早产儿振幅整合脑电图的应用

振幅整合脑电图是脑电图技术的一种简化形式,近年来已被证实可以辅助诊断足月儿缺血缺氧性脑病、预测窒息后足月儿神经发育结局,但对于早产儿应用较少.早产儿振幅整合脑电图与脑发育成熟程度相关,易受临床干预措施等多种因素影响,目前诸多研究者认为早产儿振幅整合脑电图同样有助于早产儿脑损伤诊断及神经发育结局预测.该文从早产儿振幅整合脑电图与脑发育的关系、影响因素,对脑损伤诊断价值及神经发育结局预测能力角度进行综述.     

Early single-channel aEEG/EEG predicts outcome in very preterm infants

Aim: To characterize early amplitude‐integrated electroencephalogram (aEEG) and single‐channel EEG (aEEG/EEG) in very preterm (VPT) infants for prediction of long‐term outcome. Patients: Forty‐nine infants with median (range) gestational age of 25 (22–30) weeks. Methods: Amplitude‐integrated electroencephalogram/EEG recorded during the first 72 h and analysed over 0–12, 12–24, 24–48 and 48–72 h, for background pattern, sleep–wake cycling, seizures, interburst intervals (IBI) and interburst percentage (IB%). In total, 2614 h of single‐channel EEG examined for seizures. Survivors were assessed at 2 years corrected age with a neurological examination and Bayley Scales of Infant Development‐II. Poor outcome was defined as death or survival with neurodevelopmental impairment. Good outcome was defined as survival without impairment. Results: Thirty infants had good outcome. Poor outcome (n = 19) was associated with depressed aEEG/EEG already during the first 12 h (p = 0.023), and with prolonged IBI and higher IB% at 24 h. Seizures were present in 43% of the infants and associated with intraventricular haemorrhages but not with outcome. Best predictors of poor outcome were burst‐suppression pattern [76% correctly predicted; positive predictive value (PPV) 63%, negative predictive value (NPV) 91%], IBI > 6 sec (74% correctly predicted; PPV 67%, NPV 79%) and IB% > 55% at 24 h age (79% correctly predicted; PPV 72%, NPV 80%). In 35 infants with normal cerebral ultrasound during the first 3 days, outcome was correctly predicted in 82% by IB% (PPV 82%, NPV 83%). Conclusion: Long‐term outcome can be predicted by aEEG/EEG with 75–80% accuracy already at 24 postnatal hours in VPT infants, also in infants with no early indication of brain injury.     

Amplitude-integrated electroencephalography in preterm infants with cystic periventricular leukomalacia

Aim

This study aimed to assess amplitude-integrated electroencephalography (aEEG) findings in preterm infants with cystic periventricular leukomalacia (cPVL) in the early neonatal period.

Methods

We analyzed five infants with cPVL, whose gestational age was between 27 and 30 weeks, and 15 matched control infants. Two-channel (C3-O1 and C4-O2) aEEG was obtained by digital conversion from a conventional electroencephalogram, which was recorded at days 0-5, 6-13, and 21-34 in each infant. We evaluated the averaged two-channel values of several measurements using visual and quantitative analyses.

Results

Infants with cPVL had a significant higher maximal upper-margin amplitude value, with a median of 47.5 μV (range of 42.5-60) compared with the control infants (median, 33.8; range, 23.8-50) in the second visual-analysis record. Infants with cPVL also had a significantly higher mean upper-margin amplitude value, with a median of 18.8 μV (range, 17.7-23.2) compared with the control infants (median, 16.3; range, 10.3-19.0) in the second quantitative-analysis record.

Conclusions

We demonstrated that the upper-margin amplitude of aEEG in infants with cPVL was significantly higher than that in the control infants at 6-13 days after birth.     

Amplitude-integrated electroencephalographic activity is suppressed in preterm infants with high scores on illness severity

Background

The neonatal acute physiology score, SNAP-II, reflects the severity of illness in newborns. In term newborns, amplitude integrated EEG (aEEG), is depressed following asphyxia. In preterm infants aEEG is discontinuous, and therefore more difficult to assess compared to term infants.

Aims

Our first aim was to investigate whether assessing aEEG amplitudes by calculating amplitude centiles was consistent with assessment by pattern recognition. Our second aim was to investigate whether the aEEGs of preterm infants were influenced by SNAP-II.

