Sequential 22-hour profiles of breathing patterns and heart rate in 110 full-term infants during their first 6 months of life

Sequential recordings (total number 365, mean duration 22 hours) of ECG and abdominal wall movement were obtained from 110 full-term infants up to 6 months of age. The longest pause in breathing movement per recording (maximum 21.6 seconds) decreased in duration over the first 2 weeks of life (P less than .005). Pauses greater than 18.0 seconds were not detected after seven days. The spread of values for pauses greater than or equal to 3.6 seconds duration was widest during the first 2 weeks, and their number decreased with age (P less than .001). Periodic breathing, detected in 69% to 80% of infants in all age groups, showed decreasing trends with age in total duration and maximum length of episode (P less than .005 for both). The spread of values was widest during the first 2 weeks (range for total duration 0 to 4.7 hours) and decreased with age. The mean respiratory rate during regular breathing decreased after 4 weeks (P less than .001). The spread of values was widest during the first 2 weeks and decreased with age. Birth weight was positively correlated with mean respiratory rate during the first three days of life (r = +.64, P less than .001). The mean heart rate during regular breathing increased during the first 15 days (P less than .001) and then decreased after 4 weeks (P less than .001). Higher mean heart rates were found in male infants (P less than .01).     

Breathing patterns and heart rates at ages 6 weeks and 2 years.

Forty-two randomly selected, full-term, healthy infants underwent 24-hour electrocardiographic recordings and breathing movements at about ages 6 weeks (median age, 43 days; range, 34 to 61 days) and 2 years (median age, 26 months; range, 21 to 35 months). The number and duration of apneic pauses of 3.6 seconds or longer were analyzed. Periodic apnea was defined as a sequence of three or more apneic pauses, each separated by fewer than 20 breaths. All other apneic pauses were defined as isolated. Median heart rates and respiratory rates, which were measured during regular breathing, decreased from 137/min and 35/min to 98/min and 21/min, respectively. The total duration of periodic apnea remained unchanged (median, 0.06 min/h vs 0.05 min/h). Although the median frequency of all isolated apneic pauses decreased from 3.6/h to 2.5/h, the number of those that were longer than 6 seconds increased from 0.37/h to 0.80/h, leading to an increase in the proportion of these pauses, among all isolated apneic pauses, from 10% at age 6 weeks to 32% at age 2 years. Only one apneic pause in one infant at age 6 weeks, but eight pauses in six children at age 2 years, were longer than 15 seconds. A knowledge of such normal variability in the duration of apneic pauses in older infants and young children is essential for the interpretation of pneumograms and alarms while monitoring breathing movements.     

Cardiorespiratory patterns occurring in infants during and after recovery from respiratory tract infection

During and after respiratory tract infections in 29 hospitalized infants, 12 cardiorespiratory measurements were performed on 24-hour recordings of ECG and respiratory activity. These measurements were compared with similar data obtained from 110 age-matched control infants without infection. Respiratory and heart rates during the state of regular breathing were increased during infection, as compared with recordings made after recovery. The numbers of short apneic pauses 3.6 to 6.0 seconds and greater than 6.0 to 12.0 seconds in duration, together with the duration of the overall longest apneic pause per recording, were reduced during infection compared with after recovery. The total durations of periodic breathing and of periodic apnea per recording were also reduced during infection compared with after recovery. These effects were consistent in 27 of the 29 cases, but in two, periodic breathing levels during infection exceeded the 90th percentile in age-matched controls and were reduced after recovery. Measurements made after recovery tended to conform more closely to values in the control infants. None of the 29 infants studied subsequently died or suffered chronic respiratory problems. This study suggests that prolonged apneic pauses or increased numbers of short pauses are not usually a consequence of respiratory tract infection in normal infants.     

Cardiorespiratory function in 16 full-term infants with sudden infant death syndrome

Twenty-four-hour tape recordings of ECG and breathing movements from 16 term infants (greater than or equal to 37 weeks' gestation) who subsequently died of sudden infant death syndrome (SIDS) were compared with recordings from surviving infants from the same populations. Apneic pauses of varying durations, periodic and regular breathing patterns, heart and respiratory rates during regular breathing were measured. Only one of 16 full-term infants with SIDS had findings outside the range of age-matched control infants (an excess of periodic breathing patterns and an absence of regular breathing). When the first recordings of each of infants who died of SIDS, except one who had cyanotic episodes prior to death, were compared to recordings of survivors (six for each case) closely matched for age, gestation, and weight at birth, no differences in breathing patterns or heart or respiratory rates during regular breathing could be demonstrated. These particular measurements of cardiorespiratory function were, therefore, unable to identify the majority of full-term infants at risk for SIDS.     

