Predictive Value of Neonatal MRI Showing No or Minor Degrees of Brain Injury After Hypothermia

BackgroundMagnetic resonance imaging is a surrogate biomarker for major neurodevelopmental disabilities in survivors of perinatal hypoxic-ischemic encephalopathy because injury to the basal ganglia/thalami is highly predictive of major neuromotor and cognitive problems. Major disabilities and the appearance of neonatal magnetic resonance imaging are improved with therapeutic hypothermia. We evaluated neurodevelopmental outcomes when conventional magnetic resonance imaging showed minimal or no brain injury.MethodsInstitutional review board–approved series of 62 infants (≥36 weeks; ≥1800 g; 34 boys/28 girls) cooled for hypoxic-ischemic encephalopathy between 2005 and 2011 who underwent neonatal magnetic resonance imaging and Bayley Scales of Infant and Toddler Development-III at 22 ± 7 months of age. Magnetic resonance imaging at 5-14 (mean 8) days was scored as normal (score = 0), showing focal gray or white matter injury only (score = 1), or basal ganglia/thalamic and/or watershed lesions with or without more extensive hemispheric injury (score = 2). Sensitivity, specificity, and positive and negative predictive values for magnetic resonance scores 0 and 1 and statistical interaction between magnetic resonance imaging score and age at magnetic resonance imaging were determined.ResultsMagnetic resonance score = 0 was seen in 35/62 patients; 26/35 (74%) were typically developing, seven (20%) had moderate and two (6%) had severe delay. Magnetic resonance score = 1 was seen in 17/62 (27%) patients; 5/17 (29%) were normal, 11/17 (65%) had moderate delay, and 1/17 (6%) had severe neurodevelopmental delay. Of the 52 patients with magnetic resonance scores of 0 and 1, 40% were abnormal. The negative predictive value of a normal magnetic resonance imaging was 74%. For score 1, sensitivity was 95% (confidence interval 63%-83%), specificity 84% (confidence interval 70%-90%), positive predictive value 84% (confidence interval 71%-93%), and negative predictive value 74% (confidence interval 62%-82%).ConclusionsCaution is warranted when prognosticating about neurodevelopmental status in early childhood after hypoxic ischemic encephalopathy with cooling, and longer follow-up studies are needed to determine the prognostic significance of a neonatal magnetic resonance imaging showing no or minor degrees of brain injury.     

Neuroimaging in cerebral palsy: Patterns of brain dysgenesis and injury

Despite advances in obstetric and neonatal care, the overall prevalence of cerebral palsy has remained stable, supporting the belief that pathogenesis is primarily due to prenatal brain dysgenesis and injury. Neuroimaging studies have consistently shown abnormalities in 70% to 90% of affected children, facilitating clinical classification into groups with early brain malformations, white-matter injury, neonatal encephalopathies, and a heterogeneous group of postnatally acquired disorders. White-matter injury, well seen on conventional magnetic resonance imaging (MRI), is the leading cause of cerebral palsy in children born preterm. As many as 20% of very low birthweight infants have cystic and/or diffuse white-matter injury, termed periventricular leukomalacia, with evidence of associated pathology in other cortical and subcortical structures. In the group with acute, term perinatal pathology, a variety of imaging modalities, in addition to MRI, have diagnostic utility. In general, when added to conventional MRI, advanced techniques, such as diffusion tensor imaging, diffusion-weighted imaging, and magnetic resonance spectroscopy, provide a more complete picture of structural and functional brain abnormalities. The results have led to improved understanding of pathogenesis, especially in regard to periventricular leukomalacia and hypoxic-ischemic encephalopathy. This information might lead to interventions preventing brain injury in preterm infants and asphyxiated term newborns.     

Sequential MRI in two cases with periventricular leukomalacia

We investigated two children with cystic periventricular leukomalacia, which we had detected by ultrasonography (US) during the neonatal period, with magnetic resonance imaging (MRI) of the brain at 4, 9, and 15 or 19 corrected months of age. Both inversion-recovery (IR) and T2-weighted spin-echo (SE) sequences were used for this study. We observed cysts involving the periventricular white matter at the region adjacent to bilateral frontal horns in case 1 and adjacent to the posterior horns of the lateral ventricles in case 2. MRI at 4 months showed the irregularity of the ventricular wall and delayed myelination, compared to that of an age-matched control. The T2-weighted SE and IR imaging at 9 months demonstrated abnormally increased signal in the white matter. These findings were more evident at the 3rd MRI examination. The location of end-stage periventricular leukomalacia lesions were consistent with the distribution of cystic lesions seen on US. MRI at sagittal sections was useful for the detection of main periventricular leukomalacia lesions. A possibility exists that MRI might be useful in detecting subtle lesions of periventricular leukomalacia in which we cannot find by US.     

