Model-based stability assessment of ventilatory control in overweight adolescents with obstructive sleep apnea during NREM sleep.

Obstructive sleep apnea (OSA) involves the interplay of several different factors such as an unfavorable upper airway anatomy, deficiencies in pharyngeal muscle responsiveness, a low arousal threshold, and ventilatory control instability. Although the stability of ventilatory control has been extensively studied in adults, little is known about its characteristics in the pediatric population. In this study, we developed a novel experimental setup that allowed us to perturb the respiratory system during natural non-rapid eye movement (NREM) sleep conditions by manipulating the inspiratory pressure, provided by a bilevel pressure ventilator, to induce sighs after upper airway stabilization. Furthermore, we present a modeling framework that utilizes the noninvasively measured ventilatory responses to the induced sighs and spontaneous breathing data to obtain representations of the processes involved in the chemical regulation of respiration and extract their stability characteristics. After validation with simulated data, the modeling technique was applied to data collected experimentally from 11 OSA and 15 non-OSA overweight adolescents. Statistical analysis of the model-derived stability parameters revealed a significantly higher plant gain and lower controller gain in the OSA group (P = 0.046 and P = 0.007, respectively); however, no differences were found in loop gain (LG) and circulatory time delay between the groups. OSA severity and LG, within the 0.03-0.04-Hz frequency band, were significantly negatively associated (r = -0.434, P = 0.026). Contrary to what has been found in adults, our results suggest that in overweight adolescents, OSA is unlikely to be initiated through ventilatory instability resulting from elevated chemical loop gain.

Hypoxia reveals posterior thalamic, cerebellar, midbrain, and limbic deficits in congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS) patients show deficient respiratory and cardiac responses to hypoxia and hypercapnia, despite apparently intact arousal responses to hypercapnia and adequate respiratory motor mechanisms, thus providing a model to evaluate functioning of particular brain mechanisms underlying breathing. We used functional magnetic resonance imaging to assess blood oxygen level-dependent signals, corrected for global signal changes, and evaluated them with cluster and volume-of-interest procedures, during a baseline and 2-min hypoxic (15% O(2), 85% N(2)) challenge in 14 CCHS and 14 age- and gender-matched control subjects. Hypoxia elicited significant (P < 0.05) differences in magnitude and timing of responses between groups in cerebellar cortex and deep nuclei, posterior thalamic structures, limbic areas (including the insula, amygdala, ventral anterior thalamus, and right hippocampus), dorsal and ventral midbrain, caudate, claustrum, and putamen. Deficient responses to hypoxia included no, or late, changes in CCHS patients with declining signals in control subjects, a falling signal in CCHS patients with no change in controls, or absent early transient responses in CCHS. Hypoxia resulted in signal declines but no group differences in hypothalamic and dorsal medullary areas, the latter being a target for PHOX2B, mutations of which occur in the syndrome. The findings extend previously identified posterior thalamic, midbrain, and cerebellar roles for normal mediation of hypoxia found in animal fetal and adult preparations and suggest significant participation of limbic structures in responding to hypoxic challenges, which likely include cardiovascular and air-hunger components. Failing structures in CCHS include areas additional to those associated with PHOX2B expression and chemoreceptor sites.

Decreased specific airway conductance in infant apnea.

A disorder of respiratory control is the suspected etiology in a majority of infants with apnea. Although neurologic control of breathing has been evaluated in infants surviving an apneic episode, pulmonary mechanics have not been previously measured. Pulmonary mechanics were measured during sleep in ten infants with apnea, aged 45.4 +/- 1.4 (SE) weeks postconception, and 13 control infants, aged 42.0 +/- 0.8 weeks postconception. Infant apnea patients were defined as those having at least one episode of cyanosis, limpness, and apnea requiring vigorous stimulation or resuscitation to restore normal breathing, and in whom no treatable etiology could be found. Thoracic gas volume, airway resistance, and specific airway conductance were measured in an infant body pressure plethysmograph during quiet breathing. Dynamic pulmonary compliance was measured in six infants using an esophageal balloon. Specific airway conductance was decreased in infants with apnea compared with control infants (P less than .05). Thoracic gas volume, airway resistance, and dynamic pulmonary compliance values were comparable with those of control infants. These data suggest that airway narrowing or abnormal control of airway tone during sleep may contribute to apnea in some infants.

Elevated catecholamine levels and abnormal hypoxic arousal in apnea of infancy.