Model of normal prepubertal growth

Overheating may cause terminal apnoea and cot death. Rectal temperature and breathing patterns were examined in normal infants at home during the first 6 months of life. Twenty one infants had continuous overnight rectal temperature and breathing recordings for 429 nights (mean 20.4 nights, range 7-30) spaced over the first six months of life. Periods when breathing was 'regular' were directly marked on single night records. Sleep state was determined from respiratory variables. 'Regular' breathing was a reliable marker of 'quiet' sleep (specificity 93%). The duration of 'quiet' sleep increased from 6 to 22 minutes from two weeks to three months of age and then remained static, as did the proportion of sleep spent in the quiet phase (9% to 34%). Rectal temperature fell during 66% of quiet sleep and usually rose during rapid eye movement (REM) sleep. The drop in rectal temperature was maximal at the start of quiet sleep, whereas the maximum rise during REM sleep was reached after 10 to 15 minutes. Oscillations in rectal temperature are associated with changes in sleep and breathing state. The maturation of rectal temperature patterns during the first six months of life are closely related to a maturation of sleep state and breathing patterns.     

Breathing,sleep state,and rectal temperature oscillations.

Overheating may cause terminal apnoea and cot death. Rectal temperature and breathing patterns were examined in normal infants at home during the first 6 months of life. Twenty one infants had continuous overnight rectal temperature and breathing recordings for 429 nights (mean 20.4 nights, range 7-30) spaced over the first six months of life. Periods when breathing was ''regular'' were directly marked on single night records. Sleep state was determined from respiratory variables. ''Regular'' breathing was a reliable marker of ''quiet'' sleep (specificity 93%). The duration of ''quiet'' sleep increased from 6 to 22 minutes from two weeks to three months of age and then remained static, as did the proportion of sleep spent in the quiet phase (9% to 34%). Rectal temperature fell during 66% of quiet sleep and usually rose during rapid eye movement (REM) sleep. The drop in rectal temperature was maximal at the start of quiet sleep, whereas the maximum rise during REM sleep was reached after 10 to 15 minutes. Oscillations in rectal temperature are associated with changes in sleep and breathing state. The maturation of rectal temperature patterns during the first six months of life are closely related to a maturation of sleep state and breathing patterns.     

Blood transfusion effect on the respiratory pattern of preterm infants

Anemia may increase the risk of tissue hypoxia in preterm infants. This could lead to respiratory center depression and an increased risk for apnea. Heart rate and breathing pattern were recorded in 30 preterm infants (gestational age 30.0 +/- 2.3 weeks, postnatal age 46.6 +/- 20.8 days, and weight 1,438 +/- 266 g) before and after a transfusion of 10 mL/kg of packed RBCs. All infants were stable clinically, breathing room air, and free of prolonged apneic episodes. After transfusion, hematocrit levels increased from 27.0% +/- 2.5% to 35.8% +/- 4.7%. Heart rate decreased from 157.2 +/- 13.6 beats per minute to 148.4 +/- 13.9 beats per minute. There was no change in respiratory rate or BP. The duration of periodic breathing decreased significantly, as did the duration of the longest periodic breathing episode (P less than .01). The number of respiratory pauses lasting 5 to 10 seconds and the number of pauses lasting 11 to 20 seconds also decreased significantly (P less than .05). The total duration of respiratory pauses, excluding pauses during periodic breathing, were significantly lower after transfusion (P less than .05), as was the number of episodes of bradycardia. These results indicate that preterm infants have a more irregular breathing pattern while anemic than after correction of the anemia. The irregular breathing pattern is probably caused by mild hypoxic respiratory center depression.     

