Obstructive sleep apnea in infants: relation to family history of sudden infant death syndrome, apparent life-threatening events, and obstructive sleep apnea

OBJECTIVES: Familial aggregation of obstructive sleep apnea (OSA) has been shown to be associated with sudden infant death syndrome (SIDS) and apparent life-threatening events (ALTE) in infants. We wanted to determine the incidence of OSA in infants with siblings with ALTE and SIDS referred to our sleep clinic and to ascertain whether OSA was more common in infants who have family histories of SIDS, ALTE, and OSA. STUDY DESIGN: We studied 125 infants (mean age, 11.5 +/- 0.6 weeks) who were separated into 2 groups on the basis of their family history; polysomnographic studies were performed on each infant. RESULTS: Twenty infants had a multiple family history of SIDS, ALTE, or OSA (group 1), whereas the other 105 infants (group 2) had only one case of SIDS or ALTE within the family and no known history of OSA. We found that 19 of 20 infants in group 1 had OSA, whereas only 31 of 105 infants in group 2 had OSA (chi-squared analysis, P <.05). The OSA recorded was more frequent in infants of group 1 than in those of group 2. Follow-up studies in some infants with OSA demonstrated a progressive decrease in OSA, which resolved between 6 and 12 months of age. CONCLUSION: We conclude that infants of families with multiple histories of SIDS, ALTE, and OSA are more likely to have OSA than infants of families with only one case of SIDS or ALTE.     

Altered arousal response in infants exposed to cigarette smoke.

AIMS: A failure of the arousal mechanism is a key feature in the apnoea theory for sudden infant death syndrome (SIDS). In infants studied at an age when the incidence of SIDS is highest, we evaluated whether in utero smoke exposed infants have altered arousal response to standardised auditory stimuli, and/or sleep pattern, as recorded on overnight complex sleep polysomnography. METHODS: A standardised sequence of audiology stimuli was applied binaurally to 20 in utero smoke and non-smoke exposed infants aged 8-12 weeks during a rapid eye movement (REM) and NREM epoch, in a controlled (temperature, position, pacifier use, noise) sleep environment. Infants were monitored for 10-12 hours using complex sleep polysomnography. RESULTS: Five infants exposed to in utero tobacco smoke did not have behavioural arousal response, whereas all non-smoke exposed infants aroused during NREM (p = 0.016). There was, however, no difference in REM sleep, and the groups did not differ in routine overnight complex sleep polysomnography parameters. CONCLUSION: At the age when the incidence of SIDS is at its peak, infants of smoking mothers are less rousable than those of non-smoking mothers in NREM sleep; this may partly explain why such infants are more at risk of SIDS.     

Altered arousal response in infants exposed to cigarette smoke

Aims: A failure of the arousal mechanism is a key feature in the apnoea theory for sudden infant death syndrome (SIDS). In infants studied at an age when the incidence of SIDS is highest, we evaluated whether in utero smoke exposed infants have altered arousal response to standardised auditory stimuli, and/or sleep pattern, as recorded on overnight complex sleep polysomnography. Methods: A standardised sequence of audiology stimuli was applied binaurally to 20 in utero smoke and non-smoke exposed infants aged 8–12 weeks during a rapid eye movement (REM) and NREM epoch, in a controlled (temperature, position, pacifier use, noise) sleep environment. Infants were monitored for 10–12 hours using complex sleep polysomnography. Results: Five infants exposed to in utero tobacco smoke did not have behavioural arousal response, whereas all non-smoke exposed infants aroused during NREM (p = 0.016). There was, however, no difference in REM sleep, and the groups did not differ in routine overnight complex sleep polysomnography parameters. Conclusion: At the age when the incidence of SIDS is at its peak, infants of smoking mothers are less rousable than those of non-smoking mothers in NREM sleep; this may partly explain why such infants are more at risk 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.     

Sleep organization and energy expenditure of breast-fed and formula-fed infants.

