Evolutionary perspectives on mother-infant sleep proximity and breastfeeding in a laboratory setting

Human maternal and infant biology likely coevolved in a context of close physical contact and some approximation of frequent, "infant-initiated" breastfeeding. Still, mothers and infants commonly sleep apart from one another in many western societies, indicating a possible "mismatch" between cultural norms and infant biology. Here we present data from a 3-night laboratory-based study that examines differences in mother-infant sleep physiology and behavior when mothers and infants sleep together on the same surface (bedsharing) and apart in separate rooms (solitary). We analyze breastfeeding frequency and interval data from the first laboratory night (FN) for 52 complementary breastfeeding mothers and infants (26 total mother-infant pairs), of which 12 pairs were routine bedsharers (RB) and 14 were routine solitary sleepers (RS). RB infants were 12.0 ± 2.7 (SD) weeks old; RS infants were 13.0 ± 2.4 weeks old. On the FN, RB mother-infant pairs (while bedsharing) engaged in a greater number of feeds per night compared to RS (while sleeping alone) (P < 0.001). RB also showed lower intervals (min) between feeds relative to RS (P < 0.05). When we evaluated data from all three laboratory nights (n = 36), post hoc, RB breastfed significantly more often (P < 0.01) and showed a trend towards lower intervals between feeds (P < 0.10). Given the widely known risks associated with little or no breastfeeding, the demonstrated mutually regulatory relationship between bedsharing and breastfeeding should be considered in future studies evaluating determinants of breastfeeding outcomes.     

Parent-infant bed-sharing behavior

An evolutionarily informed perspective on parent-infant sleep contact challenges recommendations regarding appropriate parent-infant sleep practices based on large epidemiological studies. In this study regularly bed-sharing parents and infants participated in an in-home video study of bed-sharing behavior. Ten formula-feeding and ten breast-feeding families were filmed for 3 nights (adjustment, dyadic, and triadic nights) for 8 hours per night. For breast-fed infants, mother-infant orientation, sleep position, frequency of feeding, arousal, and synchronous arousal were all consistent with previous sleep-lab studies of mother-infant bed-sharing behavior, but significant differences were found between formula and breast-fed infants. While breast-feeding mothers shared a bed with their infants in a characteristic manner that provided several safety benefits, formula-feeding mothers shared a bed in a more variable manner with consequences for infant safety. Paternal bed-sharing behavior introduced further variability. Epidemiological case-control studies examining bed-sharing risks and benefits do not normally control for behavioral variables that an evolutionary viewpoint would deem crucial. This study demonstrates how parental behavior affects the bed-sharing experience and indicates that cases and controls in epidemiological studies should be matched for behavioral, as well as sociodemographic, variables.     

Arousal pattern following central and obstructive breathing abnormalities in infants and children

McNamara, Frances, Faiq G. Issa, and Colin E. Sullivan.Arousal pattern following central and obstructive breathing abnormalities in infants and children. J. Appl.Physiol. 81(6): 2651-2657, 1996.We analyzed thepolysomnographic records of 15 children and 20 infants with obstructivesleep apnea (OSA) to examine the interaction between central andobstructive breathing abnormalities and arousal from sleep. Eachpatient was matched for age with an infant or child who had no OSA. Wefound that the majority of respiratory events in infants and childrenwas not terminated with arousal. In children, arousals terminated 39.3 ± 7.2% of respiratory events during quiet sleep and 37.8 ± 7.2% of events during active (rapid-eye-movement) sleep. In infants,arousals terminated 7.9 ± 1.0% of events during quiet sleep and7.9 ± 1.2% of events during active sleep. In both infants andchildren, however, respiratory-related arousals occurred more frequently after obstructive apneas and hypopneas than after central events. Spontaneous arousals occurred in all patients with OSA duringquiet and active sleep. The frequency of spontaneous arousals was notdifferent between children with OSA and their matched controls. Duringactive sleep, however, infants with OSA had significantly fewerspontaneous arousals than did control infants. We conclude that arousalis not an important mechanism in the termination of respiratory eventsin infants and children and that electroencephalographic criteria arenot essential to determine the clinical severity of OSA in thepediatric population.

