Pubmed du 30/01/20

jeudi 30 janvier 2020

1. Bathelt J, Koolschijn PC, Geurts HM. Age-variant and age-invariant features of functional brain organization in middle-aged and older autistic adults. Mol Autism. 2020 ; 11 : 9.

Background : The majority of research effort into autism has been dedicated to understanding mechanisms during early development. As a consequence, research on the broader life course of an autism spectrum condition (ASC) has largely been neglected and almost nothing is known about ASC beyond middle age. Differences in brain connectivity that arise during early development may be maintained across the lifespan and may play protective or detrimental roles in older age. Method : This study explored age-related differences in functional connectivity across middle and older age in clinically diagnosed autistic adults (n = 44, 30-73 years) and in an age-matched typical comparison group (n = 45). Results : The results indicated parallel age-related associations in ASC and typical aging for the local efficiency and connection strength of the default mode network and for the segregation of the frontoparietal control network. In contrast, group differences in visual network connectivity are compatible with a safeguarding interpretation of less age-related decline in brain function in ASC. This divergence was mirrored in different associations between visual network connectivity and reaction time variability in the ASC and comparison group. Limitations : The study is cross-sectional and may be affected by cohort effects. As all participants received their autism diagnosis in adulthood, this might hinder generalizability. Conclusion : These results highlight the complexity of aging in ASC with both parallel and divergent trajectories across different aspects of functional network organization.

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2. Brusov OS, Simashkova NV, Karpova NS, Faktor MI, Nikitina SG. [Thrombodynamic correlates of catatonia severity in children with autism]. Zh Nevrol Psikhiatr Im S S Korsakova. 2019 ; 119(12) : 57-61.

AIM : To study a correlation between the values of thrombodynamics parameters of hypercoagulation measured by the thrombodynamics test and the severity of catatonia in children with infantile psychosis in childhood autism (F84.02). MATERIAL AND METHODS : Twenty-four patients (22 boys and 2 girls) aged from 3 to 13 years, were studied. The severity of catatonia was determined by BFCRS. A thrombodynamic test was performed in platelet-free plasma using the analyzer T-2 Thrombodynamics Device (Hemacore LLC, Russia). RESULTS : Thrombodynamic (TD) parameters of clot growth rates from the activator (V, Vi and Vst) were statistically significantly higher than normal values. Similar results were obtained for Clot Size at 30 min (CS, mum) : Tlag and D values were within normal limits. The values of Time of appearance of spontaneous clots (Tsp min) were less than the lower limit values for the norm (30 min). Correlation analysis showed that the severity of catatonia is positively correlated with the initial clot growth rate (Vi) (p=0.009) and negatively with Tsp (p=0.002). With an increase in the time of appearance of spontaneous clots (due to a decrease in the procoagulant activity of platelet microparticles in the plasma of patients), the severity of catatonia in children with ASD decreases. CONCLUSION : The results suggest that normalizing plasma and platelet hemostasis is important for increasing the effectiveness of treatment of patients with ASD with catatonia.

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3. Elsabbagh M. Linking risk factors and outcomes in autism spectrum disorder : is there evidence for resilience ?. BMJ (Clinical research ed). 2020 ; 368 : l6880.

Autism spectrum disorder (referred to here as autism) is one of several overlapping neurodevelopmental conditions that have variable impacts on different individuals. This variability results from dynamic interactions between biological and non-biological risk factors, which result in increasing differentiation between individuals over time. Although this differentiation continues well into adulthood, the infancy period is when the brain and behavior develop rapidly, and when the first signs and symptoms of autism emerge. This review discusses advances in our understanding of the causal pathways leading to autism and overlapping neurodevelopmental conditions. Research is also mapping trajectories of brain and behavioral development for some risk groups, namely later born siblings of children with autism and/or infants referred because of developmental concerns. This knowledge has been useful in improving early identification and establishing the feasibility of targeted interventions for infant risk groups before symptoms arise. However, key knowledge gaps remain, such as the discovery of protective factors (biological or environmental) that may mitigate the impact of risk. Also, the dynamic mechanisms that underlie the associations between risk factors and outcomes need further research. These include the processes of resilience, which may explain why some individuals at risk for autism achieve better than expected outcomes. Bridging these knowledge gaps would help to provide tools for early identification and intervention that reflect dynamic developmental pathways from risk to outcomes.