Quantitative cranial magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy

The volume of acute injury detected by diffusion-weighted imaging and quantitative brain growth on serial cranial magnetic resonance imaging was not previously used to predict neurodevelopmental outcomes in infants with neonatal hypoxic-ischemic encephalopathy treated with head cooling. Our longitudinal study involved 16 head-cooled term infants with hypoxic-ischemic encephalopathy who underwent early and follow-up cranial magnetic resonance imaging and follow-up neurologic evaluations, out of 105 infants who received therapeutic hypothermia. The volume of acute injury was measured on initial cranial magnetic resonance imaging, using diffusion-weighted images. Total brain volumes were measured in both early and follow-up magnetic resonance imaging studies. Acute injury volume in the corpus callosum >0.5 cm(3) was associated with developing epilepsy (odds ratio, 20; 95% confidence interval, 1.01-1059.6; P = 0.013). Follow-up whole brain volume was reduced in those with unfavorable outcomes (i.e., epilepsy, cerebral palsy, and delayed developmental milestones), compared with infants without all three outcomes. Although acute brain injury volume and brain growth measurements may be useful predictors of outcomes in neonatal hypoxic-ischemic encephalopathy, the evolution of brain injury in these infants has yet to be fully understood and should be studied prospectively.     

Prognostic correlative values of the late-infancy MRI pattern in term infants with perinatal asphyxia

The aim of this study was to define the risk ratios of the late-infancy magnetic resonance imaging pattern for long-term outcome in term infants with perinatal asphyxia. We evaluated 65 term infants with perinatal asphyxia and performed magnetic resonance imaging examinations between 4-12 months of age. Magnetic resonance imaging scans were classified as follows: (1) periventricular leukomalacia in 21 (32%) infants, (2) marked cortical atrophy in 17 (26%) infants, (3) multicystic encephalomalacia in 10 (15%) infants, (4) deep gray matter involvement in 8 (12%) infants, (5) focal cortical involvement in 6 (9%) infants, (6) myelination delay in 3 (5%) infants. The overall outcome was favorable in 19 (29%) of 65 infants. Infants with diffuse cortical involvement (multicystic encephalomalacia and marked cortical atrophy) are four times (odds ratio: 4.4 and 4.1 respectively) more likely to attain the unfavorable outcome than the infants with other patterns of magnetic resonance imaging. Infants with focal cortical involvement had relatively favorable outcome in 60% of the cases. In conclusion, it appears that the overall outcome of infants with perinatal asphyxia correlated well with the magnetic resonance imaging patterns obtained between 4 and 12 months of age.     

Imaging evolution and incidence of periventricular leukomalacia in preterm infants]

During five years from 1985 to 1989, serial brain echography was performed in 399 preterm infants with gestation less than 35 weeks at Kitasato University Hospital. Twenty-eight (7.0%) infants without periventricular hemorrhage were revealed as having spastic cerebral palsy by neurodevelopmental evaluation in later infancy. Of these 28 infants, the following neonatal brain echographic findings were obtained; cystic periventricular leukomalacia in 14, and persistent periventricular echogenicity without cystic formation in 4. However, neonatal brain echograms were completely normal in 10 infants. Magnetic resonance (MR) studies were performed to find cerebral lesions in all 28 infants. Periventricular high intensity areas on T2 weighted images, irregularity of ventricular wall, ventricular dilatation, decreased volume in periventricular white matter and thinning of the posterior body of corpus callosum were common findings in those infants, and compatible with the MR findings of periventricular leukomalacia (PVL). Therefore our infants with no brain echo abnormality might have had small PVL lesions not detected by brain echography. The reliability of brain echography is still controversial in the diagnosis of nonhemorrhagic PVL. Careful follow up is essential even in the infant with no brain echo abnormality.     

