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.     

Spectral analysis assessment of respiratory sinus arrhythmia in normal infants and infants who subsequently died of sudden infant death syndrome

Reduced heart rate variability has been found in infants who later succumb to the sudden infant death syndrome (SIDS). To determine whether respiratory sinus arrhythmia, a major component of heart rate variability, is also reduced in SIDS victims, nighttime portions of eighteen 24-h recordings of ECG and respiration from infants who later died of SIDS and 52 recordings from control infants were assessed using spectral analysis. Two aspects of respiratory sinus arrhythmia were examined: "extent" (the absolute heart rate variation at the respiratory frequency) and "coherence" (the degree to which heart rate follows respiration regardless of the absolute amount of variation). Respiratory parameters were used to classify each 1-min epoch as quiet sleep, rapid eye movement sleep, waking, or indeterminate state. Median extent and coherence values across the night were then computed for each sleep-waking state. Two-way (group X state) repeated measures analysis of variance tests were then used to compare respiratory sinus arrhythmia values for 13 SIDS victims and 13 control infants matched by postnatal age, birth weight, sex, and gestational age. Extent of respiratory sinus arrhythmia was significantly lower in the SIDS victims across all sleep-waking states, a finding that persisted after adjusting for heart rate. Coherence values did not differ significantly. These results suggest that even before the time of maximal risk for the syndrome, SIDS victims, as a group, differ from controls in the extent to which cardiac and respiratory activity couple, and this difference is independent of basal heart rate.     

Infant mortality among subsequent siblings of infants who died of sudden infant death syndrome

A specially designed method for measuring infant mortality among families with subsequent siblings of sudden infant death syndrome (SIDS) victims in the state of Washington, 1969 to 1984, yielded results similar to those from an earlier study in Norway. In both studies the SIDS rates among siblings were substantially lower than prior estimates. The rate of SIDS in siblings of infants who died of SIDS did not differ significantly from the SIDS rate among control infants matched for maternal age and birth order. Total infant mortality rates in the two groups were virtually identical. From the data at hand, it appears that earlier estimates of the risk of SIDS in siblings were inflated and that parents of SIDS victims can be counseled accordingly.     

Heart rate variability in infants subsequently suffering sudden infant death syndrome (SIDS)

To study the role of the autonomic cardiovascular control in SIDS the heart rate variability (HRV) was analysed from 24 tape recordings made from a prospective population-based study on 16 term and one preterm infant suffering SIDS and compared to similar data on 23 control infants matched on birthweight, gestation and postnatal age. The number of regular breathing segments was lower in the SIDS cases than in controls (P = 0.02). No significant differences were found between the SIDS cases and their controls for average heart rate, median breathing rate, indices of overall and beat-to-beat HRV. Neither were significant intergroup differences found when the subjects were divided into neonatal and postneonatal subgroups. Analysis of HRV by power-spectral techniques did not show any significant differences between SIDS cases and controls for the general distribution of power or for the respiratory HRV. Analysis of HRV did not differentiate infants destined to die of SIDS from surviving controls in the same population.     

Dynamic analysis of cardiac R-R intervals in normal infants and in infants who subsequently succumbed to the sudden infant death syndrome.

Infants who subsequently succumb to the sudden infant death syndrome (SIDS) have higher heart rates and reduced heart rate variation compared with other infants. We examined dynamic changes in cardiac interbeat intervals to explore these differences in cardiac control. Recordings of electrocardiographic activity and respiratory movement were acquired from 13 SIDS victims before their deaths. Moment-to-moment changes in R-R intervals during quiet sleep, rapid eye movement sleep, and waking were compared with values of 13 matched control infants. For each sleep-waking state, every R-R interval was plotted against the previous interval (Poincaré plots), and each change in interbeat interval was plotted against the previous change. Dispersion of interbeat intervals at different heart rates was reduced in SIDS victims, resulting in Poincaré plots markedly different from those of controls. The dispersion, sampled at the 10th and 90th percentiles of heart rates, was reduced across all sleep-waking states in SIDS victims. At high heart rates, the difference between groups disappeared after correcting for basal rate; however, the reduced range at low heart rates was independent of basal rate. SIDS victims also showed smaller beat-to-beat changes in heart rate and fewer sustained runs of consistent heart rate changes during waking relative to controls. The differences in cardiac rate dynamics suggest altered autonomic control in infants who succumb to SIDS. We speculate that the autonomic disturbance may lead to cardiac instability or may indicate CNS alterations with the potential to affect other vital functions.     

Hypoxanthine levels in vitreous humor: evidence of hypoxia in most infants who died of sudden infant death syndrome.

