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This revision to the EEG Guidelines is an update incorporating the current electroencephalography technology and practice. It was previously published as Guideline 2. Similar to the prior guideline, it delineates the aspects of Guideline 1 that should be modified for neonates and young children. Recording conditions for photic stimulation and hyperventilation are revised to enhance the provocation of epileptiform discharges. Revisions recognize the difficulties involved in performing an EEG under sedation in young children. Recommended neonatal EEG montages are displayed for the reduced set of electrodes only since the montages in Guideline 3 should be used for a 21-electrode 10-20 system array. Neonatal documentation is updated to use current American Academy of Pediatrics term "postmenstrual age" rather than "conceptional age." Finally, because therapeutic hypothermia alters the prognostic value of neonatal EEG, the necessity of documenting the patient's temperature at the time of recording is emphasized.

Objectives To assess the effect of extra uterine life on continuity and amplitude of premature infants' cerebral activity at different gestational age as compared to soon after birth. Methods Stable infants less than 34weeks gestation were prospectively recruited and EEG was recorded bi-weekly. Interburst interval and different wavelength amplitudes were digitally measured during the most discontinuous and most continuous (periods with longest and shortest interburst intervals, respectively) parts of the tracings. Linear regression was used to assess conceptional age prediction of interburst interval and wavelength amplitudes. Significant regression results were compared to the group of babies recorded close to delivery (newborn group). Results 144 EEG tracings from 59 infants were analyzed. Interburst intervals were significantly predicted by conceptional age in the newborn group only ( p ⩽0.002). Delta and theta amplitudes were significantly predicted by conceptional age in the newborn group and most of the other conceptional age groups ( p Conclusions Our data reiterates the normal maturation of cerebral activity in the premature infant and support the concept of similar in and ex-utero maturation of cerebral activity in stable premature infants. Significance The effect of ex-utero maturation on the brain of stable premature infant is not readily discernible when using specific neonatal EEG indices.

AIM The aim of this study was to assess the motor repertoire of extremely low-birthweight infants at term-equivalent age (TEA), in relation to their neurological outcome. METHOD Using Prechtl's method, we assessed both the quality of general movements and a detailed motor optimality score in 13 extremely low-birthweight infants (four males; nine females; mean gestational age 27.9wks, SD 2.9wks; mean birthweight 798g, SD 129g) at TEA, and related them to general movements at the age of 3 months after term and neurological outcome at the age of 2 years 6 months. RESULTS At TEA, 10 of the 13 infants had abnormal general movements. All infants showed abnormal leg lifting with extended legs; nine showed stiff movements, three showed cramped movements, and two showed cramped synchronized general movements. At 3 months, three infants still had abnormal general movements. Concurrent movements were abnormal in nine infants owing to monotony and jerkiness. Abnormal posture was seen in seven infants. None developed cerebral palsy; one infant showed cognitive and motor delay. Neurological outcome was not related to general movement quality and optimality score at TEA. INTERPRETATION Abnormal general movements at TEA are common in extremely low-birthweight infants. General movements often appear stiff and cramped with extended legs. At the age of 3 months after term, general movements are mostly normal, but concurrent movements are not. Nevertheless, these abnormalities do not imply an impaired neurological outcome such as cerebral palsy.

Objective: Measure the effects of Early Intervention ad modum Katona (EI-K) in high-risk premature infants by means of clinical, neurobehavioral, and neurophysiologic tests. Method: We used the Amiel-Tison neurologic examination, the Bayley Scale of Infant Behavior, and electroencephalography (EEG) recordings at 42 weeks of conceptional age, and after 6 months of treatment EI-K (n = 14) and compared these results with those of a group of infants without early intervention (nEI) (n = 11). Results: We found better performance of infants in EI-K than nEI group after 6 months of treatment in neurologic and behavioral examination measurements, but found no differences in EEG comparisons. Conclusion: Our data suggest significant benefit of the use of EI-K program over n-EI in the neurologic and neurobe-havior examinations of premature infants after 6 months of age.