Neuron-specific enolase levels and neuroimaging in asphyxiated term newborns

The study was designed to investigate the cerebrospinal fluid and serum levels of neuron-specific enolase, along with cranial ultrasonography, magnetic resonance imaging (MRI), and electroencephalography (EEG), for predicting the clinical state and neurologic outcome of 26 asphyxiated term newborns. The babies were graded according to the Sarnat and Sarnat classification. Cerebrospinal fluid neuron-specific enolase levels of the 18 babies in the whole hypoxic-ischemic encephalopathy group were higher than the 8 babies in the "no encephalopathy" group. Cerebrospinal fluid neuron-specific enolase levels of 13 cases in the hypoxic-ischemic encephalopathy grade 2 and 3 groups (high-risk group) were higher than both the no encephalopathy and hypoxic-ischemic encephalopathy grade 1 groups when pooled. Cerebrospinal fluid neuron-specific enolase levels of the 7 newborns in the hypoxic-ischemic encephalopathy grade 3 group were also significantly higher than the 5 in the hypoxic-ischemic encephalopathy grade 1 group. The findings of cranial MRI, EEG, and cerebrospinal fluid neuron-specific enolase levels were correlated with each other and the clinical grade of the patients and also were predictive of the neurologic outcome at 1 year of age. Cerebrospinal fluid neuron-specific enolase levels, cranial MRI, and EEG are predictive of outcome of hypoxic-ischemic brain damage in asphyxiated newborns, and this predictivity would increase with the combination of these diagnostic parameters.     

Neurodevelopmental outcome of children with evidence of periventricular leukomalacia on late MRI

Fifteen children, 8 months of age or older, from a neonatal follow-up program underwent magnetic resonance imaging and neurologic, cognitive, and language evaluations. Magnetic resonance imaging findings in all children included increased white matter signal on T2-weighted images and ventricular enlargement adjacent to regions of abnormal white matter. The extent of degree of abnormal white matter signal and the degree of sulcal prominence were variable. Twelve children had cerebral palsy; 5 children, 4 of whom had cerebral palsy, manifested significant sensory impairments. The median score on cognitive testing was 89; only 2 children exhibited severe-to-profound cognitive disability. Cognitive scores were stable on retesting. The degree of motor disability was correlated with the extent of white matter signal abnormality; however, cognitive outcome was not related to the extent and degree of white matter signal abnormality or to the degree of sulcal prominence. Despite the association of a major handicapping condition and periventricular leukomalacia, cognitive and language functioning may be relatively spared.     

Magnetic resonance imaging of periventricular leukomalacia and its clinical correlation in children

The prevalence of periventricular leukomalacia and its association with clinical neurological signs in school-age preterm children are unknown. We matched 42 eight-year-old children who were born before term with birth weights lower than 1,750 gm (mean, 1,410 gm; gestational age, 31 weeks) with 42 children who were born at term and of normal birth weight, to compare clinical neurological status and magnetic resonance imaging findings. Of the children born prematurely, 9.5% had cerebral palsy and 31% had minor neurological dysfunction whereas 9% of the children born at term had minor neurological dysfunction and none had cerebral palsy. Deviations in tongue movements, heel walking, Fogs test results, and finger opposition, as well as behavioral disturbances, differentiated the preterm from the full-term group. The prevalence of periventricular leukomalacia among all children born prematurely was 32%. It was observed in all children with cerebral palsy, in 25% with minor neurological dysfunction, and in 25% of the clinically healthy preterm children. None of the children born at term had evidence of periventricular leukomalacia. Children with periventricular leukomalacia especially demonstrated poor performance on heel walking and Fogs test. Though commonly found in preterm children, periventricular leukomalacia is not uniformly associated with abnormal neurological findings. A through neurological examination is a better predictor of later developmental problems than is magnetic resonance imaging.     

Effect of erythropoietin combined with hypothermia on serum tau protein levels and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy

Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy, many neonatal patients die or suffer from severe neurological dysfunction. Erythropoietin is considered one of the most promising neuroprotective agents. We hypothesized that erythropoietin combined with hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy treatment. In this study, 41 neonates with moderate/severe hypoxic-ischemic encephalopathy were randomly divided into a control group (hypothermia alone for 72 hours, n = 20) and erythropoietin group (hypothermia + erythropoietin 200 IU/kg for 10 days, n = 21). Our results show that compared with the control group, serum tau protein levels were lower and neonatal behavioral neurological assessment scores higher in the eryth-ropoietin group at 8 and 12 days. However, neurodevelopmental outcome was similar between the two groups at 9 months of age. Thesefindings suggest that erythropoietin combined with hypothermia reduces serum tau protein levels and improves neonatal behavioral neu-rology outcome but does not affect long-term neurodevelopmental outcome.     