     

Sleep and arousal patterns of co-sleeping human mother/infant pairs: a preliminary physiological study with implications for the study of sudden infant death syndrome (SIDS)

The prevailing research design for studying infant sleep erroneously assumes the species-wide normalcy of solitary nocturnal sleep rather than a social sleeping environment. In fact, current clinical perspectives on infant sleep, which are based exclusively on studies of solitary sleeping infants, may partly reflect culturally induced rather than species-typical infant sleep patterns which can only be gleaned, we contend here, from infants sleeping with their parents--the context within which, and for well over 4 million years, the hominid infant's sleep, breathing, and arousal patterns evolved. Our physiological study of five co-sleeping mother-infant pairs in a sleep lab is the first study of its kind to document the unfolding sleep patterns of mothers and infants sleeping in physical contact. Our data show that co-sleeping mothers and infants exhibit synchronous arousals, which, because of the suspected relationship between arousal and breathing stability in infants, have important implications for how we study environmental factors possibly related to some forms of the sudden infant death syndrome (SIDS). While our data show that co-sleeping mothers and infants also experience many moments of physiological independence from each other, it is clear that the temporal unfolding of particular sleep stages and awake periods of the mother and infant become entwined and that on a minute-to-minute basis, throughout the night, much sensory communication is occurring between them. Our research acknowledges the human infant's evolutionary past and considers the implications that nocturnal separation (a historically novel and alien experience for them) has for maternal and infant well-being in general and SIDS research strategies in particular.     

Polygraphic findings in bird-like face syndrome with favorable spontaneous evolution

The syndrome characterized by acquired micrognathia, hypersomnia and periodic apneas during sleep is a rare consequence of mandibular underdevelopment. The pathogenesis is ascribed to incomplete obstruction of the upper airways associated with a hypoexcitability of the respiratory center. Tracheostomy, with the placement of a permanent tracheal cannula, has proved to be the only treatment producing clinical remission of the syndrome. Polygraphic findings were described in a case spontaneously recovered of hypersomnia and periodic apneas with acquired micrognathia due to a bilateral mastoiditis occurring in early childhood. In this patient three polygraphic recordings were carried out during diurnal and nocturnal sleep; another night sleep was recorded after a spontaneous improvement. In the early three recordings there is a prevalence of light sleep over slow-waves sleep and REM sleep is reduced in nocturnal sleep. There is a lot of periodic apneas during sleep stages. During apneas we observe an increase of heart frequency in NonREM sleep and a decrease in REM sleep. In the recording after clinical recovery we observe an improvement of sleep parameters and a disappearing of apneas in NonREM sleep. A temporary hyposensibility of respiratory centers is considered to be a possible interpretation of clinical and polygraphic improvement.     

Sleep stage and obstructive apneaic epoch classification using single-lead ECG

Background  

Polysomnography (PSG) is used to define physiological sleep and different physiological sleep stages, to assess sleep quality and diagnose many types of sleep disorders such as obstructive sleep apnea. However, PSG requires not only the connection of various sensors and electrodes to the subject but also spending the night in a bed that is different from the subject's own bed. This study is designed to investigate the feasibility of automatic classification of sleep stages and obstructive apneaic epochs using only the features derived from a single-lead electrocardiography (ECG) signal.     

Osteopathy may decrease obstructive apnea in infants: a pilot study

Background

Obstructive apnea is a sleep disorder characterized by pauses in breathing during sleep: breathing is interrupted by a physical block to airflow despite effort. The purpose of this study was to test if osteopathy could influence the incidence of obstructive apnea during sleep in infants.

Methods

Thirty-four healthy infants (age: 1.5–4.0 months) were recruited and randomized in two groups; six infants dropped out. The osteopathy treatment group (n = 15 infants) received 2 osteopathic treatments in a period of 2 weeks and a control group (n = 13 infants) received 2 non-specific treatments in the same period of time. The main outcome measure was the change in the number of obstructive apneas measured during an 8-hour polysomnographic recording before and after the two treatment sessions.

Results

The results of the second polysomnographic recordings showed a significant decrease in the number of obstructive apneas in the osteopathy group (p = 0.01, Wilcoxon test), in comparison to the control group showing only a trend suggesting a gradual physiologic decrease of obstructive apneas. However, the difference in the decline of obstructive apneas between the groups after treatment was not significant (p = 0.43).

Conclusion

Osteopathy may have a positive influence on the incidence of obstructive apneas during sleep in infants with a previous history of obstructive apneas as measured by polysomnography. Additional research in this area appears warranted.     

