Electroencephalography in premature and full-term infants. Developmental features and glossary.

Following the pioneering work of C. Dreyfus-Brisac and N. Monod, research into neonatal electroencephalography (EEG) has developed tremendously in France. French neurophysiologists who had been trained in Paris (France) collaborated on a joint project on the introduction, development, and currently available neonatal EEG recording techniques. They assessed the analytical criteria for the different maturational stages and standardized neonatal EEG terminology on the basis of the large amount of data available in the French and the English literature. The results of their work were presented in 1999. Since the first edition, technology has moved towards the widespread use of digitized recordings. Although the data obtained with analog recordings can be applied to digitized EEG tracings, the present edition, including new published data, is illustrated with digitized recordings. Herein, the reader can find a comprehensive description of EEG features and neonatal behavioural states at different gestational ages, and also a definition of the main aspects and patterns of both pathological and normal EEGs, presented in glossary form. In both sections, numerous illustrations have been provided. This precise neonatal EEG terminology should improve homogeneity in the analysis of neonatal EEG recordings, and facilitate the setting up of multicentric studies on certain aspects of normal EEG recordings and various pathological patterns.

Between-sleep states transitions in premature babies.

To assess the manner in which between-sleep state transitions occur in infants, we examined polysomnography (PSG) studies in 25 clinically and neurologically normal, appropriate-for-gestational-age, 30-to-36-week-gestational age (GA) infants. Twenty infants underwent paper PSG and five infants digitised PSG. Sleep states were coded based on concordance of REMs and the electroencephalogram (EEG) pattern. Data were analysed using a multivariate linear model, with the subject factor as a cluster. Duration of active sleep (AS) to quiet sleep (QS) transitions (median 4.8 min) was significantly longer than duration of QS to AS transitions (1.7 min) and was independent from GA and from the recording method (paper vs. digitized PSG). The sequence of modifications in parameters (REM and EEG) was invariable: REM cessation was the first change in AS to QS transitions, and REM appearance was the last change in the QS to AS transitions. Our study demonstrates a stable, well-organized pattern of between-sleep-states transitions in healthy 30-to-36-week GA premature infants. These findings are similar to those described in full-term newborns and are in agreement with our previous observations of well-defined sleep states at the age investigated here.

Patterns of EEG frequency, movement, heart rate, and oxygenation after isolated short apneas in infants.

Patterns of events occurring at the end of apneas have rarely been reported in infants. No previous studies have compared these patterns to those of spontaneous events during sleep. We examined 163 isolated apneas in 17 infants (47 +/- 4 wk postconceptional age) who underwent polysomnography for suspected upper airway problems. Mean apnea duration was 6.5+/-1.5 s (range, 5 to 11.5 s), 78% of apneas occurred in active sleep, and 67% of apneas were obstructive. We recorded the occurrence of body movement or augmented breath and analyzed changes in EEG frequency > or = 1 s, heart rate, and oxygen saturation value at the end of apneas and of a control ventilatory period defined as a period of breathing equal in duration to the apnea and preceding the apnea by 1 min. We found that 7.9% of apneas and 11.6% of control periods were followed by an augmented breath and that 14.1% of apneas and 0.5% of control periods were followed by a body movement. The percentages of motor events or no event differed significantly after the apneas (p = 0.008) compared with the control periods. A significant increase in EEG frequency was observed at the end of the apneas compared with the control periods (p < 0.04). EEG frequency increased after 61% of the apneas. Neither heart rate nor oxygen saturation value changed after the control periods. Heart rate decreased significantly after the apneas not followed by a motor event (p = 0.02) but not after the apneas followed by a body movement. We conclude that 1) at termination of isolated apneas in infants, a motor event was rare, whereas an EEG frequency increase was common; 2) event patterns at apnea termination differed from those at control period termination.

Physiological parameters evaluation following apnea in healthy premature infants.

To assess responses to central and obstructive apnea, we performed 10-hour polygraphic recordings in healthy 33-34 wGA infants. Each apnea period was paired with a control period. The presence of body movements (BM) and augmented breaths (AB), the EEG, heart rate (HR), respiratory rate, phase relationships between thoracic and abdominal respiratory movements, and changes in SaO(2) were evaluated. No apnea caused awakening. Apnea were not usually followed by motor events (no significant differences with control periods), with the exception of most obstructive apnea longer than 10 s. The mean percentage of changes following apnea, normalized to baseline values, was significant for the EEG (frequency slightly increased, mainly after obstructive apnea), HR (deceleration), and respiratory rate (increased). However, the mean values masked heterogeneity across apnea in the direction of the change in each parameter. The only significant correlation was between changes in HR and SaO(2). The increases in EEG frequency and respiratory rate seen in our study can be considered markers of CNS activation, but were small and inconsistent. The heart rate decelerations and SaO(2) changes are not activation markers. Thus, mechanisms underlying restarting of breathing efforts following apnea remain unclear in premature babies. Our investigation establishes the importance of using control data to distinguish between spontaneous and apnea-related events.