Arousal from quiet sleep in response to a hypoxic challenge fails to occur in many patients with apnea of infancy. It was hypothesized that catecholamine-mediated responses might be involved in the depressed hypoxic arousal response in apnea of infancy and that these differences would be reflected in serum catecholamine concentrations. Fifteen infants with a median age of 5.5 months and a history of unexplained apnea during sleep were studied. Two hypoxic challenges (PiO2 80 mm Hg) were given for three minutes or until arousal from quiet sleep occurred. Of the 15 patients with apnea of infancy 11 (73%) did not arouse to hypoxia. These infants had serum epinephrine levels that were elevated 4.1-fold while awake (P less than .05), 3.4-fold during quiet sleep (P less than .02), and 3.5-fold during hypoxia (P less than .05). They also had serum norepinephrine levels that were elevated threefold while awake (P less than .05), 5.3-fold during quiet sleep (P less than .001), 3.2-fold during hypoxia (P less than .02), and 12-fold during recovery from hypoxia (P less than .001) in comparison with the corresponding levels in the four (23%) infants who aroused normally to hypoxia. It is speculated that elevated circulating catecholamines are associated with abnormal hypoxic arousal responses in children with apnea of infancy.

Hypoxic arousal responses in infants with bronchopulmonary dysplasia.

Infants with bronchopulmonary dysplasia have a high incidence of sudden, unexplained death in the postneonatal period, yet the cause of these deaths is unknown. Frequent episodes of clinically unsuspected arterial oxygen desaturation have recently been described in infants with bronchopulmonary dysplasia. We hypothesized that infants with bronchopulmonary dysplasia who experience frequent episodes of hypoxia may have abnormal arousal responses to these hypoxic episodes. We studied 12 infants with bronchopulmonary dysplasia at 41.4 +/- 1.3 weeks postconceptional age. Hypoxic arousal responses were performed during quiet sleep at an inspired oxygen tension of 80 mm Hg for a maximum of three minutes or until arousal occurred. Of 12 infants, 11 (92%) aroused normally to the hypoxic challenge. However, all infants required vigorous stimulation and supplemental oxygen after the initial arousal response. Of 12 infants with bronchopulmonary dysplasia, eight (67%) experienced prolonged apnea with bradycardia, and four of 12 (33%) required brief ventilatory assistance (bag and mask) to restore normal breathing. Abnormal pneumographic findings did not predict the occurrence of these prolonged periods of apnea and bradycardia following hypoxia. We conclude that an abnormal response to hypoxia following arousal may lead to prolonged apnea and bradycardia in infants with bronchopulmonary dysplasia. We speculate that the inability to recover from this hypoxia may result in sudden death in these infants.

Hypoxic arousal responses in normal infants.

Failure to arouse in response to hypoxia has been described in infants at increased risk for sudden infant death syndrome (SIDS) and has been suggested as a possible mechanism for SIDS. However, most SIDS victims are not in a high-risk group before death. Thus, if a hypoxic arousal disorder is an important contributor to SIDS, normal infants might fail to arouse from sleep in response to hypoxia. To test this hypothesis, the authors studied hypoxic arousal responses in 18 healthy term infants younger than 7 months of age (age 12.1 +/- 1.7 [SEM] weeks; 56% girls). Hypoxic arousal challenges were performed during quiet sleep by rapidly decreasing inspired oxygen tension (PIO2) to 80 mm Hg for 3 minutes or until arousal (eye opening, agitation, and crying) occurred. Tests were performed in duplicate when possible. Only 8 infants (44%) aroused in response to one or more hypoxic challenges; arousal occurred during 8 (32%) of 25 trials. There were no significant differences in lowest PIO2 or arterial oxygen saturation during hypoxia between those infants who aroused and those who failed to arouse. All 18 infants had a fall in their end-tidal carbon dioxide tension during hypoxia, suggesting that each had a hypoxic ventilatory response despite failure to arouse in the majority. Periodic breathing occurred following hypoxia in only 1 (13%) of the 8 trials that resulted in arousal, compared with 16 (94%) of 17 trials without arousal (P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinically unsuspected hypoxia during sleep and feeding in infants with bronchopulmonary dysplasia.