Diffusion-weighted imaging in neonatal cerebral infarction: clinical utility and follow-up

We describe the clinical utility of echo-planar diffusion-weighted imaging in neonatal cerebral infarction. Eight full-term neonates aged 1 to 8 days referred for neonatal seizures were studied. Patients were followed for a mean of 17 months with detailed neurologic examinations at regular intervals. Head computed tomography (CT) and conventional magnetic resonance (MRI) and diffusion-weighted images were obtained. Percent lesion contrast was evaluated for 19 lesions on T2-weighted and diffusion-weighted images. Follow-up conventional MRIs were obtained in seven patients. The findings on diffusion-weighted imaging were correlated with CT and conventional MRI findings as well as with short-term neurodevelopmental outcome. Four patients had focal cerebral infarctions. Four patients had diffuse injury consistent with hypoxic-ischemic encephalopathy. Percent lesion contrast of all 19 lesions was significantly higher on diffusion-weighted images when compared with T2-weighted images. In five patients, there were lesions visualized only with diffusion-weighted imaging. In all patients, there was increased lesion conspicuity and better definition of lesion extent on the diffusion-weighted images compared with the CT and T2-weighted MR images. In seven of eight patients follow-up imaging confirmed prior infarctions. Short-term neurologic outcome correlated with the extent of injury seen on the initial diffusion-weighted imaging scans for all patients. Diffusion-weighted imaging is useful in the evaluation of acute ischemic brain injury and seizure etiology in neonates. In the acute setting, diffusion-weighted imaging provides information not available on CT and conventional MRI. This information correlates with short-term clinical outcome.     

Brain diffusivity in infants with hypoxic-ischemic encephalopathy following whole body hypothermia: preliminary results

Hypoxic-ischemic encephalopathy is an important cause of neuropsychological deficits. Little is known about brain diffusivity in these infants following cooling and its potential in predicting outcome. Diffusion tensor imaging was applied to 3 groups: (1) three infants with hypoxic-ischemic encephalopathy: cooled; (2) three infants with hypoxic-ischemic encephalopathy: noncooled; and (3) four controls. Diffusivity values at the corticospinal tract, thalamus, and putamen were correlated with Apgar scores and early neurodevelopmental outcome. While cooled infants exhibited lower Apgar scores than noncooled infants, their developmental scores at a mean age of 8 months were higher. All groups differed in their diffusivity values with the cooled infants showing better values compared with the noncooled, correlating with early neurodevelopmental outcome. These preliminary results indicate that diffusion tensor imaging performed at an early age in infants with hypoxic-ischemic encephalopathy may forecast clinical outcome and support the neuroprotective effect of hypothermia treatment.     

Predictive value of neonatal MRI with respect to late MRI findings and clinical outcome. A study in infants with periventricular densities on neonatal ultrasound

PURPOSE: The aim of this study was to correlate hypoxic-ischemic white matter damage on neonatal MRI with MRI appearance and neurological outcome at the age of 1 1/2 years. PATIENTS AND METHODS: A sequential cohort of infants with periventricular densities on neonatal ultrasound was studied with neonatal MRI. Images of 46 infants with a mean gestational age of 31 weeks were obtained at a mean age of 20 days after birth and at 1 1/2 years. To establish agreement between the neonatal and follow-up MRI (general, motor, and visual scores), the weighted Cohen's kappa test was used. To establish the predictive power of neonatal MRI with respect to the neurologic indices at the age of 1 1/2 years, the sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: There was a moderately good to good agreement between the general, motor, and visual neonatal and follow-up MRI scores: weighted kappa = 0.59 (95% CI: 0.44 - 0.74), 0.82 (95% CI: 0.72 - 0.93), and 0.70 (95% CI: 0.56 - 0.84), respectively. Neonatal MRI scores provided a good prediction of the three neurological outcome measures (developmental delay, cerebral palsy, and cerebral visual impairment): sensitivity, specificity, and predictive values were high, with little difference between the three MRI scores. The 32 patients with (nearly) normal neonatal MRI scores were neurologically (nearly) normal at 1 1/2 years on all three outcome measures, whereas 8 patients with seriously abnormal neonatal MRI scores were neurologically abnormal at 1 1/2 years on all three outcome measures. CONCLUSION: Neonatal MRI is able to predict the precise localization and size of perinatal leukomalacia on follow-up MRI and provides a good prediction of neurological outcome at 1 1/2 years.     