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4. Gabis LV, Shefer S, Raas-Rothschild A. Ethical Dilemmas Linked to Fragile X Testing of Minors-a Preliminary Survey Among Professionals. Journal of molecular neuroscience : MN. 2020.

Asymptomatic female carriers of the FMR1 premutation at childbearing age have been mostly identified through prenatal genetic testing, which is routinely proposed in Israel. During the last few years, a premutation phenotype in males and females has been defined-FXAND, including neuropsychiatric disorder, learning difficulties, endocrine dysfunction, and premature ovarian failure. So when a family at risk is identified, should individuals be tested for premutation even if minors ? In order to understand what professionals’ views are with regard to testing FMR1 premutation in minors, we performed a questionnaire testing both ethical attitudes and knowledge. Eighty-two percent of professionals would positively consider fragile X testing in minors, and an additional 15.4% would consider it in boys only. The specific phenotype of full mutation is recognized well by health professionals, while the premutation phenotype is not well known. There is a need to expand awareness on the fragile X premutation phenotype through better information. Testing of fragile X premutation status in minors should be considered, when at risk due to family history.

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5. Golubova TF, Tsukurova, Korsunskaya LL, Osipyan RR, Vlasenko SV, Savchuk EA. [S100B protein in the blood of children with autism spectrum disorders]. Zh Nevrol Psikhiatr Im S S Korsakova. 2019 ; 119(12) : 76-83.

AIM : To evaluate the plasma content of S100B protein in children with autism spectrum disorders (ASD). MATERIAL AND METHODS : Forty-five children with autism (item F84 of ICD-10), aged from 6 to 15 years, were examined. The control group (KG) consisted of 25 healthy children. The study included examination by specialists, an assessment of the severity of the disease using the Children’s Rating Scale of Autism scale (CARS), evaluation of S100B in blood serum. RESULTS : The content of S100B in children with autism was significantly higher in comparison with KG. The level of S100B in children with ASD with abnormal development of brain structures (MRI) was significantly higher compared with KG and a group of children without signs of disturbance of brain structures. S100B levels were higher in children with severe ASD, and differed from controls in children with moderate ASD. CONCLUSION : The majority of children with ASD show signs of stress of neuroprotective mechanisms, and children with anomalies of brain structures have signs of hypoxia of the brain and damage of the blood-brain barrier.

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6. Happe F, Frith U. Annual Research Review : Looking back to look forward - changes in the concept of autism and implications for future research. J Child Psychol Psychiatry. 2020.

The concept of autism is a significant contribution from child psychiatry that has entered wider culture and public consciousness, and has evolved significantly over the last four decades. Taking a rather personal retrospective, reflecting on our own time in autism research, this review explores changes in the concept of autism and the implications of these for future research. We focus on seven major changes in how autism is thought of, operationalised, and recognised : (1) from a narrow definition to wide diagnostic criteria ; (2) from a rare to a relatively common condition, although probably still under-recognised in women ; (3) from something affecting children, to a lifelong condition ; (4) from something discreet and distinct, to a dimensional view ; (5) from one thing to many ’autisms’, and a compound or ’fractionable’ condition ; (6) from a focus on ’pure’ autism, to recognition that complexity and comorbidity is the norm ; and finally, (7) from conceptualising autism purely as a ’developmental disorder’, to recognising a neurodiversity perspective, operationalised in participatory research models. We conclude with some challenges for the field and suggestions for areas currently neglected in autism research.

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7. Hugo M, Hedegaard J. Inclusion through folk high school in Sweden - the experience of young adult students with high-functioning autism. Disabil Rehabil. 2020 : 1-10.