[Electroencephalography of the premature and term newborn. Maturational aspects and glossary]. / Electroencéphalographie du nouveau-né prématuré et à terme. Aspects maturatifs et glossaire.

From the first publication of C. Dreyfus-Brisac and N. Monod, a strong tradition combined with tremendous development of neonatal EEG has taken place in France. After 3 years of collaborative work, 12 clinical neurophysiologists trained at the Port-Royal medical school in Paris detail in this paper the currently available neonatal EEG recording techniques. They have synthesized the criteria of maturational state analysis and have defined the normal and pathological neonatal EEG patterns, including descriptions already present in the French as well as the English literature. In this review one may find a complete description of neonatal EEG patterns according to the states of vigilance and to gestational age. Furthermore, definitions of all normal and pathological patterns are provided in a glossary. Both chapters are illustrated by numerous figures. This detailed terminology in neonatal EEG should allow a better homogeneity in EEG reports, and could lead to multicentric studies on normal, unusual or pathological patterns, according to etiology. Although based on analogic EEG data, this work can equally be applied to digitized EEG tracings.

Heart rate modifications related to spontaneous body movements in sleeping premature and full-term newborns.

Heart rate (HR) acceleration is an essential mechanism for adaptation to changes in hemodynamic and energetic needs resulting from body movements. To evaluate age-related development of coupling between spontaneous movement and HR changes, we performed polysomnographic recordings in 20 clinically and neurologically normal newborns including 10 premature (31- to 36-wk gestational age, wGA) and 10 full-term (38- to 41-wk gestational age) infants. Recordings were sampled at 286 Hz and processed using a signal-to-noise ratio algorithm for QRS complex detection. Movements were automatically detected and the logical signal obtained was sampled at QRS fiducial points and written in the attributes of each QRS. The study included the 402 movements that were less than 30 s in duration and were neither preceded nor followed by another movement or by a respiratory event (pause, sigh). The amplitude of movement-induced HR acceleration was significantly lower in premature compared with full-term newborns (p < 0.01). This difference persisted when the other factors influencing the HR response (basal HR, movement duration, and amplitude) were taken into consideration. Our data identify HR acceleration induced by spontaneous body movements as a fundamental reflex response that develops with gestational age from premature to full-term newborns.

Heart rate variability and apnea during sleep in Down's syndrome.

Autonomic system dysfunction has been reported to occur frequently in patients with Down's syndrome (DS) and is constituted mainly by an imbalance between the sympathetic and vagal systems. The analysis of heart rate variability (HRV) during sleep is a quantitative reliable method for studying such a mechanism, but it has not yet been extensively and adequately applied in DS. In this study, HRV during sleep was evaluated in seven DS patients and in six normal controls, by also controlling for the presence of sleep apnea or arousal. The main results were an increased sympathetic function (low-frequency component of HRV) and a decreased vagal activity (high-frequency component of HRV) in DS with respect to normal controls, during apnea-free periods. Moreover, the presence of apnea, in DS, induced a further significant increase in low-frequency and very low-frequency components of HRV during sleep Stage 2. This study provides additional evidence of a brainstem dysfunctioning in DS, responsible for the abnormal imbalance between the sympathetic and vagal systems and confirms the brainstem involvement already suggested in the literature in order to explain brainstem-auditory evoked potential abnormalities and central sleep apnea in these patients.

Quantitative analysis of discontinuous EEG in premature and full-term newborns during quiet sleep.

To assess the spatio-temporal structure of discontinuous EEG tracing in mature and immature newborns, we analysed mean spectral power in frequency bands between 0.8 and 16.8 Hz in 6 full-term newborns and 7 premature newborns < 32 weeks of conceptional age. The most striking results showed a significantly higher mean spectral power for the first half of bursts than for the second half recorded in > 2.8-14.8 Hz frequency bands. This pattern was more pronounced in premature than in full-term newborns. No clear differences were observed in comparisons between the first and the second half of the interburst periods. In addition, as far as mid and high frequency band spectra were considered, the mean spectral power of burst was, in both groups, higher in the right as compared to the left occipital regions.