Magnetic resonance imaging in 122 children with spastic cerebral palsy

The interrelationship between magnetic resonance imaging findings, types of cerebral palsy, and gestation was studied. We analyzed the magnetic resonance imaging of brain in 122 children with spastic cerebral palsy. Forty-three patients had spastic hemiplegia, 61 had spastic diplegia, and 18 had spastic tetraplegia. Magnetic resonance imaging abnormalities were observed in 75% of patients. Periventricular leukomalacia accounted for 66% of abnormalities observed in patients with spastic diplegia; other types of brain lesions were uncommon. In patients with spastic tetraplegia, two types of magnetic resonance imaging abnormalities predominated: congenital brain anomalies and term-type brain injuries, 42% and 33% respectively. Types of magnetic resonance imaging abnormalities were more heterogeneous in patients with spastic hemiplegia. Preterm brain injuries (periventricular leukomalacia and posthemorrhagic porencephaly) were observed often in patients born at preterm but were also observed in patients born at term. Term-type brain injuries (term-type border-zone infarct, basal ganglia-thalamic lesion, subcortical leukomalacia, and multicystic encephalomalacia) were observed only in patients born at or near term. We conclude that magnetic resonance imaging findings for patients with spastic cerebral palsy were closely related to types of cerebral palsy and gestation at birth. Magnetic resonance imaging in patients with perinatal brain injury may reflect pathologic changes and is useful in understanding and evaluating cerebral palsy.     

Neonatal encephalopathy: An inadequate term for hypoxic-ischemic encephalopathy

This Point of View article addresses neonatal encephalopathy (NE) presumably caused by hypoxia-ischemia and the terminology currently in wide use for this disorder. The nonspecific term NE is commonly utilized for those infants with the clinical and imaging characteristics of neonatal hypoxic-ischemic encephalopathy (HIE). Multiple magnetic resonance imaging studies of term infants with the clinical setting of presumed hypoxia-ischemia near the time of delivery have delineated a topography of lesions highly correlated with that defined by human neuropathology and by animal models, including primate models, of hypoxia-ischemia. These imaging findings, coupled with clinical features consistent with perinatal hypoxic-ischemic insult(s), warrant the specific designation of neonatal HIE. Ann Neurol 2012;72:156-166.     

EEG and ischemic stroke in full-term newborns]

The aims of this study were to describe EEG anomalies in unilateral neonatal ischemic stroke without hypoxic-ischemic encephalopathy, and to determine possible links between these abnormalities and long-term outcome. In 6 full-term newborns without severe fetal distress ischemic stroke was confirmed by computed tomography and/or magnetic resonance imaging. Twenty EEGs were recorded during the neonatal period, 5 in acute stage and 15 later. The duration of the follow-up ranged from 3 to 9 years. All newborns developed unilateral clonic seizures, right-sided (5 cases) or left-sided (1 case); seizures began between 14 and 48 h of life. At follow-up, 3 children were normal at 2 and 6 years of age, while the 3 others had sequelae: epilepsy at 9 years of age in one, and unilateral mild cerebral palsy in the 2 others (3 and 4 years of age), with behavioral problems in one of them. Critical EEG discharges, rhythmic sharp waves and/or slow waves were recorded on the injured side. Abnormalities of interictal activity were excess of alpha or theta rhythms, transitory EEG discontinuity or low voltage. The 2 children with cerebral palsy had numerous unilateral post-ictal positive rolandic slow sharp waves (PRSSWs), which were similar to the positive rolandic sharp waves of premature infants; the child with behavioral problems had numerous positive left-sided temporal fast sharp waves. PRSSWs could be associated with contralateral motor sequelae, while positive left temporal fast sharp waves were associated with long term behavioral problems. These findings may be used for future prospective studies aimed at specifying the relation between EEG abnormalities and long-term outcome.     

