Postnatal development of periodic breathing cycle duration in term and preterm infants

Previous studies of the maturation of periodic breathing cycle duration (PCD) with postnatal age in infants have yielded conflicting results. PCD is reported to fall in term infants over the first 6 mo postnatally, whereas in preterm infants PCD is reported either not to change or to fall. Contrary to measured values, use of a theoretical respiratory control model predicts PCD should increase with postnatal age. We re-examined this issue in a longitudinal study of 17 term and 22 preterm infants. PCD decreased exponentially from birth in both groups, reaching a plateau between 4 and 6 mo of age. In preterm infants, PCD fell from a mean of 18.3 s to 9.8 s [95% confidence interval (CI) is +/- 3.2 s]. In term infants, PCD fell from 15.4 s to 10.1 s (95% CI is +/- 3.1 s). The higher PCD at birth in preterm infants, and the similar PCD value at 6 mo in the two groups, suggest a more rapid maturation of PCD in preterm infants. This study confirms that PCD declines after birth. The disagreement between our data and theoretical predictions of PCD may point to important differences between the respiratory controller of the infant and adult.     

Periodic breathing cycle duration in preterm infants

Periodic breathing cycle duration (PCD), the time interval from the beginning of one respiratory pause to the beginning of the next pause within an episode of periodic breathing (PB), was measured by examination of 24-h impedance pneumograms in 51 preterm infants. Calculations of the SD of PCD within a given PB episode (approximately 3 s) and comparison of PCD values between two PB episodes in each infant (r = 0.68) revealed considerable variability in PCD. This variability was not related to the number of cycles in the PB episode or to the amount of PB in the recording. Contrary to the decrease in PCD from 15.0 s at 1 wk to 12.4 s at 12 wk in term infants reported previously, PCD did not vary as a function of postconceptional, gestational, or postnatal age in our preterm population. PCD has limited value as an indicator of chemoreceptor maturation in the preterm infant, and most likely reflects transient adjustments in respiratory system control.     

Apneas and periodic breathing in mature newborn infants

50 healthy term newborn infants without a history of sudden infant death syndrome among their relationship were investigated between the second and fourth day of life using a modified test of Brady and McCann. In a thermoneutral environment pneumograms (respiration by thoracic impendance, heart rate, tcpO2) were obtained with an FiO2 of 21, 16, and 30% oxygen. In 12 of the 50 sleeping infants (24%) apnea periods or periodic breathing were observed with an FiO2 of 16%. This test will bring up abnormalities in the regulation of breathing. Similarities to the SIDS are discussed.     

Optimization of inspiratory work in periodic breathing in infants

In periodic breathing, there are repeated cycles of bursts of breaths separated by pauses several seconds long. We consider the mechanics of periodic breathing in human infants using calibrated traces of tidal volume and esophageal pressure recorded during the first few days after delivery. Each cycle of periodic breathing was analyzed in terms of the inspiratory time and beginning and end inspiratory volumes for each breath, the number of breaths in the cycle, and the total observed inspiratory work. A simple model was used to characterize the mechanics of the lung during inspiration, and the recordings were used to calculate the parameters of this model. These varied from breath to breath. A theoretical formula is derived for the sum of external work performed during inspiration for each burst. It is shown mathematically that there exists a local minimum in the calculated work as the values of the individual tidal volumes in this formula are allowed to vary, with the constraint that the sum of the ventilation during the cycle is as measured. The measured values of inspiratory timing, the starting volume and pressure, and the mechanical parameters for each inspiration are also used. We show that during each cycle of periodic breathing, the total of the observed external work is highly correlated with this theoretical minimum work. In addition, during the cycle, there is a pattern of overshoot and subsequent undershoot in the work with respect to the theoretical optimum, which suggests a control process operating during the cycle to minimize the work.     