Respiratory patterns during sleep in Down's syndrome:importance of central apnoeas.

Obstructive sleep apnoea episodes have been reported repeatedly in Down's syndrome (DS) patients as a consequence of the presence of predisposing malformations or intercurrent pathology of the upper airways. There are no data on respiratory patterns of uncomplicated Down's syndrome subjects. In order to evaluate the eventual effects of central nervous system (CNS) impairment on respiration in DS, we studied the respiratory patterns during sleep of a group of 10 DS subjects, aged 8.6-32.2 y, without relevant upper airway pathology. In order to control the possible effects of sleep structure and mental retardation on the results obtained, we compared the findings in DS with those obtained from a group formed by subjects affected by fragile X syndrome (six males and one female, aged 10.0-15.42 y) another genetically determined type of mental retardation. Sleep structure was similar in both groups; however, DS subjects showed significantly higher indices of central sleep apnoea and of oxygen desaturation than fragile X patients (P < 0.005). As far as DS individuals were considered, a significant preponderance of central, as opposed to obstructive, sleep apnoeas was found (89.4% vs. 9.4%, respectively; 1.2% were mixed) which showed a significant age-related increase. Central respiratory pauses were mostly preceded by sighs, which occurred more frequently during sleep stages 1 and REM, and were often organized in long sequences of periodic-like breathing. During REM sleep, they were less frequently preceded by sighs and by body movements than during NREM sleep. Obstructive sleep apnoeas occurred more often during REM sleep and were more rarely preceded by sighs or by body movements. Both central and obstructive apnoeas induced significant oxygen desaturation in 50-69.6%. Sleep structure was not significantly modified by apnoeas and oxygen desaturation. We hypothesize that the increase in central sleep apnoeas is related to a dysfunction of the central respiratory control at a brainstem level in DS.

Respiratory characteristics during sleep in healthy small-for- gestational age newborns.

OBJECTIVE: Small-for-gestational age (SGA) infants born with intrauterine growth retardation (IUGR) differ from appropriate-for-gestational age (AGA) infants by: a) alterations in a number of neurologic and neurophysiologic characteristics; b) modified heart rate variability during the neonatal period; and c) increased morbidity rates during the first months of life. However, there are no data on the impact of IUGR on respiratory function at birth. METHODS: We studied newborns who were 35 to 36, 37 to 38, and 39 to 41 weeks' conceptional age (CA): 31 were AGA and 26 were SGA. All were clinically and neurologically normal at birth and none exhibited abnormal events during the first year of life. Polygraphic recordings were performed between two meals during the normal postnatal stay in the maternity ward. RESULTS: During both active sleep (AS) and quiet sleep (QS), SGA infants in all CA groups had significantly higher values for the incidence of 2 to 4.9 seconds and 5 to 9.9 seconds central respiratory pauses (RP), the apnea index (AI) [AI=% of nonbreathing time], and the time spent with periodic breathing (PB), as compared with AGA infants. Respiratory frequency was usually similar in SGA and AGA infants. In addition, the trend of age-related respiratory modifications was disturbed in SGA infants, as compared with AGA infants: at 39 to 41 weeks CA, SGA infants had no significant decreases in RP, AI, or PB, and no increase in respiratory frequency. However, between-state differences were similar in both groups. In all AGA and SGA infant groups respiratory frequency seemed to be an individual characteristic: infants who breathed faster during AS breathed faster during QS, and vice-versa. CONCLUSION: Our data demonstrate significant modifications in the establishment of respiratory rhythm control in SGA infants, whereas the patterns of state-related and subject-dependent breathing characteristics were similar in SGA and AGA infants. We speculate that the dysregulation of respiratory function control maturation observed in healthy SGA infants may be related to subtle brainstem modifications attributable to the decreased blood supply and chronic hypoxia associated with IUGR.

[Development of the sleep and autonomic nervous system control in premature and full-term newborn infants]. / Développement du sommeil et des fonctions sous contrôle du système nerveux autonome chez le nouveau-né prématuré et à terme.