SUMMARY The development of the blood-CSF barrier was investigated by establishing total protein, individual protein levels and cell-counts in the CSF and serum of 185 healthy children, with an age range from 27 fetal weeks to 16 years. Albumin, α2-macroglobulin and immuno-globulin G were found in all CSF specimens. With the exception of IgG, their concentrations decreased continuously until the end of the first year of life. IgM was not present in the CSF and IgA was found in only a few cases. Serum: CSF ratios of individual proteins increased continuously from the fetal period to the first year and there was a decline in barrier selectivity during the same period. Maturation of the barrier was maximal during the third month of life, decreasing quickly thereafter. The barrier condition of preterm infants was closely related to conceptional age, but not to the time of birth. RESUME Le developpement de la barriere cerebro-meningee (barriere-sang-LCR) Le developpement de la barriere-sang-LCR a eteetudie depuis la periode foetale jusqua l'adolescence. Les proteines totales, les taux de proteines particulieres et les comptes cellulaires ont ete mesures dan le LCR et le serum de 185 enfants en bonne sante (ages de 27 semaines conceptionnelles jusqu'a a 16 ans). L'albumine, la α2-macroglobuline et les immunoglobulines G etaient presents dans tous les echantillons de LCR. A l'exception des IgG, leur concentration est apparue en decroissance reguliere jusqu'a la fin de la premiere annee de vie. Les IgM n'etaient jamais presentes dans le LCR et les IgA dans quelques cas seulement. Les rapports serum/LCR des proteines particulieres s'accroissent regulierement depuis la periode foetale jusqu'a la premiere annee de vie. II y a aussi un declin de la selectivite de la barriere durant la mĉme periode. La vitesse de maturation de la barriere est a son maximum durant le troisieme mois de vie et decroit ensuite rapidement. Chez les prematures, les caracteristiques de la barriere sont etroitement reliees a l'âge conceptuel et ne dependent pas de la date effective de naissance. ZUSAMMENFASSUNG Die Entwicklung der Blut-Liquor-Schranke Es wurde eine Untersuchung uber die Entwicklung der Blut-Liquor-Schranke von der Fetalperiode bis zum Jugendlichenalter durchgefuhrt. Bei 185 gesunden Kindern (von der 27sten Fetalwoche bis zu 16 Jahren) wurden Gesamtprotein, individuelle Proteinspiegel und Zellzahlen im Liquor und im Serum bestimmt. Albumin, α2-Makroglobulin und Immunoglobulin G wurden in allen Liquorproben nachgewiesen. Mit Ausnahme des IgG nimmt ihre Konzentration bis zum Ende des ersten Lebensjahres stetig ab. IgM war im Liquor nicht nachweisbar und IgA nur in wenigen Fallen. Der Serum/liquor Quotient der individuellen Proteine nimmt von der Fetalperiode bis zum ersten Lebensjahr kontinuierlich zu. In derselben Zeitspanne findet sich auch eine Abnahme der Schrankenselektivitat. Die Reifungsgeschwindigkeit der Schranke ist im dritten Lebensmonat am grosten und nimmt danach rasch ab. Bei Frugeborenen ist die Schrankenentwicklung eng an das Konzeptionsalter gebunden und nicht vom Geburtstermin abhangig. RESUMEN El desarrollo de la barrera hemato-encefalica Se ha investigado el desarrollo de la barrera hemato-encefalica desde el pereodo fetal hasta la adolescencia. Se determinaron las proteinas totales, y los niveles individuals de proteinas y de elementos celulares en el LCR y en el suero obtenido de 185 ninos sanos (desde las 27 semanas fetales a los 16 anos de edad). En todas las muestras de LCR estaba presente la albumina, la α2-macroglobulin y la immunoglobulina G. Con la excepcion de la IgG, sus concentraciones disminuian continuamente hasta el final del primer ano de vida. La IgM no estaba presente en el LCR y la IgA solo lo estaba en algunos casos. La relacion suero/LCR de las proteinas individuales aumentaba progresivamente desde el periodo fetal hasta el primer ano de vida. Hay tambien un declive de la selectividad de la barrera durante el mismo periodo. La velocidad de la maduracion de la barrera alcanza el maximo durante el tercer mes de vida, disminuyendo despues con rapidez. En los pretermino, las caracteristicas de la barrera estan intimamente relacionadas con le edad concepcional, y no con el momento del parto.

This study compares the neurobehavioral status of 118 low-birthweight infants tested at 40 weeks conceptional age with that of 76 normal fullterm infants. A neonatal neurobehavioral examination comprising 21 test and four summary items was used. The most striking differences between the groups were found in visual and auditory orienting, with approximately two-thirds of the low-birthweight infants falling below the range of performance of the fullterm group. Items testing motor performance showed a lower incidence of deviant performance among the low-birthweight infants. Of the 21 test items, 19 could be assigned cut-off scores, below which infants can be considered deviant on the specific items.

One objective of this paper is to confirm the coupling between heart rate (HR) changes and electroencephalographic (EEG) bursts (as reported for the first time in Pfurtscheller et al. [K. Pfurtscheller, G.R. Muller-Putz, B. Urlesberger, W. Muller, G. Pfurtscheller, Relationship between slow-wave EEG bursts and heart rate changes in preterm infants, Neurosci. Lett. 385 (2) (2005) 126-130]) in a larger group of preterm infants. Other objectives are to report on semi-automatic detection of burst-to-burst intervals (BBI, time period between the onsets of 2 consecutive EEG bursts) and on correlations between BBI and HR changes. A group of 34 preterm infants with a conceptional age (CA) of 35.9+/-0.6 weeks (mean+/-S.D.) was studied. Periods with a length of about 10 min with low HR variability and discontinuous EEG were selected from long-term EEG and ECG registrations and analyzed. From the automated detection of EEG bursts, an estimate for the mean burst-to-burst interval was obtained. EEG trials with a duration of 16s and a single EEG burst in the middle, were selected and averaged together with the corresponding instantaneous HR trials. It was found that preterm infants without evidence of neurological deficit and with normal development revealed a mean BBI of 13.4+/-2.6s (mean+/-S.D.) and a HR increase of 1.7+/-0.9 bpm (mean+/-S.D.) during the occurrence of EEG bursts. This HR increase is comparable with the earlier reported increase of 1.9+/-0.8 bpm. A significant negative correlation of r=0.453 (p

The nineteen-item assessment of newborn neurologic maturity developed by Koenigsberger was applied to 682 infants born to women enrolled in a randomized controlled trial of nutritional supplementation in a poor, urban, black, clinic population. The total score of the neurologic scale, four clusters of items derived from principal component factor analysis followed by a varimax rotation, and the four clusters taken simultaneously (using Cohen's method of set correlation) were related to the conceptional age, weight, length, and head circumference of the infants. Taken in any of these ways, neurologic maturity was more strongly related to somatic development than to conceptional age. Although these results are consistent with a set pattern and order of neurologic development, they are incompatible with such a pattern following a rigid and universal time scale. Rather, at all stages of conceptional age, there appears to be a range of neurologic maturity, related more strongly to concurrent somatic development than to the child's conceptional age.