Purpose : The purpose of this study is to provide a description of the learning environment at Folk High School for participants with high-functioning autism and to examine their learning experience at Folk High School.Methods : A qualitative interview study was conducted with 21 participants who were enrolled at Folk High School which had been adapted to suit young adults with high-functioning autism. The interviews were analysed by means of a thematic content analysis which resulted in the identification of 6 themes related to learning experiences at Folk High School.Results : The participants enjoyed themselves and felt secure at Folk High School. They felt that they and their academic endeavours were suitably recognised, acknowledged, and understood. They reported that the teaching was suitably adapted for them and they felt that they could succeed in their studies. A frequent report that they made concerned their experience of clear structures in the teaching process and its predictability. The participants stated that Folk High School has the ability to satisfy each participant’s needs, which entailed lower levels of perceived stress than what they had experienced in their previous schooling. The participants experienced personal development during their time at Folk High School.Conclusions : Folk High School, and its special character, is able to successfully satisfy the needs of participants with high-functioning autism. Many of the participants, for the first time in their lives, experienced a sense of inclusion in an educational system and felt that they could succeed in their studies. However, there exists a risk that they become institutionalised, which entails that the participants function well primarily in Folk High School’s safe and caring environment.Implications for rehabilitationA supportive environment including both formal and social learning is paramount for people with high-functioning autism.Individually adapted teaching that is structured and predictable improve the conditions under which they can focus on their studies and enjoy academic success.The teachers’ relational competence and ability to show interest in each individual are crucial.Social- and special-pedagogic competencies need to co-exist so as to improve learning conditions.Internship/workplace training can provide an important social learning experience for participants, as they learn about themselves and others and as they develop their social competence.To practice living on one’s own is a significant challenge, but it can create opportunities to learn about one’s self and to develop a sense of responsibility and other social skills.

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8. Lobzhanidze G, Japaridze N, Lordkipandize T, Rzayev F, MacFabe D, Zhvania M. Behavioral and Brain Ultrastructural Changes Following Systemic Administration of Propionic Acid in Adolescent Male Rats. Further Development of a Rodent Model of Autism. Int J Dev Neurosci. 2020.

Short chain fatty acids, produced as gut microbiome metabolites but also present in diet, exert broad effects in host physiology. Propionic acid (PPA), along with butyrate and acetate, plays a growing role in health, but also in neurological conditions. Increased PPA exposure in humans, animal models and cell lines elicit diverse behavioral and biochemical changes consistent with organic acidurias, mitochondrial disorders and autism spectrum disorders (ASD). ASD is considered a disorder of synaptic dysfunction and cell signaling, but also neuroinflammatory and neurometabolic components. We examined behavior (Morris water and radial arm mazes) and the ultrastructure of the hippocampus and medial prefrontal cortex (electron microscopy) following a single intraperitoneal (i.p.) injection of PPA (175 mg/kg) in male adolescent rats. PPA treatment showed altered social and locomotor behavior without changes in learning and memory. Both transient and enduring ultrastructural alterations in synapses, astro- and microglia were detected in the CA1 hippocampal area. Electron microscopic analysis showed, PPA treatment significantly decreased total number of synaptic vesicles, presynaptic mitochondria and synapses with a symmetric active zone. Thus, brief systemic administration of this dietary and enteric short chain fatty acid produced behavioral and dynamic brain ultrastructural changes, providing further validation of the PPA model of ASD.

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9. Pi X, Liu C, Li Z, Guo H, Jiang H, Du M. A Meta-Analysis of Oral Health Status of Children with Autism. The Journal of clinical pediatric dentistry. 2020 ; 44(1) : 1-7.

Purpose : To present a meta-analysis whether the risks of caries and periodontal problems in autistic children are higher than those in healthy children. Study design : A literature search that included PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure (CNKI), Wan fang, and Chinese Scientific and Technological Journal (VIP) databases was conducted. The primary outcomes of interest included the DMFT index, Plaque index (PI), Gingival index (GI), and Salivary pH. Quality assessment was performed in accordance with the Newcastle-Ottawa Scale (NOS). Dichotomous variables are presented as relative risk (RR), and continuous variables are presented as weighted mean difference (WMD). Results : Eight studies were included in this meta-analysis. Among these 8 studies, six studies compared the DMFT index, three studies compared PI, three studies compared GI, and three studies compared salivary pH. Meta-analysis showed that the mean DMFT index in autistic children was higher than that in healthy children, and the difference was statistically significant MD = 0.50, 95% CI [0.04-0.96], P<0.00001. Similarly, PI and GI in autistic children were higher than those in healthy children, and the difference between PI was statistically significant MD = 0.59, 95%CI [0.36-0.82], P=0.02, while the difference between GI was not statistically significant MD = 0.52, 95%CI [0.30-0.75], P=0.08. But the salivary pH in autistic children was lower than that in healthy children MD = -0.28, 95%CI [-0.54—0.02], P = 0.02, and the difference was statistically significant. Conclusion : The present analysis suggests that children with autism have poorer oral hygiene, higher risk of caries, and a lower salivary pH than healthy children.

