A L Stewart

Brain structure and neurocognitive and behavioural function in adolescents who were born very preterm

BACKGROUND Infants born very preterm (<33 weeks) are at increased risk of neurocognitive deficits. Their neurodevelopmental outcome up to age 8 years can be predicted by neonatal ultrasonography, but little is known of their later function. We investigated the effect of very preterm birth on brain structure and neurocognitive and behavioural functioning in adolescence. METHODS A cohort of 105 infants born before 33 weeks of gestation in 1979-80 had ultrasonographic scans at University College Hospital, London, and were prospectively examined at 1, 4, and 8 years. At age 14-15 years, 72 of those who remained in UK (cases) and 21 age-matched full-term controls underwent brain magnetic resonance imaging (MRI), as well as neurological, cognitive, and behavioural assessment. MRI images were assessed by two neuroradiologists unaware of ultrasonographic findings or case or control status. FINDINGS Of the 72 cases, 40 had unequivocally abnormal MRI and 15 had equivocal scans. Of the 21 controls, one had abnormal and five equivocal MRI. Abnormalities of ventricles, corpus callosum, and white matter were especially common in cases. More brain lesions were identified by MRI than by neonatal ultrasonography. The cases had significantly more reading, adjustment, and neurological impairments than controls, but their behaviour was significantly related to MRI abnormality. INTERPRETATION Individuals born very preterm show an excess of neurocognitive and behavioural problems in adolescence, and more than half have abnormal MRI brain scans.

Outcome for infants of very low birthweight: survey of world literature.

Reports from developed countries world wide describing the outcome for infants of very low birthweight (VLBW, less than or equal to 1500 g) born since 1946 show that, in general, mortality rates and the prevalence of major handicap in survivors were high until 1960. Since then the chances of healthy survival have trebled, whereas the handicap-rate has remained stable and relatively low at 6--8% of VLBW live births.

Relation of deranged neonatal cerebral oxidative metabolism with neurodevelopmental outcome and head circumference at 4 years

Cerebral oxidative metabolism was studied using phosphorus magnetic resonance spectroscopy during the first week of life and neurodevelopmental outcome was assessed at 4 years in 62 infants who had clinical and/or biochemical evidence consistent with birth asphyxia (critically impaired intrapartum gas exchange). Twenty‐one died and the neurodevelopmental status of the 41 who survived was assessed by a range of tests at age 4 years. The minimum recorded values for the cerebral phosphocreatine:inorganic phosphate concentration ratio (an index of oxidative metabolism) were related to outcome. The results showed significant relations between the extent of derangement of neonatal oxidative metabolism and a range of adverse outcomes, including death, and at 4 years reduced head growth and the presence and severity of neuromotor impairments, overall neurodevelopmental impairments, and cognitive functioning. Strong correlations between the extent of derangement of neonatal oxidative metabolism and outcome at 1 and 4 years were also shown. We conclude that the severities of adverse outcomes at 1 and 4 years of age were closely related to the extent of cerebral energy derangement in the first week of life, and we also conclude that primary intrapartum hypoxic‐ischaemic cerebral injury was generally responsible for the events that led to death, microcephaly, and impaired

Probability of neurodevelopmental disorders estimated from ultrasound appearance of brains of very preterm infants.

The neurodevelopmental status of 342 very preterm infants who had undergone prospective ultrasound brainscans was assessed at a median corrected age of 52 weeks. The probabilities for neurodevelopmental disorders were calculated according to the ultrasound findings. The results showed that the probabilité of a major or minor disorder was low for infants whose scans did not show periventricular haemorrhage or markedly increased parenchymal echodensities in the first week of life, and for those whose scans at discharge gave no evidence of ventricular dilatation, hydrocephalus or cerebral atrophy. By contrast, the probabilité of a disorder was very high for infants with markedly increased parenchymal echodensities in the first week, and for infants with evidence of cerebral atrophy at discharge. The majority of the infants could be assigned, on the basis of the ultrasound scan at discharge, either to a large group who were at low risk of neurodevelopmental disorders or to a small group who were at high risk; the remainder were at intermediate risk. These findings may be used as a guide to the prognosis for other infants whose ultrasound scans show similar appearances.

Neuropsychological outcome at adolescence of very preterm birth and its relation to brain structure.