Sleep organization of infants may be influenced by differences in nutrient intakes from human milk and formula. Because sleep/awake and sleep stage patterns affect energy expenditure, we hypothesized that differences in sleep organization between breast-fed and formula-fed infants might account in part for differences in energy expenditure between feeding groups. Sleep stages and cycling of 4-mo-old breast-fed (n = 10) formula-fed (n = 10) infants were studied with simultaneous measurements of energy expenditure. EEG, electrooculogram, body movement by triaxial accelerometry, heart rate, and oxygen saturation were monitored during an overnight sleep session. Sleep stages, nonrapid eye movement (NREM), and rapid eye movement (REM) were determined. Behavioral observations were recorded by video tape and by a technologist. Oxygen consumption and carbon dioxide production were measured with an indirect calorimeter. Total number and duration of sleep cycles, REM latency, number of NREM and REM epochs, and duration of NREM epochs did not differ between feeding groups. Sleep latency was shorter (p < 0.05) and duration of REM epochs longer (p < 0.01) in the formula-fed group. Formula-fed infants spent a higher percentage of sleep time in REM compared with the breast-fed infants (42 versus 34%) (p < 0.003). Conversely, breast-fed infants spent a higher percentage of sleep time in NREM sleep and their heart rates during sleep were lower (114 versus 126 bpm; p < 0.01). Energy expenditure during REM sleep was 13.0 +/- 4.4% higher than during NREM sleep (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Epidemiology of apparent life threatening events.

AIMS: To investigate the epidemiology and risk factors of apparent life threatening events (ALTE). METHODS: A prospective study enrolled all live-born infants in the Tyrol (1993-2001). Information on pregnancy, sociodemographic characteristics, child care practices, and infant's behaviour in the first four to six weeks of life was collected with a standardised questionnaire, and was available for 44,184 infants. ALTE was identified from hospital admission records. RESULTS: During the study period 164 ALTE cases were identified, corresponding to an incidence of 2.46/1000 live births. In 73 of these infants no cause for the event and no comorbidity could be found (idiopathic ALTE). On average ALTE manifested ten weeks earlier than SIDS. Of various SIDS risk factors in the survey area, the prone sleeping position, smoking during pregnancy, low gestational age, profuse night sweating, and family history of infant death showed a moderate relation to the risk of overall ALTE, but only smoking maintained significance in the multivariate risk model. None of these variables was associated with idiopathic ALTE. In contrast to SIDS the frequency of ALTE did not change during the study period. None of the ALTE infants experienced SIDS later in life. Behavioural abnormalities such as feeding difficulties, episodes of pallor, cyanotic episodes, and repeated apnoea episodes were strongly associated with an increased risk of overall and idiopathic ALTE. CONCLUSIONS: Although there are some similarities in the clinical presentation and epidemiology of SIDS and ALTE, differences clearly predominate. Accordingly, ALTE and SIDS should not be considered different manifestations of the same disease process.     

Epidemiology of apparent life threatening events

Aims: To investigate the epidemiology and risk factors of apparent life threatening events (ALTE). Methods: A prospective study enrolled all live-born infants in the Tyrol (1993–2001). Information on pregnancy, sociodemographic characteristics, child care practices, and infant''s behaviour in the first four to six weeks of life was collected with a standardised questionnaire, and was available for 44 184 infants. ALTE was identified from hospital admission records. Results: During the study period 164 ALTE cases were identified, corresponding to an incidence of 2.46/1000 live births. In 73 of these infants no cause for the event and no comorbidity could be found (idiopathic ALTE). On average ALTE manifested ten weeks earlier than SIDS. Of various SIDS risk factors in the survey area, the prone sleeping position, smoking during pregnancy, low gestational age, profuse night sweating, and family history of infant death showed a moderate relation to the risk of overall ALTE, but only smoking maintained significance in the multivariate risk model. None of these variables was associated with idiopathic ALTE. In contrast to SIDS the frequency of ALTE did not change during the study period. None of the ALTE infants experienced SIDS later in life. Behavioural abnormalities such as feeding difficulties, episodes of pallor, cyanotic episodes, and repeated apnoea episodes were strongly associated with an increased risk of overall and idiopathic ALTE. Conclusions: Although there are some similarities in the clinical presentation and epidemiology of SIDS and ALTE, differences clearly predominate. Accordingly, ALTE and SIDS should not be considered different manifestations of the same disease process.     

