Association of cerebral activity with MRI scans in infants with neonatal encephalopathy undergoing therapeutic hypothermia.

We aimed to correlate amplitude-integrated EEG (aEEG) in neonatal hypoxic ischemic encephalopathy (HIE) with early magnetic resonance imaging (MRI). In this retrospective study, 32 neonates over 35 weeks' gestation with moderate/severe HIE who were treated with hypothermia were included. Early MRI scans and daily aEEG background were categorized to mild/normal, moderate, and severely abnormal. Time to sleep cycling was noted on aEEG. Mantel-Haenszel test for trends was used to explore associations between aEEG and MRI and outcome. LOESS regression was used for exploring the association of cycling with MRI scores. MRI was normal/mildly abnormal in 20 (63%) infants; in 9 (28%), moderately abnormal; and in 3 (9%), severely abnormal. Twenty-seven (84%) infants s urvived. MRI severity score was significantly associated with aEEG background score on the third and fourth days of life (p < 0.01). An increase in the MRI severity score was noted if sleep cycling appeared after the fifth day of life.Conclusions: Depressed aEEG at the third and fourth days of life and appearance of cycling beyond the fifth day of life are associated with cerebral MRI abnormalities and may be associated with increased risk of abnormal outcome. What is known: • Since therapeutic hypothermia has been shown to change long-term outcome, amplitude-integrated EEG in infants with hypoxic ischemic neonatal encephalopathy soon after birth have a limited predictive power for long-term outcome in treated infants. • Brain MRI after therapeutic hypothermia in the above infants has a significant predictive value for long-term outcome What is new: • Background amplitude-integrated EEG activity depression at the age of 3 and 4 days and delay of appearance of cycling activity are associated with worse MRI scores and may be predictive of worse long-term outcome.

The Association of Therapeutic Hypothermia With Seizure Burden in Neonates With Hypoxic-Ischemic Encephalopathy.

OBJECTIVES: To compare seizure burden between newborn infants treated with therapeutic hypothermia (TH) and those that were not and to compare the need for antiseizure medications (ASM) in a cohort of infants who were diagnosed with neonatal hypoxic-ischemic encephalopathy (HIE). METHODS: This was a retrospective cohort study on infants born after 35 weeks' gestation, diagnosed with moderate to severe HIE, monitored with amplitude-integrated electroencephalography (aEEG) and eligible for TH. Infants born before the implementation of TH in 2008 were compared with infants born thereafter who received TH. Seizure burden was assessed from aEEG as total time in minutes of seizures activity per hour of recording. Other clinical and demographic data were retrieved from a prospective local database of infants with HIE. RESULTS: Overall, 149 of 207 infants were included in the study: 112 exposed to TH and 37 not exposed. Cooled infants had a lower seizure burden overall (0.4 vs 2.3 min/h, P < 0.001) and were also less likely to be treated with ASM (74% vs 100%, P < 0.001). In multivariable regression models, not exposed to TH, having a depressed aEEG background, and having higher Apgar scores were associated with higher seizure burden (incidence rate ratio: 4.78 for noncooled infants, P < 0.001); also, not exposed to TH was associated with a higher likelihood of multidrug ASM (odds ratio: 4.83, P < 0.001). CONCLUSIONS: TH in infants with moderate to severe HIE is associated with significant reduction of seizure burden and ASM therapy.

Effect of morphine on cerebral activity of extremely premature infants.

BACKGROUND: Morphine is widely used for sedation in premature infants and may have long-term effects on neurodevelopmental outcome. AIMS: To assess its effect on cerebral activity of extremely preterm infants. METHODS: Retrospective study in infants less than 28 weeks of gestational age (GA), treated with morphine and monitored with amplitude integrated EEG (aEEG), that were assessed at baseline and 6 consecutive 2 h periods. At each period, the background activity score and presence of cycling were determined. RESULTS: A total of 140 infants were included. Background aEEG activity score worsened in 40% of the infants by 6 h after morphine initiation and cycling, initially present in 70% of the infants, could be detected in only 10% after 10 h. On multivariable analysis, adjusted for baseline aEEG score and GA, the background activity decreased by 0.85 (95% confidence interval (CI): 0.74-0.97) immediately after morphine initiation, 0.72 (CI: 0.63-0.83) at 2 h later and on average by 0.64 (CI: 0.57-0.71) at each subsequent 2 h periods. The relative risk of cycling loss at 2 h and 4 h after morphine administration was 1.58 (CI: 1.15-2.16) and 3.37 (CI: 2.23-5.08), respectively. CONCLUSIONS: Continuous infusion of morphine in extremely preterm infants significantly depresses their cerebral activity soon after its commencement.