Postmortem changes of the hypoxanthine in vitreous humor in humans were investigated. Hypoxanthine is formed from hypoxic degradation of adenosine monophosphate. Repeated sampling was performed in 13 deceased adults. Keeping the bodies at +6 degrees C, the increase of the hypoxanthine levels was estimated to 3.5 mumol/L per hour when sampling was started more than 12 hours after death (range 2.8 to 5.6 mumol/L per hour). Results of hypoxanthine measurements from vitreous humor in 73 infants with sudden infant death syndrome, 17 infants and children who died sudden violent deaths, and 6 neonates who died suddenly without hypoxemia prior to death were corrected according to the expected postmortem hypoxanthine increase. The time between death and autopsy was similar in the three groups studied. The corrected median hypoxanthine level in the group with sudden infant death syndrome was 227 mumol/L, which is significantly higher than in the other groups; 22 mumol/L in the group who had violent deaths (P less than .01), and 0 mumol/L in the neonate group (P less than .01). The findings seem to confirm that sudden infant death is preceded by a relatively long period of tissue hypoxia in most cases.     

An assessment of behavioural characteristics in infants who died of sudden infant death syndrome using the Early Infancy Temperament Questionnaire

An assessment of the behavioural peculiarities of infants dying of sudden infant death syndrome (SIDS) was carried out using the Early Infancy Temperament Questionnaire (EITQ). Thirty-six infants (25 boys and 11 girls aged 14 months) in whom the diagnosis of SIDS was confirmed by full necropsy and who died in St Petersburg from 1990 to 1992 entered the study, and the families were approached contemporaneously. A control group consisted of an equal number of age, sex, geographic distribution and date of birth matched live infants from the same city. The infants who died of SIDS had significantly lower estimates of activity in comparison with the babies from the control group. Behavioural defects may be a contributory factor and a sign of increased risk in some babies presenting with SIDS.     

Sleep apnea in infants who succumb to the sudden infant death syndrome

Previous studies have shown the frequency of respiratory pauses to be altered in groups of infants at risk for the sudden infant death syndrome (SIDS). In this study, we assess the frequency of apneic pauses during quiet sleep and rapid eye movement sleep in control infants and infants who subsequently died of SIDS. Sleep states were identified in 12-hour physiological recordings of SIDS victims and matched control infants, and the number of respiratory pauses from 4 to 30 seconds in duration was computed for quiet sleep and rapid eye movement sleep. SIDS victims 40 to 65 days of age showed significantly fewer apneic pauses than did age-matched control infants across the two sleep states. Fewer short respiratory pauses accounted for most of the reduction in number of apneic events in the SIDS victims during both sleep states. During the first month of life, SIDS victims did not differ significantly from control neonates on this measure. The finding that this respiratory difference exists during the second month of life, just before the period of maximal risk for SIDS, but not earlier, may have implications for the etiology of SIDS deaths.     

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.     

Care of infants with near-miss sudden infant death syndrome

The purpose of this study was to evaluate the effectiveness of home management of life-threatening apnea in infants with near-miss sudden infant death syndrome (SIDS). A total of 84 infants were monitored with apnea monitors for an average of seven months (range 1 to 27). A group of 27 infants had episodes of apnea requiring resuscitation during home monitoring, all of whom were successfully resuscitated by their parents on at least one occasion using bag and mask resuscitation, and 17 infants required more than one resuscitation. Subsequent resuscitation was unsuccessful with four infants. Infants who experienced more than ten episodes of prolonged sleep apnea (apnea longer than 20 seconds) during home monitoring had a significantly increased risk of requiring resuscitation than other infants being studied. With the use of home monitoring of these infants and parents trained in cardiopulmonary resuscitation, the survival rate was 93.4%.     

Identifying infants at risk for sudden infant death syndrome

PURPOSE OF REVIEW: This review examines recent research relevant to the underlying pathophysiology and risk factors for sudden infant death syndrome. RECENT FINDINGS: Current research focuses on the linkage between known risk factors and vulnerability, genetic contributions, and the role of dysfunctional brainstem neurotransmission in the pathogenesis of this syndrome. While social inequalities, prematurity, maternal smoking, infant sleeping practices and sleep environment, arousal failures and environmental pollutants remain important risk factors, new evidence is emerging that certain genetic polymorphisms may contribute to vulnerability. New neuropathological studies have provided strong support for abnormal brainstem serotonergic function. Since serotonin influences a wide range of physiological systems including breathing, the cardiovascular system, temperature, and sleep-wake cycles, this finding strongly supports the hypothesis that sudden infant death syndrome is the result of dysregulation of the autonomic nervous system and provides biological plausibility for certain risk reduction strategies. SUMMARY: Despite a putative diagnostic shift, sudden infant death syndrome remains the most common cause of death from 1 month to 1 year of age. Recent studies confirmed established risk factors and have suggested new genetic vulnerabilities. Finally, new evidence supports a key role for abnormalities in brainstem serotonin systems in the pathophysiology of this syndrome.     