Continuous transepidermal water loss measurement in sleeping infants

Transepidermal water evaporation rate was measured continuously in 8 infants with the use of an evaporimeter during one night of polygraphic sleep recording. Evaporation rates were significantly lower during REM than during NREM sleep. In both sleep stages it decreased during the night with the lowest values between 02.00 and 04.00 h. Evaporation values showed cyclic changes which were studied by measuring minute-by-minute differences between the maximum and the minimum values (the "amplitude variability") and the number of evaporation peaks per minute (the "peak density"). Both the "amplitude variability" and the "peak density" were smaller in REM than in NREM sleep. The "amplitude variability" decreased during the night with lowest values seen between 02.00 and 04.00 h. These changes in evaporation rates could reflect autonomic nervous system activity as well as basal metabolic activity and should be taken into account whenever such measurements are performed in sleeping infants.     

Continuous Transepidermal Water Loss Measurement in Sleeping Infants

ABSTRACT. Transepidermal water evaporation rate was measured continuously in 8 infants with the use of an evaporimeter during one night of polygraphic sleep recording. Evaporation rates were significantly lower during REM than during NREM sleep. In both sleep stages it decreased during the night with the lowest values between 02.00 and 04.00 h. Evaporation values showed cyclic changes which were studied by measuring minute-by-minute differences between the maximum and the minimum values (the "amplitude variability") and the number of evaporation peaks per minute (the "peak density"). Both the "amplitude variability" and the "peak density" were smaller in REM than in NREM sleep. The "amplitude variability" decreased during the night with lowest values seen between 02.00 and 04.00 h. These changes in evaporation rates could reflect autonomic nervous system activity as well as basal metabolic activity and should be taken into account whenever such measurements are performed in sleeping infants.     

癫癎儿童发作间期癫癎样放电特点初步研究

目的：癫癎发作及癫癎样放电具有昼夜倾向,睡眠是诱发癫癎的重要因素之一,但睡眠触发癫癎的易感性在不同的睡眠时相对发作及发作间期癫癎样放电的影响并不相同。该文主要研究局灶性及全面性癫癎儿童发作间期睡眠和觉醒状态癫癎样放电的特点。方法：采用24 h动态脑电图、多导睡眠脑电图及长程视频脑电图仪描记48例原发性癫癎儿童的全夜睡眠（至少一个完整的睡眠周期）和睡眠前后觉醒状态的脑电资料,统计分析觉醒期及各睡眠期棘/尖波、棘/尖慢波等癫癎样波的放电指数的差异,比较局灶性和全面性发作类型癫癎儿童癫癎样放电阳性率的差异。结果：局灶性癫癎儿童组发作间期脑电图癫癎样放电的阳性率高于全面性癫癎儿童组（16/25,64.0%）vs（9/25,36.0%）,（P<0.05）。癫癎患儿非快速动眼睡眠各期（S1~S4）癫癎样波放电指数为21.13±19.96,19.59±17.76,22.85±18.99,20.37±16.63,均高于觉醒期的8.20±6.21（P<0.05）。非快速动眼睡眠期S3期癫癎样波放电指数明显高于快速动眼睡眠期（22.85±18.99 vs 12.91±10.95）,（P<0.05）。结论：局灶性癫癎儿童发作间期脑电图癫癎样放电的阳性率较全面性癫癎儿童癫癎样放电阳性率高。睡眠,尤其是非快速动眼睡眠期对癫癎儿童癫癎样放电具有易化作用。     

Decreased autonomic responses to obstructive sleep events in future victims of sudden infant death syndrome.