Objective To develop an electrode cap with high number of electrodes for recording very small preterm babies, to assess the physiological stress imposed by the application of this cap on babies, and to estimate what added information could be potentially obtained with more electrodes in this age group. Methods We recruited eleven extremely small preterm babies (conceptional age 25–29 weeks) to record their EEG with a custom-tailored high-density EEG cap (20 channels), coupled with a Full-band EEG amplifier. Physiological stress caused by the cap placement was assessed by recording heart rate and arterial oxygen saturation before and during EEG cap placement, as well as before and during a routine care procedure of the given baby. The quality of novel information obtained with this system was assessed by comparing the full signal to a set of EEG signals where we deliberately distorted and omitted major signal components to make it appear as in the conventional EEG systems. Results The changes in heart rate or oxygen saturation caused by the cap placement are fully comparable to the changes seen after any normal care procedure in the same baby. Our recordings did also reveal that brain activity in the small premies is highly focal, and often confined to only one or two electrodes. Hence it cannot be pertinently localized with the currently used low number of recording electrodes. Moreover, recordings from babies with focal intracerebral hemorrhages showed that changes after vascular insults are clearly more prominent and hence easier to detect visually from multichannel recordings. Conclusions Recording of high-fidelity EEG (high-density caps and FbEEG system) is practical in the incubator environment, and the application of a proper EEG cap is not more stressful to the baby than a routine care procedure. Moreover, these achievable amendments in the recording system seem to disclose major physiological and pathological signal components in the as yet poorly explored patient group. Significance Introduction of a technically feasible and physically gentle enough EEG recording system will enable further development of clinical neurophysiological understanding, as well as the design of pertinent brain monitors, which is urgently needed in these patients.

Objective The aim of this prospective and longitudinal study was to characterize EEG patterns during the first weeks of life in extremely premature infants. Methods Twenty-five extremely premature infants were included and weekly EEG recordings were obtained between 24 and 36 weeks of conceptional age (CA). Results Central (rolandic) positive slow waves (CPSW) were found to be the most reliable and characteristic pattern. CPSWs were frequent at 24 weeks CA and progressively diminished and disappeared around 34 weeks CA. CPSWs appeared isolated or in sequences, they occurred during periods of continuous or discontinuous EEG activity, during bursts or during intervals of discontinuous activity, and unilaterally or bilaterally. Temporal positive slow waves and theta rhythms occurred less often and did not decrease as a function of CA. In addition, the amount of discontinuity progressively decreased until 36 weeks CA. The duration of bursts stayed constant, while inter-burst intervals decreased as a function of CA. Conclusions Central positive slow waves are characteristic features of the EEG in the extremely premature infant. Significance The presence of CPSWs and their progressive disappearance until 34 weeks CA may represent a maturational marker in the EEG.

Non-nutritive sucking (NNS) patterns in full-term newborn and preterm infants were studied at term conceptional age. The preterm group showed a distinct NNS pattern with a higher frequency and lower amplitude. In the preterm group, gender differences were observed, the girls having higher frequency and larger amplitude. The full-term infants' NNS patterns were also related to pacifier use during early childhood. Experience, gender, maturity and level of tension are suggested as explanatory factors for differences in NNS patterns.

The objective of the study is to explore interactions between cortical and autonomic functions in the first weeks of postnatal life. We investigated the behaviour of one-channel electroencephalogram (EEG) patterns and heart rate (HR) dynamics in preterm infants. In a group of 15 healthy preterm infants with a mean conceptional age (CA) of 36 weeks and a mean postnatal age of 17.5 days simultaneous registration of amplitude integrated EEG (aEEG) and HR pattern was performed during interfeeding intervals. Periods with a discontinuous EEG activity and a low heart-rate variability (HRV) were selected for further processing and averaging. It was found that spontaneous activity transients (SATs) or slow wave EEG bursts during "Tracé alternant" (TA) can be accompanied by an HR acceleration of 1-2% (mean: 1.9, range: 0.6-3.5 beats/min) lasting approximately 5s (mean, range: 3.6-7.1s). The aim of the study is to give evidence of a coherent behaviour of EEG bursts and HR in the developing nervous system of preterm infants.

Neonatal electroencephalography (EEG) presents some of the most difficult challenges in EEG interpretation. It differs significantly in many ways from EEG of older children and adults. Technologically, acquisition of a neonatal EEG is significantly more difficult and different than an adult EEG. There are numerous features that are age-specific and change almost week-to-week in the preterm infant. Some features may be normal at one age and abnormal if they persist for several weeks. Many of these features also have different implications in neonates as compared to older individuals. These issues mandate a different approach to neonatal EEG interpretation. In this article an overview of neonatal EEG is presented. After a brief discussion of relevant technical issues, various normal EEG features encountered in neonates are discussed. This is followed by a discussion of the ontogeny of EEG, starting from the age of viability to the first few months of life. A description of various abnormalities follows. Finally, an approach to analysis of a neonatal EEG is presented.

Background: Although newborns are presumed to have cognitive ability, studies on the objective cognitive ability of neonates are making little progress. Methods: We gave auditory and visual stimuli to newborns whose conceptional age ranged from 35 to 43 weeks and recorded the mismatch negativity (MMN) that is said to reflect the process by which stimuli are detected automatically. We compared the waveform and latency of the MMN. Results: The mismatch negativity waveform in newborns was similar to that of adults. The MMN latency tended to shorten with an advance in conceptional age and was especially shortened between 36 and 37 weeks of fetal life. In some newborns whose clinical course indicated a possibility of their having cognitive dysfunction, the MMN latency was prolonged. Conclusions: Newborns also have cognitive ability and MMN is useful for objectively evaluating the cognitive ability in newborns.