Polysomnographic studies and home monitoring of siblings of SIDS victims and of infants with no family history of sudden infant death

We report preliminary results of a prospective study conducted to prevent sudden death in asymptomatic infants. From 1977–1984, 3658 infants were studied polygraphically. There were 923 siblings of SIDS victims and 2735 infants with no personal of family history of SIDS. The infants were studied at 8 weeks of age. Polygraphic risk factors were defined by central apnoeas longer than 15s; periodic breathing above 5% sleep time; or obstructive apnoeas above 3s. In 937 infants risk factors were seen and a second study was requested 4 weeks later. Out of 891 infants re-studied at 12 weeks, 153 still presented some risk factors and were selected for a home monitoring programme; 150 families agreed to monitor their infants at home with a cardiorespiratory monitor with the alarms set at 20s apnoea, and 50 beats per min bradycardia. Repeated alarms were reported for 97/150 (65%) infants; 48/150 (32%) infants were stimulated and 8/150 (5.3%) were resuscitated on at least one occasion. No death occurred during monitoring, which could be interrupted before the end of the first year of life in all infants. In the group of 3459 infants with normal results and not monitored, three siblings (0.35%) and one infant without history (0.04%) died of SIDS. Of the infants with abnormal polygraphic results, one sibling not returned for the second recording, and two out of three infants for whom the parents refused monitoring, died of SIDS. It is concluded that the programme, may prevent the death of some infants, but that the outcome of a child with normal results cannot be foreseen.Abbreviation SIDS sudden infant death syndrome     

Ventilatory chemosensitivity in parents of infants with sudden infant death syndrome

We measured ventilatory responses to progressive isocapnic hypoxia and to hyperoxic hypercapnia (CO2) using rebreathing techniques in 16 parents of infants with autopsy-confirmed sudden infant death syndrome (SIDS) and 18 control parents matched for age, sex, and body size. Response to ventilatory loading was assessed by repeating the CO2 test with an inspiratory flow-resistive load (16 cm H2O/L/sec). During loaded and unloaded CO2 tests, respiratory effort was also assessed by measuring the pressure generated in the first 0.1 second (P0.1) of the subsequent inspiratory effort after brief manual occlusion of the inspiratory line. Ventilatory responses of the parents of victims of SIDS to chemical and mechanical stimulation were not significantly different from those of control parents. Responses in both groups were similar to previously reported normal values. There was a linear increase in ventilation (VE) in response to hypercapnia and hypoxia and in P0.1 in response to hypercapnia. We found expected increases in P0.1/PCO2 and decreases in VE/PCO2 slopes during loaded breathing in all subjects, but no difference between groups. We conclude that parents of SIDS victims have normal ventilatory chemosensitivity and respiratory drive.     

The QT interval in aborted sudden infant death syndrome infants.

The QT interval was measured in 12 normal and 7 aborted sudden infant death syndrome (SIDS) infants in rapid eye movement (REM) and quiet sleep at monthly intervals through the age of 4 months. An accuracy of better than 2 msec was assured by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. In contrast to current speculations, the QT index was significantly smaller in the infants with aborted SIDS than in the normal infants in both REM and quiet sleep (P less than 0.05). In addition, as in normal infants, the QTc was smaller in REM than in quiet sleep (P less than 0.01). Although these results offer no support for the hypothesis that SIDS results from prolongation of the QT interval, they suggest that aborted SIDS infants have a functional abnormality in the autonomic nervous system.     

Cardiorespiratory function in 16 full-term infants with sudden infant death syndrome

Twenty-four-hour tape recordings of ECG and breathing movements from 16 term infants (greater than or equal to 37 weeks' gestation) who subsequently died of sudden infant death syndrome (SIDS) were compared with recordings from surviving infants from the same populations. Apneic pauses of varying durations, periodic and regular breathing patterns, heart and respiratory rates during regular breathing were measured. Only one of 16 full-term infants with SIDS had findings outside the range of age-matched control infants (an excess of periodic breathing patterns and an absence of regular breathing). When the first recordings of each of infants who died of SIDS, except one who had cyanotic episodes prior to death, were compared to recordings of survivors (six for each case) closely matched for age, gestation, and weight at birth, no differences in breathing patterns or heart or respiratory rates during regular breathing could be demonstrated. These particular measurements of cardiorespiratory function were, therefore, unable to identify the majority of full-term infants at risk for SIDS.     

Periodic breathing in infants with near-miss sudden infant death syndrome.

Twelve-hour nocturnal home recordings of respiration and heart rates were obtained during sleep in 32 infants with near-miss sudden infant death syndrome (SIDS) and in 32 control infants, and the recordings were analyzed for periodic breathing. An episode of periodic breathing was defined as three or more apneic pauses of three or more seconds. The duration of respirations interrupting the pauses was 20 seconds or less. Analysis revealed a statistically significant difference (P less than .001) between the two groups, using criteria of percent of periodic breathing episodes, number of periodic breathing episodes/100 min of recorded sleep time, average duration of all episodes, and duration of the longest episode of periodic breathing. It is concluded that periodic breathing is present in excessive amounts during sleep in infants with near-miss sudden infant death syndrome.