Physiology of ventilatory regulation during sleep

During light slow-wave sleep, ventilation is principally regulated by automatic metabolic control system. An instability in the respiratory control may be the predominant disturbance leading to very irregular or periodic breathing. During deep sleep, ventilation is progressively more stable. During REM sleep, automatic regulation is abolished and ventilation is particularly dependent on the compartmental control system. The reduction in airways and respiratory muscles tone favors the occurrence of obstructive apneas. The elevation in arousal threshold leads prolongation of the obstructive events.     

Respiratory events and periodic breathing in cyclists sleeping at 2,650-m simulated altitude.

We examined the initial effect of sleeping at a simulated moderate altitude of 2,650 m on the frequency of apneas and hypopneas, as well as on the heart rate and blood oxygen saturation from pulse oximetry (SpO2) during rapid eye movement (REM) and non-rapid eye movement (NREM) sleep of 17 trained cyclists. Pulse oximetry revealed that sleeping at simulated altitude significantly increased heart rate (3 +/- 1 beats/min; means +/- SE) and decreased SpO2 (-6 +/- 1%) compared with baseline data collected near sea level. In response to simulated altitude, 15 of the 17 subjects increased the combined frequency of apneas plus hypopneas from baseline levels. On exposure to simulated altitude, the increase in apnea was significant from baseline for both sleep states (2.0 +/- 1.3 events/h for REM, 9.9 +/- 6.2 events/h for NREM), but the difference between the two states was not significantly different. Hypopnea frequency was significantly elevated from baseline to simulated altitude exposure in both sleep states, and under hypoxic conditions it was greater in REM than in NREM sleep (7.9 +/- 1.8 vs. 4.2 +/- 1.3 events/h, respectively). Periodic breathing episodes during sleep were identified in four subjects, making this the first study to show periodic breathing in healthy adults at a level of hypoxia equivalent to 2,650-m altitude. These results indicate that simulated moderate hypoxia of a level typically chosen by coaches and elite athletes for simulated altitude programs can cause substantial respiratory events during sleep.     

Protoveratrines A and B increase sleep apnea index in Sprague-Dawley rats

Trbovic, Sinisa M., Miodrag Radulovacki, and David W. Carley. Protoveratrines A and B increase sleep apneaindex in Sprague-Dawley rats. J. Appl.Physiol. 83(5): 1602-1606, 1997.The action ofprotovertarines A and B, which stimulate carotid sinus baroreceptorsand vagal sensory endings in the heart as well as pulmonary bed, wereassessed on spontaneous and postsigh central sleep apneas in freelymoving Sprague-Dawley rats. During the 6-h recording period, animalswere simultaneously monitored for sleep by using electroencephalogramand electromyogram recordings, for respiration by single-chamberplethysmography, and for blood pressure and heart period by usingradiotelemetry. After administration of 0.2, 0.5, or 1 mg/kg sc ofprotoveratrines, cardiopulmonary changes lasting at least 6 h wereobserved in all three behavioral states [heart period increasedup to 23% in wakefulness, 21% in non-rapid-eye-movement (non-REM)sleep, and 20% in REM sleep; P < 0.005 for each]. At the same time, there was a substantial increase in the number of spontaneous (375% increase;P = 0.04) and postsigh (268%increase, P = 0.0002) apneas. Minuteventilation decreased by up to 24% in wakefulness, 25% in non-REM,and 35% in REM sleep (P < 0.05 foreach). We conclude that pharmacological stimulation of baroreflexespromotes apnea expression in the sleeping rat.

     

Effects of increase in body temperature on the breathing pattern in premature infants

This study was designed to determine the effects of a mild increase in body temperature within the physiological range (0.8 degrees C) in healthy premature infants. Seven unsedated premature infants (38.4 wk +/- 1.5 postconceptional age) were monitored polygraphically during "morning naps" in an incubator under two different environmental temperatures: (1) normothermia with the incubator temperature set at 25 degrees C and the rectal temperature equal to 36.9 degrees C +/- 0.1; (2) hyperthermia with the incubator temperature set at 35 degrees C and the rectal temperature equal to 37.7 degrees C +/- 0.15. Respiratory frequency and heart rate, respiratory events, i.e., central and obstructive apnea, and periodic breathing with and without apneic oscillations were tabulated. Results for respiratory events were expressed as (1) indices of the total number of respiratory events, and of specific respiratory events per hour of total, quiet and active sleep times; (2) duration of total and specific respiratory events expressed as a percentage of total sleep, quiet and active sleep times. Respiratory frequency and heart rate were significantly increased by hyperthermia (P less than 0.05). Hyperthermia did not significantly modify the indices or the duration of central and obstructive apnea. But the indices and the duration of periodic breathing with and without apneic oscillations were significantly increased by hyperthermia during active sleep (P less than 0.05) but not during quiet sleep. The present study shows that a mild increase in body temperature within the physiological range in premature infants enhances the instability of the breathing pattern during active sleep.     

