Hepatic microsomal glucose-6-phosphatase system and sudden infant death syndrome.

Microassay techniques and monospecific antibodies were used to study the hepatic glucose-6-phosphatase system in liver samples from 55 infants who had died suddenly and unexpectedly, including 38 victims of sudden infant death syndrome (SIDS). Raised hepatic glycogen was found in 10, all of whom had a diagnosis of SIDS, and in 1 other infant who was already known to have type 1b glycogen storage disease (deficiency of transport protein T1). Of the 10 infants with raised hepatic glycogen who had a diagnosis of SIDS, 8 had glucose-6-phosphatase deficiency (type 1a glycogen storage disease), and 2 had transport protein T2 deficiency (type 1c glycogen storage disease).

Respiratory control in infants at increased risk for sudden infant death syndrome.

There is much debate relating to possible abnormalities in respiratory control mechanisms in infants considered at increased risk for sudden infant death syndrome (SIDS). The P0.1 occlusion technique was used to assess the central respiratory response to hyperoxic hypercapnia during quiet sleep in 21 normal infants, 13 siblings of SIDS victims, and 17 infants with apparent life threatening events. The slope of P0.1 plotted against carbon dioxide concentration increased exponentially with age, independent of body weight in each group. Birth weight has a significant effect on slope with a lower weight predisposing to a lower slope. Siblings as a group had a significantly lower slope at any given age than normal infants, whereas the infants who had had apparent life threatening events were not significantly different from the controls. As intragroup variation in both siblings and control groups greatly exceeded the significant intergroup differences observed, the technique cannot identify individual infants as belonging to one or other group.

Polysomnographic sleep and waking states are similar in subsequent siblings of SIDS and control infants during the first six months of life.

Twenty-five subsequent siblings of infants who died of Sudden Infant Death Syndrome (SIDS) underwent 12-h overnight polygraphic recordings during the first week of life and at 1, 2, 3, 4, and 6 months of age. The polygraphic tracings from these infants were compared with those from 25 infants without a family history of SIDS. One dozen sleep and waking parameters were examined including state transition probabilities, the ratio between quiet sleep (QS) and active sleep (AS), the incidence and duration of sustained states and the stability of an infant's sleep and waking during the first half year of life. Variability within and between infants was marked with a reduction of variability in measures of QS at 3 months and of AS at 4 months of age. The similarities between subsequent siblings of SIDS and control infants far outweighted the differences. However, subsequent siblings exhibited a tendency, once asleep, to remain asleep longer than controls. This finding was observed in a comparison of 20 infants in each group. When five infants were added to each group, infants in both groups tended to awaken equally from QS, but once in AS the subsequent siblings tended to proceed into QS instead of awaken as the controls did.

Impaired arousal from sleep: relationship to sudden infant death syndrome.

There is a relationship between deficient sleep arousal response to asphyxia, the presence of symptomatic apnea, and the risk for recurrent episodes of life-threatening sleep apnea. This documented abnormality in arousal responsiveness, which could result in the inability to respond to apnea-induced asphyxia, is the only respiratory control deficit that could result in sudden death. Inability to arouse from sleep in response to asphyxia may also be the underlying abnormality explaining numerous other behavioral deficits reported in infant groups with symptomatic apnea or otherwise thought to be at increased risk for sudden infant death syndrome (SIDS), including awake behavioral differences in temperament. An arousal response deficit to asphyxia may thus be a critically important and fundamental pathophysiological component of the essential defect necessary for the occurrence of sudden death during sleep. As with any other observed abnormality, however, it has not yet been possible to design an asphyxic arousal response test with sufficient accuracy and sensitivity to identify prospectively those infants otherwise destined to die of SIDS. Although an impairment in arousal responsiveness may be necessary for SIDS to occur such a deficit may not be sufficient to cause SIDS unless or until another factor(s) occurs that can cause sleep-related asphyxia. Although impaired respiratory control appears to be the likely precipitating cause of sleep-related asphyxia, it is also possible that factors unrelated to respiratory control are important in causing asphyxia; superimposed on an underlying arousal deficit, these could result in SIDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart rate variation in normal infants and victims of the sudden infant death syndrome.

Infants who later succumb to the sudden infant death syndrome (SIDS) exhibit lower overall heart rate variability during waking than do other infants. This study attempts to determine which type or types of heart rate variation are reduced in SIDS victims. Long-term recordings of heart rate and respiration were obtained from normal infants and infants who later died of SIDS, and heart rate variation in three frequency bands was examined: respiratory sinus arrhythmia (periods 0.9-3.0 s), 'mid-frequency' (periods 4.0-7.5 s) and 'low-frequency' (periods 12-30 s). All three types of heart rate variation were diminished in SIDS victims under 1 month of age during waking and rapid eye movement (REM) sleep compared with controls. Partitioning heart rate effects showed that in waking, and to a lesser extent in REM sleep, the reduction in all types of heart rate variation exceeded that which would have been predicted based on higher heart rates in SIDS victims. No heart rate-independent reduction in any type of heart rate variation was observed in quiet sleep. This state-dependent reduction in three types of heart rate variation could indicate an abnormality of autonomic control mechanisms during waking and REM sleep in infants who later succumb to SIDS.