Well defined periods of active (AS) and quiet sleep (QS) are detected as early as 27 weeks gestational age (w GA). Beyond 35 w GA, the amount of indeterminate sleep is reduced to < 10% and, up to the normal term, sleep is marked by the prevalence of AS. AS differs from QS by faster respiratory and heart rates, more central respiratory pauses, lower amplitude of high frequency heart rate variability (parasympathetico-dependent) and higher amplitude of low frequency heart rate variability (sympathetico-dependent). In artificially ventilated infants, breathing is more dependent on the ventilator in QS than in AS. When they reach term, compared with normal full-term newborns, infants with intra-uterine growth retardation or prematurity do not show significant differences of sleep structure, but present in both AS and QS, faster heart and respiratory rates, more respiratory pauses and less heart rate variability; however, sleep-states-related cardio-respiratory modulations appear similar.

Modulation of motor activity patterns and sleep states in low-risk prematurely born infants reaching normal term: a comparison with full-term newborns.

To evaluate the influence of prematurity and postnatal age on the relationship between motor activity (MA) and sleep states, forty clinically and neurologically normal infants were recorded polygraphically and grouped according to their gestational (GA, prematures: < 36 weeks, full-term: 37-41 weeks) and conceptional (CA, 37-38 and 39-41 weeks) ages. Sleep states (active: AS, and quiet: QS) were defined by the concordance of EEG and rapid eye movement criteria. Movements of both upper (UL) and lower (LL) limbs were independently recorded. In all groups the amount of MA in both UL and LL clearly predominated in AS compared with QS (p < 0.02). Contrariwise, both the longest period without movement and the no-movement 20-sec epochs were significantly higher in QS than in AS (p < 0.005). In AS, age-related modifications and modulation of MA amount throughout the state were similar for PRT and FT groups: a) in both groups a significant decrease of MA with advancing CA was observed (p < 0.05); b) MA throughout the state was randomly distributed regardless of CA. In QS, however, PRT were distinguishable from FT by the absence of: a) a significant decrease of MA amount with advancing CA, together with a reduced increase of both the longest period without movements and the no-movement 20-sec epochs; b) prevalence of MA in LL compared with UL; c) modulation of the distribution of MA throughout the state.

Effect of state of alertness on the heart rate response to ocular compression in human infants.

Because the state of alertness exerts a profound influence on autonomic cardiac control, we hypothesized, that the heart rate response to a vagal stimulus, i.e., ocular compression, may differ during different states of alertness. We studied 8 healthy infants with a postconceptional age of 35-41 weeks (mean +/- SD 37.9 +/- 2.1 weeks). They underwent a standardized ocular compression test during polygraphically controlled wakefulness, rapid eye movement (REM) sleep, and non-REM (NREM) sleep. The R-R intervals were measured (1) during the 60 s preceding the ocular compression test, to determine the mean control R-R interval, and (2) during compression. Percent R-R interval was defined as the longest R-R interval in milliseconds during the test divided by the mean control R-R interval and multiplied by 100. The longest R-R interval during the test was significantly greater in REM sleep than in wakefulness (p < 0.05) and in NREM sleep (p < 0.01):939 +/- 360, 623 +/- 355, and 538 +/- 60 ms, respectively. The percent R-R interval was significantly greater in REM sleep than in NREM sleep (p < 0.01):236 +/- 91 and 129 +/- 16, respectively. The time from the longest R-R interval to return to mean control R-R interval, i.e., vagal escape, was significantly shorter in REM sleep than in NREM sleep and in wakefulness (p < 0.01): 843 +/- 168, 2,131 +/- 712, and 2,078 +/- 913 ms, respectively. This study indicates that the state of alertness should be defined when performing tests on autonomic reflexes in infants.

Heart rate variability during sleep in infants with bronchopulmonary dysplasia. Effects of mild decrease in oxygen saturation.

We sought to determine whether abnormal heart rate modulation by the autonomic nervous system occurs in patients with severe bronchopulmonary dysplasia (BPD) in relation to sleep stages and mild changes in arterial oxygen saturation SaO2. On 10 oxygen-dependent 7- to 29-month-old infants with BPD, polygraphic recordings, including heart and respiratory rate and body movement detection, were performed. Heart rate variability was evaluated in high (HF), mid, and low (LF) frequency bands. Parameters were analyzed in two ranges of SaO2: normal range, (SaO2 greater than 95%), and mild decrease in (SaO2, values of 90 to 94%). In contrast to what is normally observed, LF at normal SaO2 was less marked in rapid eye movement, (REM) sleep than in non-rapid eye movement (NREM) sleep stage 2. A mild decrease in SaO2, as compared with a normal SaO2 value, was associated with: (1) a heart and respiratory rate acceleration, (2) a decrease in HF in REM sleep (p < 0.02); (3) an increase in LF in NREM sleep stage 2 (p < 0.02), intensifying the change observed in a normal SaO2 level. These data show that a mild decrease in SaO2 increases modifications of autonomic control observed in infants with severe BPD.