Predictive Value of Early Amplitude Integrated EEG in Extremely Premature Infants.

Amplitude integrated EEG (aEEG) is increasingly utilized in preterm infants. The aim of the study was to evaluate whether semiquantitative visual assessment of aEEG background during the first 72 hours of life is associated with long-term outcome in a group of premature infants born less than 28 weeks' gestation. Infants were prospectively enrolled and monitored in the first 72 hours after birth. aEEG was classified daily according to background activity, appearance of cyclical activity and presence of seizures activity. Log-rank and multivariable cox analysis were used to explore associations of background aEEG activity with short and long-term outcome. Overall, 51 infants were enrolled into the study. Depressed aEEG background on the third day of life was associated with poor outcome (P = .028). Similarly, absence of cycling on the third day of life was associated with death or poor outcome (P = .004 and .012, respectively). In different multivariable models adjusted for gestational age, severe intraventricular hemorrhage or use of sedative medication, neither background nor cycling activities were associated with outcome. Depressed aEEG background and absence of aEEG cycling on the third day of life are associated with poor outcome in univariable analysis. Although continuous aEEG monitoring of premature infants can provide real-time assessment of cerebral function, its use as a predictive tool for long-term outcome using visual analysis requires caution as its predictive power is not greater than that of gestational age or intraventricular hemorrhage.

Seizures in Premature Infants Born at Less than 28 Weeks' Gestation.

BACKGROUND: The incidence of seizures in the neonatal period is thought to be high due to a lower seizure threshold of the immature brain. Data on seizures in extremely premature infants are scarce. OBJECTIVES: The aim of this study was to determine whether seizures are an independent risk factor for in-hospital death and to determine the incidence of seizures in extremely premature infants. METHODS: This was a retrospective cohort study. Included were infants born under 28 weeks' gestation and monitored with amplitude-integrated electroencephalography (aEEG) over the first 3 days of life. The number and duration of seizures was retrieved from aEEG recordings together with clinical data. The association of seizures and other parameters with mortality was assessed using univariable analyses methods. Relevant parameters were used for a multivariable Cox regression analysis. RESULTS: Overall, 229 infants were included in the study. Forty-six infants had at least one seizure episode yielding an incidence of 20%. In univariable analyses, gestational age (p < 0.001), birthweight Z-score (p < 0.001), seizures (p = 0.025), suppressed background aEEG (p < 0.001), and severe intraventricular hemorrhage (IVH; p < 0.001) were associated with death before discharge. In multivariable analysis, gestational age (HR = 0.61, p < 0.001), background aEEG activity (HR = 0.30, p < 0.001), birth weight Z-score (HR = 0.51, p = 0.04), and severe IVH (HR = 2.60, p < 0.001) were found to be significant predictors of mortality while the presence of seizures in the first 3 days of life trended to significantly predict an increased risk of mortality (HR = 1.53, p = 0.09). CONCLUSIONS: Although seizure incidence was relatively high in this cohort of extremely preterm infants and infants with seizures were more likely to die, seizures alone are not a predictor for early death. However, they may be an important indicator of pathologies that are not immediately diagnosed yet could eventually lead to death among this vulnerable population.

Comparison of Amplitude-Integrated EEG and Conventional EEG in a Cohort of Premature Infants.

