Can EEG accurately predict 2-year neurodevelopmental outcome for preterm infants?

OBJECTIVE: Establish if serial, multichannel video electroencephalography (EEG) in preterm infants can accurately predict 2-year neurodevelopmental outcome. DESIGN AND PATIENTS: EEGs were recorded at three time points over the neonatal course for infants <32 weeks' gestational age (GA). Monitoring commenced soon after birth and continued over the first 3 days. EEGs were repeated at approximately 32 and 35 weeks' postmenstrual age (PMA). EEG scores were based on an age-specific grading scheme. Clinical score of neonatal morbidity risk and cranial ultrasound imaging were completed. SETTING: Neonatal intensive care unit at Cork University Maternity Hospital, Ireland. MAIN OUTCOME MEASURES: Bayley Scales of Infant Development III at 2 years' corrected age. RESULTS: Sixty-seven infants were prospectively enrolled in the study and 57 had follow-up available (median GA 28.9 weeks (IQR 26.5-30.4)). Forty had normal outcome, 17 had abnormal outcome/died. All EEG time points were individually predictive of abnormal outcome; however, the 35-week EEG performed best. The area under the receiver operating characteristic curve (AUC) for this time point was 0.91 (95% CI 0.83 to 1), p<0.001. Comparatively, the clinical course AUC was 0.68 (95% CI 0.54 to 0.80, p=0.015), while abnormal cranial ultrasound was 0.58 (95% CI 0.41 to 0.75, p=0.342). CONCLUSION: Multichannel EEG is a strong predictor of 2-year outcome in preterm infants particularly when recorded around 35 weeks' PMA. Infants at high risk of brain injury may benefit from early postnatal EEG recording which, if normal, is reassuring. Postnatal clinical complications can contribute to poor outcome; therefore, we state that a later EEG around 35 weeks has a role to play in prognostication.

Mathematical Analysis of EEG Concordance in Preterm Twin Infants.

PURPOSE: Preterm twins are at higher risk of neurodisability than preterm singletons, with monochorionic-diamniotic (MCDA) twins at higher risk than dichorionic-diamniotic (DCDA) twins. The impact of genetic influences on EEG concordance in preterm twins <32 weeks of gestational age is not established. This study aims to investigate EEG concordance in preterm MCDA and dichorionic-diamniotic twins during maturation. METHODS: Infants <32 weeks of gestational age had multichannel EEG recordings for up to 72 postnatal hours, with repeat recordings at 32 and 35 weeks of postmenstrual age. Twin pairs had synchronous recordings. Mathematical EEG features were generated to represent EEG power, discontinuity, and symmetry. Intraclass correlations, while controlling for gestational age, estimated similarities within twins. RESULTS: EEGs from 10 twin pairs, 4 MCDA and 6 dichorionic-diamniotic pairs, and 10 age-matched singleton pairs were analyzed from a total of 36 preterm infants. For MCDA twins, 17 of 22 mathematical EEG features had significant (>0.6; P < 0.05) intraclass correlations at one or more time points, compared with 2 of 22 features for DCDA twins and 0 of 22 for singleton pairs. For MCDA twins, all 10 features of discontinuity and all four features of symmetry were significant at one or more time-points. Three features of the MCDA twins (spectral power at 3-8 Hz, EEG skewness at 3-15 Hz, and kurtosis at 3-15 Hz) had significant intraclass correlations over all three time points. CONCLUSIONS: Preterm twin EEG similarities are subtle but clearly evident through mathematical analysis. MCDA twins showed stronger EEG concordance across different postmenstrual ages, thus confirming a strong genetic influence on preterm EEG activity at this early development stage.

A standardised assessment scheme for conventional EEG in preterm infants.

OBJECTIVE: To develop a standardised scheme for assessing normal and abnormal electroencephalography (EEG) features of preterm infants. To assess the interobserver agreement of this assessment scheme. METHODS: We created a standardised EEG assessment scheme for 6 different post-menstrual age (PMA) groups using 4 EEG categories. Two experts, not involved in the development of the scheme, evaluated this on 24 infants <32 weeks gestational age (GA) using random 2 hour EEG epochs. Where disagreements were found, the features were checked and modified. Finally, the two experts independently evaluated 2 hour EEG epochs from an additional 12 infants <37 weeks GA. The percentage of agreement was calculated as the ratio of agreements to the sum of agreements plus disagreements. RESULTS: Good agreement in all patients and EEG feature category was obtained, with a median agreement between 80% and 100% over the 4 EEG assessment categories. No difference was found in agreement rates between the normal and abnormal features (p = 0.959). CONCLUSIONS: We developed a standard EEG assessment scheme for preterm infants that shows good interobserver agreement. SIGNIFICANCE: This will provide information to Neonatal Intensive Care Unit (NICU) staff about brain activity and maturation. We hope this will prove useful for many centres seeking to use neuromonitoring during critical care for preterm infants.

