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 (r(c)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 -r(c)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 r(c)SO2 and FTOE contributed to outcome. RESULTS: We followed up 67 infants. The lower quartile (P(25-50)) and highest quartile (P(75-100)) of r(c)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 r(c)SO2 was associated with poorer cognitive outcome (p=0.014). The lower quartile (P(25-50)) AUC of r(c)SO2 was associated with poorer fine motor outcome (p=0.004). The amount of time r(c)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 r(c)SO2 on day 1 were associated with poorer neurodevelopmental outcome.

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.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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. KEY POINTS: Magnetic resonance spectroscopy can identify brain metabolic changes in perinatal asphyxia. Choline and lactate levels in grey matter seem the best indicators of survival. 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<.001. In a multivariate model including abnormal aEEG background patterns, failure to achieve seizure control nearly reached significance towards an increased risk of poor outcome, OR 5.72, 95%-CI 0.99-32.97, P=.051. We found no association between seizure aetiology and outcome. 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.

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. Posthemorrhagic 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.

Indicators of long chain polyunsaturated fatty acid status of exclusively breastfed infants at delivery and after 20-22 days

The fatty acid composition of plasma cholesterol esters (CE), erythrocytes (RBC) and mature milk from seven lactating women and their exclusively breastfed newborns, living on Dominica, were studied. Blood samples were taken from umbilical cord and mother at birth. A sample of breastmilk was collected on day 20-22 postpartum, together with a blood sample from the baby. At birth, cord blood plasma CE and RBC total long chain polyunsaturated fatty acid (LC-PUFA) contents were higher, and linoleic (18:2c, omega 6) and alpha-linolenic (18:3c, omega 3) acid contents lower, than in corresponding maternal compartments. Cord blood RBC LC-PUFA omega 3 content was lower and LC-PUFA omega 6 content higher than in maternal RBC. After birth, feeding with human milk led to a drop in LC-PUFA content in the plasma CE fraction, whereas RBC LC-PUFA content remained virtually constant. Current understanding of the origin and relative affinity of fatty acids incorporated in plasma CE and RBC suggests that RBC LC-PUFA content is a more reliable parameter for LC-PUFA status than plasma CE LC-PUFA content. The RBC LC-PUFA data suggest therefore that at birth the newborn has a lower LC-PUFA omega 3 status than the mother, and that this does not change during three weeks of exclusive breastfeeding (AU)

Obstetrical condition and neonatal neurological outcome in Dominica, the Caribbean - a comparative study

Risk factors during pregnancy and delivery and neurological morbidity of newborns were assessed in a birth cohort in Dominica, the Caribbean. The data were compared with two reference groups, one from Grenada, the Caribbean, and the other from Groningen, the Netherlands. Despite variations in cultural and socio-economic situation, the similarities in obstetrical conditions, neonatal neurological morbidity and perinatal relationships between the three groups were more striking than the differences. The Dominican group showed a significantly higher rate of preterm births than the two other groups. Preterm birth was associated with a significant increase in neurological deviancy. In general motility and muscle tone were found to be lower in the Caribbean region than in the Netherlands (AU)

Long chain polyunsaturated fatty acid status of the exclusively breastfed infant in Dominica at delivery and after 20-22 days - abstract

The fatty compositions of plasma cholesterol esters (CE) and erythrocytes (RBC) from five lactating women and their exclusively breastfed newborns, living in Dominica, were studied. Blood samples were taken from the umbilical cord and mother at birth. A second blood sample of the newborn and a sample of breast milk were taken on day 20-22 postpartum. Fatty acids were determined by capillary gas chromatography. At birth, cord blood plasma CE and RBC long chain polyunsaturated fatty acids (LC-PUFA) contents were higher, and linoleic acid (18:2c, w6) contents lower, than in corresponding maternal compartments. Accretion of LC-PUFA by the foetus may be accomplished by a-fetoprotein , that has a high affinity for LC-PUFA and is taken up by a variety of foetal tissues in a receptor-mediated fashion. After birth breastfeeding leads to a drop of LC-PUFA content in the plasma CE fraction, whereas RBC LC-PUFA content remains constant. Is is conceivable that RBC LC-PUFA content is a more reliable parameter for LC-PUFA status than the plasma CE LC-PUFA (AU)

Obstetrical condition and neonatal neurological outcome in Dominica, the Caribbean: a comparative study - abstract

The risk factors during pregnancy and delivery and neurological morbidity of the newborn were assessed in a birth cohort in Dominica, West Indies. The data were compared with those from 2 reference groups from Grenada, West Indies and Groningen, the Netherlands. Despite variations in cultural and socio-economic factors among the 3 groups, the similarities in obstetrical status, neonatal neurological morbidity and perinatal relationships were more striking than the differences. The Dominican group showed a significantly higher rate of preterm births than the other 2 groups. Preterm birth was associated with a significant increase in neurological deviancy. In general, motility and muscle tone were found to be lower in West Indians than in Netherlands newborns (AU)