[The autonomic nervous system in sudden infant death syndrome. Analysis of heart rate and sinusal variability on Holter monitoring of infants who died]. / Le système nerveux autonome dans le syndrome de la mort subite du nourrisson. Analyse du rythme cardiaque et de la variabilité sinusale sur les enregistrements Holter d'enfants décédés du syndrome.

To evidence abnormality of cardiac control by the autonomic nervous system in the sudden infant death syndrome (SIDS) we retrospectively analysed the Holter recordings and cardiopneumograms of 19 infants (11 boys, 8 girls) of mean +/- SD age 2.3 +/- 1.5 months who had subsequently died of SIDS. Two infants were regarded as normal and the reference diagnoses in the remaining 17 infants were: apparent life threatening event (8), SIDS siblings (8) and prematurity (1). At the time of death the age was 4.2 +/- 2 months. Each of these infants was matched with three control infants in term of postnatal age, gestational age and reference diagnosis, but without SIDS at follow-up of at least one year. Nine hours of Holter recordings (9 p.m. to 6 a.m.) were analysed in term of mean heart rate and sinus oscillations waves. To differentiate between short oscillations of 4 to 6 RR, which are induced by respiration and reflect vagal activity, and long oscillations of 20 to 32 RR, which reflect both neurogenic sympathetic and vagal activity, we used a new method which measures the number and the amplitude in milliseconds of each type of oscillations. The results are expressed as the logarithm of the product of these two variables. Heart rate, correlated to age in both groups, is higher in the deceased infants group (141 +/- 14 mn and 135 +/- 15; p less than 0.05: analysis of covariance with age as an independent variable). Short oscillations, also correlated to age, are lower in the deceased infants group (3.35 +/- 0.59 and 3.65 +/- 0.61; p less than 0.05: analysis of covariance with age).(ABSTRACT TRUNCATED AT 250 WORDS)

Pneumogram recordings in infants resuscitated for apnea of infancy.

Infants who sustained a spell of apnea of infancy during which they were resuscitated have been shown to be at increased risk for sudden infant death syndrome. To determine the value of the pneumogram as a predictor of outcome in this population, the first pneumogram obtained of 51 such infants was analyzed. The infants were grouped on the basis of subsequent outcome during a course of monitoring: group 1--infants who died during a subsequent event; group 2--infants who received resuscitation or vigorous stimulation to terminate a subsequent spell; group 3--infants who survived and did not have a significant subsequent episode. The results for these infants were compared with those of a control group matched for age and sex. A detailed, blinded computer analysis revealed no significant difference in the results of the pneumogram analysis between the three groups. It did not identify the infants in whom apneic spells necessitating resuscitation subsequently developed or those who died. However, when compared with the control group, infants with apnea of infancy had significantly higher mean respiratory rates, heart rates, and tachycardia indexes. It is concluded that, although the first pneumogram does not predict the risk of an adverse outcome in a population of infants with severe apnea of infancy, it does reveal subtle cardiorespiratory differences between study and control infants.

Sleep phase and gastro-oesophageal reflux in infants at possible risk of SIDS.

The association between gastro-oesophageal reflux and sleep state in 24 infants with confirmed or suspected gastro-oesophageal reflux was studied by monitoring both the pH in the lower oesophagus and polygraphic tracings made during sleep at night. Gastro-oesophageal reflux during the night was confirmed in 20 infants. Three hundred and sixteen precipitous drops of more than one unit of pH were recorded during the studies, 186 during periods of wakefulness. Of 130 drops in pH during sleep, 62 (48%) began during active sleep and 62 during indeterminate sleep. Of the latter, 56 (90%) were associated with brief gross body movements. Only five of the drops in pH (4%) began during quiet sleep. Gastro-oesophageal reflux stopped during active sleep on 56 occasions (43%), in indeterminate sleep in 62 (47%), and in quiet sleep in 12 (9%). Episodes of gastro-oesophageal reflux starting or ending in quiet sleep were uncommon. The occurrence of gastro-oesophageal reflux during active sleep may partly explain why reflux during sleep is a risk factor for pulmonary disease.

Hypoxia reinforces laryngeal reflex bradycardia in infants.