To evaluate changes in autonomic nervous system controls in response to obstructive events in future victims of sudden infant death syndrome (SIDS), we studied the polysomnographic sleep recordings of 18 future SIDS infants and those of 36 matched control infants. A heart rate autoregressive power spectral analysis was performed preceding and after the obstructive apneas. The low-frequency to high-frequency power ratio was computed to evaluate sympathovagal balance. Future SIDS victims had significantly more obstructive apneas (p = 0.001) and mixed apneas (p = 0.005) than control infants. Obstructive events occurred mainly during rapid eye movement sleep in the two populations (84.5% in future SIDS victims and 95.8% in control infants; p = NS). Comparing heart rate power spectral analysis before and after obstructive apneas in rapid eye movement sleep, high-frequency power values were significantly lower and low-frequency to high-frequency power ratios higher in future SIDS victims than in control infants. Compared with preapnea values, low-frequency to high-frequency power ratios significantly decreased after obstructive apneas in control infants (p < 0.001) but not in the future SIDS victims. When the obstructive apneas were divided according to duration, the findings were seen mainly for long apneas. In conclusion, future SIDS victims were characterized by different autonomic status and responses to obstructive apneas during sleep. These findings could be relevant to mechanisms implicated in some cases of SIDS.     

Ventilation and ventilatory pattern during sleep in aborted sudden infant death syndrome

To assess ventilatory control during sleep in infants at risk for the sudden infant death syndrome (SIDS), we made serial measurements of resting tidal volume (Vt), respiratory cycle time (Ttot), and the ventilatory changes resulting from inhalation of 2% CO2 in aborted SIDS infants in rapid eye movement and quiet sleep and compared them to a group of normal infants during the first 4 months of life. Ventilation was measured by the barometric method, and sleep was staged using electroencephalogram, electrooculogram, and electromyogram and behavioral criteria. Although resting instantaneous minute ventilation (Vt/Ttot) was virtually the same in both groups of infants, Vt tended to be smaller (by up to 50% in the first 2 months) and Ttot tended to be shorter in aborted SIDS than in normal infants in both rapid eye movement and quiet sleep. The increase in the mean Vt/Ttot with 2% CO2 is greater by about 5 to 20% in aborted SIDS than in normal infants at 3 and 4 months of age in both sleep states. These findings, together with our previous findings that aborted SIDS infants have an increase in heart rate and a shortening of the QT interval, provide indirect evidence that infants at high risk for SIDS may have increased sympathoadrenal activity.     

Abnormal heart rate response to hypercapnia in boys with an apparent life-threatening event

AIM: To determine instantaneous cardiac variability responses to increased carbon dioxide (CO2) during quiet sleep in infants who may be at risk for the Sudden Infant Death syndrome (SIDS). METHODS: The cardiac rate variability before, during and after a CO2 challenge was examined in 41 infants who had experienced an apparent life-threatening event (ALTE) and 41 gender- and age-matched control infants. RESULTS: The ALTE infants responded to CO2 breathing with a significant increase in R-R intervals, i.e. decreases in heart rate, compared to the controls (45.1% increase in R-R intervals vs. 41.4%; p = 0.005). The differences between ALTE infants and controls depended primarily on the boys' responses. CONCLUSION: ALTE infants, particularly ALTE boys, have an autonomic dysfunction-lower sympathetic stimulation and/or inhibited vagal withdrawal when stressed with CO2. The outcome might provide clues to the mechanisms underlying the cardiovascular processes contributing to the terminal event in SIDS.     