Infants with bronchopulmonary dysplasia have a high incidence of sudden, unexplained death in the postneonatal period; yet the cause of these deaths is unknown. It was hypothesized that infants with bronchopulmonary dysplasia, thought to be well oxygenated based on awake PaO2 values, would have clinically unsuspected arterial oxygen desaturation during sleep and that these would correlate with the severity of pulmonary function abnormalities. The infants studied were 14 with bronchopulmonary dysplasia, 15 who were preterm, had no bronchopulmonary dysplasia, but did have neonatal respiratory distress syndrome, and eight who were full term and used for control at 37 to 45 weeks postconception. Continuous noninvasive monitoring of oxygenation (arterial oxygen saturation [SaO2, pulse oximetry] and transcutaneous oxygen tension was performed during sleep, wakefulness, and feeding. Greater than 80% of each recording was free of artifact for SaO2. Preterm infants with bronchopulmonary dysplasia and respiratory distress syndrome spent greater time at SaO2 less than 90% than control infants. Most desaturations occurred during feeding and to a lesser extent during wakefulness, active sleep, and quiet sleep. Episodes of desaturation (SaO2 less than 90%) lasted 15 to 20 seconds and were not associated with apnea, bradycardia, cyanosis, or changes in transcutaneous PO2. Only infants with bronchopulmonary dysplasia showed severe desaturations (SaO2 less than 80%). Total desaturation in those infants correlated with airway resistance (body pressure plethysmography). Abnormal pneumographic findings did not predict abnormal desaturations. It was concluded that clinically unsuspected oxygen desaturation occurs frequently in preterm infants with and without bronchopulmonary dysplasia, and profound hypoxemia may be responsible for sudden unexplained deaths in these infants.

Effect of isoproterenol inhalation on airway resistance in chronic bronchopulmonary dysplasia.

The effects of isoproterenol inhalation on pulmonary mechanics in ten infants with bronchopulmonary dysplasia (BPD), aged 41 +/- 1 (SE) weeks postconception, with gestational age at birth 30 +/- 1 weeks, and birth weight 1,590 +/- 200 g were studied. The infants had: (1) hyaline membrane disease requiring mechanical ventilation in the first five days of life, (2) mechanical ventilation and/or FIo2 greater than 30% for at least 30 days, and (3) stage III or IV radiographic changes. Thoracic gas volume, airway resistance, and specific airway conductance were measured in an infant body pressure plethysmograph during quiet breathing. Dynamic pulmonary compliance was measured using an esophageal balloon. These infants with BPD had greater airway resistance, lower specific airway conductance, and lower dynamic pulmonary compliance than 16 normal control infants (age 40 +/- 1 weeks postconception). In the infants with BPD, measurements were obtained before and 1/2, 1, 2, and 6 hours after the administration of isoproterenol aerosol 0.1% inhalation or saline aerosol placebo, five breaths by slow inflation of the lungs with an anesthesia bag. Within 30 minutes after isoproterenol inhalation, airway resistance decreased 28% +/- 5% and specific airway conductance increased 53% +/- 15%. Thoracic gas volume and dynamic pulmonary compliance did not change. There were no changes following administration of the placebo. Isoproterenol inhalation is associated with rapid short-term improvement in airway resistance and specific airway conductance in infants with BPD.

Pulmonary function abnormalities in symptom-free children after bronchiolitis.

Twenty-three children less than 18 months old who had clinical and radiological evidence of bronchiolitis and remained symptom-free thereafter were studied to determine pulmonary function ten years later. Abnormal Pao2, Viso V and RV/TLC ratio were found in the majority of subjects, and 31.3% had abnormalities in all three tests; four and one-half percent had exercise-induced bronchospasm. These changes indicate a residual parenchymal or airways lesion following bronchiolitis.

Hypercapneic arousal responses in children with congenital central hypoventilation syndrome.