Effects of nasal CPAP therapy on respiratory and spontaneous arousals in infants with OSA.

Obstructive sleep apnea (OSA) in infants has been shown to resolve frequently without a cortical arousal. It is unknown whether infants do not require arousal to terminate apneas or whether this is a consequence of the OSA. We studied the apnea and arousal patterns of eight infants with OSA before and after treatment with nasal continuous positive airway pressure (CPAP). These infants were age matched to eight untreated infants with OSA and eight normal infants. Polysomnographic studies were performed on each infant. We found that the majority of central and obstructive apneas were terminated without arousal in all OSA infants. After several weeks of nasal CPAP treatment, the proportion of apneas terminating with an arousal during rapid-eye-movement sleep increased in treated infants compared with untreated infants. Spontaneous arousals during rapid-eye-movement sleep were reduced in all OSA infants; however, during CPAP treatment, the spontaneous arousals increased to the normal control level. We conclude that OSA in infants possibly depresses the arousal response and treatment of these infants with nasal CPAP partially reverses this depression.     

Effects of sleep deprivation on respiratory events during sleep in healthy infants

This study was designed to determine the effects of sleep deprivation on respiratory events during sleep in healthy infants. Ten unsedated full-term infants (1-6 mo) were monitored polygraphically during "afternoon naps" on a control day and on the day after sleep deprivation. Respiratory events, i.e., central apnea, obstructive apnea and hypopnea, and periodic breathing were tabulated. Results for respiratory events were expressed as 1) indexes of the total number of respiratory events and of specific respiratory events per hour of total sleep (TST), "quiet" sleep (QS) and "active" sleep (AS) times; 2) total duration of total and specific respiratory events, expressed as a percentage of TST, QS, and AS times. After sleep deprivation, significant increases were observed for 1) respiratory event (P less than 0.001), central apnea (P less than 0.05), and obstructive respiratory event (P less than 0.01) indexes; 2) respiratory event time as a percentage of TST (P less than 0.002) and as a percentage of AS time (P less than 0.001); 3) obstructive respiratory event time as a percentage of TST (P less than 0.01), QS (P less than 0.05), and AS times (P less than 0.002). The present study shows that short-term sleep deprivation in healthy infants increases the number and timing of respiratory events, especially obstructive events in AS.     

Nonnutritive swallowing and respiration relationships in preterm lambs.

The aim of the present study was to assess the effects of the different states of alertness on 1) nonnutritive swallowing (NNS) frequency, 2) the relationship between NNS and the respiratory cycle, and 3) the association of NNS with spontaneous apneas. Recordings of sleep states, diaphragm and laryngeal constrictor electrical activity, nasal flow, electrocardiogram, respiratory inductance plethysmography, and pulse oximetry were obtained from six preterm lambs without sedation. Analysis of 2,468 NNS showed that 1) NNS frequency was higher during quiet wakefulness and active sleep (AS) than in quiet sleep; 2) in all states of alertness, a greater number of NNS (38%) were preceded and followed by an inspiration; 3) although NNS and central apneas were rarely coincidental, AS appeared to favor their association; and 4) most obstructive apneas occurred in AS and were coincidental with bursts of NNS. Compared with results in full-term lambs, premature birth does not modify the NNS-respiratory coordination. However, AS in preterm lambs is characterized by a higher association of NNS bursts with obstructive apneas.     

Site and mechanics of spontaneous, sleep-associated obstructive apnea in infants.