Study Design and Subjects

We recorded aEEGs in 38 infants with a mean gestational age of 29.7 weeks (26.0-31.8 weeks) during the first five days of life. The mean recording time was 130 min. The aEEGs were assessed by pattern recognition, by calculating Burdjalov score, and by calculating the mean values of the 5th, 50th, and 95th centiles of the aEEG amplitudes. Illness severity was determined within the first 24 h.

Results

We assessed 151 recordings and found strong correlations between the 5th and 50th amplitude centiles and the Burdjalov scores (r = 0.71, p < 0.001 and r = 0.47, p < 0.001, respectively). The 5th and 50th amplitude centiles correlated with SNAP-II (r = − 0.34, p < 0.0001 and r = − 0.27, p = 0.001). These correlations were the strongest on the first day of life (r = − 0.55, p = 0.005 and r = − 0.47, p = 0.018, respectively). The 5th and the 50th amplitude centiles were best predicted by gestational age, SNAP-II, and low blood pressure.

Conclusions

Severe illness as measured by the SNAP-II, and low blood pressure had a negative influence on the aEEGs of preterm infants.     

Amplitude-integrated EEG differences in premature infants with and without bronchopulmonary dysplasia: a cross-sectional study

Aim: To evaluate differences in amplitude‐integrated electroencephalogram (aEEG) recordings of infants with and without bronchopulmonary dysplasia (BPD). Methods: This is a cross‐sectional study of infants ≤27 weeks at birth who did (n = 17) or did not develop BPD (n = 17). aEEG tracings were recorded at 36⁰–36⁶ weeks post‐menstrual age for 6 h using the BrainZ BRM3 monitor. A cross‐cerebral channel was evaluated using offline software Analyze (BrainZ). Results: Infants with BPD had lower gestational age and higher male predominance (25 ± 1 weeks, 70%) compared with non‐BPD infants (26 ± 1 weeks, 30%, all p ≤ 0.03), but similar birth weight (704 ± 195 vs. 796 ± 167 g, p = 0.1). During active sleep, infants with BPD had wider span voltage (p = 0.03), higher lower border voltage (p < 0.03), as well as less periods of quiet sleep per hour (p < 0.01) compared with non‐BPD infants. These differences persisted after adjustment for covariates. Conclusion: Infants with BPD have small but significant differences in their aEEG tracings compared with infants without BPD at 36 weeks. Further study of infants with BPD using aEEG appears justified to determine whether aEEG variables correlate with neurodevelopmental outcome.     

Functional connectivity in preterm infants derived from EEG coherence analysis

ObjectiveTo quantify the neuronal connectivity in preterm infants between homologous channels of both hemispheres.MethodsEEG coherence analysis was performed on serial EEG recordings collected from preterm infants with normal neurological follow-up. The coherence spectrum was divided in frequency bands: δnewborn(0–2 Hz), θnewborn(2–6 Hz), α_newborn(6–13 Hz), β_newborn(13–30 Hz). Coherence values were evaluated as a function of gestational age (GA) and postnatal maturation.ResultsAll spectra show two clear peaks in the δ_newborn and θ_newborn-band, corresponding to the delta and theta EEG waves observed in preterm infants. In the δ_newborn-band the peak magnitude coherence decreases with GA and postnatal maturation for all channels. In the θ_newborn-band, the peak magnitude coherence decreases with GA for all channels, but increases with postnatal maturation for the frontal polar channels. In the β_newborn-band a modest magnitude coherence peak was observed in the occipital channels, which decreases with GA.ConclusionsInterhemispherical connectivity develops analogously with electrocortical maturation: signal intensities at low frequencies decrease with GA and postnatal maturation, but increase at high frequencies with postnatal maturation. In addition, peak magnitude coherence is a clear trend indicator for brain maturation.SignificanceCoherence analysis can aid in the clinical assessment of the functional connectivity of the infant brain with maturation.     

Amplitude-integrated electroencephalography for seizure detection in newborn infants

The amplitude-integrated electroencephalogram (aEEG) is a filtered and compressed EEG trend that can be used for long-term monitoring of brain function in patients of all ages. aEEG is increasingly used in neonatal intensive care units since several studies have shown its utility in high-risk newborn infants. Main indications for aEEG monitoring include early evaluation of brain function after perinatal asphyxia and seizure detection. The aEEG is usually recorded from one or two channels derived from parietal, central, or frontal leads. Although the aEEG is very useful for identifying high-risk infants and infants with seizures, the compressed trend has limitations with regards to detection of individual seizures. However, modern monitors also display the corresponding EEG (aEEG/EEG), which increases the probability of detecting single brief seizures. For improved evaluation of electrocortical brain activity the aEEG/EEG should be assessed together with repeated conventional EEGs or multi-channel EEG monitoring in a multi-disciplinary team.     

