ireland. SUBJECTS: 52 infants dying from SIDS and 19 control infants aged > 7 days and < 1 year. RESULTS: The median concentration of antimony in the liver and brain of infants dying of SIDS was < 1 ng/g, with no difference detected between the infants dying from SIDS and the control infants. The range of antimony in the serum of infants dying of SIDS was 0.09-0.71 microg/litre (median, 0.26). Although no difference was found between infants dying from SIDS and control infants, SIDS infants were found to have higher concentrations when compared with healthy infants in the 1st year of life, probably as a result of release of antimony into serum after death. Urine antimony concentrations in infants dying from SIDS were < 3.91 ng/mg (corrected for creatinine) and similar to values found both in control infants and healthy infants. CONCLUSION: There is no evidence to support a causal role for antimony in SIDS.     

Cardiorespiratory patterns in siblings of babies with sudden infant death syndrome.

Clinical data and 24 hour tape recordings of electrocardiogram (ECG) and abdominal breathing movements were collected from 301 infants who had had a sibling who had suffered the sudden infant death syndrome (SIDS). Of these, 261 were referred cases, and 40 were recorded prospectively as part of a population based study; none of the 301 subsequently died. Fifty five of the referred siblings who had been born at full term (greater than or equal to 37 week gestation) were randomly selected for a detailed analysis of heart rate and breathing patterns, as were all siblings born at full term from the prospective study (16 with a previous sibling in whom SIDS had occurred and seven with a sibling born at full term and in whom SIDS had subsequently occurred). The control group consisted of 197 recordings on 170 infants born at full term and matched by postnatal age. The mothers of the siblings smoked and consumed alcohol more often during pregnancy than the mothers of control babies. The siblings had lower Apgar scores and were more often breast fed than controls. There were no significant differences in the number of apnoeic pauses in the quantities of periodic breathing or in the heart and respiratory rates during regular breathing between the siblings and the controls.     

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.     

Liver iron concentrations in sudden infant death syndrome.

To determine the biological significance of high concentrations of non-haem iron in the livers of infants dying from sudden infant death syndrome (SIDS), liver samples were obtained at necropsy from 66 infants who died from SIDS and 28 control infants who died before 2.5 years of age. All were full term deliveries. Liver iron concentrations decreased rapidly with age in the two groups. Liver iron concentrations in the SIDS infants and controls were compared for those infants who died between 1 month and 1 year of age. The median liver iron concentration in the SIDS infants was 296 micrograms/g wet weight; significantly higher than the median of 105 micrograms/g in controls. There was an inverse relation between iron concentration and age in the two groups, but an analysis of covariance confirmed the significantly lower values in controls. The frequency (22%) of HLA-A3 in SIDS infants was similar to that expected for the United Kingdom population (25%) and does not implicate the gene for haemochromatosis as a cause of high liver iron concentrations. These findings show that the peak incidence of SIDS occurs when mean concentrations of iron in liver tissue are higher than at any other time of life. Although a primary causal connection seems unlikely, high tissue iron concentrations may lower resistance to infection and enhance free radical formation, leading to tissue damage.     

Liver iron concentrations in sudden infant death syndrome

To determine the biological significance of high concentrations of non-haem iron in the livers of infants dying from sudden infant death syndrome (SIDS), liver samples were obtained at necropsy from 66 infants who died from SIDS and 28 control infants who died before 2.5 years of age. All were full term deliveries. Liver iron concentrations decreased rapidly with age in the two groups. Liver iron concentrations in the SIDS infants and controls were compared for those infants who died between 1 month and 1 year of age. The median liver iron concentration in the SIDS infants was 296 micrograms/g wet weight; significantly higher than the median of 105 micrograms/g in controls. There was an inverse relation between iron concentration and age in the two groups, but an analysis of covariance confirmed the significantly lower values in controls. The frequency (22%) of HLA-A3 in SIDS infants was similar to that expected for the United Kingdom population (25%) and does not implicate the gene for haemochromatosis as a cause of high liver iron concentrations. These findings show that the peak incidence of SIDS occurs when mean concentrations of iron in liver tissue are higher than at any other time of life. Although a primary causal connection seems unlikely, high tissue iron concentrations may lower resistance to infection and enhance free radical formation, leading to tissue damage.     

Cry features in siblings of SIDS

AIM: To examine the acoustic features of crying demonstrated by infants whose older sibling died of sudden infant death syndrome (SIDS) and compare these features to a nonrisk group of infants. METHODS: Pain-induced crying episodes were collected from a group of healthy term (HT) infants and siblings of SIDS infants. One complete crying episode was obtained from each infant and analyzed acoustically with regard to durational and spectral features. RESULTS: The cries of SIDS siblings were found to be significantly higher in pitch and reflected hyperadductory vocal fold vibratory behaviour compared to the HT group. There were no group differences with regard to durational features of crying. CONCLUSIONS: The laryngeal behaviour of infant crying, as inferred via acoustic analyses, differs between HT infants and siblings of SIDS infants. Accordingly, acoustic features of infant crying may serve as an additional diagnostic marker in the identification of children who may be at risk for SIDS.     

