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.

/pdf/brain-injury-in-premature-infants-a-complex-amalgam-of-44m95zo04a.pdf

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.

/pdf/meta-analysis-of-neurobehavioral-outcomes-in-very-preterm-eci7fw9h5c.pdf

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

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

BACKGROUND Advances in perinatal care have increased the number of premature babies who survive. There are concerns, however, about the ability of these children to cope with the demands of adulthood. METHODS We linked compulsory national registries in Norway to identify children of different gestational-age categories who were born between 1967 and 1983 and to follow them through 2003 in order to document medical disabilities and outcomes reflecting social performance. RESULTS The study included 903,402 infants who were born alive and without congenital anomalies (1822 born at 23 to 27 weeks of gestation, 2805 at 28 to 30 weeks, 7424 at 31 to 33 weeks, 32,945 at 34 to 36 weeks, and 858,406 at 37 weeks or later). The proportions of infants who survived and were followed to adult life were 17.8%, 57.3%, 85.7%, 94.6%, and 96.5%, respectively. Among the survivors, the prevalence of having cerebral palsy was 0.1% for those born at term versus 9.1% for those born at 23 to 27 weeks of gestation (relative risk for birth at 23 to 27 weeks of gestation, 78.9; 95% confidence interval [CI], 56.5 to 110.0); the prevalence of having mental retardation, 0.4% versus 4.4% (relative risk, 10.3; 95% CI, 6.2 to 17.2); and the prevalence of receiving a disability pension, 1.7% versus 10.6% (relative risk, 7.5; 95% CI, 5.5 to 10.0). Among those who did not have medical disabilities, the gestational age at birth was associated with the education level attained, income, receipt of Social Security benefits, and the establishment of a family, but not with rates of unemployment or criminal activity. CONCLUSIONS In this cohort of people in Norway who were born between 1967 and 1983, the risks of medical and social disabilities in adulthood increased with decreasing gestational age at birth.

/pdf/long-term-medical-and-social-consequences-of-preterm-birth-vs5cf544nh.pdf

Long-term medical and social consequences of preterm birth.

BACKGROUND AND METHODS\nSmall studies show that many children born as extremely preterm infants have neurologic and developmental disabilities. We evaluated all children who were born at 25 or fewer completed weeks of gestation in the United Kingdom and Ireland from March through December 1995 at the time when they reached a median age of 30 months. Each child underwent a formal assessment by an independent examiner. Development was evaluated with use of the Bayley Scales of Infant Development, and neurologic function was assessed by a standardized examination. Disability and severe disability were defined by predetermined criteria.\n\n\nRESULTS\nAt a median age of 30 months, corrected for gestational age, 283 (92 percent) of the 308 surviving children were formally assessed. The mean (+/-SD) scores on the Bayley Mental and Psychomotor Developmental Indexes, referenced to a population mean of 100, were 84+/-12 and 87+/-13, respectively. Fifty-three children (19 percent) had severely delayed development (with scores more than 3 SD below the mean), and a further 32 children (11 percent) had scores from 2 SD to 3 SD below the mean. Twenty-eight children (10 percent) had severe neuromotor disability, 7 (2 percent) were blind or perceived light only, and 8 (3 percent) had hearing loss that was uncorrectable or required aids. Overall, 138 children had disability (49 percent; 95 percent confidence interval, 43 to 55 percent), including 64 who met the criteria for severe disability (23 percent; 95 percent confidence interval, 18 to 28 percent). When data from 17 assessments by local pediatricians were included, 155 of the 314 infants discharged (49 percent) had no disability.\n\n\nCONCLUSIONS\nSevere disability is common among children born as extremely preterm infants.