Electrographic Seizures during the Early Postnatal Period in Preterm Infants.

OBJECTIVE: To investigate the frequency and characteristics of electrographic seizures in preterm infants in the early postnatal period. STUDY DESIGN: Infants <32 weeks gestational age (GA) (n = 120) were enrolled for continuous multichannel electroencephalography (EEG) recording initiated as soon as possible after birth and continued for approximately up to 72 hours of age. Electrographic seizures were identified visually, annotated, and analyzed. Quantitative descriptors of the temporal evolution of seizures, including total seizure burden, seizure duration, and maximum seizure burden, were calculated. RESULTS: Median GA was 28.9 weeks (IQR, 26.6-30.3 weeks) and median birth weight was 1125 g (IQR, 848-1440 g). Six infants (5%; 95% CI, 1.9-10.6%) had electrographic seizures. Median total seizure burden, seizure duration, and maximum seizure burden were 40.3 minutes (IQR, 5.0-117.5 minutes), 49.6 seconds (IQR, 43.4-76.6 seconds), and 10.8 minutes/hour (IQR, 1.6-20.2 minutes/hour), respectively. Seizure burden was highest in 2 infants with significant abnormalities on neuroimaging. CONCLUSION: Electrographic seizures are infrequent within the first few days of birth in very preterm infants. Seizures in this population are difficult to detect accurately without continuous multichannel EEG monitoring.

Heart rate variability in hypoxic ischemic encephalopathy during therapeutic hypothermia.

BACKGROUND: Therapeutic hypothermia (TH) aims to ameliorate further injury in infants with moderate and severe hypoxic ischemic encephalopathy (HIE). We aim to assess the effect of TH on heart rate variability (HRV) in infants with HIE. METHODS: Multichannel video-electroencephalography (EEG) and electrocardiography were assessed at 6-72 h after birth in full-term infants with HIE, recruited prior to (pre-TH group) and following (TH group) the introduction of TH in our neonatal unit. HIE severity was graded using EEG. HRV features investigated include: mean NN interval (mean NN), standard deviation of NN interval (SDNN), triangular interpolation (TINN), high-frequency (HF), low-frequency (LF), very low-frequency (VLF), and LF/HF ratio. Linear mixed model comparisons were used. RESULTS: 118 infants (pre-TH: n = 44, TH: n = 74) were assessed. The majority of HRV features decreased with increasing EEG grade. Infants with moderate HIE undergoing TH had significantly different HRV features compared with the pre-TH group (HF: P = 0.016, LF/HF ratio: P = 0.006). In the pre-TH group, LF/HF ratio was significantly different between moderate and severe HIE grades (P = 0.002). In the TH group, significant differences were observed between moderate and severe HIE grades for SDNN: P = 0.020, TINN: P = 0.005, VLF: P = 0.029, LF: P = 0.010, and HF: P = 0.006. CONCLUSION: The HF component of HRV is increased in infants with moderate HIE undergoing TH.

Predicting 2-y outcome in preterm infants using early multimodal physiological monitoring.

BACKGROUND: Preterm infants are at risk of adverse outcome. The aim of this study is to develop a multimodal model, including physiological signals from the first days of life, to predict 2-y outcome in preterm infants. METHODS: Infants <32 wk gestation had simultaneous multi-channel electroencephalography (EEG), peripheral oxygen saturation (SpO2), and heart rate (HR) monitoring. EEG grades were combined with gestational age (GA) and quantitative features of HR and SpO2 in a logistic regression model to predict outcome. Bayley Scales of Infant Development-III assessed 2-y neurodevelopmental outcome. A clinical course score, grading infants at discharge as high or low morbidity risk, was used to compare performance with the model. RESULTS: Forty-three infants were included: 27 had good outcomes, 16 had poor outcomes or died. While performance of the model was similar to the clinical course score graded at discharge, with an area under the receiver operator characteristic (AUC) of 0.83 (95% confidence intervals (CI): 0.69-0.95) vs. 0.79 (0.66-0.90) (P = 0.633), the model was able to predict 2-y outcome days after birth. CONCLUSION: Quantitative analysis of physiological signals, combined with GA and graded EEG, shows potential for predicting mortality or delayed neurodevelopment at 2 y of age.