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10. Putkonen N, Laiho A, Ethell D, Pursiheimo J, Anttonen AK, Pitkonen J, Gentile AM, de Diego-Otero Y, Castren ML. Urine microRNA Pro fi ling Displays miR-125a Dysregulation in Children with Fragile X Syndrome. Cells. 2020 ; 9(2).

A triplet repeat expansion leading to transcriptional silencing of the FMR1 gene results in fragile X syndrome (FXS), which is a common cause of inherited intellectual disability and autism. Phenotypic variation requires personalized treatment approaches and hampers clinical trials in FXS. We searched for microRNA (miRNA) biomarkers for FXS using deep sequencing of urine and identi fi ed 28 differentially regulated miRNAs when 219 reliably identi fi ed miRNAs were compared in dizygotic twin boys who shared the same environment, but one had an FXS full mutation, and the other carried a premutation allele. The largest increase was found in miR-125a in the FXS sample, and the miR-125a levels were increased in two independent sets of urine samples from a total of 19 FXS children. Urine miR-125a levels appeared to increase with age in control subjects, but varied widely in FXS subjects. Should the results be generalized, it could suggest that two FXS subgroups existed. Predicted gene targets of the differentially regulated miRNAs are involved in molecular pathways that regulate developmental processes, homeostasis, and neuronal function. Regulation of miR-125a has been associated with type I metabotropic glutamate receptor signaling (mGluR), which has been explored as a treatment target for FXS, reinforcing the possibility that urine miR-125a may provide a novel biomarker for FXS.

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11. Sala G, Hooley M, Stokes MA. Romantic Intimacy in Autism : A Qualitative Analysis. J Autism Dev Disord. 2020.

Although autistic people have difficulties with social-emotional reciprocity, most still desire intimate romantic relationships. This study sought to identify enablers and barriers to emotional and physical intimacy for Autistic (n = 31) and non-autistic (n = 26) individuals. All participants completed an online survey including demographic information, the Autism Spectrum Quotient and questions on intimacy which were subject to thematic analysis. Enablers of intimacy for both groups included communication, sharing and similarity, respect and safety for self and other, and working on the relationship. Barriers for both groups included intra- and interpersonal conflicts ; autistic people specifically highlighted uncertainty about relationships and communication. These findings suggest autistic and non-autistic people have similar notions of intimacy, yet have different challenges in experiencing it.

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12. Scott TM, Guo H, Eichler EE, Rosenfeld JA, Pang K, Liu Z, Lalani S, Weimin B, Yang Y, Bacino CA, Streff H, Lewis AM, Koenig MK, Thiffault I, Bellomo A, Everman DB, Jones JR, Stevenson RE, Bernier R, Gilissen C, Pfundt R, Hiatt SM, Cooper GM, Holder JL, Jr., Scott DA. BAZ2B haploinsufficiency as a cause of developmental delay, intellectual disability and autism spectrum disorder. Human mutation. 2020.

The bromodomain adjacent to zinc finger 2B gene (BAZ2B) encodes a protein involved in chromatin remodeling. Loss of BAZ2B function has been postulated to cause neurodevelopmental disorders. To determine whether BAZ2B deficiency is likely to contribute to the pathogenesis of these disorders, we performed bioinformatics analyses that demonstrated a high level of functional convergence, during fetal cortical development, between BAZ2B and genes known to cause autism spectrum disorder and neurodevelopmental disorder. We also found an excess of de novo BAZ2B loss-of-function variants in exome sequencing data from previously published cohorts of individuals with neurodevelopmental disorders. We subsequently identified seven additional individuals with heterozygous deletions, stop-gain, or de novo missense variants affecting BAZ2B. All of these individuals have developmental delay, intellectual disability and/or autism spectrum disorder. Taken together, our findings suggest that haploinsufficiency of BAZ2B causes a neurodevelopmental disorder whose cardinal features include developmental delay, intellectual disability and autism spectrum disorder. This article is protected by copyright. All rights reserved.