The consequences of prematurity and prenatal cocaine exposure on early neurobehavior and physical growth were examined longitudinally in a sample of 20 cocaine-exposed and 20 non-exposed preterm neonates. The magnitude of the difference in physical growth acceleration related to prenatal cocaine exposure increased with increasing birth gestational age, whereas growth rate differences in irritability decreased. In contrast, prenatal cocaine exposure, independent of prematurity, was related to reduced attention skills at 36 weeks conceptional age and increased rates of neurobehavioral change. The effects of prenatal cocaine exposure differed with respect to the degree of prematurity, depending on the nature of the outcome examined, suggesting differing windows of vulnerability for different outcome domains. The usefulness of a developmental growth perspective was demonstrated.

This study focuses on the characteristics of frontal sharp transients (FST), a normal variant of neonatal EEG, in newborns with hypoglycemia.The EEG from 20 newborns with symptomatic hypoglycemia were compared with a control group of normal newborns matched by conceptional age. The dynamics of these transients were evaluated concerning sleep stages. The density, type and bilateral synchrony of FST were also calculated. The results were compared in the two groups by Student's t test.When compared with controls, hypoglycemic newborns have increased density of frontal sharp transients in all sleep stages but less bilateral synchrony (P0.05). FST density was even higher in small for gestational age newborns.The data suggests that normal patterns of neonatal EEG as FST can be influenced by systemic disturbances.

Natus-ALGO 2e, an automated ABR screener(Natus Medical, Foster City, CA, USA), compares the V wave of ABR evoked by 35-dB-nHL click stimuli by using a template-matching detection algorithm that provides only a pass-refer outcome. The aim of this study was to compare Natus-ALGO 2e with conventional ABR, and to evaluate its usefulness. The Natus-ALGO 2e screener was used to screen 202 ears of 101 neonates in our neonatal intensive care unit. The mean conceptional age at the time of screening was 40.4 +/- 3.0 weeks. 60 ears of 30 infants at high-risk of hearing impairment, including "refer" infants, were tested by the Natus-ALGO 2e and conventional ABR methods, and the results were compared. All neonates were tested with the Natus-ALGO 2e screener in a state of natural sleep, and screening time averaged 2 minutes 58 seconds. There were 97 cases in which both ears were passed, 3 cases in which both ears were referred, and one case in which one ear was referred. In comparison with conventional ABR, 53 of the 60 ears of 30 high-risk infants passed by the Natus-ALGO 2e method, whereas 14 of the 53 ears initially failed the conventional ABR screening. Of these 14 ears disagreements (the results of the Natus-ALGO 2e method passed, but the results of the conventional ABR failed), the results of the ABR screening changed to normal in 11 ears, and ABR showed improved threshold and latency in the other 3 ears after 5 weeks to 12 months. Among those that passed the Natus-ALGO 2e screening, the number of sweeps that failed the ABR screen was significantly greater than with normal ABR. Of the 7 ears of 4 patients that were referred on the basis of the Natus-ALGO 2e screening and failed by the conventional ABR method, 3 ears screened by the ABR method were normal when retested, and one ear passed by the Natus-ALGO 2e screening 12 weeks to 11 months later. In conclusion, Natus-ALGO 2e is useful for screening infant hearing because it can be performed quickly while the patient is sleeping naturally. In infants at high-risk for hearing impairment, the results of Natus-ALGO 2e and conventional ABR screening conflicted in numerous sweeps. Therefore, when there are many sweeps in high-risk infants, a retest should be performed that includes conventional ABR, even if they passed with Natus-ALGO 2e.

Age dependent EEG signatures were detected in the EEG of 71 neonates of 28-100 weeks of conceptional age (CA). Using the new method presented, neonates were automatically classified in three age groups (28-35 weeks CA), (36-40 weeks CA) and (41-100 weeks CA). Analysis was performed employing relative distance functions for the complete frequency spectra of the EEG registered by electrodes in C3 and C4 positions. The analysis was successful in automatic identification of individuals showing EEG anomalies. Polysomnographic analysis demonstrated these to be apnea risk patients. Accordingly, a purely EEG based detection of neonates that are medically at risk becomes feasible.

In this study we report on the maturation of the auditory cortical evoked response (ACR) waveform between (preterm) birth and 14 years of age. From the results it can be concluded that the ACR waveform morphology shows substantial age-dependent changes until the age of 14 years. Two transitional periods could be recognized. The first between 36 and 41 weeks conceptional age; the second between 4 and 6 years of age. The adult waveform complex is achieved between 14 and 16 years of age. Further research is needed to determine whether these transitional periods in the maturation of ACRs correspond with important functional changes of the central auditory system.

The mismatch negativity (MMN) is a pre-attentive change-specific component of the event-related brain potentials (ERPs). During the last decade this response has been intensively studied in adults, but investigations in children and especially in infants are still rare. Recent studies, however, have shown that MMN is also elicited in infants in response to changes in pure tones as well as in phonemes. The present study compared MMN in pre-term infants (conceptional age at the time of recording, 30-35 weeks), full-term newborns and full-term 3-month-old infants. Stimuli were Klatt-synthesized Finnish vowels /y/ and /i/. Previous studies have reported larger MMN amplitudes in school-age children compared with those obtained in adults. According to the results, however, the infant MMN amplitude seems to resemble that of adults. No significant differences in MMN amplitudes were found between the three age groups either. The mean MMN latency, however, decreased significantly with age, although in 3-month-old infants it was not much longer than in a previous study conducted in adults with the same stimuli.