The laryngeal chemoreflex involves bradycardia, apnea, swallowing and peripheral vasoconstriction. This reflex was studied in twelve infants, aged 5 days-28 weeks, who had sustained an apparent life-threatening event or were siblings of infants who had died of the sudden infant death syndrome. The bradycardic and apneic components of the reflex were found to be significantly, and sometimes powerfully, reinforced when elicited by pharyngeal water instillation during acute, mild hypoxia (transcutaneous PO2 4.6-8.3 kPa). Apnea duration during normoxia was 0.7-15 sec, and during hypoxia 2-30 sec. Heart rate change ranged from +26% to -21% during normoxia, as compared with -4% to -63% during hypoxia. The percentage change in heart rate was found to inversely correlate with the transcutaneous PO2-level prevailing when the reflex was elicited. The conclusion is that there is a significant reinforcement of the cardiorespiratory adjustments when the laryngeal reflex is activated during simultaneous excitation of the peripheral arterial chemoreceptors. One infant, showing a particularly strong increase of the cardiorespiratory response to laryngeal receptor stimulation during hypoxia, later died of sudden infant death syndrome.

[Sudden death syndrome in the newborn infant and sleep]. / Syndrome de mort subite du nourrisson et sommeil.

It seem increasingly obvious that sudden death is a multifactorial syndrome, the result of respiratory and/or cardiac dysfunction in responses to various causes. Cardiorespiratory and neurophysiological explorations performed during sleep have considerably increased our understanding of the syndrome. They have been at the root of all recent theories, and they make it possible to rule out a likely cause in infants "rescued" from sudden death. Some of these explorations may be used for screening purposes, as they sometimes evaluate the risk of apnea or cardiac accident capable of causing sudden death. The development of sleep during the first 6 months of life plays de determinant role in the syndrome. Slightly more than 80 p. 100 of deaths occur during a period of presumed sleep. The 1 to 6 months period is characterized by very rapid changes in the quality and organization of sleep: there is a substantial increase in quite sleep time, during which the child is most probably vulnerable, and a decrease in agitated sleep time which at that age is thought to protect against sudden death. This is also the period of life where sleep stability increases and where al circadian rhythms are constituted and harmonized with each other. The rapidity and nature of these changes probably makes this period a time of risk. Another factor of importance is the problem of sudden infant death is the ability to wake up. Recent studies have shown that infants believed to be at risk of sudden death seem to have disturbed awakening mechanisms.

[Sudden infant death--the QT interval in ECG and bradyarrhythmias]. / Krybbedød--QT-intervallet i EKG og bradyarytmier.

Prolongation of ventricular repolarization, as evidenced from an increased QT-interval, makes the ventricles more susceptible to fibrillation. The theory has previously been advanced that some cases of sudden infant death syndrome may be due to a non-hereditary QT-prolongation, resulting in fibrillation and cardiac death. This theory has been seriously doubted, since in subsequent long series of recordings in newborns the QT-interval has been found normal at rest. However, the QT-theory has recently been revived by a report that in some babies with sudden infant death syndrome the ability to shorten the QT-interval as the heart rate increases is impaired, an observation which is consistent with the QT-theory. The present experiments on infant and adult rodents have shown that during the innate fear paralysis reflex, elicited by a variety of frightening stimuli of a type that commonly occur during ordinary daily life, the QT-interval may be transiently prolonged and is usually associated with bradycardia and changes of the ST-segment and T-wave. The fear paralysis reflex has previously been proposed as a triggering mechanism for SIDS. These findings lend support both to the fear paralysis theory and the QT-theory. The reflex may represent an external cause of QT-prolongation which adds to the intrinsic impairment of repolarization resulting in a condition which favours ventricular fibrillation. A second unfavourable intrinsic factor is chronic hypoxia.

Polygraphic features of a victim of sudden infant death syndrome and of infants with apparent life-threatening event.

We analyzed a polygram of a victim of sudden infant death syndrome (SIDS) which had been taken five weeks prior to his death. The findings are discussed in association with the serial polygraphic observations of four infants who had suffered from apparent life-threatening event (ALTE), and twenty neurologically normal infants. Frequencies of respiratory pauses were high in SIDS, and average durations of respiratory pauses showed higher values in ALTE than in the controls. Normal paradoxical motions between chest and abdominal wall during active sleep period (AS) were completely abolished in the records of SIDS and of one ALTE. Normal developmental decreases of localized movements (LMs) on mental muscle with age were insufficient in ALTE. The numbers of twitch movements (TMs) were low in SIDS and in two of ALTE, while those of gross movements in the subjects were identical with those in the controls. Dissociation indexes (ratio of the number of TMs against the sum of the numbers of TMs and LMs) were low in SIDS and in two of ALTE. These findings seemed to be the physiological reflection of the impairment of arousal responsiveness and of the developmental disturbance of the brainstem in SIDS and ALTE. Polygraphic evaluations on the respiratory pattern during AS and the dissociation state of TMs from LMs may be helpful in the early detection of SIDS and/or ALTE in asymptomatic infants.