To examine the mechanics of infantile obstructive sleep apnea (OSA), airway pressures were measured using a triple-lumen catheter in 19 infants (age 1-36 wk), with concurrent overnight polysomnography. Catheter placement was guided by correlations between measurements of magnetic resonance images and body weight of 70 infants. The level of spontaneous obstruction was palatal in 52% and retroglossal in 48% of all events. Palatal obstruction predominated in infants treated for OSA (80% of events), compared with 38.6% from infants with infrequent events (P = 0.02). During obstructive events, successive respiratory efforts increased in amplitude (mean intrathoracic pressures -11.4, -15.0, and -20.4 cmH(2)O; ANOVA, P < 0.05), with arousal after only 29% of the obstructive and mixed apneas. The soft palate is commonly involved in the upper airway obstruction of infants suffering OSA. Postterm, infant responses to upper airway obstruction are intermediate between those of preterm infants and older children, with infrequent termination by arousal but no persisting "upper airway resistance" and respiratory efforts exceeding baseline during the event.     

Influence of sleep state on frequency of swallowing, apnea, and arousal in human infants.

Apnea and arousal are modulated with sleep stage, and swallowing may interfere with respiratory rhythm in infants. We hypothesized that swallowing itself would display interaction with sleep state. Concurrent polysomnography and measurement of swallowing allowed time-matched analysis of 3,092 swallows, 482 apneas, and 771 arousals in 17 infants aged 1-34 wk. The mean rates of swallowing, apnea, and arousal were significantly different, being 23.3 +/- 8.5, 9.4 +/- 8.8, and 15.5 +/- 10.6 h(-1), respectively (P < 0.001 ANOVA). Swallows occurred before 25.2 +/- 7.9% and during 74.8 +/- 6.3% of apneas and before 39.8 +/- 6.0% and during 60.2 +/- 6.0% of arousals. The frequencies of apneas and arousals were both strongly influenced by sleep state (active sleep > indeterminate > quiet sleep, P < 0.001), whether or not the events coincided with swallowing, but swallowing rate showed minimal independent interaction with sleep state. Interactions between swallowing and sleep state were predominantly influenced by the coincidence of swallowing with apnea or arousal.     

Bed-Sharing in the Absence of Hazardous Circumstances: Is There a Risk of Sudden Infant Death Syndrome? An Analysis from Two Case-Control Studies Conducted in the UK

Objective

The risk of sudden infant death syndrome (SIDS) among infants who co-sleep in the absence of hazardous circumstances is unclear and needs to be quantified.

Design

Combined individual-analysis of two population-based case-control studies of SIDS infants and controls comparable for age and time of last sleep.

Setting

Parents of 400 SIDS infants and 1386 controls provided information from five English health regions between 1993–6 (population: 17.7 million) and one of these regions between 2003–6 (population:4.9 million).

Results

Over a third of SIDS infants (36%) were found co-sleeping with an adult at the time of death compared to 15% of control infants after the reference sleep (multivariate OR = 3.9 [95% CI: 2.7–5.6]). The multivariable risk associated with co-sleeping on a sofa (OR = 18.3 [95% CI: 7.1–47.4]) or next to a parent who drank more than two units of alcohol (OR = 18.3 [95% CI: 7.7–43.5]) was very high and significant for infants of all ages. The risk associated with co-sleeping next to someone who smoked was significant for infants under 3 months old (OR = 8.9 [95% CI: 5.3–15.1]) but not for older infants (OR = 1.4 [95% CI: 0.7–2.8]). The multivariable risk associated with bed-sharing in the absence of these hazards was not significant overall (OR = 1.1 [95% CI: 0.6–2.0]), for infants less than 3 months old (OR = 1.6 [95% CI: 0.96–2.7]), and was in the direction of protection for older infants (OR = 0.1 [95% CI: 0.01–0.5]). Dummy use was associated with a lower risk of SIDS only among co-sleepers and prone sleeping was a higher risk only among infants sleeping alone.

Conclusion

These findings support a public health strategy that underlines specific hazardous co-sleeping environments parents should avoid. Sofa-sharing is not a safe alternative to bed-sharing and bed-sharing should be avoided if parents consume alcohol, smoke or take drugs or if the infant is pre-term.     

Influence of testosterone on breathing during sleep

Apneas and hypopneas during sleep occur more frequently in men than women. Disordered breathing is also reported to increase in hypogonadal men following testosterone administration. This suggests a hormonal influence on sleeping respiratory pattern. We therefore studied respiratory rhythm during sleep in 11 hypogonadal males both on and off testosterone-replacement therapy. In four subjects the anatomy (computerized tomography) and airflow resistance of the upper airway were also determined on both occasions. Sleep stage distribution and duration were unchanged following androgen administration. However, both apneas and hypopneas increased significantly during testosterone replacement so that the total number of disordered breathing events (apneas + hypopneas) per hour of sleep rose from 6.4 +/- 2.1 to 15.4 +/- 7.0 (P less than 0.05). This was a highly variable event with some subjects demonstrating large increases in apneas and hypopneas when androgen was replaced, whereas others had little change in respiration during sleep. Upper airway dimensions, on the other hand, were unaffected by testosterone. These results suggest that testosterone contributes to sleep-disordered breathing through mechanisms independent of anatomic changes in the upper airway.     

