Arousal and ventilatory responses to mild hypoxia in sleeping preterm infants.

A failure to adequately respond to hypoxia has been implicated in the Sudden Infant Death Syndrome (SIDS). Preterm infants are at increased risk for SIDS, thus we compared ventilatory and arousal responses to mild hypoxia [15% oxygen (O2)] in preterm and term infants. Eight preterm and 15 term infants were serially studied with daytime polysomnography during which nasal airflow was monitored by pneumotachograph at 2-5 weeks, 2-3 and 5-6 months. At each age, in both groups, hypoxia induced a significant decrease in oxygen saturation (SpO2) during both active sleep (AS) and quiet sleep (QS). Infants invariably aroused in AS; and in QS either aroused or failed to arouse. In preterm infants arousal latency in AS was longer than in term infants (P < 0.05) at 2-5 weeks. Compared with term infants, preterm infants reached significantly lower SpO2 levels at 2-5 weeks in both AS and QS non-arousing tests and at 2-3 months in QS. A biphasic hypoxic ventilatory response was observed in QS non-arousing tests in both groups of infants at all three ages. We conclude that the greater desaturation during a hypoxic challenge combined with the longer arousal latency in preterm infants could contribute to greater risk for SIDS.

Maturation of the initial ventilatory response to hypoxia in sleeping infants.

In infants most previous studies of the hypoxic ventilatory response (HVR) have been conducted only during quiet sleep (QS) and arousal responses have not been considered. Our aim was to quantify the maturation of the HVR in term infants during both active sleep (AS) and QS over the first 6 months of life. Daytime polysomnography was performed on 15 healthy term infants at 2-5 weeks, 2-3 and 5-6 months after birth and infants were challenged with hypoxia (15% O2, balance N2). Tests in AS always resulted in arousal; in QS tests infants either aroused or did not arouse. A biphasic HVR was observed in non arousing tests at all three ages studied. The fall in SpO2 was more rapid in arousal tests at all three ages. At 2-5 weeks, in non-arousing QS tests, there was a greater fall in respiratory frequency (f) despite a smaller fall in SpO2 compared with 2-3 and 5-6 months. When infants aroused there was no difference in the HVR between sleep states or with postnatal age. However, when infants failed to arouse from QS, arterial desaturation was less in the younger infants despite a poorer HVR. We suggest that arousal in response to hypoxia, particularly in AS, is a vital survival mechanism throughout the first 6 months of life.

Variability of the initial phase of the ventilatory response to hypoxia in sleeping infants.

Most of the available data on the hypoxic ventilatory response (HVR) in infants has been obtained in quiet sleep (QS), and only one study has made repeated tests in the same infant. We aimed to gain a more complete knowledge of the maturation and consistency of the initial phase of the HVR by performing multiple tests in both QS and active sleep (AS) over the first 6 mo of life in term infants. Fifteen healthy term infants were studied with daytime polysomnography longitudinally at 2-5 wk, 2-3 mo, and 5-6 mo after birth. Each infant received multiple hypoxic (15% O2, balance N2) challenges (three or more) in both AS and QS. In AS, infants consistently aroused to hypoxia; however, in QS, infants both aroused and failed to arouse. The initial phase of the HVR varied considerably between infants with the changes in ventilation/kg [SD of inspired minute ventilation per kilogram of body weight (V(I)/kg)] being more variable during AS than QS at all three ages and overall decreasing with postnatal age in both sleep states. The variability between replicate V(I)/kg measurements was also significantly greater in AS compared with QS at 2-5 wk postnatal age. There was no evidence of habituation to repeated hypoxic tests in either sleep state. Our study has demonstrated that the initial phase of the HVR is variable both between and within term infants in both AS and QS, with responses being markedly more variable during AS, and becoming more consistent with increasing postnatal age. By performing only one test or by failing to account for arousal responses, previous studies may not have detected the natural variation of the infant HVR.

Postnatal development of ventilatory and arousal responses to hypoxia in human infants.

During the first year of life there is significant maturation of the hypoxic ventilatory response (HVR) in human infants. Compared with adults, healthy term infants have an immature HVR until at least 6 months of age. There are few studies in infants on the effects of sleep state on the HVR but these suggest that at early postnatal ages there is initially no sleep-state related difference; this is followed by a developmental trend towards the adult situation in which the response is depressed in REM sleep compared with NREM. Maternal cigarette smoking is a major risk factor for SIDS and the mechanism for this may involve a depressed HVR in the exposed infant; however studies are limited and the wide variation in cigarette consumption makes interpretation of results difficult. Arousal responses to hypoxia are of vital importance and a failure to arouse has been implicated in SIDS. Sleeping infants frequently fail to arouse in response to hypoxia in QS, whereas in AS they invariably arouse; furthermore arousal latency is longer in QS compared with AS. The oxygen saturation at which infants arouse is not different between sleep states, suggesting that desaturation is more rapid in AS. In QS younger infants arouse more readily than at older ages and arousal is depressed by maternal smoking. These findings suggest that depression of the arousal response to hypoxia in AS may have life-threatening consequences. Infants at increased risk for SIDS have been shown to have both depressed ventilatory and arousal responses to hypoxia, thus they may be at even greater risk.