Heart rate variability in hypoxic ischemic encephalopathy: correlation with EEG grade and 2-y neurodevelopmental outcome.

BACKGROUND: The study aims to describe heart rate variability (HRV) in neonatal hypoxic ischemic encephalopathy (HIE) and correlate HRV with electroencephalographic (EEG) grade of HIE and neurodevelopmental outcome. METHODS: Multichannel EEG and electrocardiography (ECG) were assessed at 12-48 h after birth in healthy and encephalopathic full-term neonates. EEGs were graded (normal, mild, moderate, and severe). Neurodevelopmental outcome was assessed at 2 y of age. Seven HRV features were calculated using normalized-RR (NN) interval. The correlation of these features with EEG grade and outcome were measured using Spearman's correlation coefficient. RESULTS: HRV was significantly associated with HIE severity (P < 0.05): standard deviation of NN interval (SDNN) (r = -0.62), triangular interpolation of NN interval histogram (TINN) (r = -0.65), mean NN interval (r = -0.48), and the very low frequency (VLF) (r = -0.60), low frequency (LF) (r = -0.67) and high frequency (HF) components of the NN interval (r = -0.60). SDNN at 24 and 48 h were significantly associated (P < 0.05) with neurodevelopmental outcome (r = -0.41 and -0.54, respectively). CONCLUSION: HRV is associated with EEG grade of HIE and neurodevelopmental outcome. HRV has potential as a prognostic tool to complement EEG.

Global suppression of electrocortical activity in unilateral perinatal thalamic stroke.

We present an unusual case of persistent generalized electroencephalography (EEG) suppression and right-sided clonic seizures in a male infant born at 40(+2) weeks' gestation, birthweight 3240g, with an isolated unilateral thalamic stroke. The EEG at 13 hours after birth showed a generalized very low amplitude background pattern, which progressed to frequent electrographic seizures over the left hemisphere. The interictal background EEG pattern remained grossly abnormal over the next 48 hours, showing very low background amplitudes (<10µV). Magnetic resonance imaging revealed an isolated acute left-sided thalamic infarction. This is the first description of severe global EEG suppression caused by an isolated unilateral thalamic stroke and supports the role of the thalamus as the control centre for cortical electrical activity.

Neurologic outcomes in very preterm infants undergoing surgery.

OBJECTIVE: To investigate the relationship between surgery in very preterm infants and brain structure at term equivalent and 2-year neurodevelopmental outcome. STUDY DESIGN: A total of 227 infants born at <30 weeks gestation or at a birth weight of <1250 g were prospectively enrolled into a longitudinal observational cohort for magnetic resonance imaging and developmental follow-up. The infants were categorized retrospectively into either a nonsurgical group (n=178) or a surgical group (n=30). Nineteen infants were excluded because of incomplete or unsuitable data. The surgical and nonsurgical groups were compared in terms of clinical demographic data, white matter injury, and brain volume at term. Neurodevelopmental outcome was assessed at age 2 years. RESULTS: Compared with the nonsurgical group, the infants in the surgical group were smaller and more growth-restricted at birth, received more respiratory support and oxygen therapy, and had longer hospital stays. They also had smaller brain volumes, particularly smaller deep nuclear gray matter volumes. Infants who underwent bowel surgery had greater white matter injury. Mental Developmental Index scores were lower in the surgical group, whereas Psychomotor Developmental Index scores did not differ between the groups. The Mental Developmental Index difference became nonsignificant after adjustment for confounding variables. CONCLUSION: Preterm infants exposed to surgery and anesthesia had greater white matter injury and smaller total brain volumes, particularly smaller deep nuclear gray matter volumes. Surgical exposure in the preterm infant should alert the clinician to an increased risk for adverse cognitive outcome.

Single versus bihemispheric amplitude-integrated electroencephalography in relation to cerebral injury and outcome in the term encephalopathic infant.