Congenital central hypoventilation syndrome (CCHS, Ondine's curse) is generally thought to be due to insensitivity of the central chemoreceptors to carbon dioxide. Children with CCHS have absent ventilatory responses to both hypercapnea and hypoxia, suggesting either abnormal central and peripheral chemoreceptor function or abnormal central integration of chemoreceptor input. Because ventilatory and arousal responses to respiratory stimuli are distinct from each other, if children with CCHS have complete chemoreceptor dysfunction, one would predict that both ventilatory and arousal responses to respiratory stimuli would be abnormal. However, if they have abnormal central integration of chemoreceptor input for ventilation, they may still arouse to respiratory stimuli despite the absence of a ventilatory response. Hypercapneic arousal responses were tested in eight children with CCHS, aged 5.8 +/- 1.2 (SEM) years, and seven healthy control subjects, aged 4.4 +/- 1.1 years. Children were studied during sleep while normal ventilation was maintained using their home ventilators. Hypercapneic challenges were performed by rapidly increasing the inspired carbon dioxide tension to 60 mm Hg and maintaining this level until the child aroused or for a maximum of 3 minutes. Of children with CCHS, 87.5% aroused to hypercapnea, compared with 100% of control children. There was no significant difference in arousal between children with CCHS and normal control subjects. It is concluded that most children with CCHS arouse to hypercapnea, indicating the presence of some central chemoreceptor function. It is speculated that because these children do respond to hypercapnea, the most probable mechanism for CCHS is a brainstem lesion in the area where input from both chemoreceptors is integrated.

Obstructive sleep apnea in children with Down syndrome.

Children with Down syndrome have many predisposing factors for the obstructive sleep apnea syndrome (OSAS), yet the type and severity of OSAS in this population has not been characterized. Fifty-three subjects with Down syndrome (mean age 7.4 +/- 1.2 [SE] years; range 2 weeks to 51 years) were studied. Chest wall movement, heart rate, electroculogram, end-tidal PO2 and PCO2, transcutaneous PO2 and PCO2, and arterial oxygen saturation were measured during a daytime nap polysomnogram. Sixteen of these children also underwent overnight polysomnography. Nap polysomnograms were abnormal in 77% of children; 45% had obstructive sleep apnea (OSA), 4% had central apnea, and 6% had mixed apneas; 66% had hypoventilation (end-tidal PCO2 greater than 45 mm Hg) and 32% desaturation (arterial oxygen saturation less than 90%). Overnight studies were abnormal in 100% of children, with OSA in 63%, hypoventilation in 81%, and desaturation in 56%. Nap studies significantly underestimated the presence of abnormalities when compared to overnight polysomnograms. Seventeen (32%) of the children were referred for testing because OSAS was clinically suspected, but there was no clinical suspicion of OSAS in 36 (68%) children. Neither age, obesity, nor the presence of congenital heart disease affected the incidence of OSA, desaturation, or hypoventilation. Polysomnograms improved in all 8 children who underwent tonsillectomy and adenoidectomy, but they normalized in only 3. It is concluded that children with Down syndrome frequently in have OSAS, with OSA, hypoxemia, and hypoventilation. Obstructive sleep apnea syndrome is seen frequently in those children in whom it is not clinically suspected. It is speculated that OSAS may contribute to the unexplained pulmonary hypertension seen in children with Down syndrome.

Effects of gravity on tracheal mucus transport rates in normal subjects and in patients with cystic fibrosis.

A noninvasive, radionuclide imaging technique for measuring the rate of mucus clearance in the trachea (RT), was used to study gravitational effects on mucus clearance in 13 patients with cystic fibrosis (CF), average age 17 years; 7 normal, nonsmoking adults, average age 26 years; and a normal subject who was recovering from an acute upper respiratory tract infection (URTI). In the upright position, nine of the CF patients and the subject with URTI demonstrated abnormal tracheal mucus clearance which approached normal when they were placed in 25 degrees headdown position. The normal subjects and two of the CF patients showed no significant difference in the RT measured in the two positions. The results of the study indicate that the force of gravity can be a major influence on tracheal mucus clearance in CF and URTI subjects. This conclusion supports the use of postural drainage as an effective form of therapy in patients with cystic fibrosis.

Distance running improves fitness in asthmatic children without pulmonary complications or changes in exercise-induced bronchospasm.

The effect of a distance running program was studied in 15 children with severe chronic asthma. Following a 6-week control period, the subjects ran four days a week for 6 weeks. The distance was increased gradually to 3.2 km. Clinical status and need for treatment did not change. Episodes of exercise-induced bronchospasm were readily reversed. Fitness improved as measured by the distance run in 12 minutes (P less than .005). Resting pulmonary function did not change. Exercise-induced bronchospasm following a bicycle ergometer stress test under comparable conditions did not change. Ventilatory muscle strength, measured as the maximal inspiratory pressure, and endurance, measured as the sustainable inspiratory pressure, were at a high level initially and did not change. It is concluded that distance running is safe and can increase the fitness of asthmatic children who are receiving adequate therapy.

