Development of NREM Sleep Instability-Continuity (Cyclic Alternating Pattern) in Healthy Term Infants Aged 1 to 4 months

AGE IS THE MOST IMPORTANT PHYSIOLOGIC FACTOR MODULATING HUMAN SLEEP AND ALSO INFLUENCES THE ELECTROENCEPHALOGRAPHIC (EEG) PATTERNS and contributes to the occurrence and features of arousals. Arousal can be considered as a short transient intrusion of wakefulness EEG rhythms into sleep and probably has a protective physiologic role in counteracting various endogenous or exogenous stimuli, such as loud noises, tactile stimuli, and temperature changes.1 The analysis of arousals has many clinical implications: an increased level of arousability might be related to sleep fragmentation, excessive arousals from sleep in infants may impair development, and a low level of arousability might play a role in the pathogenesis of the sudden infant death syndrome.1–4 Different criteria for scoring arousals in infants have been reported in the literature.1–4 The International Pediatric Work Group on Arousals, comprising a group of sleep experts, has recently defined a method for the scoring of arousals in infants.3 Scoring includes the differentiation between subcortical activation, with (apparently) no visible changes in the EEG, and cortical arousals associated with EEG changes, during quiet sleep (QS) and active sleep (AS). On the contrary, an American Pediatric Task Force has recently provided an evidence-based review of the age-related development of the polysomnographic features of sleep in neonates, infants, and children and opted not to support scoring of subcortical activations until more evidence is available regarding their clinical significance.1 In the last years, many studies have focused their attention on other methods of scoring arousal not limited to the American Sleep Disorder Association criteria,5 using pulse transit time6 or cyclic alternating pattern (CAP).7–9 It was initially hypothesized that the trace alternant (TA) could represent a precursor of CAP in neonates, but this has never been demonstrated, and a paper has reported significant EEG structure differences.10 The term TA was used to describe the periodic discontinuity of QS recorded in premature and term babies after 37 weeks conceptional age.11,12 TA usually disappears between 3 and 4 weeks after birth; the disappearance of TA and the appearance of sleep spindles lead to the constitution of the NREM sleep stage 2, reflecting the maturation of the thalamocortical pathways and rostro-caudal pons-thalamus connections.13 Sleep is characterized by an oscillating pattern that exhibits different levels of arousal, mostly during NREM periods, resembling some features of TA. This physiologic oscillating pattern has been coded as CAP and is considered important for sleep building and maintenance.9 Terzano et al14 have published an atlas of CAP with recording techniques and rules for its scoring in human sleep, mostly related to adulthood. CAP is a spontaneous rhythm detectable during NREM sleep in form of EEG amplitude oscillations composed of an EEG transient pattern (phase A of the cycle) separated by intervals of background activity (phase B of the cycle). Three main EEG patterns have been described according to the prevalence of EEG synchrony (subtype A1), prevalence of EEG desynchrony (subtype A3), or a combination of both (subtype A2).14 It has been highlighted that CAP is one of the most systematic and expressive constructs devised to describe arousals, their composition, and their timing during sleep.15 Normative data about CAP parameters during NREM sleep have been provided for preschool-aged children,16 school-aged children,17 and adolescents.18–19 The analysis of CAP in school-aged children is characterized by a high CAP rate during slow wave sleep (SWS) and a high percentage of A1 phases. The distribution of intervals between consecutive A1 phases shows a peak around 25 seconds.17 The analysis of CAP in preschool-aged children shows a lower percentage of A1 with an increase of A2, compared with prepubertal children, reflecting a higher sleep instability in this age group.16 The analysis of the A1-interval distribution shows the same periodicity as that of school-aged children. The CAP rate tends to increase with age from preschool- to school-aged children, and these data suggest that CAP rate might be very low during the first months of life, considering the maturations of thalamocortical pathways, in contrast with the high frequency of oscillations that characterize TA of newborns. Normative data on CAP parameters in healthy newborns and infants are not available, and the occurrence of CAP patterns during the first months of life has never been evaluated. The aim of our study was to perform CAP analysis in the first months of life in a group of healthy infants to derive more information on the maturation of arousal mechanisms during NREM sleep and to set normative data of CAP parameters in this age range (from 1 to 4 months of life).