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13. Shaffer RC, Schmitt L, John Thurman A, Abbeduto L, Hong M, Pedapati E, Dominick K, Sweeney J, Erickson C. The Relationship between Expressive Language Sampling and Clinical Measures in Fragile X Syndrome and Typical Development. Brain Sci. 2020 ; 10(2).

Language impairment is a core difficulty in fragile X syndrome (FXS), and yet standardized measures lack the sensitivity to assess developmental changes in the nature of these impairments. Expressive Language Sampling Narrative (ELS-N) has emerged as a promising new measure with research demonstrating its usefulness in a wide range of ages in developmental disabilities and typical development. We examined ELS-N results in FXS and age-matched typically developing (TD) controls along with cognitive, adaptive, and clinical measures. We found the groups differed significantly on all ELS-N variables. Cognitive abilities were related to lexical diversity, syntactic complexity, and unintelligibility for the FXS group, but only verbal abilities were related to syntactic complexity in TD. Autism spectrum disorder (ASD) symptomatology was related to less intelligibility in speech. Measures of hyperactivity were related to increased talkativeness and unintelligibility. In addition, FXS males in comparison to FXS females were more impaired in cognitive ability, ASD symptoms, hyperactivity, and anxiety. This study extends the previous ELS research, supporting its use in FXS research as a measure to characterize language abilities. It also demonstrates the relationships between ELS-N variables and measures of cognitive, adaptive, ASD symptoms, and clinical symptoms.

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14. Smolich L, Charen K, Sherman SL. Health knowledge of women with a fragile X premutation : Improving understanding with targeted educational material. Journal of genetic counseling. 2020.

Women who carry a fragile X premutation are at risk for at least two major health conditions and for transmitting fragile X syndrome (FXS) to their children. The two health concerns include fragile X-associated primary ovarian insufficiency (FXPOI) and fragile X-associated tremor/ataxia syndrome (FXTAS). The aim of this study was to evaluate whether written educational information about these conditions would increase knowledge and facilitate communication. Women with a premutation (N = 142) completed an online pre-test to assess their knowledge of premutation-associated conditions, and 135 women who provided an address received a booklet titled Women’s Health and the Fragile X Premutation. After 3 months, 51.1% completed the post-test. Major gaps in knowledge were related to FXPOI and factors associated with repeat expansion. To determine whether the booklet helped to fill gaps in knowledge, we compared pre- and post-test scores. Scores were significantly increased after receipt of the booklet (p < .05, Wilcoxon signed rank test). Participants answered that the booklet was ’very helpful’ (44.6%) or ’somewhat helpful’ (38.5%). Twenty-four participants (34.8%) reported using the booklet to explain concepts to family members. Although we found that the booklet provided women with needed information, we found that gaps in knowledge still exist.

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15. Stefanelli A, Zanchetta S, Furtado EF. Auditory hyper-responsiveness in autism spectrum disorder, terminologies and physiological mechanisms involved : systematic review. CoDAS. 2020 ; 32(3) : e20180287.

PURPOSE : this paper aims to identify the most used terminologies to designate the disproportional behavior to sounds in the autism spectrum disorder (ASD) and its relationship with the respective tools for its investigation, as well as its occurrence and outcomes. RESEARCH STRATEGIES : the databases used were PubMed, PsycINFO, Web of Science, Scielo and Lilacs. The keywords used were "autism", "hyperacusis" and "auditory perception", with the following combinations : "autism AND hyperacusis" and "autism AND auditory perception". SELECTION CRITERIA : individuals diagnosed with ASD of any age group ; available abstract ; papers in English, Spanish and Brazilian Portuguese ; case series, prevalence and incidence studies, cohort and clinical trials. DATA ANALYSIS : we analyzed studies with individuals diagnosed with ASD of any age group ; reference in the title and/or summary of the occurrence of disproportional behavior to sounds, accepting the terms hyper-responsiveness, hypersensitivity and hyperacusis ; summary available ; papers in English, Spanish and Brazilian Portuguese ; series of cases, prevalence and incidence studies, cohort and clinical trials. RESULTS : Of the 692 studies resulting from the consultation, 13 studies could achieve the established requirements. CONCLUSION : The term auditory hypersensitivity was the most commonly used to designate disproportional behavior to sounds, followed by hyperacusis. There was no relationship between the terms and the respective research tool, and the questionnaires were the most used to designate the referred behavior, whose reported frequency was from 42.1% to 69.0%. The auditory behavior tests when performed showed the involvement of the auditory, afferent and efferent neural pathways.