Patterns of oxygenation during periodic breathing in preterm infants

The characteristics of the arterial oxygen saturation (SaO2) signal during episodes of hypoxaemia (SaO2 less than or equal to 80% for greater than or equal to 4 s) associated with periodic and non-periodic apnoeic pauses were studied in 16 preterm infants with cyanotic episodes (patients). and 15 asymptomatic preterm infants (controls), matched on birthweight and gestational age. The patients showed a significantly higher percentage of apnoeic pauses followed by a hypoxaemic episode (25 vs. 6%, P less than 0.01), and a two-fold increase in the slope of the desaturation curve (8.4 vs. 4.3% per s, P less than 0.005) in periodic compared with non-periodic breathing. All other characteristic of oxygenation (baseline SaO2 before episodes of hypoxaemia, delay between onset of apnoeic pause and onset of desaturation, lowest SaO2 during episodes of hypoxaemia) were similar for periodic and non-periodic breathing patterns. Similar, but not significant, differences between isolated and periodic apnoeic pauses were also present in the controls. An analysis of episodes of bradycardia (less than or equal to 100 beats per minute (bpm] showed that out of 121 episodes in the patients 118 were accompanied by a fall in SaO2 to less than or equal to 80%, and in the remaining three SaO2 fell to 82%, 85% and 86%, respectively. Thus all episodes of bradycardia (less than or equal to 100 bpm) were associated with a fall in SaO2 detected by beat-to-beat pulse oximetry. Examination of hypoxaemic episodes and their relationship with bradycardia and with apnoeic pauses, periodic and non-periodic, may help the further understanding of the control of arterial oxygenation in preterm infants with cyanotic episodes.     

Respiratory EMG findings in relation to periodic breathing in infants

Intercostal and diaphragm EMG activity was analysed in periodically breathing infants. The aim was to investigate relationships between changes in tonic activity in the respiratory muscles and switches in spontaneous breathing pattern from periodic to continuous and vice versa. A heterogeneous group of 13 normal and neurologically suspect infants was studied. They had all previously undergone polygraphic investigation and were selected because their polygraphic records showed at least three minutes uninterrupted periodic breathing (PB). PB appeared to represent an oscillation with a length of about 16 seconds superimposed on the basic state related irregular and regular breathing patterns. The development of a normal level of tonic activity in the respiratory muscles at the transition from state 2 to state 1 coincided with the switching from periodic to continuous breathing. Continuation of PB throughout a state 1 epoch in the presence of tonic respiratory muscle activity was exceptional. Sighs alone or sighs together with brief movements during state 1 were followed on occasion by a drop in tonic activity and a switch from continuous to periodic breathing. If the tonic activity rose again, PB either stopped or became less pronounced. TcPO2 level measured in four infants rose when tonic activity rose and was lower during PB than during continuous breathing. The observations made in this study suggest that mechanical or chemical changes caused by changes in tonic activity level may affect the stability of respiratory control in infancy.     

Apnea, transient episodes of bradycardia, and periodic breathing in preterm infants

The occurrence of central apnea of 15 seconds or longer, transient episodes of bradycardia (TEB), and periodic breathing were studied in 66 healthy premature infants when at least 1 week old and between 32 and 36 weeks postconceptual age. Eight-hour cardiorespiratory recordings were visually scanned for the presence of these patterns. Central apnea of 15 seconds or longer was seen in almost half of the infants. The TEB were numerous, and the majority were not associated with central apnea; however, all but five of the apneic episodes that lasted 15 seconds or longer were accompanied by a TEB. Infants spent as much as 40% of their time in periodic breathing. The frequency with which these patterns are seen in healthy premature infants strongly suggests that they are normal findings. Our results do not support the opinion that brief periods of apnea are abnormal when accompanied by a TEB.     

Oral breathing in newborn infants

Newborn infants are considered obligate nasal breathers, hence dependent on a patent nasal airway for ventilation. The conditions under which oral breathing could occur and the contribution of oral ventilation to total ventilation were studied in 30 healthy term infants (aged 1 to 3 days). Nasal and oral airflow were measured using two resistance-matched pneumotachometers, and heart rate, tcPO2, etCO2, and sleep state were continuously recorded. In three of 10 infants studied in undisturbed sleep, spontaneous oronasal breathing was noted during both active and quiet sleep (mean duration 19 +/- 25 minutes), the distribution of tidal volume being 70% +/- 12% nasal and 30% +/- 12% oral. Episodes of oronasal breathing were also observed after crying in six infants (mean duration 21 +/- 19 seconds). In an additional 20 infants, multiple 15-second end-expiratory nasal occlusions were performed; eight (40%) of these infants initiated and sustained oral breathing in response to nasal occlusion. Respiratory rate, tidal volume, heart rate, and tcPO2 did not change when oral breathing occurred in response to nasal occlusion, although minute ventilation decreased from 265 to 199 ml/min/kg (P less than 0.05). These results demonstrate that newborn infants may use the oral airway for ventilation, both spontaneously and in response to complete nasal occlusion.     