Increased inspiratory effort in infants with a history of apparent life-threatening event

The objective of this study was to compare the results of polysomnography between infants with a history of apparent life-threatening event (ALTE) and controls. In this case-control study, 40 full-term ALTE infants, aged 2-36 wk at the time of the event, were compared with 40 age- and sex-matched randomly selected controls. SaO2, tcpO2, tcpCO2, heart rate (HR), vector of rib cage and abdominal respiratory movements (phase angle, as an index of inspiratory effort) were recorded during natural nocturnal active and quiet sleep (AS, QS). SaO2, tcpO2, tcpCO2 were similar in ALTE and controls in both sleep states. Phase angle was increased in ALTE infants in both AS (59+/-46 vs 26+/-17 degrees) and QS (53+/-46 vs 18+/-14, p < 0.001). Eleven ALTE infants (27.5%) experienced SaO2 < 90%, with a mean decrease in SaO2 to 86+/-1.6% (mean +/- SD), compared with 10% for controls (p=0.003). In eight ALTE infants, SaO2 values <90% were linked to thoracoabdominal asynchrony. SaO2 < 90% in conjunction with HR <100 bpm were detected in three ALTE infants and one control. Periodic breathing was observed in 45% of ALTE infants and 40% of controls. CONCLUSION: The mean values of oxygen saturation, tcpO2 and carbon dioxide levels in ALTE infants are comparable with those of healthy controls but the ALTE infants exhibit more hypoxaemic episodes and increased inspiratory effort during sleep.     

Increased cerebrospinal fluid beta-endorphin immunoreactivity in infants with apnea and in siblings of victims of sudden infant death syndrome

To gain further insight into the possible role of endogenous opioid peptides in the respiratory difficulties associated with the apnea of infancy and other disorders possibly related to apnea, the levels of beta-endorphin immunoreactivity were measured in the cerebrospinal fluid (CSF) of five groups of infants: (1) infants with proved apnea, (2) infants with histories of an apparent life-threatening event (ALTE), (3) siblings of victims of the sudden infant death syndrome (SIDS), (4) infants with suspected but unproved apnea, and (5) infants undergoing investigation for other acute illnesses. Twenty-two infants considered at risk for an ALTE (groups 1 to 3) had significantly higher CSF beta-endorphin equivalents (88 +/- 7 pg/mL) than did the 22 control patients in groups 4 and 5 (31 +/- 3 pg/mL). Plasma beta-endorphin immunoreactivity, which was also measured in some of the infants, did not correlate with levels in CSF and, in fact, was significantly lower in the groups at risk for an ALTE (50 +/- 9 pg/mL; n = 14) than in the control subjects (80 +/- 6 pg/mL; n = 11). These studies indicate that elevated beta-endorphin immunoreactivity in CSF may be a marker in infants who have apnea and who may be considered at risk for an ALTE.     

Parental compliance with home cardiorespiratory monitoring.

AIMS: To evaluate parental compliance with home cardiorespiratory monitoring of premature infants with apnoea, siblings of infants who died of sudden infant death syndrome (SIDS), and infants with an apparent life threatening event (ALTE), during the first month of use. METHODS: A retrospective review of the first month's recordings was conducted on 39 premature infants with apnoea, 13 siblings of SIDS, and 16 infants with ALTE. All infants were singletons. Recommendations during the study period (1992-1994) were for daily use for 23 hours per day. Measurements were average daily hours of use and consistency of use (daily or variable). Gestational age, maternal age, and socioeconomic status as measured by receipt of public assistance were also recorded. RESULTS: Siblings of SIDS were monitored for fewer hours than were premature or ALTE infants. Only 54% of sibings of SIDS were monitored daily, compared to 87% of premature infants and 93% of ALTEs. Within each diagnostic category socioeconomic status did not affect average hours of monitoring. Consistency of use was more evident in those with private insurance, although the trend did not reach significance. CONCLUSIONS: Parents of infants with apnoea of prematurity or ALTE are highly compliant with cardiorespiratory monitoring recommendations in the first month of monitor usage. Siblings of SIDS are monitored for fewer hours and are less likely to be monitored on a daily basis.     