Spindles develop in a man at 6 weeks conceptional age, at first at a low amplitude, gradually increasing in amplitude but especially in duration to a maximum at 13 weeks (mean, 6 sec; longest, 21 sec), rapidly decreasing in duration with age to 23 weeks (mean, 2.5 sec) and then slowly decreasing to the end of the first year (mean, 1.5 sec). The pause between the spindles is usually inversely related to the spindle duration and stabilizes after 23 weeks at 7 sec. The complex of spindle and pause is the longest at 10 weeks (12.5 sec), decreasing with age and stabilizing at 17 weeks at 8.1 sec. Thus, from 17 weeks until the end of the first year, spindles tend to recur every 8-9 sec, although variability is evident, especially in the duration of the pause. Synchronous spindles develop from a low value of 10% to around a 30% value until the end of the year, and asynchronous ones tend to have the same value (30%) for most of the year, except in the youngest patients. The reticular nucleus of the thalamus is known to be the generator of spindles and an increase in some size may be related to the great increase in duration, peaking at 13 weeks, and an increase in the development of the dendritic tree of this nucleus may be related to the many changes that stabilize at 23 weeks of age.

Bilateral ABRs were recorded from 452 infants 32–45 weeks conceptional age. Differences in laterality, gender and appropriateness for gestational age were investigated in order to increase our understanding of developmental processes in early life. Rate effects were also studied in a subsample of infants (145 ears). All subjects were free of conditions known to affect ABR parameters. Left/right differences were evident for all ABR measures except the amplitude of wave I. Shorter interwave intervals and larger amplitudes were consistently observed on the right. Females exhibited shorter absolute latencies for waves III and V and larger wave I amplitudes than males. Small for gestational age (SGA) infants displayed shorter wave V latencies and interwave intervals relative to AGA infants. These differences, however, disappeared by term age whereas the contrasts in laterality persisted. Increasing the rate of stimulation reduced wave I amplitude irrespective of conceptional age and increased wave V amplitude prior to term. An increase in wave V latency was more pronounced at the higher rate on the left than the right. There was no interaction between rate and appropriateness for gestational age, although SGA infants had shorter wave V and interwave latencies. Our data indicate a slight but significant right ear advantage in the processing of auditory signals. Gender differences were apparent as well. While research on adults and older children have reported similar findings, no other studies to date have observed these results in neonates. The present work also lends support to the view that accelerated neurological development occurs in growth-retarded infants.

Acoustic features of expiratory cry vocalizations were studied in 125 pre-term infants prior to being discharged from a level-3 neonatal intensive care unit. The purpose was to describe various phonatory behaviors in infants in whom significant hearing loss could be ruled out. We also compared these results with normal-hearing full-term infants, and evaluated whether linkage exists among acoustic cry features and various anthropometric, diagnostic and treatment variables obtained throughout the peri- and neonatal periods. Our analysis revealed that cry duration was significantly related to total days receiving respiratory assistance. The occurrence of other complex spectral and temporal aspects of acoustic cry vocalizations including harmonic doubling and vibrato also increased in infants receiving some form of respiratory assistance. The presence of harmonic doubling also depended on weight and conceptional age at test. The discussion focuses on the implication of these relationships and directions for future research.

Spontaneous movements of premature infants between 25 and 34 weeks conceptional age were observed for 1 hr on two or three occasions. Subjects had low-risk prognoses and were clinically stable at the time of testing. Behavioral acts were scored using a 0/1 time sampling technique in 60 continuous, 1-min time blocks. Temporal associations between individual movements were found using chi-square analyses. Some associated behaviors contained combinations consistent with neonatal action patterns, for example, single and bilateral leg kicking, head turning, and mouthing. Features of state organization were also evident in that general motor activity (GM), which has been used as a marker of active sleep (AS) in neonates, was found to cluster temporally with startle, facial, and head movements but not eye movements. Behavioral quiescence (> or = 5 s) was dissociated from AS-related behaviors (GM, facial, head, and eye movements). Combinations of state-segregated behaviors were more likely to exhibit co-occurrence within 1-min intervals in infants 30 weeks conceptional age and older.

Five-hundred-sixty-eight fetuses were observed at a clinic by using four-dimensional ultrasonography, and 31 fetuses who showed smiles were selected. The range of conceptional age was from 156 days to 214 days. The participants exhibited 51 smiles in 62 min of recording. The average duration of smiles was 3.21s (SD = 1.98). This must be the first study which collected fetal smiles intensively. The age effect on the frequency and duration of fetal smiles is not examined in this study. In comparison with previous studies, the average duration of fetal smiles and that of spontaneous smiles in preterm neonates (3.28s; Kawakami et al., 2008) were not significantly different, but they were significantly longer than that of spontaneous smiles in full-term neonates (1.97s; Kawakami et al., 2006). The fact that fetuses show a lot of smiles makes us reconsider the meanings of spontaneous smiles; fetal smiles must not result from social effects.