Effect of body temperature on the pattern of spontaneous breathing in extremely low birth weight infants supported by proportional assist ventilation

The optimum body temperature for infants <1000 g is unknown. We investigated body temperature effects on spontaneous breathing using proportional assist ventilation (PAV), because this mode supports spontaneous breathing such that all breathing pattern variables remain controlled by the infant. Minute volume (MV), respiratory rate (RR), tidal volume (Vt), incidence and duration of respiratory pauses, arterial oxygen desaturations <85%, and arterial Pco2 levels will remain unaffected by targeting core body temperature to 36.1-36.5 degrees C (low normal range) versus 37.7-37.9 degrees C (upper normal). Twenty infants (mean +/- SD: birth weight, 696 +/- 155 g; gestational age, 25 +/- 1 wk; age, 5 +/- 3 d) who were supported by PAV were exposed to each target temperature range on 2 consecutive days in four 2-h intervals for a total of 8 h with the sequence of the temperature ranges randomized. Core body temperature was 36.5 +/- 0.2 degrees C and 37.9 +/- 0.2 degrees C in the two conditions. MV was 291 and 314 mL. min-1. kg-1, respectively (7% difference; p < 0.001) as a result of a difference in RR (8%; p < 0.001). The infants maintained their blood CO2 levels and Vt (5.25 +/- 0.6 versus 5.19 +/- 0.6 mL/kg). Incidence and duration of respiratory pauses were not different between conditions. Extremely immature infants who are supported by PAV modify their spontaneous breathing in response to changes in thermal environment such that Pco2 levels are appropriately maintained early in postnatal life. This response pattern occurred consistently and is currently of uncertain clinical significance.     

Respiratory muscle EMG in newborns: a non-intrusive method

A non-intrusive method of recording the EMG of respiratory muscles with electronic suppression of the ECG artifact and averaging with a running window was employed in newborn infants at term to study respiratory patterns in different behavioural states. There are clear state-related differences in the diphragmatic and intercostal activity patterns. During most of the time in state 1 (quiet sleep) sustained tonic activity is found in the diaphragm as well as in intercostal muscles, but is virtually absent during state 2 (active sleep). During state 1 intercostal activity slightly precedes diaphragmatic activity whereas in state 2 both muscles contract about synchronously and vary widely in their amplitude. During periodic breathing the inspiratory EMG activity is absent in the pauses, but tonic activity may be present during periodic breathing in state 1. Isolated respiratory pauses with silence in the respiratory muscles occur in state 1 after sighs and starties with deep inspirations. During state 2 many respiratory pauses accompany gross movements and simultaneous laryngeal muscle activity suggests upper airway occlusion. Respiratory pauses without movements cannot be due to general alpha-motoneuron inhibition, because chin muscle activity may be seen at the same time. Gross movements often act as a reset mechanism for increase or decrease in tonic activity and phasic respiratory activity. Some speculations on the neural mechanisms of respiratory control based on the preliminary findings from the EMG recordings are mentioned.     

Cardiorespiratory patterns in siblings of babies with sudden infant death syndrome.

Clinical data and 24 hour tape recordings of electrocardiogram (ECG) and abdominal breathing movements were collected from 301 infants who had had a sibling who had suffered the sudden infant death syndrome (SIDS). Of these, 261 were referred cases, and 40 were recorded prospectively as part of a population based study; none of the 301 subsequently died. Fifty five of the referred siblings who had been born at full term (greater than or equal to 37 week gestation) were randomly selected for a detailed analysis of heart rate and breathing patterns, as were all siblings born at full term from the prospective study (16 with a previous sibling in whom SIDS had occurred and seven with a sibling born at full term and in whom SIDS had subsequently occurred). The control group consisted of 197 recordings on 170 infants born at full term and matched by postnatal age. The mothers of the siblings smoked and consumed alcohol more often during pregnancy than the mothers of control babies. The siblings had lower Apgar scores and were more often breast fed than controls. There were no significant differences in the number of apnoeic pauses in the quantities of periodic breathing or in the heart and respiratory rates during regular breathing between the siblings and the controls.     

Effects of theophylline on the pattern of spontaneous breathing in preterm infants less than 1000 g of birth weight

Proportional assist ventilation (PAV) amplifies the ventilatory effect of the spontaneous respiratory effort and therefore allows analysis of drug-induced changes in the spontaneous breathing pattern of subjects who depend on mechanical ventilatory assistance. We hypothesized that theophylline will reduce the number and duration of respiratory pauses and apneic events in infants less than 1000 g of birth weight on PAV. Twelve infants were studied: median birth weight was 773 g; gestational age 26.0 weeks and postnatal age 9 days. Measurements were obtained over a 2-h period before and after 5 mg/kg of intravenous theophylline. A respiratory pause was defined as cessation of breathing for at least the duration of three preceeding breaths. The total number of respiratory pauses and the number of apneas followed by either cardiac slowing (decrease in heart rate more than 10%) or bradycardia decreased significantly. Minute ventilation increased due to a rise in tidal volume from 5.6+/-1.3 to 6.1+/-1.2 ml/kg (p=0.004). The duration of respiratory pauses, the respiratory rate, and the number of apneas followed by desaturation did not change significantly. We conclude that theophylline stimulates spontaneous breathing in infants less than 1000 g, reduces the number of apneas, and increases minute volume by increasing the tidal volumes.     

