Special Care and School Difficulties in 8-Year-Old Very Preterm Children: The Epipage Cohort Study

OBJECTIVES: To investigate school difficulties, special care and behavioral problems in 8 year-old very preterm (VPT) children. PATIENT AND METHODS: Longitudinal population-based cohort in nine regions of France of VPT children and a reference group born at 39-40 weeks of gestation (WG). The main outcome measures were information about school, special care and behavioral problems using Strengths and Difficulties Questionnaire from a questionnaire to parents. RESULTS: Among the 1439 VPT children, 5% (75/1439) were in a specialised school or class, 18% (259/1439) had repeated a grade in a mainstream class and 77% (1105/1439) were in the appropriate grade-level in mainstream class; these figures were 1% (3/327) , 5% (16/327) and 94% (308/327) , respectively, for the reference group. Also, 15% (221/1435) of VPT children in a mainstream class received support at school versus 5% (16/326) of reference group. More VPT children between the ages of five and eight years received special care (55% (794/1436)) than children born at term (38% (124/325)); more VPT children (21% (292/1387)) had behavioral difficulties than the reference group (11% (35/319)). School difficulties, support at school, special care and behavioral difficulties in VPT children without neuromotor or sensory deficits varied with gestational age, socioeconomic status, and cognitive score at the age of five. CONCLUSIONS: Most 8-year-old VPT children are in mainstream schools. However, they have a high risk of difficulty in school, with more than half requiring additional support at school and/or special care. Referral to special services has increased between the ages of 5 and 8 years, but remained insufficient for those with borderline cognitive scores

Determinants of cognitive function in childhood: A cohort study in a middle income context

BACKGROUND: There is evidence that poverty, health and nutrition affect children's cognitive development. This study aimed to examine the relative contributions of both proximal and distal risk factors on child cognitive development, by breaking down the possible causal pathways through which poverty affects cognition. METHODS: This cohort study collected data on family socioeconomic status, household and neighbourhood environmental conditions, child health and nutritional status, psychosocial stimulation and nursery school attendance. The effect of these on Wechsler Pre-School and Primary Scale of Intelligence scores at five years of age was investigated using a multivariable hierarchical analysis, guided by the proposed conceptual framework. RESULTS: Unfavourable socioeconomic conditions, poorly educated mother, absent father, poor sanitary conditions at home and in the neighbourhood and low birth weight were negatively associated with cognitive performance at five years of age, while strong positive associations were found with high levels of domestic stimulation and nursery school attendance. CONCLUSION: Children's cognitive development in urban contexts in developing countries could be substantially increased by interventions promoting early psychosocial stimulation and preschool experience, together with efforts to prevent low birth weight and promote adequate nutritional status

Immunogenicity and efficacy of oral vaccines in developing countries: lessons from a live cholera vaccine

Oral vaccines, whether living or non-living, viral or bacterial, elicit diminished immune responses or have lower efficacy in developing countries than in developed countries. Here I describe studies with a live oral cholera vaccine that include older children no longer deriving immune support from breast milk or maternal antibodies and that identify some of the factors accounting for the lower immunogenicity, as well as suggesting counter-measures that may enhance the effectiveness of oral immunization in developing countries. The fundamental breakthrough is likely to require reversing effects of the 'environmental enteropathy' that is often present in children living in fecally contaminated, impoverished environments

A Brain Region-Specific Predictive Gene Map for Autism Derived by Profiling a Reference Gene Set

Molecular underpinnings of complex psychiatric disorders such as autism spectrum disorders (ASD) remain largely unresolved. Increasingly, structural variations in discrete chromosomal loci are implicated in ASD, expanding the search space for its disease etiology. We exploited the high genetic heterogeneity of ASD to derive a predictive map of candidate genes by an integrated bioinformatics approach. Using a reference set of 84 Rare and Syndromic candidate ASD genes (AutRef84), we built a composite reference profile based on both functional and expression analyses. First, we created a functional profile of AutRef84 by performing Gene Ontology (GO) enrichment analysis which encompassed three main areas: 1) neurogenesis/projection, 2) cell adhesion, and 3) ion channel activity. Second, we constructed an expression profile of AutRef84 by conducting DAVID analysis which found enrichment in brain regions critical for sensory information processing (olfactory bulb, occipital lobe), executive function (prefrontal cortex), and hormone secretion (pituitary). Disease specificity of this dual AutRef84 profile was demonstrated by comparative analysis with control, diabetes, and non-specific gene sets. We then screened the human genome with the dual AutRef84 profile to derive a set of 460 potential ASD candidate genes. Importantly, the power of our predictive gene map was demonstrated by capturing 18 existing ASD-associated genes which were not part of the AutRef84 input dataset. The remaining 442 genes are entirely novel putative ASD risk genes. Together, we used a composite ASD reference profile to generate a predictive map of novel ASD candidate genes which should be prioritized for future research

Integrins as therapeutic targets: lessons and opportunities.

The integrins are a large family of cell adhesion molecules that are essential for the regulation of cell growth and function. The identification of key roles for integrins in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders, has revealed their substantial potential as therapeutic targets. However, so far, pharmacological inhibitors for only three integrins have received marketing approval. This article discusses the structure and function of integrins, their roles in disease and the chequered history of the approved integrin antagonists. Recent advances in the understanding of integrin function, ligand interaction and signalling pathways suggest novel strategies for inhibiting integrin function that could help harness their full potential as therapeutic targets

What Do We Know About Neuropsychological Aspects Of Schizophrenia?

Application of a neuropsychological perspective to the study of schizophrenia has established a number of important facts about this disorder. Some of the key findings from the existing literature are that, while neurocognitive impairment is present in most, if not all, persons with schizophrenia, there is both substantial interpatient heterogeneity and remarkable within-patient stability of cognitive function over the long-term course of the illness. Such findings have contributed to the firm establishment of neurobiologic models of schizophrenia, and thereby help to reduce the social stigma that was sometimes associated with purely psychogenic models popular during parts of the 20th century. Neuropsychological studies in recent decades have established the primacy of cognitive functions over psychopathologic symptoms as determinants of functional capacity and independence in everyday functioning. Although the cognitive benefits of both conventional and even second generation antipsychotic medications appear marginal at best, recognition of the primacy of cognitive deficits as determinants of functional disability in schizophrenia has catalyzed recent efforts to develop targeted treatments for the cognitive deficits of this disorder. Despite these accomplishments, however, some issues remain to be resolved. Efforts to firmly establish the specific neurocognitive/neuropathologic systems responsible for schizophrenia remain elusive, as do efforts to definitively demonstrate the specific cognitive deficits underlying specific forms of functional impairment. Further progress may be fostered by recent initiatives to integrate neuropsychological studies with experimental neuroscience, perhaps leading to measures of deficits in cognitive processes more clearly associated with specific, identifiable brain systems