Neuropsychological outcome at 14 to 15 years of age of a cohort of 75 participants (39 male, 36 female) born at <33 weeks’gestation was investigated. Research was conducted parallel to a recent MRI study by Stewart and colleagues which reported that 55% of this cohort had evidence of brain abnormality. One aim of the study was to compare neuropsychological function in those very preterm children with and without MRI abnormality. Compared to a control sample of term adolescents, very preterm participants had impairment only on a measure of word production. On measures of attention, memory, perceptual skill, and visuomotor and executive function, the adolescents born very preterm performed in the normal range, whether or not they had evidence of MRI abnormality. Our findings are encouraging as the neuropsychological consequences of damage to the very preterm brain, still evident on MRI at 14 to 15 years of age, appear to be minor.

PREDICTION OF DEATH AND MAJOR HANDICAP IN VERY PRETERM INFANTS BY BRAIN ULTRASOUND

A linear-array real-time ultrasound scanner was used to examine the brains of all 95 infants born at less than 33 weeks of gestation who were admitted to the neonatal unit of University College Hospital in 1979. Abnormalities were detected in 41 (43%). 36 infants had haemorrhages into the germinal layer (GLH) and/or ventricles (IVH). 8 infants had cerebral atrophy (together with GLH/IVH in 5 infants). 8 (13%) of 63 infants with normal scans or small (grade-I) GLH/IVHs died, whereas 19 (59%) of 32 infants with larger haemorrhages or other intracranial lesions died (p less than 0.0005). At follow-up, at a median corrected age of 45 weeks, only 2 (4%) of 53 infants with normal scans or grade-I haemorrhages had evidence of major neurodevelopmental handicaps, but 5 (38%) of 13 infants with more extensive haemorrhages or cerebral atrophy had major handicaps (p less than 0.005). Brain scanning with ultrasound in the first days of life identified most infants in the population studied who subsequently died or survived with handicaps severe enough to be detected within the first year.

Neurodevelopmental status at 1 year predicts neuropsychiatric outcome at 14–15 years of age in very preterm infants

BACKGROUND Neurodevelopmental and behavioural problems have been repeatedly reported in very preterm survivors, often showing themselves later in childhood as poor school performance. Early identification of problems would mean that appropriate remedial therapy can be implemented. We have previously shown that neurodevelopmental status at 1 year was predictive of outcome at 8 years in a cohort of preterm infants. The aim of this paper was to see if neurodevelopmental outcome in adolescence could be predicted by assessment by 1 year in the same cohort of preterm infants. STUDY DESIGN Prospective cohort study. SUBJECTS 150 adolescents, born before 33 weeks gestation. OUTCOME MEASURES Neurological examination, developmental quotient, vision and hearing by 1 year. At 14-15 years, neurological examination, school performance questionnaire, Schonnell test of reading age, a premorbid adjustment score, Rutter behavioural score and for those born from 1981, cognitive tests (WISC-R). RESULTS A highly significant relationship existed between neurological status by 1 year and the need for extra educational provision, overall neurodevelopmental status, cognitive function in those that had their IQs measured and premorbid adjustment score of prepsychotic symptoms in adolescence. However, status at 1 year was not predictive of adolescent reading age or behavioural score. CONCLUSIONS Neurodevelopmental assessment at 1 year is predictive of school performance and outcome in the adolescent period.

Lateralisation of language function in young adults born very preterm

Objective: To explore, using functional magnetic resonance imaging (MRI), the functional organisation of phonological processing in young adults born very preterm. Subjects: Six right handed male subjects with radiological evidence of thinning of the corpus callosum were selected from a cohort of very preterm subjects. Six normal right handed male volunteers acted as controls. Method: Blood oxygenation level dependent contrast echoplanar images were acquired over five minutes at 1.5 T while subjects performed the tasks. During the ON condition, subjects were visually presented with pairs of non-words and asked to press a key when a pair of words rhymed (phonological processing). This task alternated with the OFF condition, which required subjects to make letter case judgments of visually presented pairs of consonant letter strings (orthographic processing). Generic brain activation maps were constructed from individual images by sinusoidal regression and non-parametric testing. Between group differences in the mean power of experimental response were identified on a voxel wise basis by analysis of variance. Results: Compared with controls, the subjects with thinning of the corpus callosum showed significantly reduced power of response in the left hemisphere, including the peristriate cortex and the cerebellum, as well as in the right parietal association area. Significantly increased power of response was observed in the right precentral gyrus and the right supplementary motor area. Conclusions: The data show evidence of increased frontal and decreased occipital activation in male subjects with neurodevelopmental thinning of the corpus callosum, which may be due to the operation of developmental compensatory mechanisms.