Respiratory control and arousal in sleeping infants.

Control of the cardiovascular and respiratory systems undergoes rapid maturation during infancy. Sleep is at a lifetime maximum during this period and has a marked influence on cardiorespiratory function. The mechanisms leading to sudden infant death syndrome (SIDS) may include a failure in the neural integration of the cardiovascular and respiratory systems, with a concomitant failure to arouse from sleep. Studies have shown that sleep states exert a marked influence on respiratory control and arousability. Infants are more arousable in active sleep compared with quiet sleep from both somatosensory and respiratory stimuli. Post-natal and gestational age at birth also have a marked influence on arousability. Arousability is depressed by the major risk factors for SIDS (prone sleeping, maternal smoking, prematurity and recent infection) and is increased by factors that decrease the risk for SIDS (e.g. use of dummies, breastfeeding).

Arousal and ventilatory responses to hypoxia in sleeping infants: effects of maternal smoking.

Our aim was to determine whether maternal cigarette smoking affects arousal and ventilatory responses to hypoxia in infants. Infants born to non-smoking (NS, n = 15) and smoking mothers (SM, n= 9) were studied at 2-5 weeks, 2-3 and 5-6 months. Ventilatory responses to 15% O(2) were determined preceding arousal. At each age and in both groups, infants aroused more frequently and earlier to hypoxia in active sleep (AS) than quiet sleep (QS). Arousal latency was longer in SM infants (in QS) at 5-6 months (P < 0.05). Baseline respiratory parameters were not different between groups, except that, at 2-3 months, SM infants had higher SP(O2) during AS than NS infants. Maternal smoking did not affect ventilatory responses preceding hypoxia-induced arousal in either sleep-state at any age. We conclude that mild hypoxia stimulates ventilation and arousal in infants up to 6 months and that arousability is depressed in SM infants at 5-6 months; however, ventilatory responses preceding arousal are not adversely affected by smoking.

Of sleep state and postnatal age on arousal responses induced by mild hypoxia in infants.

STUDY OBJECTIVES: It has been suggested that mild hypoxia may not be a potent stimulus for arousal during sleep in infants because infants frequently fail to arouse from quiet sleep (QS). Our aim was to characterize arousal responses of sleeping infants in both active sleep (AS) and QS under normoxic and mildly hypoxic (15% O2) conditions over the first 6 months of life. PARTICIPANTS: Five healthy term and 6 healthy preterm infants were each studied at 2 to 5 weeks, 2 to 3 months, and 5 to 6 months postterm. All infants underwent daytime polysomnography during which nasal airflow was monitored using a purpose-built pneumotachograph. All infants were studied under both normoxic (21% O2) and hypoxic (15% O2, balance N2) conditions (presentation order randomized) in each sleep state at each study age. Tests were terminated at arousal, O2 saturation falling below 85%, or 5 minutes (failure to arouse). MEASUREMENTS: Probability of failure to arouse and mean arousal latency were compared between each experimental condition, with each infant serving as its own control. RESULTS: Infants aroused more frequently under hypoxic conditions than under normoxic conditions. Overall, arousal latencies were shorter during hypoxia compared to normoxia in both sleep states at each age. Arousal latencies were longer in QS compared to AS in both hypoxic and normoxic conditions. CONCLUSION: In sleeping infants, mild hypoxia serves as a stimulus for arousal in both AS and QS. Of particular significance is our finding that arousal from AS is readily elicited by mild hypoxia.

Arousal responses to somatosensory and mild hypoxic stimuli are depressed during quiet sleep in healthy term infants.