Parental compliance with home cardiorespiratory monitoring

AIMS—To evaluate parental compliance with home cardiorespiratory monitoring of premature infants with apnoea, siblings of infants who died of sudden infant death syndrome (SIDS), and infants with an apparent life threatening event (ALTE), during the first month of use.METHODS—A retrospective review of the first month''s recordings was conducted on 39 premature infants with apnoea, 13 siblings of SIDS, and 16 infants with ALTE. All infants were singletons. Recommendations during the study period (1992-1994) were for daily use for 23hours per day. Measurements were average daily hours of use and consistency of use (daily or variable). Gestational age, maternal age, and socioeconomic status as measured by receipt of public assistance were also recorded.RESULTS—Siblings of SIDS were monitored for fewer hours than were premature or ALTE infants. Only 54% of sibings of SIDS were monitored daily, compared to 87% of premature infants and 93% of ALTEs. Within each diagnostic category socioeconomic status did not affect average hours of monitoring. Consistency of use was more evident in those with private insurance, although the trend did not reach significance.CONCLUSIONS—Parents of infants with apnoea of prematurity or ALTE are highly compliant with cardiorespiratory monitoring recommendations in the first month of monitor usage. Siblings of SIDS are monitored for fewer hours and are less likely to be monitored on a daily basis.     

Heart rate variability in infants with apparent life-threatening events

Heart rate variability (HRV) is often used as an index of sympatho-vagal balance. A decreased HRV has been observed in patients with central hypoventilation and in infants who have later succumbed to sudden infant death syndrome (SIDS). The aim of the present study was to investigate whether HRV is altered in infants with apparent life-threatening events (ALTE), a group with an increased risk of SIDS. Fifty infants with ALTE were compared with 50 age- and sex-matched controls. ECG was recorded overnight in all infants. Two sequences of RR intervals free of artefacts were selected from each sleep state and spectral analysis of RR variability was performed. The mean and SD of RR and the low (LFPow) and high (HFPow) frequency power were analysed. In active sleep (AS) the LF/HF ratio was lower in ALTE infants, but no differences were seen in either the LFPow or the HFPow. In quiet sleep (QS), however, ALTE infants had higher SD-RR (p = 0.006), greater HFPow (p = 0.02) and VLFPow (very low frequency power, p = 0.02) than the control infants. The same results were seen when the two sleep states were combined for analysis, ALTE infants had higher SD-RR (p = 0.004), HFPow (p = 0.006) and VLFPow (p = 0.04). Conclusion: The different HRV pattern in ALTE infants compared to healthy controls suggests an altered autonomic control.     

Heart rate variability in response to the sleep-related movements in infants with and without colic

The activity of the autonomic nervous system depends on sleep stage. The imbalance of the autonomic nervous system together with over-reactivity to stimuli has been suggested to be an etiologic factor for infantile colic. This study was designed to estimate the reactivity of the autonomic nervous system to a sleep-time stimulus in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep stages and in colic and control infants. Overnight sleep polygraphic recordings were performed for 12 colic and 14 control infants at the age of 8 weeks. Movements were detected by a static-charge-sensitive bed. Extent of heart rate variability (HRV) was measured in response to spontaneous sleep-related movements. HRV analysis was performed over 2-min segments during NREM and REM sleep before and after 5-36-s long movement periods. Total (0.04-1.0 Hz), low (0.04-0.15 Hz) and high frequency (0.15-1.0 Hz) HRV increased after the movement periods in light NREM sleep (p < 0.001). These changes were not observed in REM sleep. No differences were found between the colic and the control groups in HRV. The observed difference in the response of the HRV between sleep stages is likely to reflect the different characteristics of heart rate control in NREM and REM sleep, but our results do not suggest that colic infants would have abnormal autonomic reactivity to stimuli while asleep.     

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.