Brain injury in premature infants is of enormous public health importance because of the large number of such infants who survive with serious neurodevelopmental disability, including major cognitive deficits and motor disability. This type of brain injury is generally thought to consist primarily of periventricular leukomalacia (PVL), a distinctive form of cerebral white matter injury. Important new work shows that PVL is frequently accompanied by neuronal/axonal disease, affecting the cerebral white matter, thalamus, basal ganglia, cerebral cortex, brain stem, and cerebellum. This constellation of PVL and neuronal/axonal disease is sufficiently distinctive to be termed "encephalopathy of prematurity". The thesis of this Review is that the encephalopathy of prematurity is a complex amalgam of primary destructive disease and secondary maturational and trophic disturbances. This Review integrates the fascinating confluence of new insights into both brain injury and brain development during the human premature period.

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Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances

OBJECTIVE: Sequelae of academic underachievement, behavioral problems, and poor executive function (EF) have been extensively reported for very preterm (≤33 weeks9 gestation) and/or very low birth weight (VLBW) (≤1500 g) children. Great variability in the published results, however, hinders the field in studying underlying dysfunctions and developing intervention strategies. We conducted a quantitative meta-analysis of studies published between 1998 and 2008 on academic achievement, behavioral functioning, and EF with the aim of providing aggregated measures of effect size for these outcome domains. METHODS: Suitable for inclusion were 14 studies on academic achievement, 9 studies on behavioral problems, and 12 studies on EF, which compared a total of 4125 very preterm and/or VLBW children with 3197 term-born controls. Combined effect sizes for the 3 outcome domains were calculated in terms of Cohen9s d. Q-test statistics were performed to test homogeneity among the obtained effect sizes. Pearson9s correlation coefficients were calculated to examine the impact of mean birth weight and mean gestational age, as well as the influence of mean age at assessment on the effect sizes for academic achievement, behavioral problems, and EF. RESULTS: Combined effect sizes show that very preterm and/or VLBW children score 0.60 SD lower on mathematics tests, 0.48 SD on reading tests, and 0.76 SD on spelling tests than term-born peers. Of all behavioral problems stacked, attention problems were most pronounced in very preterm and/or VLBW children, with teacher and parent ratings being 0.43 to 0.59 SD higher than for controls, respectively. Combined effect sizes for parent and teacher ratings of internalizing behavior problems were small ( 0.51). CONCLUSIONS: Very preterm and/or VLBW children have moderate-to-severe deficits in academic achievement, attention problems, and internalizing behavioral problems and poor EF, which are adverse outcomes that were strongly correlated to their immaturity at birth. During transition to young adulthood these children continue to lag behind term-born peers.

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Meta-analysis of neurobehavioral outcomes in very preterm and/or very low birth weight children.

QUITE apart from the academic consideration that vital and medical statistics now form an obligatory part of the education of students seeking the University of London's diploma in public health, the demand for information about the methods of vital and medical statistics is increasing. The most casual reader of the newspapers is now aware that population problems are of serious practical importance and that the publications of the General Register Office cannot be ignored. It is scarcely an exaggeration to say that the recently issued preliminary report on the census of 1931 is one of the most sensational documents which has appeared for years, and that he who reads it intelligently will understand what is meant by saying that civilisation is in the melting pot. An Introduction to Medical Statistics. By Hilda M. Woods William T. Russell. Pp. x + 125. (London: P. S. King and Son, Ltd., 1931.) 7s. 6d.

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An Introduction to Medical Statistics

tical perspective. For instance, there are only three passing references to kuru in a book of 650 pages. This edition reflects the renewed interest in the immunological theories of multiple sclerosis. More than half the text is devoted to Professor Lumsden's analysis of the pathoIogy and, in particular, the chemical pathology of the immune response. There is a great deal of original work devoted to the chemistry and behaviour of the immunoglobulins. Much of this appears in specialist journals and one must be grateful for the critical summary provided here. Professor Lumsden unequivocally sees the key to the problem of multiple sclerosis in the study of its immunochemistry, relegating infection by a virus or a slow virus to a quite subsidiary role. The clinical studies drawing on wide practical experience help to get one's prejudices about the illness onto a more reasoned footing. The section on treatment is still sadly limited. Dr. McAlpine found little to add to the regime which he described in 1955. McAlpine, Lumsden, and Acheson's reappraisal is an essential reference for the practising neurologist and the new edition makes important modification of and changes in emphasis from the edition of 1965.