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.     

Sudden infant death syndrome and prolongation of the QT interval

A standard lead II ECG was recorded during either the first or the fourth week of life or at both ages from 30 neonates whose sibling had died of the sudden infant death syndrome (SIDS). Electrocardiographic recordings also were obtained from 75 control neonates and from 52 adults who had had an infant who died of SIDS. The neonatal data revealed that the QT interval, corrected for heart rate (QTC), was longest during NREM (vs rapid eye movement [REM]) sleep. Furthermore, the QTC interval was longer within the fourth week than in the first week of life. However, the QTC interval of siblings of SIDS victims did not differ from that of the control infants, nor did the QT interval of parents of SIDS victims differ from published normal values. One neonate who subsequently died of SIDS did not have an abnormally long QTC interval. These data do not support the hypothesis that genetically determined prolongation of the QT interval plays a major role in SIDS.     

Gluconeogenic enzymes in fibroblasts from infants dying of the sudden infant death syndrome (SIDS)

The activities of mitochondrial phosphoenolpyruvate carboxykinase (PEPCK), pyruvate carboxylase (PC), and total malic enzyme (ME) were determined in cultured fibroblasts from 74 infants diagnosed as having died from the Sudden Infant Death Syndrome (SIDS) and 36 infants who died from known causes. In addition, the glycemic state of infants was measured by determining the 'maximum' glucose present in plasma and cerebral spinal fluid (CSF) based on the following formula: glucose (maximum) = glucose + 1/2 (lactate). There were no statistical differences between SIDS and control infants in any of the three enzymatic activities measured in fibroblasts or in the estimated 'maximum' glucose values in plasma or CSF. The present results do not support the involvement of hypoglycemia as a cause of death in SIDS.     

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.     

Clothing and bedding and its relevance to sudden infant death syndrome: Further results from the New Zealand Cot Death Study

As part of a large nationwide case-control study covering a region with 78% of all births in New Zealand during 1987–90, the clothing and bedding of infants dying of sudden infant death syndrome (SIDS) and that of an appropriate control group were recorded. Cases consisted of 81% (n= 393) of all cases of SIDS in the study area and 88.4% (n= 1592) of 1800 control infants randomly selected from the hospital births and who completed a home interview. Use of a wool ‘waterproof’ underblanket was associated with a significantly reduced risk of SIDS (adjusted OR 0.44; 95% CI: 0.26-0.73) while sheepskin use was not. Firm tucking was identified as contributing to a reduced risk of SIDS even after adjusting for potentially confounding variables (adjusted OR 0.63, 95% CI: 0.46–0.86). Sixty case infants (15.6% of cases) were found dead with the head covered but there were no equivalent data for controls. Having been found previously completely covered by bedding was equally common in cases and controls (28.8% cases and 30.6% of control infants). Other differences of bedding and clothing between cases and controls were small; mattress characteristics were not studied. The exact methods in which babies are cared for are important and this study suggests that infants are at lower risk of SIDS when firmly tucked in and when sleeping on a ‘waterproof wool underblanket.     

Pre- and perinatal clinical characteristics of infants who suffer sudden infant death syndrome

In a population-based study, clinical and physiological data were collected in the neonatal period on 7,496 full-term (greater than or equal to 37 weeks) infants of birthweights greater than 2.50 kg born in 3 hospitals. The sample excluded a small number of infants who were born with severe illnesses from which there was no period of recovery before death in the neonatal period. Twenty-seven of the infants had died by the time all of the population had passed their third birthday. Twenty-one of these cases died suddenly and unexpectedly, and in 13 there was no adequate explanation for death (sudden infant death syndrome-SIDS). Pre- and early postnatal clinical data on the infants who had died were compared to a randomly selected sample of 478 survivors. This analysis showed that the infants who suffered SIDS showed similar clinical characteristics to those previously reported. Unlike the SIDS group, however, the prenatal histories of the non-SIDS deaths were similar to controls, showing no evidence of a sub-optimal intra-uterine environment.     

Pneumograms in infants who subsequently died of sudden infant death syndrome

Victims of sudden infant death syndrome (SIDS) have occasionally been reported to have had prolonged apnea or an increased frequency of short apnea prior to their deaths. To examine the extent of these abnormalities, we compared pneumograms obtained in 17 infants who subsequently died of SIDS (10 with history of apnea) with those of 34 age- and sex-matched controls. The recordings were analyzed by a computer program that avoided observer bias. SIDS infants had significantly greater mean heart rate (P less than 0.05) and periodic breathing during quiet time (P less than 0.003) than control infants had. The apnea in SIDS infants tended to be more periodic than in control infants (P less than 0.002). In addition, the incidence of bradycardia was greater in SIDS (three infants) than in controls (none) (P less than 0.03). These differences suggest a disturbance of autonomic function prior to death in some victims of SIDS.     