BACKGROUND: The demand for early diagnosis and prognostication of cerebral injury in the encephalopathic term infant is increasing to facilitate appropriate management. The single-channel amplitude-integrated electroencephalogram (S-aEEG) has been shown to have predictive utility for the severely encephalopathic infant. New bedside aEEG devices with more channels are entering the neonatal environment. Little data are available to compare the utility of two channels (B-aEEG) with that of an S-aEEG recording. AIM: To compare the utility of the S-aEEG and the B-aEEG in the prediction of cerebral injury, as determined by magnetic resonance imaging (MRI), and neurodevelopmental outcome in the term encephalopathic infant. METHODS: Term encephalopathic infants, with or without seizures, admitted to a level III NICU were included in this study. These infants had simultaneous S-aEEG and B-aEEG recordings. MRI was undertaken during the clinical course and classified as to the extent of cerebral injury. Neurological outcome was assessed at 2 years of age. RESULTS: Twenty-eight encephalopathic term infants were included in the study. There was high level of agreement between both brain monitors (Kappa = 0.68, P < 0.001), but there was disagreement in the classification in four cases where the S-aEEG was normal when the B-aEEG was severely abnormal (McNemar's test P = 0.046). Of note in these four cases, all had a severely abnormal MRI and poor neurodevelopmental outcome at 2 years. CONCLUSION: Amplitude measurements by the B-aEEG appear more sensitive in detecting cerebral injury in comparison with the S-aEEG, particularly in the setting of unilateral injury.

Monitoring the neonatal brain: a survey of current practice among Australian and New Zealand neonatologists.

AIMS: There is considerable variation in the use of brain imaging and electrophysiological monitoring of encephalopathic term infants. The aims of this study were (i) to document the current practice among Australian and New Zealand neonatologists; and (ii) to identify the factors that influence local practice. METHODS: A postal questionnaire was sent to all 152 neonatologists in Australia and New Zealand. A hypothetical scenario of an encephalopathic term infant was presented and clinicians were asked a series of questions relating to their use of magnetic resonance imaging (MRI), computed tomography, ultrasound, electroencephalography and amplitude integrated electroencephalography. RESULTS: There was a 62% response rate. Twenty-two per cent of respondents would not routinely perform an MRI brain scan in the given scenario. Limited availability, expense, logistics of transport and a lack of confidence in the ability of MRI to provide additional clinical information appear to be the main factors affecting practice. When a scan is performed, the majority of respondents (72%) perform the scan on day 5 or later. Twenty-three per cent of respondents experience significant delays when they request an MRI scan. Regarding electrophysiological monitoring, amplitude integrated electroencephalography would be used by 62% of respondents in the given scenario. CONCLUSIONS: This study demonstrates that MRI is now widely used by neonatologists in Australia and New Zealand. However, local resource limitations and a lack of confidence in the utility of MRI continue to limit its use.

Neonatal hypoglycemia and occipital cerebral injury.

Occipital brain injury associated with neonatal hypoglycemia can result in long-term disability, epilepsy, and visual impairment. The etiology of this pattern of injury is unclear; however, transient hyperinsulinism may be an independent risk factor. Magnetic resonance brain imaging can delineate the extent of brain injury and guide follow-up.

Combination pharmacotherapy for severe neonatal pulmonary hypertension.

Pulmonary hypertension can complicate the early clinical course in newborn infants with congenital diaphragmatic hernia. We report the successful use of combination therapy with enteral sildenafil and intravenous prostaglandin E1 in a preterm infant with severe pulmonary hypertension and right heart failure early after congenital diaphragmatic hernia repair.

Spontaneous liver hemorrhage during laparotomy for necrotizing enterocolitis: a potential role for recombinant factor VIIa.

Necrotizing enterocolitis remains a serious condition in very low birth weight infants, particularly in those infants who require surgery. Perioperative hemorrhage is a potentially fatal complication in this population. We describe our experience in 4 premature infants with necrotizing enterocolitis who received recombinant factor VIIa to manage life-threatening intraoperative hemorrhage.

An under-recognised malposition of neonatal long lines.

UNLABELLED: We report two cases of malposition of percutaneous central venous catheters into the left ascending lumbar vein. The level of awareness amongst clinicians of this potentially fatal complication appears to be low. CONCLUSION: The recognition of unusual patterns of contrast medium dispersal is important in the diagnosis of catheter malposition.