Heart rate and heart rate variability during sleep in small-for-gestational age newborns.

To assess the influence of intrauterine growth retardation on heart rate (HR) and HR variability during sleep, we performed polygraphic recordings in 10 small-for-gestational age (SGA) and 16 appropriate-for-gestational age (AGA) newborns. Both groups were clinically and neurologically normal and were at 37 to 41 wk conceptional age. RR intervals were analyzed using the short-time Fourier transform in three frequency bands: 1) high frequency, with a period 3-8 heartbeat; 2) mid frequency, with a period 10-25 heartbeat; and 3) low frequency, with a period 30-100 heartbeat. In both active and quiet sleep, SGA newborns significantly differed from AGA newborns by having a shorter RR interval (p < 0.01) and lower amplitude of HR variability in all bands (p < 0.05) except low frequency in quiet sleep. Quiet sleep differed from active sleep by having a longer RR interval (p < 0.05), higher high-frequency variability (p < 0.02) in both SGA and AGA newborns, and lower low-frequency variability (p < 0.005 for AGA newborns). Our data give evidence of clear modifications of both sympathetic and parasympathetic HR control in the at-risk SGA population. Similarity of between-state characteristics suggests maintained CNS control of HR in SGA as well as in AGA newborns. We speculate that between-group HR and HR variability differences may be related to augmented metabolic rate in SGA compared with AGA newborns.

Sleep state organization in premature infants of less than 35 weeks' gestational age.

To assess sleep organization in premature infants of < 35 wk gestational age (w GA), we performed polygraphic recordings in 24 neurologically normal neonates (eight per group): artificially ventilated 27-30 and 31-34 w GA infants and nonventilated 31-34 w GA infants. Sleep states were defined by concordance of EEG and rapid eye movement criteria. Uninterrupted active sleep periods of > 13 min and quiet sleep periods of > 5 min were observed in all babies, except in one 33 w GA ventilated infant. Intervals from the beginning of recording to the 1st quiet sleep period varied from 0 to 63 min and intervals to the beginning of the longest sleep cycle varied from 5 to 84 min. Nonventilated 31-34 w GA infants had longer sleep cycles (p < 0.02), principally because of longer active sleep periods. However, percentages of different states in the cycles were similar in all groups. When body movements were required for state definition, amounts of active and quiet sleep diminished and the percentage of indeterminate sleep was augmented significantly. In conclusion, our study demonstrated that 1) sleep state differentiation is present as soon as 27 w GA; and 2) artificial ventilation, performed in a highly specialized neonatal intensive care unit, does not modify sleep organization of neurologically normal premature infants. We hypothesize that this "earlier" sleep state differentiation, compared with previous data, may be related to improvements in neonatal intensive care over recent years.

Heart-rate variability in low-risk prematurely born infants reaching normal term: a comparison with full-term newborns.

To investigate the influence of prematurity and postnatal age on the maturation of the autonomic nervous system function, we analysed heart-rate and heart-rate variability in twelve prematurely born infants (< 37 weeks gestational age) reaching the conceptional age of 37-41 weeks. These neonates were compared with sixteen 37-41 week conceptional age newborns (< 10 days postnatal age). Heart-rate variability was analysed by spectral analysis of interbeat intervals using Short-Time Fourier Transform. We found that during both active and quiet sleep, the durations of RR-intervals were shorter and the amplitude of heart-rate variability in different frequency bands was lower in prematures reaching term than in newborns of the same conceptional age (P < 0.001). Between-state comparison showed differences in both groups. In both groups, low-frequency heart-rate variability was higher in active sleep than in quiet sleep. Between-state differences of RR-intervals and high-frequency heart-rate variability were present only in newborns (P < 0.01). Discrimination between newborns and prematures reaching term, based on RR-intervals and heart-rate variability, was correct in both sleep states with errors between 7 to 16%. However, in both newborns and prematures reaching term, between-state discrimination showed less reliable results, especially for quiet sleep discrimination with 24% (in PRT) and 20% (in NB) of errors. Our results, especially information given by factor analysis, suggest that the differences between newborns and prematures reaching term, concerning RR-interval and heart-rate variability, may be related to a changed balance between the sympathetic and parasympathetic nervous systems with a diminished parasympathetic component of heart rate control in prematures reaching term, as compared to newborns.