Babies sleeping with parents: case-control study of factors influencing the risk of the sudden infant death syndrome. CESDI SUDI research group

ObjectiveTo investigate the risks of the sudden infant death syndrome and factors that may contribute to unsafe sleeping environments.DesignThree year, population based case-control study. Parental interviews were conducted for each sudden infant death and for four controls matched for age, locality, and time of sleep.SettingFive regions in England with a total population of over 17 million people.Subjects325 babies who died and 1300 control infants.ResultsIn the multivariate analysis infants who shared their parents'' bed and were then put back in their own cot had no increased risk (odds ratio 0.67; 95% confidence interval 0.22 to 2.00). There was an increased risk for infants who shared the bed for the whole sleep or were taken to and found in the parental bed (9.78; 4.02 to 23.83), infants who slept in a separate room from their parents (10.49; 4.26 to 25.81), and infants who shared a sofa (48.99; 5.04 to 475.60). The risk associated with being found in the parental bed was not significant for older infants (>14 weeks) or for infants of parents who did not smoke and became non-significant after adjustment for recent maternal alcohol consumption (>2 units), use of duvets (>4 togs), parental tiredness (infant slept ⩽4 hours for longest sleep in previous 24 hours), and overcrowded housing conditions (>2 people per room of the house).ConclusionsThere are certain circumstances when bed sharing should be avoided, particularly for infants under four months old. Parents sleeping on a sofa with infants should always be avoided. There is no evidence that bed sharing is hazardous for infants of parents who do not smoke.

Key messsages

• Cosleeping with an infant on a sofa was associated with a particularly high risk of sudden infant death syndrome
• Sharing a room with the parents was associated with a lower risk
• There was no increased risk associated with bed sharing when the infant was placed back in his or her cot
• Among parents who do not smoke or infants older than 14 weeks there was no association between infants being found in the parental bed and an increased risk of sudden infant death syndrome
• The risk linked with bed sharing among younger infants seems to be associated with recent parental consumption of alcohol, overcrowded housing conditions, extreme parental tiredness, and the infant being under a duvet

     

Effects of inhaled CO2 and added dead space on idiopathic central sleep apnea

Xie, Ailiang, Fiona Rankin, Ruth Rutherford, and T. DouglasBradley. Effects of inhaledCO₂ and added dead space on idiopathic central sleep apnea. J. Appl.Physiol. 82(3): 918-926, 1997.We hypothesizedthat reductions in arterial PCO₂ (Pa_CO2) below the apnea threshold play akey role in the pathogenesis of idiopathic central sleep apnea syndrome(ICSAS). If so, we reasoned that raisingPa_CO2 would abolish apneas in thesepatients. Accordingly, patients with ICSAS were studied overnight onfour occasions during which the fraction of end-tidalCO₂ and transcutaneous PCO₂ were measured: during room airbreathing (N1), alternating room airand CO₂ breathing(N2),CO₂ breathing all night(N3), and addition of dead space viaa face mask all night (N4).Central apneas were invariably preceded by reductions infraction of end-tidal CO₂. Bothadministration of a CO₂-enrichedgas mixture and addition of dead space induced 1- to 3-Torr increasesin transcutaneous PCO₂, whichvirtually eliminated apneas and hypopneas; they decreased from43.7 ± 7.3 apneas and hypopneas/h onN1 to 5.8 ± 0.9 apneas andhypopneas/h during N3(P < 0.005), from 43.8 ± 6.9 apneas and hypopneas/h during room air breathing to 5.9 ± 2.5 apneas and hypopneas/h of sleep duringCO₂ inhalation during N2 (P < 0.01), and to 11.6% of the room air level while the patients werebreathing through added dead space duringN4 (P < 0.005). Because raisingPa_CO2 through two different meansvirtually eliminated central sleep apneas, we conclude that centralapneas during sleep in ICSA are due to reductions inPa_CO2 below the apnea threshold.