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16. Umesawa Y, Matsushima K, Atsumi T, Kato T, Fukatsu R, Wada M, Ide M. Altered GABA Concentration in Brain Motor Area Is Associated with the Severity of Motor Disabilities in Individuals with Autism Spectrum Disorder. J Autism Dev Disord. 2020.

Several motor disabilities accompanied with autism spectrum disorder (ASD) are widely known despite limited reports of underlying neural mechanisms. Gamma-aminobutyric acid (GABA) levels in the motor-related cortical areas modulate several motor performances in healthy participants. We hypothesized that abnormal GABA concentrations in the primary motor area (M1) and supplementary motor area (SMA) associate with different motor difficulties for ASD adolescents/adults. We found that increased GABA concentrations in M1 measured using (1)H-magnetic resonance spectroscopy exhibited lower motor performance in tasks requiring increased muscle strength while lower GABA concentrations in SMA were associated with lower scores in tests measuring body coordination. The degrees of neural inhibition in the M1 and SMA regions would contribute to different dimensions of motor disabilities in autism.

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17. Vovou F, Hull L, Petrides KV. Mental health literacy of ADHD, autism, schizophrenia, and bipolar disorder : a cross-cultural investigation. Journal of mental health (Abingdon, England). 2020 : 1-11.

Background : Mental health literacy (MHL) is linked to help-seeking behaviours. Although lay people are not always well aware of mental health conditions, few international campaigns and interventions have been developed to raise awareness across cultures.Aims : To investigate MHL cross-culturally and to identify factors that are associated with MHL.Method : Using an online survey, 506 participants (103 Greek, 108 UK, 146 USA, 149 other nationality) read and labelled five vignettes of individuals with Autism, ADHD, Schizophrenia, Bipolar disorder and a healthy control. Factors influencing response, confidence and accuracy were compared across all participants, and the effect of various demographics on accurate labelling was compared between countries.Results : Recognition rates were higher than in previous investigations : 75.5% of participants recognised the Healthy vignette, 71.1% ADHD, 61.7% Autism, 56.6% Schizophrenia and 31.6% Bipolar. MHL varied across different countries, with religion, language spoken, and education having the greatest effects. Personal experience of mental illness partially affected MHL.Conclusions : MHL is relatively high for some mental health conditions, but public knowledge of other conditions is still poor. Factors influencing MHL vary across countries.

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18. Zavadenko NN, Davydova LA. [Neurological and neurodevelopmental disorders in preterm-born children (with extremely low, very low or low body weight)]. Zh Nevrol Psikhiatr Im S S Korsakova. 2019 ; 119(12) : 12-9.

AIM : To evaluate the incidence of neurological diseases and neurodevelopmental disorders in preterm-born children, aged 5-8 years, with extremely low (ELBW), very low (VLBW) or low body weight (LBW) at birth. MATERIAL AND METHODS : One hundred and twenty-two preterm-born children, including 36 born with ELBW, 36 born with VLBW and 50 born with LBW, were examined in the age from 5 years 0 months to 8 years 0 months. Presenting complaints were assessed by means of the structured parents’ questionnaire. Diagnosis of the nervous system diseases was based on the criteria of ICD-10 and DSM-V. RESULTS AND CONCLUSION : Based on the assessment results, there was no any neurological or neurodevelopmental disorder in 8.3% (n=3) of children with ELBW, 16.7% (n=6) with VLBW, 22.0% (n=11) with LBW at birth. Compared to the general pediatric population, more preterm-born children with ELBW, VLBW or LBW, aged 5-8 years, had developmental dyspraxia, chronic motor tics, tension type headaches and enuresis. Moreover, the higher incidence was found for neurodevelopmental disorders, including attention deficit hyperactivity disorder, autism spectrum disorders, specific learning disabilities, compared with population rates. All conditions were more prevalent in boys than in girls, with the exception of tension type headaches. The frequency of disorders was inversely correlated with gestational age and body weight. However, the results demonstrate reserve capacities of the developing brain in children born preterm and suffered early brain damage.

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