STUDY OBJECTIVES: To compare arousal responses to somatosensory and hypoxic stimuli in sleeping human infants and to determine whether sleep state and postnatal age exerted similar changes in these arousal responses. DESIGN: We delivered somatosensory (nasal air-jet) stimulation and mild hypoxia (15% oxygen) to 10 healthy term infants aged 2 to 4 weeks, 2 to 3 months, and 5 to 6 months during identified sleep states. Hypoxic challenges were terminated at arousal, when the oxygen saturation fell below 85%, or at 5 minutes (failure to arouse). RESULTS: Infants failed to arouse to a greater percentage of hypoxia tests during quiet sleep (QS) than during active sleep (AS) at 2 to 3 months and 5 to 6 months of age (P < 0.01). Infants failed to arouse to a greater percentage of hypoxic challenges during QS at 2 to 3 months and 5 to 6 months than at 2 to 4 weeks of age. Arousal latency to hypoxia was significantly longer in QS than in AS at each study age; however, arousal latency was not affected by postnatal age. Arousal thresholds to somatosensory stimulation were significantly greater in QS than in AS, except at 2 to 4 weeks of age. In AS, arousability to the air-jet was greater at 2 to 3 months compared to 2 to 4 weeks of age (P < 0.05); in QS it was lower at 5 to 6 months compared to 2 to 4 weeks of age (P < 0.05). Arousal latency to hypoxia and arousal thresholds to air-jet stimulation were not correlated within infants. CONCLUSION: We conclude that arousal responses of infants to somatosensory and respiratory stimuli are similarly affected by sleep state and postnatal age. Infants are less arousable to both stimulus modalities in QS than in AS, and less arousable at 5 to 6 months of age than at 2 to 4 weeks in QS.

Ventilatory responses preceding hypoxia-induced arousal in infants: effects of sleep-state.

Augmented ventilation and/or arousal in response to hypoxia are important protective mechanisms during sleep. We aimed to quantify ventilatory responses preceding hypoxia-induced arousal in infants and determine the effects of sleep-state. Fifteen term infants were studied at 2-4 weeks, 2-3 and 5-6 months of age. Ventilatory responses to 15% oxygen inhalation were expressed as breath-by-breath changes from normoxic levels and averaged over 5, 10 and 15 breaths preceding arousal. Minute ventilation preceding arousal significantly increased above normoxic levels only in AS at 5-6 months. There were no sleep-state related differences in minute ventilation, oxygen saturation or carbon dioxide levels (expressed as changes from normoxic values) at 5, 10 or 15 breaths preceding arousal. However, the rate of oxygen desaturation during hypoxia in AS was two to four times faster than in QS at each age. We conclude that the ventilatory responses preceding hypoxia-induced arousal do not differ between sleep-states and that arousal occurs at similar levels of desaturation in both states.

Temperament ratings do not predict arousability in normal infants and infants at increased risk of sudden infant death syndrome.

This study sought to determine whether temperament was an indicator of arousability from sleep in infants. We hypothesized that the "threshold" dimension would be the most predictive characteristic because it measures the stimulus intensity required to evoke a discernible response. Healthy term, healthy preterm, and preterm infants with a neonatal history of apnea underwent polysomnography at 2 to 3 months. Arousal was induced using air-jet stimulation of the nostrils in active (AS) and quiet sleep (QS). Temperament was assessed using the Early Infancy Temperament Questionnaire. Arousal thresholds were elevated in QS compared with AS in each group ( <.001), and preterm infants with a neonatal history of apnea were less arousable than healthy preterm infants ( <.05). Temperament was not a predictor of arousability in AS. "Adaptability" was the only significant predictor of arousability in QS. This study demonstrates that temperament characteristics as measured by questionnaire may not be reliable indicators of arousability from sleep.

Arousal responses and risk factors for sudden infant death syndrome.

BACKGROUND: Failure to arouse from sleep has been postulated as a mechanism to explain the final pathway of sudden infant death syndrome (SIDS). METHODS: We have reviewed the effects of the major risk factors for SIDS, prone sleep position, maternal smoking, prematurity and recent infection on arousability from sleep. In human infants it has been consistently demonstrated that arousal from sleep in response to a variety of stimuli is more difficult to induce from quiet sleep (QS) compared to active sleep (AS) over the first 6 months of life. RESULTS: In the prone position both stimulus-induced and spontaneous arousability from both QS and AS were impaired at 2-3 weeks and 2-3 months, but not at 5-6 months of age in both term and preterm infants. In term infants exposed to maternal smoking during pregnancy both stimulus-induced and spontaneous arousability were impaired when infants slept supine in QS at 2-3 months of age. Healthy preterm infants showed no impairment in arousability compared with term infants at matched postconceptional ages. However, preterm infants with a history of apnoea and bradycardia of prematurity showed decreased arousal responses in both QS and AS and this impairment was positively correlated to their 'perinatal risk score'. Infants who had recently suffered an infection requiring hospitalization showed decreased arousability in QS on the day of discharge when compared to 2 weeks later when they were completely well. CONCLUSIONS: In summary it has been found that the major risk factors for SIDS identified from epidemiological studies also decrease arousability from sleep in infants. We propose that this decreased arousability from sleep may be involved in the final pathway of SIDS.