Pulmonary function abnormalities in thalassemia patients on a hypertransfusion program.

Pulmonary function tests were performed in 12 thalassemia patients on a hypertransfusion program (age 18.4 +/- 2.6 SEM years) to determine the presence of any abnormalities of lung function. These included spirometry, expiratory flow rates, body plethysmography, single-breath nitrogen washout, single breath carbon monoxide diffusing capacity, and arterial blood gases. Only one patient had normal pulmonary function. Arterial hypoxemia was present in ten of 12 patients at rest. The total lung capacity (TLC) was normal. The residual volume was abnormally increased in five of 12 patients. The slope of phase III of single breath nitrogen washout curve was abnormal in five of 12 patients, but the closing volume was normal. The maximal expiratory flow rate at 60% total lung capacity was decreased in four of 12 patients, suggesting the presence of small airway disease. The single breath carbon monoxide diffusing capacity was normal in all patients. These pulmonary function abnormalities did not correlate with age or the cumulative amount of iron via blood transfused. The small airway obstruction, hyperinflation; and hypoxemia observed in thalassemia patients on a hypertransfusion program may result from the basic disease, iron deposition in the lungs, or other factors.

Effect of oral diuretics on pulmonary mechanics in infants with chronic bronchopulmonary dysplasia: results of a double-blind crossover sequential trial.

In a randomized double-blind crossover trial with sequential analysis, the effects of oral diuretics were compared with the effects of placebo on pulmonary mechanics in ten infants with bronchopulmonary dysplasia (BPD). Pulmonary mechanics were measured before and at the end of a week of treatment with oral diuretics (chlorothiazide, 20 mg/kg/dose and spironolactone, 1.5 mg/kg/dose) given twice daily, or placebo. Mean airway resistance decreased 35.3 cm H2O/L/s, mean specific airway conductance increased 0.095 1/L/s/cm H2O, and mean dynamic pulmonary compliance increased 1.74 mL/cm H2O during treatment with diuretics (all P less than .001), but not during treatment with placebo. The infants' rate of weight gain decreased on the first three days of diuretic treatment, but was thereafter comparable with weight gain during treatment with placebo. Fluid intake was similar in infants receiving diuretics and placebo. But, infants receiving diuretics not only had significantly increased urine output, osmolal clearance, and potassium and phosphorus excretion, but these infants also retained less fluid, and, in addition, excreted less calcium than infants receiving placebo. It is concluded that oral diuretics improve lung function in infants with chronic bronchopulmonary dysplasia; however, potassium and phosphorus depletion are potential complications of treatment.

Growth failure in infants with bronchopulmonary dysplasia: nutrition and elevated resting metabolic expenditure.

The mechanisms underlying growth failure in infants with bronchopulmonary dysplasia are poorly understood. Thirteen infants with bronchopulmonary dysplasia at 6 months of corrected age and 12 full-term healthy control infants matched for age or size were studied. Resting oxygen consumption was measured during natural sleep, and an estimation of the resting metabolic expenditure by indirect calorimetry was performed. Growth parameters were measured, and a nutritional profile including dietary intake, stool analysis, and serum albumin, cholesterol, glucose, and prealbumin was obtained. Seven of the 13 infants with bronchopulmonary dysplasia had growth failure (defined as length and weight less than the tenth percentile of the Babson growth curves). These infants had lower birth weight, lower gestational age, and a greater number of days spent in supplemental oxygen or on mechanical ventilation. There was no statistical difference between the bronchopulmonary dysplasia-growth failure and bronchopulmonary dysplasia-normal growth infants for dietary intake or stool or serum analyses. However, serum prealbumin showed a significant linear correlation with body weight in infants with bronchopulmonary dysplasia. Resting metabolic expenditure was elevated in infants with bronchopulmonary dysplasia with growth failure and was inversely correlated with body weight in all infants with bronchopulmonary dysplasia. Thus, infants with bronchopulmonary dysplasia and growth failure have increased metabolic demands and decreased prealbumin values suggesting a relative state of protein-calorie malnutrition.

Hypoxic and hypercapneic arousal responses and prediction of subsequent apnea in apnea of infancy.