The maturation of respiratory patterns in normal full term infants during the first six postnatal months. I: Sleep states and respiratory variability.

ABSTRACT. Four term healthy infants had their respiratory pattern monitored during a 2-hour afternoon nap recording period at monthly intervals up to six months of age. The time spent asleep significantly decreased with a marked reduction in active sleep (66% to 10%) while maintaining one long epoch of quiet sleep (mean 31 mins). Mean breathing rate at one week was higher in active sleep than quiet sleep (47 vs 41 breaths/min.) and decreased by 6 months in both sleep states (31 breaths/min. in both). Variability of breathing rate at 1 week was significantly increased in active sleep compared to quiet sleep and both decreased by 6 months. These findings confirm a significant maturational change in the respiratory pattern and variability of normal infants in the afternoon nap from 1 to 6 months.     

Periodic breathing in infants with near-miss sudden infant death syndrome.

Twelve-hour nocturnal home recordings of respiration and heart rates were obtained during sleep in 32 infants with near-miss sudden infant death syndrome (SIDS) and in 32 control infants, and the recordings were analyzed for periodic breathing. An episode of periodic breathing was defined as three or more apneic pauses of three or more seconds. The duration of respirations interrupting the pauses was 20 seconds or less. Analysis revealed a statistically significant difference (P less than .001) between the two groups, using criteria of percent of periodic breathing episodes, number of periodic breathing episodes/100 min of recorded sleep time, average duration of all episodes, and duration of the longest episode of periodic breathing. It is concluded that periodic breathing is present in excessive amounts during sleep in infants with near-miss sudden infant death syndrome.     

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.     

Periodic breathing and apnea in preterm infants

The relationship between periodic breathing and idiopathic apnea of prematurity was investigated. We recorded respiratory impedance, heart rate, pulse oximetry and end-tidal CO2 from 68 untreated infants of less than or equal to 34 wk gestation with a diagnosis of idiopathic apnea of prematurity. Mean birth wt was 1476 g (SD 420) and mean gestational age was 29.9 wk (SD 2.6). Apneas of more than 15 s duration that were associated with hypoxemia or bradycardia were identified by semiautomated analysis of computerized records. A total of 1116 significant apneic spells were identified, only one of which occurred during an epoch of periodic breathing, five others occurred within 2 min of the end of an epoch of periodic breathing. Less than 0.6% of significant apneic spells occur within 2 min of periodic breathing. In all of the 12 infants that were monitored starting in the first 12 h of life, significant apneic spells were identified before 36 h of age and no precipitating factors were identified. Periodic breathing did not occur during the first 48 h of life, a finding that supports the concept that the peripheral chemoreceptor is inactive in the first 48 h of life. Periodic breathing in the premature infant is not a precursor to significant apnea.     

Hypoxaemia in infants with respiratory tract infections

Nineteen infants who were graduates from special care baby units underwent two overnight tape recordings of oxygen saturation (SaO2) and breathing movements; one during an upper (n = 12) or lower (n = 7) respiratory tract infection and the other when free of infection. Baseline SaO2 was lower during infection (median 99.6 vs 100%, p less than 0.01), with four patients having values (84.3-95.5%) below the normal lower limit for full-term infants (97%). The median number of apnoeic pauses was also lower during respiratory tract infection (4.7 vs 15.7/h, p less than 0.02). The median number of episodic desaturations (SaO2 less than or equal to 80%) did not change significantly (1.3 vs 1.9/h, p greater than 0.05), with the exception of one patient who had extremely increased values during infection for both apnoeic pauses (63/h) and desaturations (112/h). No infant, however, was considered clinically hypoxaemic. Clinically unsuspected hypoxaemia may thus occur during respiratory tract infection in a proportion of infants graduating from special care baby units. Such hypoxaemia may have potentially deleterious effects.     