https://jnnp.bmj.com/content/jnnp/36/5/894.3.full.pdf

The assessment of aphasia and related disorders

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(09)61037-0.pdf

Adverse health effects of non-medical cannabis use

Very preterm (VPT) birth is associated with altered cortical development and long-term neurodevelopmental sequelae. We used voxel-based morphometry to investigate white (WM) and grey matter (GM) distribution in VPT adolescents and controls, and the association with gestational age and neonatal ultrasound findings in the VPT individuals. GM and WM volumes were additionally investigated in relation to adolescent neurodevelopmental outcome. Structural MRI data were acquired with a 1.5 Tesla machine in 218 VPT adolescents (<33 weeks, gestation) and 128 controls aged 14-15 years, and analysed using SPM2 software. VPT individuals compared to controls showed reduced GM in temporal, frontal, occipital cortices and cerebellum, including putamen, insula, cuneus, fusiform gyrus, thalamus and caudate nucleus, and increased GM predominantly in temporal and frontal lobes, including cingulate and fusiform gyri and cerebellum. WM loss was concentrated in the brainstem, internal capsule, temporal and frontal regions and the major fasciculi. WM excesses were observed in temporal, parietal and frontal regions. Investigation of the inter-relationships between brain regions and changes revealed that all selected areas where between-group increased and decreased WM and GM volumes differences were observed, were structurally associated, highlighting the influence that abnormalities in one brain area may exert over others. VPT individuals with evidence of periventricular haemorrhage and ventricular dilatation on neonatal ultrasound exhibited the greatest WM and GM alterations. VPT adolescents obtained lower scores than controls on measures of language and executive function and were more likely to show cognitive impairment compared to controls (27% versus 14%, respectively). Several areas where VPT individuals demonstrated decreased GM and WM volume were linearly associated with gestational age and mediated cognitive impairment. To summarize, our data demonstrates that VPT birth is associated with altered brain structure in adolescence. GM and WM alterations are associated with length of gestation and mediate adolescent neurodevelopmental impairment. Thus, anatomical brain changes may contribute to specific cognitive deficits associated with VPT birth and could be used in the identification of those individuals who may be at increased risk for cognitive impairment.

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Grey and white matter distribution in very preterm adolescents mediates neurodevelopmental outcome.

Individuals born very preterm (VPT) are at increased risk of perinatal brain injury and long-term cognitive and behavioral problems. Executive functioning, in particular, has been shown to be impaired in VPT children and adolescents. This study prospectively assessed executive function in young adults who were born VPT (<33 weeks of gestation) [n = 61; mean age, 22.25 (+/-1.07) years; range, 20.62-24.78 years] and controls [n = 64; mean age, 23.20 (+/-1.48) years; range, 19.97-25.46 years]. Tests used comprised the Wechsler Abbreviated Scale of Intelligence (WASI), the Hayling Sentence Completion Test (HSCT), the Controlled Oral Word Association Test (COWAT), the Animal and Object test, the Trail-Making Test (TMT), and the Test of Attentional Performance (TAP). VPT participants showed specific executive function impairments in tasks involving response inhibition and mental flexibility, even when adjusting for IQ, gender, and age. No significant associations were observed between executive function test scores and perinatal variables or neonatal ultrasound classification. The results suggest that, although free from major physical disability, VPT young adults perform worse than controls on tasks involving selective aspects of executive processing, such as mental flexibility and response inhibition.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S1355617707070725

Impaired executive functioning in young adults born very preterm.

Background. There is evidence that cannabis use might be relevant to the aetiology of schizophrenia. We aimed to measure any change in cannabis use over time in those first presenting with schizophrenia in South-East London from 1965 to 1999, and compare this with change in use in those presenting with non-psychotic psychiatric disorders.Method. The rate of cannabis use in the year prior to first ever presentation was measured over seven time periods. Logistic regression modelling was used to determine (a) whether cannabis use changed over time, after controlling for age, sex and ethnicity, and (b) whether there was an interaction between diagnosis and time.Results. Cannabis use increased over time in both the schizophrenia group [odds ratio per time period (OR) 2·03, 95% confidence interval (CI) 1·74–2·38, p<0·0001] and the non-psychotic disorders group (OR 1·24, 95% CI 1·05–1·47, p=0·012), after controlling for age, sex and ethnicity. However, the effect of time was significantly greater in the schizophrenia group than in the non-schizophrenia group (χ2=17, p<0·0001).Conclusion. Cannabis use in the year prior to presentation with schizophrenia increased markedly between 1965 and 1999, and disproportionately so compared to increase in cannabis use in other psychiatric disorders.

E Giouroukou

Papers

Grey and white matter distribution in very preterm adolescents mediates neurodevelopmental outcome.

Impaired executive functioning in young adults born very preterm.

Trends in cannabis use prior to first presentation with schizophrenia, in South-East London between 1965 and 1999.

A comparison of symptoms and family history in schizophrenia with and without prior cannabis use: implications for the concept of cannabis psychosis.