AIM The aim of this study was to assess the motor repertoire of extremely low-birthweight infants at term-equivalent age (TEA), in relation to their neurological outcome. METHOD Using Prechtl's method, we assessed both the quality of general movements and a detailed motor optimality score in 13 extremely low-birthweight infants (four males; nine females; mean gestational age 27.9wks, SD 2.9wks; mean birthweight 798g, SD 129g) at TEA, and related them to general movements at the age of 3 months after term and neurological outcome at the age of 2 years 6 months. RESULTS At TEA, 10 of the 13 infants had abnormal general movements. All infants showed abnormal leg lifting with extended legs; nine showed stiff movements, three showed cramped movements, and two showed cramped synchronized general movements. At 3 months, three infants still had abnormal general movements. Concurrent movements were abnormal in nine infants owing to monotony and jerkiness. Abnormal posture was seen in seven infants. None developed cerebral palsy; one infant showed cognitive and motor delay. Neurological outcome was not related to general movement quality and optimality score at TEA. INTERPRETATION Abnormal general movements at TEA are common in extremely low-birthweight infants. General movements often appear stiff and cramped with extended legs. At the age of 3 months after term, general movements are mostly normal, but concurrent movements are not. Nevertheless, these abnormalities do not imply an impaired neurological outcome such as cerebral palsy.

This study examined instrumental learning in premature infants by using a teddy bear that «breathed» quietly at a rate that reflected the infant's respiration rate. At 33 weeks conceptional age (CA), 45 infants were provided either a Breathing Bear (BrBr) or a Nonbreathing Bear (N-BrBr). The baby was monitored by time-lapse video for 3-day periods at the beginning and end of a 2-week intervention period. The BrBr babies decreased their latency to contact the bear over time, whereas the N-BrBr babies showed the opposite pattern. For the BrBr babies, decreased contact latencies were correlated with increased total contact and increased contact frequencies. Thus, by 35 weeks CA, premature infants learned to find and make contact with a reinforcing source of stimulation

Brainstem auditory evoked potentials (BAEPs) at three stimulus rates (20, 41.3 and 61.3 c/s) were recorded in 104 normal preterm infants, distributed in four age groups between 32 and 39 weeks (conceptional age), and in 20 normal adults. The latency shifts between 61.3 c/s and 20 c/s, and between 41.3 c/s and 20 c/s, were calculated for each wave, and studied as a function of age. A significant effect of conceptional age was shown on the ‘61.3–20 c/s’ and the ‘41.3–20 c/s’ wave V latency shifts, and a significant difference between adults and newborns was noted for the wave V and wave III latency shifts. No significant difference was obtained for the wave I latency shifts. This suggests that the changes of auditory adaptation with maturation may be predominantly at a central level, i.e. on central synapses.

Summary Differentiation of motor and automatic function control during different sleep states appears early in human ontegeny. Time of first appearance, magnitude of between-state differences and modifications with age depend on which particular parameters are considered. For some parameters, significant between-state differences appear at 31 weeks conceptional age (wk CA). For nearly all parameters, this difference is clear from 35 wk CA onwards. The analysis presented herein is based on studies of body movements, spontaneous skin potential responses, respiratory characteristics, heart rate and heart rate variability, and correlations between different functions. It examines clinically and neurologically normal premature and full-term neonates of 28 – 41 wk CA.

This study was conducted to quantify sequential changes in electroencephalogram (EEG) continuity for 24 h in very premature infants. For a total of 122 days, continuous 2-channel EEG recording was conducted for 28 premature infants from 26 to 33 weeks of conceptional age (CA). None of the infants showed evidence of neurological impairment during hospitalization. Normal neurological outcome was noted at a minimum 12 months of age. By classifying each 5.5 min epoch according to EEG continuity, the number of contiguous epochs of each series of discontinuous type (DTs) and the number of epochs between two series of discontinous type (IDTIs) were counted at each CA. The duration of DT decreased with increasing CA. The mean duration remained at 13–16 min after 29 weeks CA. The mean duration of each IDTI increased with CA, up to about 1 h at 33 weeks. A constant period of DTs was noted at longer intervals with increasing CA. These changes appear related to the development of sleep state organization with CA.

OBJECTIVE: To study the significance of electroencephalographic background activity and positive sharp waves in neonatal electroencephalogram as prognostic of cerebral palsy. METHOD: We studied prospectively and sequentially 73 newborns who had severe neonatal complications (neonatal anoxia, seizures, respiratory distress, sepsis, and meningitis). Nineteen newborns were excluded and 54 children formed the object of our study and were followed for 2 years. We analyzed gestational age, conceptional age, electroencephalographic background activity and positive sharp waves, which were correlated with cerebral palsy. RESULTS: There were no statistically significant correlation between gestational age and conceptional age and cerebral palsy; the electroencephalographic background activity was correlated with cerebral palsy as well as the positive sharp waves. CONCLUSION: Children with electroencephalographic background activity markedly abnormal and accompanied by positive sharp waves were associated with a worse prognosis.

In determining the detectability of brainstem, middle latency and cortical auditory evoked responses in preterm newborns, one has to deal with the ongoing maturation of the auditory system. In the preterm period the detectability of evoked responses is closely related to the appearance of the individual evoked response components. The detectability of the individual evoked response components in preterm infants is important, because low detectability rates make the absence of a particular evoked response component irrelevant with respect to the clinical-neurophysiological correlation. In a longitudinal study we determined the detectability and cumulative detectability, i.e. the presence of individual evoked response components in one or more recordings of evoked response components in 37 low risk preterm infants between 30 and 41 weeks conceptional age (CA). On the basis of their detectability it is concluded that evoked response components, determined between 30 and 34 weeks CA, are generally of limited use for clinical application, except for auditory brainstem response (ABR) components I, IIn, V and Vc and middle latency response (MLR) component Na. Our study made clear that improvement can be achieved by performing more than one examination within a period of approximately 4 weeks between the recording sessions. The cumulative detectability rates after two recordings showed improvement for all components involved in this study. The cumulative detectability rates of ABR components I, II, IIN, III, V, IIc, IIINc, Vc, MLR components Na and P0, and auditory cortical response (ACR) components PbP1 and N2p are sufficient to use as measures in the neurophysiological judgement of functional integrity of the central auditory pathway in preterm infants.