Pacifier use and sudden infant death syndrome: results from the CESDI/SUDI case control study. CESDI SUDI Research Team.

OBJECTIVES: To investigate the relation between pacifier use and sudden infant death syndrome (SIDS). DESIGN: Three year population based, case control study with parental interviews for each death and four age matched controls. SETTING: Five regions in England (population > 17 million). SUBJECTS: 325 infants who had died from SIDS and 1300 control infants. RESULTS: Significantly fewer SIDS infants (40%) than controls (51%) used a pacifier for the last/reference sleep (univariate odds ratio (OR), 0.62; 95% confidence interval (CI), 0.46 to 0.83) and the difference increased when controlled for other factors (multivariate OR, 0.41; 95% CI, 0. 22 to 0.77). However, the proportion of infants who had ever used a pacifier for day (66% SIDS v 66% controls) or night sleeps (61% SIDS v 61% controls) was identical. The association of a risk for SIDS infants who routinely used a pacifier but did not do so for the last sleep became non-significant when controlled for socioeconomic status (bivariate OR, 1.39 (0.93 to 2.07)). CONCLUSIONS: Further epidemiological evidence and physiological studies are needed before pacifier use can be recommended as a measure to reduce the risk of SIDS.     

Sudden infant death syndrome: abnormalities in short term fluctuations in heart rate and respiratory activity

In order to test the hypothesis that a defect in cardiorespiratory regulation contributes to death of infants from sudden infant death syndrome (SIDS), we analyzed the power spectra of heart rate and respiratory activity during 256-sec epochs of quiet sleep. Data were obtained from pneumogram recordings performed for 12 h at night on eight infants who subsequently died from SIDS and 22 age-matched control infants. We computed the heart rate and respiratory power spectra from a single epoch on each infant using an algorithm developed for an 8085 microprocessor system dedicated to this investigation. There was no statistically significant difference between SIDS and controls based on mean respiratory and heart rates. Spectral analysis revealed enhancement of low frequency power in the 0.02 to 0.1 Hz band in the heart rate power spectrum in the SIDS group compared to control (p less than 0.002) and dispersion in respiratory frequency as determined by the respiratory band width (p less than 0.00001). These data suggest that a predisposition to SIDS manifests itself in an abnormal pattern of fluctuations in heart rate and respiratory activity.     

Recurrence incidence of sudden infant death syndrome.

The incidence of sudden infant death syndrome (SIDS) between birth and 2 years of age in South Australia was found to be 2.1/1000 live births. The incidence in previous siblings was 10 times that expected, in second degree relatives five times, and in third degree relatives four times that expected for the community. The minimum incidence in the next subsequent sibling was five times that expected. Except for one family in which both twins died during the same night, the surviving twin has never died (23 infants). The incidence of SIDS in adopted infants was similar to the incidence in natural born infants. Families in which two or more siblings died from SIDS differed from families in which only one infant died from SIDS in several ways. More infants were over 12 months old, and the mothers had an increased incidence of previous miscarriage and threatened miscarriage during the pregnancy with the infant who died. In one family both infants had bronchomalacia, and two families were severely socially deprived. For most families (92%) in which an infant died from SIDS the risk of recurrence is small (less that twice the expected risk). We have identified a small subgroup (8%) with a significantly increased risk of recurrence.     

Signs and symptoms of illness in early infancy: associations with sudden infant death.

AIMS: to describe a pattern of illness in "normal" infants, and to assess to what extent this may differ in infants who die suddenly and unexpectedly. METHODS: All infants are on the CONI (Care of the Next Infant) scheme in which mothers record symptoms and signs of illness prospectively, on a daily basis from birth to approximately age 6 months. The symptoms of infants who die suddenly and unexpectedly are compared with those of a consecutive sample of infants who survive. Twenty one babies died suddenly, of whom 11 were cot deaths and 10 had "known causes" of death. Ninety eight infants who survived were used as consecutive controls. Prospective daily records of the presence or absence of 26 signs and symptoms were kept by all of the mothers, commencing at birth and lasting an average of 176 days in survivors; 84 days in SIDS; and 93 days in infants who died of known causes. RESULTS: Standardised for age and the time of year, on any given day, the mothers of the SIDS infants were over eight times more likely to record their child as being pale, six times more likely to be sweating, and twice as likely to be irritable. Other signs and symptoms which were three times more likely to be recorded were sore gums, dry stools, and coldness. Infants who died of known causes generally had fewer symptoms. CONCLUSIONS: Cot death infants have a range of symptoms which appear to be of a general nature, and not related to any one system. Symptoms are seen throughout life and not related to the time of death.