OBJECTIVE: To compare amplitude-integrated EEG (aEEG) and conventional EEG (EEG) activity in premature neonates. METHODS: Biweekly aEEG and EEG were simultaneously recorded in a cohort of infants born less than 34 weeks gestation. aEEG recordings were visually assessed for lower and upper border amplitude and bandwidth. EEG recordings were compressed for visual evaluation of continuity and assessed using a signal processing software for interburst intervals (IBI) and frequencies' amplitude. Ten-minute segments of aEEG and EEG indices were compared using regression analysis. RESULTS: A total of 189 recordings from 67 infants were made, from which 1697 aEEG/EEG pairs of 10-minute segments were assessed. Good concordance was found for visual assessment of continuity between the 2 methods. EEG IBI, alpha and theta frequencies' amplitudes were negatively correlated to the aEEG lower border while conceptional age (CA) was positively correlated to aEEG lower border ( P < .001). IBI and all frequencies' amplitude were positively correlated to the upper aEEG border ( P ≤ .001). CA was negatively correlated to aEEG span while IBI, alpha, beta, and theta frequencies' amplitude were positively correlated to the aEEG span. CONCLUSIONS: Important information is retained and integrated in the transformation of premature neonatal EEG to aEEG. SIGNIFICANCE: aEEG recordings in high-risk premature neonates reflect reliably EEG background information related to continuity and amplitude.

In and ex utero maturation of premature infants electroencephalographic indices.

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<0.004). No significant differences were detected between the different groups. 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.

Influence of respiratory acidosis and blood glucose on cerebral activity of premature infants.

Fluctuations of physiologic parameters in extremely preterm infants may significantly affect their cerebral activity. This study assessed the correlation between blood gas indices and other clinical parameters with cerebral activity, as recorded by amplitude integrated electroencephalography in the first three days of life of a prospective cohort study of infants born at <28 weeks gestation. Amplitude integrated electroencephalography was assessed according to a nine-grade pattern scale. For univariate analysis, the Spearman rank coefficient, Student t test, and χ(2) test were used. For multivariate analysis, generalized estimating equations were used. Overall, 255 blood samples from 24 recruited infants were analyzed. The pattern scale demonstrated a significant positive correlation with pH (ρ = 0.45, P < 0.0001) and base excess (ρ = 0.37, P < 0.0001), and a significant negative correlation with partial pressure of carbon dioxide (pCO(2)) (ρ = -0.35, P < 0.0001) and blood dextrose (ρ = -0.36, P < 0.0001). When amplitude integrated electroencephalography was used as dependent variable, the best generalized estimating equation models yielded significant correlations for pH, pCO(2), and HCO(3)(-). When pH was used as dependent variable, the best models yielded significant correlations for amplitude integrated electroencephalography pattern scale and blood dextrose. We suggest that depression in cerebral function early in life should prompt clinicians to assess acid/base status and respiratory parameters of the extremely premature infant as well as other known causes of cerebral depression.

Neonatal seizure recognition--comparative study of continuous-amplitude integrated EEG versus short conventional EEG recordings.

OBJECTIVES: This study aims to detect seizures by amplitude-integrated electroencephalography (EEG) (aEEG) as compared with conventional EEG (cEEG) by clinicians with different levels of expertise. METHODS: Simultaneous 10 min aEEG/cEEG recordings were time-locked and assessed for seizure activity. aEEG was assessed by a neonatologist, a fellow and a medical student and cEEG by two child neurologists and a neonatologist. RESULTS: A total of 265 paired epochs from 38 simultaneous recording were assessed. Forty-one seizure episodes were diagnosed in 31 epochs in the cEEG recordings of 10 infants. Sensitivity and specificity ranged from 68% to 84% and from 71% to 84%, respectively, per detection of epochs with seizures and from 71% to 84% and from 36% to 96% per detection of individual seizures. No agreement was found between the observations of the student, and those of the fellow or neonatologist. Substantial agreement was found between the fellow and neonatologist. Before cEEG was commenced, seizures were detected by aEEG in 22 infants. CONCLUSIONS: aEEG has high sensitivity and specificity in the hands of experienced users. Inexperienced new users may have a high rate of misdiagnosed seizures. Early recording of high-risk infants can help in the early diagnosis and treatment of seizures. SIGNIFICANCE: Diagnosis and treatment of seizures in aEEG should be carried out by experienced users and should be supplemented with cEEG when available.