We measured skin conductance continuously from the sole of a foot in babies of different conceptional ages before, during, and for 10 minutes after a 'heel prick' carried out for routine blood sampling. We studied 82 healthy babies whose gestational and postnatal ages ranged from 25-42 weeks, and 1-73 days. The median skin conductance level (preheel prick) in babies of 40-43 weeks' conceptional age was 0.6 microS (microsiemens) and differed significantly between awake babies (1.2 microS) and those who were asleep (0.5 microS). In contrast babies less than 40 weeks had a significantly lower median skin conductive level (0.3 microS) which was identical in awake and asleep babies. In response to the heel prick all babies became aroused and skin conductance rose sharply and immediately in 21 out of 22 (95%) babies 40-43 weeks' conceptional age, and in seven out of 23 (30%) babies 36-39 weeks. The median rise at one minute in babies of 40-43 weeks was significantly higher than those 36-39 weeks (2.7 microS compared with 0.5 microS). No babies less than 36 weeks had a change in their skin conductance after the heel prick. These results are consistent with the notion that 'emotional sweating' is a function of maturity and does not develop until 36 weeks' conceptional age.

Multimodality-evoked potentials are widely used in newborns to assess the maturation and integrity of the sensory pathways. Reliable normative data are needed to maximize the utility of this technique as a diagnostic and research tool. Several electrophysiologic studies on the maturational changes of the auditory brain-stem response have demonstrated that latency measurements decrease as a function of increasing conceptional age. However, maturational studies of the somatosensory-evoked potential, particularly in low-risk premature infants, are limited. The existing evoked potential literature in healthy newborns proposes that maturation of the central nervous system occurs at a predictable rate, irrespective of a given gestational age at birth. Behavioral studies of premature infants suggest that neurologic development may be altered by early extrauterine exposure. The purpose of this study was to determine whether brain-stem auditory- or somatosensory-evoked potential conduction times were comparable in premature and full-term infants matched for conceptional age. The results of this study suggest that myelination is determined by conceptional age, independent of premature birth. ( J Child Neurol 1990;5:329-335).

We studied the electrically and mechanically elicited blink reflexes in 2 groups of subjects, i.e., 237 newborn infants, 25-41 weeks of conceptional age, and 74 children, 1 month-12 years of age. In infants after 25 weeks of conceptional age we could usually induce the early response (R1) and ipsilateral late response (R2), while the contralateral late response (R2') of the electrical blink reflex became apparent after 33 weeks of conceptional age and the frequency of the appearance of R2' reached more than 60% after 38 weeks of conceptional age. After 7 months of age, R2' was usually observed. The R1 latency in full-term newborns was close to adult values, while the R2 and R2' latencies reached adult values at 7-12 years. After 1 year of age the latency of the R2 mechanical blink reflex had a tendency to be shorter than that of the electrical blink reflex. Under 35 weeks of conceptional age, the recovery curves of the blink reflex were considerably different from those of full-term infants, and premature infants showed little or no evidence of inhibition. These results indicate the absence of inhibitory interneurones in premature infants.

The EEG is an excellent method for measuring brain maturation in premature neonates. Characteristic patterns typify each conceptional age (CA) (age in weeks from conception) and allow the experienced reader to predict within +/- 2 weeks the infant's CA. This paper reviews from an historical perspective (beginning with Berger) the dramatic changes the EEG undergoes from early premature birth (CA, 26 weeks) to term (CA, 40 weeks). The important features of normal EEG development are discussed as well as the clinical significance of an apparent arrest or delay of the normal developmental process, the so-called "dysmature" pattern. It is proposed that close attention to the stage of brain maturation in normal and abnormal EEGs might allow more accurate timing of the brain insult in infants with neurological sequelae.

The purpose of this study was to document joint range of motion of premature, very low birthweight infants and to describe developmental changes in joint range in the first year of life. The relationship between a group of three central nervous system complications and obtained range of motion was investigated. A longitudinal descriptive design was used documenting joint range of motion values over the first year of life in 65 premature, very low birthweight infants. Joint range of motion values were obtained using a plastic goniometer. Measures were based on an adaptation of the Amiel-Tison assessment. Infants were tested at the time of hospital discharge, and at 4, 8, and 12 months chronological age. The obtained values were summarized through descriptive statistical methods. Longitudinal trends in the sample demonstrated changes in joint range of motion over time. However, the preterm infants never displayed the high amount of flexion characteristic of full-term babies. The premature infants in the present study demonstrated more hip extension as they approached term conceptional age than previously reported values for full-term newborns. The present sample also had more elbow extension and less ankle dorsiflexion in comparison with previously reported findings for term infants. These findings may have developmental implications for a divergent course of neuromotor development in premature infants.

Summary Objectives To provide age-equivalent norms for a 500 Hz logon evoked ABR obtained in a group of children ranging 40 weeks–4 years old and compare these 500 Hz tonal norms to age-equivalent norms for click-evoked ABR. Methods Seventy-seven infants and children ranging from conceptional age of 40 weeks (term babies) to 4 years were tested with both click and tonal ABR without any risk factors for hearing loss. Results Data analyses were consisted of 6 age groups. Mean wave V latencies were compared with the adult norms. Latencies were decreased by age in both click and tonal ABR recordings. Conclusion Five hundred Hertz of tonal ABR wave V latency did not mature until to 2–4 years old but, click ABR wave V latency reached maturity at the same age range.