Sigh-related heart rate changes during sleep in premature and full-term newborns.

The functional linkage in the cardio-respiratory system demands precise coordination of their activity. Sighs provide an opportunity to study the interaction and the maturation of the autonomic nervous system. In 4 groups of normal, sleeping newborns (31 to 41 weeks conceptional age [wCA], 2 to 10 days postnatal age) we investigated heart rate changes caused by sighs by means of polygraphy. In full-term (39-41 wCA) and near-term newborns (37-38 wCA) sighs during quiet sleep (QS) were accompanied by heart rate acceleration (p < 0.01) and thereafter by heart rate deceleration (p < 0.01). During active sleep (AS) only heart rate acceleration (p < 0.01) was observable. In prematures (35-36 wCA) acceleration could be observed in QS (p < 0.01) and AS (p < 0.01) but no deceleration in QS. In prematures of 31-34 wCA no changes during AS and QS could be detected. Body movements caused heart rate acceleration but no heart rate deceleration. In conclusion, it can be hypothesized that heart rate acceleration may be caused by reduced vagotonus initiated by augmented lung volume and movements. Sigh-related changes responsible for heart rate deceleration occur solely during quiet sleep. In prematures of 31-34 wCA these reflexes are not developed.

Neonatal pattern of breathing during active and quiet sleep after maternal administration of meperidine.

The aim of this study was to reappraise the effects of maternal meperidine administration on breathing pattern during the first hours of life taking into account the state of alertness. Because breathing instability is more pronounced during active sleep, we hypothesized that meperidine administration might create a greater risk for respiratory instability during active sleep, the prominent sleep state in newborns. We studied eight full-term, healthy newborns whose mothers had received a continuous i.v. infusion of meperidine (81 +/- 9 mg) that was terminated 5.5 +/- 2.1 h before delivery. These infants were compared with a control group of eight full-term newborns whose mothers did not receive any opioids. In both groups, all babies were delivered vaginally after a normal labor and had Apgar scores of 9 or 10 at 1 and 5 min. Neonatal gastric secretion and maternal venous and umbilical venous blood were sampled at delivery for determination of meperidine concentration. From 60 to 300 min after delivery, behavioral sleep states and thoracic and abdominal movement as well as transcutaneous arterial oxygen saturation (SaO2) were monitored continuously. The number of apneic spells lasting more than 3 s during 100 min of recording and the percentage of time with SaO2 below 90% in each sleep state were recorded. During quiet sleep, all respiratory variables were similar in both groups. During active sleep, there were significantly more apneic episodes (37.1 +/- 25.1 versus 11.2 +/- 13.9) and a higher percentage of time with SaO2 less than 90% (14.3 +/- 16.7% versus 1.3 +/- 1.5%) in the meperidine group than in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac, respiratory, and arousal responses to an esophageal acid infusion test in near-term infants during active sleep.

This study was designed to determine the cardiac, respiratory, and arousal responses to an esophageal acid infusion test in near-term infants free from neurological, gastroesophageal, and cardiopulmonary disease at time of testing during active sleep. Eight infants (gestational age 28-37.5 weeks, postconceptional age 36-40 weeks) were tested. Using standardized procedures and timing, we compared the cardiac, respiratory and arousal responses during a control period and during distal esophageal saline and acid infusion periods. The duration of each of these periods was 5 min. The pH of the acid infusion was 2.2. We found that this mild distal esophageal acid infusion test induced significant prolongation of the interval between successive electrocardiogram R waves compared with control and saline infusion periods (806.5 +/- 145.7 ms, 478.8 +/- 49.4 ms, and 468.8 +/- 37.2 ms, respectively; p less than 0.01) and of the duration of the respiratory cycle (2.9 +/- 0.7 s, 1.5 +/- 0.3 s, and 1.5 +/- 0.2 s, respectively; p less than 0.01). Esophageal acid infusion elicited significant electroencephalogram (EEG) arousal responses. The number of the EEG arousals was significantly increased during the acid period as compared with control and saline infusion periods (2.9 +/- 1.4, 0.5 +/- 0.5, and 0.4 +/- 0.5, respectively; p less than 0.01). Total arousal duration was significantly increased during acid as compared with control and saline infusion periods (42 +/- 17.5 s, 4.5 +/- 5.1 s, and 3.5 +/- 5.0 s, respectively; p less than 0.01). We conclude that distal esophageal acid stimulation elicits significant cardiac, respiratory, and EEG arousal responses in near-term infants during active sleep.