Gray matter heterotopia and acute necrotizing encephalopathy in trichothiodystrophy

Trichothiodystrophy was diagnosed in a 3-year-old male presenting with speech delay, brittle hair, chronic neutropenia, and a history of febrile convulsions. Cranial magnetic resonance imaging revealed a focal subcortical and periventricular gray matter heterotopia. An acute encephalopathy with status epilepticus and coma occurred when he was 4 years of age during an upper respiratory tract infection. Magnetic resonance imaging revealed multifocal T₂-weighted hypersignal lesions involving mainly the thalami, hippocampi, midbrain, and pons. Analysis of cerebrospinal fluid revealed hyperproteinorachia without pleocytosis. Results of an extensive metabolic evaluation of this acute brain injury, resembling the syndrome of acute necrotizing encephalopathy of childhood described in Japan, were negative. Focal neuronal migration disorder and acute encephalopathy with symmetric thalamic involvement are newly described neurologic manifestations of syndromes with trichothiodystrophy, which suggests that these conditions may have a common genetic background.     

Diffusion-weighted images in neonatal cerebral hypoxic-ischemic injury

Diffusion-weighted images of magnetic resonance imaging, obtained by mapping apparent diffusion coefficients, are more sensitive than other magnetic resonance imaging sequences in the earliest detection of acute cytotoxic injury. The usefulness of diffusion-weighted images in focal ischemic brain injury has been documented in children and adults. We report eight full-term neonates with global cerebral hypoxic-ischemic injury and abnormalities on diffusion-weighted images. Distribution of diffusion-weighted imaging abnormalities in the eight neonates was consistent with global hypoxic-ischemic injury in full-term neonates, with diffuse cortical necrosis, border-zone infarcts, or basal ganglia/thalamic injury. Magnetic resonance imaging scans with diffusion-weighted images were obtained within the first 4 days of age in all eight neonates. In each patient, standard magnetic resonance imaging sequences substantially underestimated the extent of injury when compared with diffusion-weighted images in unmyelinated neonatal brains. Extensive injury bilaterally with basal ganglia and thalamic and widespread multifocal cortical injury correlated with a severe neurologic outcome. Lesser degrees of injury, limited to smaller sectors of cortical or border zone involvement, were associated with better neurologic outcome. The high sensitivity of diffusion-weighted images to map the extent of hypoxic-ischemic injury in neonates makes it a potentially useful tool for assessing future neuroprotective strategies for neonatal hypoxic-ischemic injury.     

Magnetic resonance imaging in children with bilateral spastic forms of cerebral palsy

We analyzed the relationship between magnetic resonance image findings in children with bilateral spastic cerebral palsy and its stages of severity in term and preterm children. Magnetic resonance image findings of 102 children (66 male and 36 female) with bilateral spastic cerebral palsy (median age, 2.5 years; range, 3 months to 15 years) were reevaluated. The study group consisted of children with confirmed perinatal asphyxia. Hypoxic-ischemic events were diagnosed in 64% of the children. Significant abnormalities relevant to cerebral palsy were evident on imaging in 85/102 (83%) children (in 77% of term and 93% of preterm children). Enlargement of the ventricles alone (48%) or accompanied by periventricular white-matter damage (25%) was the most frequent finding in term and preterm children, but was more highly expressed in preterm children (P < 0.05). White-matter damage was more often found in preterm children (P < 0.05). Enlargement of the lateral ventricles and periventricular leukomalacia may be attributable to ischemic damage to the neonatal brain. Significant correlations were found between magnetic resonance image findings and severity of cerebral palsy (P < 0.05). Detection of brain abnormalities in children with cerebral palsy may prove useful in prognoses as well as in medical consultations and management.     

Predictive value of amplitude-integrated electroencephalography pattern and voltage in asphyxiated term infants

The aim of this study was to correlate amplitude-integrated electroencephalography soon after birth with neurodevelopmental outcome in children who suffered from hypoxic-ischemic encephalopathy. Near term infants with hypoxic-ischemic encephalopathy and amplitude-integrated electroencephalography recording before 6 hours of age were included. Neurologic and cognitive outcome were assessed at 30 months of age and over. Outcome was correlated with either the pattern or voltage of the tracing. Thirty-nine infants were included. Eight died in the immediate neonatal period. At the age of 3 and 6 hours, sensitivity of low voltage to poor outcome was 33% and 42% respectively and of burst suppression pattern to poor outcome was 83% and 75% respectively. Association of voltage to outcome was significant only at 6 hours of age (P = 0.025). Association of pattern to outcome was significant both at 3 and 6 hours of age (P = 0.003, 0.008). These data on amplitude-integrated electroencephalography predictive value early in life were similar to previous studies. Burst suppression pattern, as early as 3 hours of age, is associated with poor outcome. At the age of 6 hours, both low voltage and burst suppression are associated with poor outcome. Pattern seems more sensitive than voltage.