The prognostic value of multivoxel magnetic resonance spectroscopy determined metabolite levels in white and grey matter brain tissue for adverse outcome in term newborns following perinatal asphyxia

Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia by providing ratios of metabolites, such as choline (Cho), creatine (Cr), N-acetyl aspartate (NAA) and lactate (Lact) [Cho/Cr, Lact/NAA, etc.]. The purpose of this study was to quantify the separate white and grey matter metabolites in a slab cranial to the ventricles and relate these to the outcome. A standard 2D-chemical shift imaging protocol was used for measuring a transverse volume of interest located cranial to the ventricles allowing for direct comparison of the metabolites in white and grey matter brain tissue in 24 term asphyxiated newborns aged 3 to 16 days. Cho, NAA and Lact showed significant differences between four subgroups of asphyxiated infants with more and less favourable outcomes. High levels of Cho and Lact in the grey matter differentiated non-survivors from survivors (P = 0.003 and P = 0.017, respectively). In perinatal asphyxia the levels of Cho, NAA and Lact in both white and grey matter brain tissue are affected. The levels of Cho and Lact measured in the grey matter are the most indicative of survival. It is therefore advised to include grey matter brain tissue in the region of interest examined by multivoxel MR spectroscopy. aEuro cent Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia. aEuro cent Choline and lactate levels in grey matter seem the best indicators of survival. aEuro cent Both grey and white matter should be examined during spectroscopy for perinatal asphyxia

Long-term neurological outcome of term-born children treated with two or more anti-epileptic drugs during the neonatal period

Background: Neonatal seizures may persist despite treatment with multiple anti-epileptic drugs (AEDs). Objective: To determine in term-born infants with seizures that required two or more AEDs, whether treatment efficacy and/or the underlying disorder were related to neurological outcome. Design/methods: We included 82 children (born 1998-2006) treated for neonatal seizures. We recorded mortality, aetiology of seizures, the number of AEDs required, achievement of seizure control, and amplitude-integrated-EEG (aEEG) background patterns. Follow-up consisted of an age-adequate neurological examination. Surviving children were classified as normal, having mild neurological abnormalities, or cerebral palsy (CP). Results: Forty-seven infants (57%) had status epilepticus. The number of AEDs was not related to neurological outcome. Treatment with three or four AEDs as opposed to two showed a trend towards an increased risk of a poor outcome, i.e., death or CP, odds ratio (OR) 2.74; 95% confidence interval (CI) 0.98-7.69; P=.055. Failure to achieve seizure control increased the risk of poor outcome, OR 6.77; 95%-CI 1.42-32.82, P=.016. Persistently severely abnormal aEEG background patterns also increased this risk. OR 3.19; 95%-CI 1.90-5.36; P Conclusions: In term-born infants with seizures that required two or more AEDs outcome was poorer if seizure control failed. The number of AEDs required to reach seizure control and seizure aetiology had limited prognostic value. (C) 2011 Elsevier Ireland Ltd. All rights reserved

Functional Outcome at School Age of Preterm Infants With Periventricular Hemorrhagic Infarction

OBJECTIVES. Our objective was to determine motor, cognitive, and behavioral outcome at school age in preterm children with periventricular hemorrhagic infarction and to identify cerebral risk factors for adverse outcome. METHODS. This was a prospective cohort study of all preterm infants who were <37 weeks' gestation, had periventricular hemorrhagic infarction, and were admitted between 1995 and 2003. Ultrasound scans were reviewed for characteristics of periventricular hemorrhagic infarction and other cerebral abnormalities. At 4 to 12 years of age, motor outcome was assessed by the Gross Motor Function Classification System and the Manual Ability Classification System, by a neurologic examination (Touwen), an intelligence test (Wechsler Intelligence Scale III/Wechsler Preschool and Primary Scale of Intelligence-Revised), and tests for visual-motor integration, visual perception, and verbal memory. Behavior was assessed by using the Child Behavior Checklist and the Behavior Rating Inventory of Executive Function. RESULTS. Of 38 infants, 15 (39%) died. Twenty-one of the 23 survivors were included in the follow-up. Four infants were neurologically normal, 1 had minor neurologic dysfunction, 13 had unilateral spastic cerebral palsy, and 3 had bilateral cerebral palsy. Coordination, associated movements, and fine manipulative abilities were affected most according to the neurologic examination. Gross Motor Function Classification System scores were level 1 (7 children), level 2 (7 children), level 3 (1 child), and level 4 (2 children). Manual Ability Classification System scores were normal (4 children), level 1 (8 children), level 2 (7 children), and level 3 (2 children). The mean and median total IQ was 83. Visual perception was normal in 88% of children, visuomotor integration was normal in 74%, and verbal memory was normal in 50%. Behavior was normal in 53% of children, and executive functions were normal in 65% and 29% of children (by parent and teacher report, respectively). Characteristics of the periventricular hemorrhagic infarction were not related to functional motor outcome and intelligence. Post-hemorrhagic ventricular dilatation was a risk factor for poorer total and performance intelligence and abnormal fine manipulative abilities. CONCLUSIONS. The majority of surviving preterm children with periventricular hemorrhagic infarction had cerebral palsy with limited functional impairment at school age. Intelligence was within 1 SD of the norm of preterm children without lesions in 60% to 80% of the children. Verbal memory, in particular, was affected. Behavioral and executive function problems occurred slightly more than in preterm infants without lesions. The functional outcome at school age of preterm children with periventricular hemorrhagic infarction is better than previously thought. Pediatrics 2009; 123: 1493-150

Cerebral oxygenation is associated with neurodevelopmental outcome of preterm children at age 2 to 3 years

AIM: The aim of the study was to determine whether regional cerebral tissue oxygen saturation (rc SO2 ) and fractional tissue oxygen extraction (FTOE), using near-infrared spectroscopy, are associated with neurodevelopmental outcome of preterm infants. METHOD: We measured rc SO2 on days 1, 2, 3, 4, 5, 8, and 15 after birth in 83 preterm infants (<32wks gestational age), and calculated FTOE=(SpO2 -rc SO2 )/SpO2 . Cognitive, motor, neurological, and behavioural outcomes were determined at 2 to 3 years using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), an age-specific neurological examination, and the Child Behavior Checklist (CBCL) respectively. Multiple linear regression analyses were used to determine whether rc SO2 and FTOE contributed to outcome. RESULTS: We followed up 67 infants. The lower quartile (P25-50 ) and highest quartile (P75-100 ) of rc SO2 on day 1 were associated with poorer cognitive outcome (p=0.044 and p=0.008 respectively). A lower area under the curve (AUC; over 15d) of rc SO2 was associated with poorer cognitive outcome (p=0.014). The lower quartile (P25-50 ) AUC of rc SO2 was associated with poorer fine motor outcome (p=0.004). The amount of time rc SO2 <50% on day 1 was negatively associated with gross motor outcome (p=0.002). The highest quartile of FTOE on day 1 was associated with poorer total motor outcome (p=0.041). INTERPRETATION: Cerebral oxygen saturation during the first 2 weeks after birth is associated with neurodevelopmental outcome of preterm infants at 2 to 3 years. High and low rc SO2 on day 1 were associated with poorer neurodevelopmental outcome