Maturational changes in automated EEG spectral power analysis in preterm infants

Our study aimed at automated power spectral analysis of the EEG in preterm infants to identify changes of spectral measures with maturation. Weekly (10-20 montage) 4-h EEG recordings were performed in 18 preterm infants with GA <32 wk and normal neurological follow-up at 2 y, resulting in 79 recordings studied from 27(+4) to 36(+3) wk of postmenstrual age (PMA, GA + postnatal age). Automated spectral analysis was performed on 4-h EEG recordings. The frequency spectrum was divided in delta 1 (0.5-1 Hz), delta 2 (1-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-30 Hz) band. Absolute and relative power of each frequency band and spectral edge frequency were calculated. Maturational changes in spectral measures were observed most clearly in the centrotemporal channels. With advancing PMA, absolute powers of delta 1 to 2 and theta decreased. With advancing PMA, relative power of delta 1 decreased and relative powers of alpha and beta increased, respectively. In conclusion, with maturation, spectral analysis of the EEG showed a significant shift from the lower to the higher frequencies. Computer analysis of EEG will allow an objective and reproducible analysis for long-term prognosis and/or stratification of clinical treatment.     

振幅整合脑电图在足月儿缺氧缺血性脑病早期诊断和预后评估的意义

目的对足月新生儿缺氧缺血性脑病（HIE）生后6h内振幅整合脑电图（aEEG）的变化及其在HIE早期诊断和神经学预后评估的价值进行初步探讨。方法对2003年5月至2005年2月间在我院新生儿病房住院的33例足月HIE患儿在生后6h内进行aEEG描记,并将aEEG监测结果与HIE患儿临床分度及18个月时的神经学预后进行相关性分析,分析其在HIE早期诊断和神经学预后预测中的价值。结果33例HIE患儿中,aEEG正常20例（60．6％）,轻度异常5例（15．2％）,重度异常8例（24．2％）。33例HIE患儿中,轻度HIE 17例（51．5％）,中度HIE 9例（27．3％）,重度HIE 7例（21．2％）。25例进行神经预后分析,其中19例神经学预后正常,1例伤残（智力缺陷）,5例死亡。aEEG分类结果与HIE临床分度及其神经学预后均相关性强。aEEG异常预测新生儿中重度HIE的敏感性为100％,特异性为81．3％,阳性预测值为85．0％,阴性预测值为100％;预测HIE异常神经学预后的敏感性为100％、特异性为90．9％、阳性预测值为93．3％和阴性预测值为100％。结论对足月HIE新生儿生后6h内aEEG监测能早期预测HIE病情轻重程度并预测其神经学预后。     

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??Premature infants often suffer from chronic respiratory diseases and need supplementary oxygen at home after being discharged??and there exists increased rehospitalization?? more frequent cough and wheezing symptoms?? and abnormal lung function reflecting airway obstruction?? hyper-responsiveness and air-trapping. Also?? the neurological problems are more common in preterm survivors with bronchopulmonary dysplasia ??BPD?? compared to those without BPD. Severe BPD could be a predictor for poor neurodevelopmental outcome in certain type of patients.     

Influence of early diet on outcome in preterm infants

Despite intensive research in infant nutrition over the past 50 years, uncertainty exists in nearly every major area of practice. A key factor in this uncertainty has been the lack of knowledge on whether diet or nutritional status in early life has a long-term or permanent influence on health, growth or performance. The possibility that early nutrition has long-term consequences in man has been much debated. There have been limited opportunities to perform formal randomized studies on the effect of early nutrition in humans and many studies have been flawed by problems with study design. Infants born preterm are a special group. At the start of our study in 1982, evidence on which to base choice of diet was inconsistent and related only to short-term outcome, and diets available for such babies differed greatly in nutrient content. In this group it was both ethical and practical to conduct a formal, randomized trial of early diet and outcome and the results were clearly needed for management decisions. We have undertaken a long-term prospective outcome study on 926 preterm infants randomly assigned to the diet received in the neonatal period. Surviving children have been followed at 9 months, 18 months and now 7.5-8 years of age. Our findings suggest that human milk may contain factors which promote brain growth or development and also bone mineralization later in childhood. Outcome data from the randomized trials show that a very brief period of dietary manipulation (on average for the first 4 weeks of life) influences later development.     