Characterization of neural breathing pattern in spontaneously breathing preterm infants

The aim was to characterize the neural breathing pattern in nonintubated preterm infants. The diaphragm electrical activity (EAdi) and heart rate were simultaneously measured repeatedly for 1 h over several days using a modified feeding tube equipped with miniaturized sensors. The EAdi waveform was quantified for phasic and tonic activity, neural timings, and prevalence of recurring patterns, including central apnea. Ten infants with mean age 7 d (range, 3-13 d) were studied. Their birth weight was 1512 g (1158-1800 g) and GA at birth 31 wk (28-36 wk). Neural inspiratory and expiratory times were 278 ms (195-450 ms) and 867 ms (668-1436 ms) and correlated with GA (p < 0.001). Tonic EAdi represented 29.5% of phasic EAdi (16-40%) and was related to GA (r = 0.61, p < 0.001). For the group, 68% of the time was regular phasic breathing (without tonic activity) and 29% of the time with elevated tonic activity. Central apneas >5 s occurred on average 10 times per hour (2-29). Heart rate reductions were correlated to central apnea duration. In conclusion, esophageal recordings of the EAdi waveform demonstrate that neural breathing pattern is variable, with regards to timing, amplitude, and pattern with a distinct amount of tonic diaphragm activity.     

Sleep state, hypoxia and periodic breathing in the neonate

The influence of sleep state on hypoxia-induced periodic breathing was evaluated in full-term babies studied during the first week of life. Following exposure to 15% O2, periodic breathing occurred in 7 of 42 babies during quiet sleep, and 5 of 20 during active sleep (p less than 0.05). The median levels of transcutaneous pO2 at which periodic breathing occurred during hypoxia, and was abolished on reoxygenation were similar in each sleep state. The median duration of periodic apnoea was significantly greater in quiet than active sleep. In 7 babies the occurrence of periodic breathing during hypoxia was accompanied by a change in sleep state. This was probably coincidental in 3 cases, but in the other 4 babies hypoxia may have induced both the change in state and breathing pattern.     

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.     

Prolonged periodic breathing: significance in sleep studies.

Periodic breathing (PB) is a pattern of breathing that is frequently recognized in infants being studied for possible sleep apnea. Infants presenting to a sleep laboratory over a 3 1/2-year period who had evidence on their initial study of prolonged (greater than 15% of total sleep time) PB were prospectively studied in an effort to determine the significance of this pattern of breathing. Of the 331 infants studied, 40 demonstrated prolonged PB. Sixteen of these infants, who were of 37 weeks' gestation or greater at birth and did not receive pharmacologic therapy, were studied on at least two occasions (group 1). Of the remaining 24 infants, 11 were treated with methylxanthines by their attending physician (group 2), and 13 did not return for sequential studies (group 3). All infants who were of less than 37 weeks' gestation at birth were separately evaluated (group 4). For group 1, who were studied at a mean age of 15 postnatal weeks, there was a mean of 36.4% periodicity which decreased on the second study to 18.0%. By the fourth study, this had decreased to 9.2%. In group 2, there was a mean of 41.3% periodicity during the first study which decreased to 6.4% on the second study. Infants of group 3 had a mean of 31.4% PB on their initial study and the premature infants, group 4, had 30.1% PB. All infants showed a decrease in PB with sequential studies and no infant was known to have died of sudden infant death syndrome or any other disorder in the first year of life.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prone position in spontaneously breathing infants with pneumonia

This study was designed to evaluate further the effect of prone positioning on oxygen saturation (SpO2) and respiratory mechanics in spontaneously breathing infants with pneumonia. SpO2 and respiratory mechanics were measured in the supine and prone positions in 17 infants. Prone positioning resulted in statistically significant increases in mean (+/- SD) SpO2 (95.52+/-2.87 to 98.00+/-2.40%, p = 0.0002) and respiratory system compliance (5.99+/-2.52 to 7.93+/-4.30 ml/cm H2O, p = 0.02). This suggests that prone positioning is another beneficial supportive measure for spontaneously breathing infants with pneumonia.