Hypoxic and hypercapneic arousal responses from quiet sleep were tested in 56 infants with apnea of infancy (one or more episodes of cyanosis, limpness, and apnea requiring vigorous stimulation or resuscitation with no treatable cause; age 6.8 +/- 1.1 [SEM] months). Responses were compared with those of nine control infants ranging from 1 to 25 months of age. To assess hypercapneic arousal, the inspired PCO2 was rapidly increased during quiet sleep to 60 mm Hg or until arousal (restlessness, agitation, eye opening) occurred. All control infants and those with apnea of infancy aroused to hypercapnea, but control infants aroused at a lower inspired PCO2 (inspired PCO2 40.1 +/- 2.6 mm Hg) than those with apnea of infancy (inspired PCO2 46.9 +/- 1.5 mm Hg, P less than .05). To assess hypoxic arousal, the inspired PO2 was rapidly decreased during quiet sleep to 80 mm Hg or until arousal occurred. All control infants aroused to hypoxia (inspired PO2 78.3 +/- 2.1 mm Hg). However, only 38% of those with apnea of infancy aroused (inspired PO2 78.1 +/- 0.8 mm Hg), indicating an abnormality in recognition of hypoxia, or central brainstem response to hypoxia. During the 10.4 +/- 1.2 months of follow-up, there was a high incidence of subsequent apneas (greater than 20 seconds) during sleep at home in 50 apneic infants. Infants with abnormal hypoxic arousal responses had more severe subsequent apneas than those with normal hypoxic arousal responses (P less than .05).

Absent hypoxic and hypercapneic arousal responses in children with myelomeningocele and apnea.

Hypoxic and hypercapneic arousal responses from quiet sleep were tested in seven infants with myelomeningocele and Arnold-Chiari malformation who were symptomatic with apnea and/or hypoventilation. All infants with myelomeningocele required tracheostomy and posterior fossa decompression. Responses were compared with those of nine healthy control infants. To assess hypoxic arousal, inspired PO2 was decreased until the end-tidal (alveolar) PO2 reached 45 mm Hg for a maximum of three minutes. Eleven studies were performed in seven infants with myelomeningocele, and arousal occurred in only two studies (18.2%). Eight of nine control infants aroused to hypoxia (89%). To test hypercapneic arousal, inspired PCO2 was increased until end-tidal PCO2 reached 60 mm Hg for a maximum of three minutes. Eight studies were performed on six infants with myelomeningocele, and arousal occurred in three studies (37.5%). All seven control infants studied aroused to hypercapnea (100%). Three infants with myelomeningocele subsequently died. Infants with myelomeningocele, Arnold-Chiari malformation, and apnea or hypoventilation have arousal deficits to respiratory stimuli.

Diaphragm strength in near-miss sudden infant death syndrome.

Diaphragm muscle strength was measured as maximal transdiaphragmatic pressure during airway occlusion in ten near-miss sudden infant death syndrome infants aged 4.1 +/- 0.6 (SE) months post-term, range 2 to 7 months, and ten control infants aged 4.5 +/- 0.8 months post-term, range 0.8 to 8 months. In the near-miss sudden infant death syndrome group, the mean maximal transdiaphragmatic pressure was 106 +/- 6 cm H2O, range 78 to 132 cm H2O, compared with a mean maximal transdiaphragmatic pressure 86 +/- 4 cm H2O, range 69 to 106 cm H2O, in the control group. Diaphragm strength is normal or increased in near-miss sudden infant death syndrome infants.

Sudden infant death syndrome in infants evaluated by apnea programs in California.

Home apnea/bradycardia monitoring is frequently used in the management of infants at increased risk for sudden infant death syndrome (SIDS). However, some infants have died despite evaluation by infant apnea programs, and the benefits of home monitoring remain unproven. To determine the SIDS rate and risk factors of infants evaluated by infant apnea programs, 31 apnea programs and ten home monitor vendors in California were surveyed. Eleven (35%) of the apnea programs and four (40%) of the vendors responded. Information was obtained on 26 infants who died. Thirteen (50%) deaths were due to SIDS. Abnormal sleep studies did not predict death. Fifteen infants died despite a recommendation for home monitoring. Seven deaths occurred in association with technical errors or noncompliance with monitoring. Four deaths were due to nonaccidental trauma. The apnea programs evaluated 3,406 infants during a 5-year period; 1,841 had monitoring recommended. Term infants with apnea, subsequent siblings of SIDS victims, and infants evaluated at referral centers were more likely to have monitoring recommended than premature infants with apnea or infants evaluated at nonreferral centers (P less than .0001). Infants who had monitoring recommended were at equal risk of dying of SIDS as those who did not.