Periventricular leucomalacia and neurodevelopmental outcome in preterm infants.

During an 18 month period, 120 preterm infants of 34 weeks'' gestation or less were prospectively examined for periventricular leucomalacia (PVL) by cerebral ultrasound. Neurological and developmental assessment was carried out at 18 months of age corrected for prematurity in 82 surviving neonates. The developmental outcome (Griffiths development quotient) was above 80 and similar in infants with normal scans (n = 41), isolated periventricular-intraventricular haemorrhage (n = 13), and post-haemorrhagic hydrocephalus (n = 4), and no major handicap was diagnosed in these groups. By contrast, the prognosis was variable and poorer in infants with PVL (n = 24) and depended on the extent and site of the lesion. Infants with frontal PVL (n = 13) developed normally. Major sequelae (n = 8) were closely related to frontal-parietal PVL and frontal-parietal-occipital PVL and could be ascribed to the presence of cysts as well as to a persistent hyperechogenic ultrasonographic PVL appearance. A relation between size and site of the lesion and type and severity of the handicap was established.     

Effect of chorioamnionitis on neurodevelopmental outcome in preterm infants

OBJECTIVE: To assess the association of neurodevelopmental outcome with the placental diagnosis of chorioamnionitis in very low-birth-weight infants. METHODS: One hundred seventy-seven surviving very low-birth-weight infants, 22 to 29 weeks' gestational age, born after varying severity of chorioamnionitis, were evaluated at a mean +/- SD age of 19 +/- 6 months' corrected age with Bayley Scales of Infant Development II and neurologic examination. Select maternal and infant variables were abstracted from the medical records. Neonatal morbidities, Mental Developmental Index (MDI) score, Psychomotor Developmental Index (PDI) score, probability of normal MDI and PDI scores (>84), and cerebral palsy between the chorioamnionitis and the control groups were assessed, controlling for gestational age, sex, and the maternal use of steroids and antibiotics. RESULTS: The chorioamnionitis group of 102 infants was compared with 75 control infants (mean +/- SD birth weight, 947 +/- 236 g and 966 +/- 219 g, respectively; mean +/- SD gestational age, 26.1 +/- 2.8 weeks and 27.1 +/- 1.5 weeks, respectively). Infants with chorioamnionitis, compared with controls, had a significantly higher incidence of intraventricular hemorrhage (30% vs 13%) and retinopathy of prematurity (68% vs 42%). Cerebral palsy was diagnosed in 8.6% of the infants with chorioamnionitis and 6.6% of the controls. The MDI and PDI scores were similar between the chorioamnionitis and control groups (mean +/- SD MDI score, 96 +/- 16 vs 97 +/- 18 and mean +/- SD PDI score, 94 +/- 19 vs 92 +/- 19, respectively). CONCLUSIONS: In very low-birth-weight infants we found a higher incidence of intraventricular hemorrhage and retinopathy of prematurity but similar MDI and PDI scores and risk of cerebral palsy associated with chorioamnionitis.     

Serum chemokine levels and developmental outcome in preterm infants

Background

Cytokines and chemokines during perinatal period may involve the neurological development of newborns.

Aims

We investigated the association of circulating chemokines during neonatal period with the outcome of premature infants.

Study design

The prospective study enrolled 29 very low birth weight (< 1500 g) and appropriate-for-date infants having no underlying diseases. Serum concentrations of chemokines (CXCL8, CXCL9, CXCL10 and CCL2) and cytokines at birth and 4 weeks postnatal age were measured. Developmental quotients (DQ) at 3 years of age by the Kyoto Scale of Psychological Development were studied for the association with chemokine/cytokine levels and clinical variables including chorioamnionitis, Apgar scores, ventilator treatment and supplemental oxygen.