Neurologic and developmental disability after extremely preterm birth

Preterm birth and structural brain alterations in early adulthood

INTRODUCTION: Very preterm birth (VPT; <33 weeks' gestation) is associated with later neuromotor and cognitive impairment, reduced school performance, and psychiatric morbidity. Several follow-up studies have demonstrated increased anxiety and social rejection and reduced self-esteem in preterm children and adolescents, but few studies have examined the effects of preterm birth on adult personality. METHODS: We assessed 108 VPT individuals and 67 term-born controls at ages 18 to 19 years with the Eysenck Personality Questionnaire-Revised, short form (EPQ-RS). This questionnaire rates 3 dimensions of personality: extraversion (sociability, liveliness, sensation seeking); neuroticism (anxiety, low mood, low self-esteem); and psychoticism (coldness, aggression, predisposition to antisocial behavior). A fourth scale, "lie," which measures dissimulation, is also derived. RESULTS: VPT individuals had significantly lower extraversion scores, higher neuroticism scores, and higher lie scores than term-born controls, after controlling for age at assessment and socioeconomic status. P scores were not significantly different between the 2 groups. There was a gender difference in that the increased neuroticism and decreased extraversion scores were accounted for mainly by VPT females. Associations between EPQ-RS scores and neonatal status, adolescent behavioral ratings, and body size at 18 to 19 years were assessed by using Kendall partial correlations, correcting for age at assessment and socioeconomic status. Gestational age, indices of neonatal hypoxia, and neonatal ultrasound ratings were not correlated with EPQ-RS scores. Birth weight was weakly associated with increased lie scores. Rutter Parents' Scale score, a measure of adolescent psychopathology, was associated with an increased neuroticism score. Poor social adjustment in adolescence was associated with an increased lie score. Height and weight at 18 to 19 years were not associated with EPQ-RS, but reduced occipitofrontal circumference was associated with both decreased extraversion and increased lie scores. CONCLUSIONS: Young adults who are born VPT have different personality styles from their term-born peers. This may be associated with an increased risk of psychiatric difficulties.

Personality in Young Adults Who Are Born Preterm

Background: Adolescence is a critical period of brain structural reorganisation and maturation of cognitive abilities. This relatively late developmental reorganisation may be altered in individuals who were born preterm. Methods: We carried out longitudinal neuropsychological testing in 94 very preterm individuals (VPT; before 33 weeks’ gestation) and 44 term born individuals at mean ages of 15.3 years (adolescence) and 19.5 years (young adulthood). Results: Full scale, verbal and performance IQ and phonological verbal fluency were significantly lower in the VPT group than the term group at both ages. Repeated measures ANOVA showed only one group by time point interaction for semantic verbal fluency (F = 10.25; df = 107; p = 0.002). Paired-sample t tests showed that semantic verbal fluency increased significantly in the term group over adolescence (t = −5.10; df = 42; p Conclusion: Decrements of intellectual functioning in VPT individuals persist into adulthood. Additionally, there is a deficit in the adolescent maturation of semantic verbal fluency in individuals born VPT.

https://jnnp.bmj.com/content/jnnp/79/4/381.full.pdf

Cognitive maturation in preterm and term born adolescents

Very preterm birth (before 33 weeks gestation) is associated with the white matter damage, and a common sequel is reduced size and altered shape of the corpus callosum. We used diffusion tensor MRI to assess the corpus callosum in 63 very preterm and 45 term-born young adults. Indices of white matter microstructure [fractional anisotropy (FA) and mean diffusivity (MD)] were obtained for the genu, body and splenium. Very preterm females had higher MD in the genu than term-born females, indicating altered white matter microstructure. This was associated with lower performance IQ. The groups demonstrated different patterns of correlations between verbal learning and tract-specific FA and MD, consistent with the reorganization of white matter structure in adults born very preterm.

Diffusion tensor MRI of the corpus callosum and cognitive function in adults born preterm.

Objective: Individuals born before 33 weeks’ gestation (very preterm, VPT) have an increased likelihood of neurological abnormality, impaired cognitive function, and reduced academic performance in childhood. It is currently not known whether neurological signs detected in VPT children persist into adulthood or become attenuated by maturation of the CNS. Method: We assessed 153 VPT individuals and 71 term-born controls at 17–18 years old, using a comprehensive neurological examination. This examination divides neurological signs into primary and integrative domains, the former representing the localising signs of classical neurology, and the latter representing signs requiring integration between different neural networks or systems. Integrative signs are sub-divided into three groups: sensory integration, motor confusion, and sequencing. The VPT individuals have been followed up since birth, and neonatal information is available on them, along with the results of neurological assessment at 4 and 8 years of age and neuropsychological assessment at 18 years of age. Results: The total neurology score and primary and integrative scores were significantly increased in VPT young adults compared to term-born controls. Within the integrative domain, sensory integration and motor confusion scores were significantly increased in the VPT group, but sequencing was not significantly different between the VPT and term groups. Integrative neurological abnormalities at 18 were strongly associated with reduced IQ but primary abnormalities were not. Conclusions: Neurological signs are increased in VPT adults compared to term-born controls, and are strongly associated with reduced neuropsychological function.

/pdf/neurological-abnormalities-in-young-adults-born-preterm-23r1f21fb5.pdf

M Cuddy

Papers

Preterm birth and structural brain alterations in early adulthood

Personality in Young Adults Who Are Born Preterm

Cognitive maturation in preterm and term born adolescents

Diffusion tensor MRI of the corpus callosum and cognitive function in adults born preterm.

Neurological abnormalities in young adults born preterm