Developmental patterns of heart rate and variability in prematurely-born infants with apnea of prematurity

At equivalent post-conceptional ages, prematurely-born infants have higher heart rates and reduced heart rate variability, relative to full-term neonates. Premature birth might exert long-lasting effects on central and peripheral mechanisms that control cardiovascular activity. We assessed development of heart rate and heart rate variability in symptomatic preterm infants up to 6 months of age. Fifty 6.5-h evening recordings of EKG and breathing were obtained from prematurely-born infants (gestational ages: 24–35 weeks). Cardiac R-R intervals were captured with a resolution of ±0.5 msec. One-min epochs were selected from three periods of regular respiration in recordings from premature infants and 72 recordings of full-term infants at comparable post-conceptional ages. Mean heart rate and heart rate variability were determined for each recording. At 40 weeks post-conception, prematurely-born infants with apnea of prematurity showed higher heart rates and reduced heart rate variability than did full-term neonates. These differences between premature and full-term infants persisted throughout the next 6 months in those infants born prior to 30 weeks gestation, and in those infants born at 30–35 weeks who experienced respiratory distress syndrome (RDS) during the neonatal period. The findings suggest that premature delivery, or complications thereof, exerts long-lasting effects on cardiac control.     

Analysis of heart rate and respiratory patterns in sudden infant death syndrome victims and control infants

Retrospective analyses of patterns of breathing and heart rate variability obtained by visual inspection and spectral analysis of ECG and respiratory activity have provided markers associated with subsequent death in a referred population of infants at high risk for sudden infant death syndrome (SIDS). Such markers include breathing patterns characterized by excessive apneic pauses and periodic breathing, heart rate spectra characterized by increased low frequency oscillations, and respiratory activity spectra characterized by a widened "bandwidth" during regular breathing. To test whether such measurements could distinguish SIDS cases and randomly selected controls from a population study the data from 10 cases and 100 age-matched control subjects were analyzed blind. The code was disclosed after completion of the analysis. We found that none of the markers served to distinguish the SIDS cases from the controls in the population at large. This observation may indicate important physiological differences between infants destined to die in the referred high risk population and infants who die of SIDS at large. The possible reasons for our inability to identify the group of SIDS in the general population, as compared to the group of deaths in the referred high risk group are: (1) different disease processes in the two groups, (2) difference responses to the same disease process in the two groups, (3) a response reflecting the psychosocial setting of the referred high risk population, (4) methodological differences between this and previous studies. We conclude that these markers are not of value in screening the population at large.     

Heart rate variability analysis in full-term infants: spectral indices for study of neonatal cardiorespiratory control

The heart rate and respirations of twenty healthy full-term infants between 30 and 60 h postnatal age were studied during quiet sleep with the objective of defining spectral indices which represent normal neonatal heart rate variability (HRV) characteristics. Total HRV power and the distribution of power across different frequency bands varied considerably among infants. Cluster analysis on the measured variables indicated that the population divided into two groups that represented significantly different patterns of HRV behavior. In one group (11 subjects), infants had lower breathing rates and HRV power in a band about the respiration frequency [respiratory sinus arrhythmia (RSA) band] was more than 20% of the total power (TP). Additionally, the ratio of low frequency band power to RSA band power was less than 4. The other group of neonates (nine subjects) had relatively higher breathing rates, RSA power less than 20% of total power, and low frequency to RSA power ratio greater than 4. Regression analysis of low frequency versus TP and RSA versus TP graphs gave strong support to the hypothesis that there were indeed two distinct patterns of HRV behavior. Separation of apparently normal neonates into two groups may be attributed partially to differences in respiratory rates and breathing patterns. However, it is possible that differences in the balance between sympathetic and parasympathetic nervous system control, perhaps related to autonomic maturation, also contribute to group separation. The indices developed from HRV spectral analysis in this investigation may be of value in the study of cardiorespiratory control in neonates.     

Cardiorespiratory patterns in infants presenting with apparent life-threatening episodes

A total of 305 infants presenting with apparent life-threatening events (ALE) were referred by their paediatricians and underwent 24-hour tape recordings of electrocardiogram and abdominal breathing movements (from a pressure capsule transducer). Seventy-seven of these infants, all full-term (greater than or equal to 37 weeks of gestation), were randomly selected, followed up for clinical outcome, and their recordings subjected to a detailed analysis of heart and respiratory rates and breathing patterns. Recordings on 157 age-matched, full-term controls were similarly analysed for comparison purposes. One of the 77 patients suffering from ALE had a pre-existing neurodevelopmental problem, and 4 more cases showed this at follow-up, including 1 case whose ALE was subsequently diagnosed as originating from non-accidental injury. Compared with controls and as a group, the patients suffering from ALE showed higher numbers of apnoeic pauses (p less than 0.001), larger quantities of periodic breathing (p less than 0.01) and lower respiratory rates during regular breathing (p less than 0.01).