Often ABR threshold testing employs clicks to assess high-frequency hearing, and low-frequency tone bursts to assess low-frequency sensitivity. While a maturation effect has been shown for click stimuli, similar data are lacking for low-frequency toneburst stimuli. Thus, 305 infants ranging in conceptional age (CA) from 33 weeks to 74 weeks were tested. Absolute latencies were measured for wave V at 55, 35, and 25 dB nHL in response to a click and for wave V500 in response to a 500 Hz tone burst. Major wave latency in response to 500 Hz tone bursts decreases with age and do not stabilize by 70 weeks CA. Likewise, waves III and V latencies in response to clicks decrease with age, as has been reported by others, and do not stabilize by 70 weeks CA. Wave I latency produced by clicks did not decrease with age, being mature by 33 weeks CA.

SUMMARY The purpose of this work was to examine whether the clinical eruption of the permanent first molars and incisors is affected by pre-term birth. The data applied to 328 prematurely born white and black children and 1804 control children who participated in the Collaborative Perinatal Project (USA) in the early 1960s and 1970s. The dental examinations had been performed in a cross-sectional manner at ages varying from 6 to 12 years in 95 per cent of cases (range 5‐14 years). Dental casts were placed in matched pairs by sex, race and conceptional age for comparison of the four clinical stages of eruption of the permanent incisors and first molars between the pre-term and control children. The results showed significantly (P < 0.05) earlier tooth eruption in the pre-term children. The findings suggest that the eruption process is earlier in those teeth that go through a sensitive period circumnatally, being at the pre-eruptive stages and entering the first phases of mineralization under the influence of various neonatal systemic factors and accelerated growth period (catch-up growth) with related unknown mechanisms, which may influence the eruption of the permanent incisors and first molars in prematurely born children.

Brain maturation at early stages may be assessed by changes in electroencephalographic connectivity (Grieve et al., 2008). We determined the differences in brain maturation between infants born at different gestational age (GA) by comparing connectivity measures obtained at comparable post-conceptional age. Electroencephalogram was recorded on twenty-six infants (23–35 weeks GA) at 35 post-conceptional weeks. Infants were divided in groups according to GA: 23–27 (ELGA), 28–32 (VLGA) and 34–35 (LGA) weeks. Data were recorded on Fp1, Fp2, Fz, C3, Cz, C4, T3, T4, O1 and O2 channels referred to linked mastoids and transformed into the frequency domain using a Fast Fourier Transformation algorithm. A single- subject-connectivity-matrix approach was used to obtain measures of global/local connectivity (clustering coefficients, strength and modularity) in delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz) and beta (13–30 Hz) bands. Functional connectivity measures were compared between subgroups. A greater mean coherence strength of the theta band of the right hemisphere in LGA compared with ELGA (p = .006) were found. The comparison at the same post- conceptional age of infants born at different gestational weeks allowed to emerge early differences in brain electrical activity suggesting altered developmental trajectories for premature infants born at lower gestational ages.

Heart rate variability (HRV) analysis of 24 healthy newborn sleeping babies was performed by a short-time Fourier transform in three frequency bands, reflecting the activity of both branches of the autonomic nervous system (ANS), vagal and sympathetic. The means of the three extracted time signals, computed over records of 512 heartbeats, were used as a material for principal component analysis, and for discriminant factor analyses, to separate sleep states and conceptional age (CA) groups. This study suggests that sleep state discrimination, on the basis of an opposition between high (purely vagal in its origin) and low (vagal and sympathetic) frequency HRV, is regularly improved from 31 to 41 weeks CA; and a strong increase in ANS activity, mainly vagal, as reflected by high-frequency HRV, occurs precociously, not later than 38 weeks CA. >

This study addresses the value of operator-independent computer processing of ultrasonograms of the developing brain. With this aim, routine cranial ultrasonograms obtained from 39 term and preterm infants without clinical or sonographic evidence of brain damage were analyzed by five observers. The procedure, respectively, included: 1. the definition of four regions of interest (ROI), one white matter and one grey matter area on each side of the brain; 2. digitization of the sonogram data within these ROIs; 3. correction for the equipment settings, using data from a tissue-mimicking phantom as a reference; and 4. calculation of four sonogram characteristics (i.e., mean echo level, MEAN, signal-to-noise ratio, SNR, and axial and lateral correlation, CORAX and CORLAT, of the echo level co-occurrence matrix). Significant differences between both sides of the brain or a significant influence of ROI size were not found. The interobserver spread was considerable, but less than the intersubject spread. Two sonogram characteristics seemed strongly correlated in white and grey matter (CORAX and CORLAT) and another only in white matter (SNR with CORAX and CORLAT). MEAN seemed not to be correlated with any other characteristic. Furthermore, it was found that maturation equally decreases white and grey matter MEAN and, thus, hardly affects the ratio between the two. An effect on the other sonogram characteristics was only found in the white matter (i.e., an increase of SNR and a decrease of CORAX and CORLAT). Except for MEAN, the grey matter sonogram characteristics seem hardly affected by maturation. In view of these findings, we conclude that quantitative ultrasonography reveals white and grey matter maturation and, furthermore, provides a conceptional-age-independent reference (MEAN white:grey matter ratio) that might be found to facilitate the detection of pathologic brain alterations.