Results

CXCL8 levels at birth and days of ventilator treatment were negatively, CCL2 levels at 4 weeks after birth and 5-minute Apgar scores were positively correlated with the DQ of postural-motor [P-M] area at 3 years of age, respectively (CXCL8: correlation coefficient [CC] = − 0.394, p = 0.037, ventilation: CC = − 0.518, p = 0.006, CCL2: CC = 0.528, p = 0.013, and Apgar score: CC = 0.521, p = 0.005). Infants showing both ≥ 50 pg/ml of CXCL8 at birth and < 250 pg/ml of CCL2 4 weeks after birth had lower DQ of P-M than those who did not (p < 0.001). Multivariate analyses indicated that CCL2 levels at 4 weeks of age were higher in infants who attained normal DQ of P-M (≥ 85) (adjusted mean, 338.4 [95% confidence interval, 225.5-507.8]) than in those who did not (< 85) (159.0, [108.2-233.7]) (p = 0.019).

Conclusion

Circulating patterns of CXCL8 (IL-8) and CCL2 (MCP-1) during the neonatal period might affect the neurological development of preterm infants.     

Plasma prolactin and clinical outcome in preterm infants.

Plasma prolactin was measured weekly in 280 preterm infants. The complex gestational age dependent pattern of postnatal prolactin release has been defined and reference standards provided. Plasma prolactin was higher in girls, with increasing divergence between the sexes from the third week onwards, and higher after two weeks, in infants of mothers with pregnancy related hypertension. Diet, assigned randomly, exerted a major effect on plasma prolactin, with significantly higher values in infants fed donor breast milk or standard formula than in those fed a protein, energy, and mineral enriched preterm formula. After adjusting for confounding factors, infants with the lowest plasma prolactin concentrations (less than 1000 mU/l, 32.9 micrograms/l) occurring usually at a nadir between days 5 and 12, showed a 120% increase in the duration of ventilatory assistance required, a 20% increase in the number of days to attain full enteral feeds, and a 30% decrease in length gain. We suggest preterm birth disrupts the normal perinatal pattern of prolactin release and that those infants who develop relatively low plasma concentration have an adverse outcome. Our data add to the broader debate on whether preterm infants require multiple endocrine replacement treatment.     

Neurodevelopmental status at 1 year predicts neuropsychiatric outcome at 14-15 years of age in very preterm infants

BACKGROUND: Neurodevelopmental and behavioural problems have been repeatedly reported in very preterm survivors, often showing themselves later in childhood as poor school performance. Early identification of problems would mean that appropriate remedial therapy can be implemented. We have previously shown that neurodevelopmental status at 1 year was predictive of outcome at 8 years in a cohort of preterm infants. The aim of this paper was to see if neurodevelopmental outcome in adolescence could be predicted by assessment by 1 year in the same cohort of preterm infants. STUDY DESIGN: Prospective cohort study. SUBJECTS: 150 adolescents, born before 33 weeks gestation. OUTCOME MEASURES: Neurological examination, developmental quotient, vision and hearing by 1 year. At 14-15 years, neurological examination, school performance questionnaire, Schonnell test of reading age, a premorbid adjustment score, Rutter behavioural score and for those born from 1981, cognitive tests (WISC-R). RESULTS: A highly significant relationship existed between neurological status by 1 year and the need for extra educational provision, overall neurodevelopmental status, cognitive function in those that had their IQs measured and premorbid adjustment score of prepsychotic symptoms in adolescence. However, status at 1 year was not predictive of adolescent reading age or behavioural score. CONCLUSIONS: Neurodevelopmental assessment at 1 year is predictive of school performance and outcome in the adolescent period.     

晚期早产儿早期智能发育结局的研究

目的探讨晚期早产儿(LPI)早期智能发育结局。方法选择2012年1月至2015年1月新生儿病房收治的出生胎龄34~36+6周、治愈出院并定期规律随访的106例早产儿为晚期早产儿组;随机抽取同期120例健康足月儿(FPI)为对照组。对校正年龄40周的晚期早产儿及40周龄的足月儿进行新生儿神经行为测定(NBNA),晚期早产儿校正龄3、6、12月龄或者足月儿3、6、12月龄时采用Gesell发育量表进行评估。结果 LPI组NBNA评分低于37分,低于FTI组(P0.05)。校正龄3月龄时,LPI组大运动、精细运动、个人社交落后于FTI组(P0.05);校正龄6月龄时,LPI组适应性、大运动、精细运动落后于FTI组(P0.05);校正年龄12月龄时,LPI组适应性、大运动、个人社交测评明显低于FTI组(P0.05)。结论晚期早产儿早期智能发育迟缓,需加强神经发育监测。