Preventive effects of resveratrol against early-life impairments in the animal model of autism induced by valproic acid.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by social interaction deficits and repetitive/stereotyped behaviors. Its prevalence is increasing, affecting one in 36 children in the United States. The valproic acid (VPA) induced animal model of ASD is a reliable method for investigating cellular, molecular, and behavioral aspects related to the disorder. Trans-Resveratrol (RSV), a polyphenol with anti-inflammatory and antioxidant effects studied in various diseases, has recently demonstrated the ability to prevent cellular, molecular, sensory, and social deficits in the VPA model. In this study, we examined the effects of prenatal exposure to VPA and the potential preventive effects of RSV on the offspring. Method: We monitored gestational weight from embryonic day 6.5 until 18.5 and assessed the onset of developmental milestones and morphometric parameters in litters. The generalized estimating equations (GEE) were used to analyze longitudinal data. Results: Exposure to VPA during rat pregnancy resulted in abnormal weight gain fold-changes on embryonic days 13.5 and 18.5, followed by fewer animals per litter. Additionally, we discovered a positive correlation between weight variation during E15.5-E18.5 and the number of rat pups in the VPA group. Conclusion: VPA exposure led to slight length deficiencies and delays in the onset of developmental milestones. Interestingly, the prenatal RSV treatment not only prevented most of these delays but also led to the early onset of certain milestones and improved morphometric characteristics in the offspring. In summary, our findings suggest that RSV may have potential as a therapeutic intervention to protect against the negative effects of prenatal VPA exposure, highlighting its importance in future studies of prenatal neurodevelopmental disorders.

Stroke in children and adolescents: Analysis of electrophysiological and behavioral assessment findings of auditory processing.

PURPOSE: This study aimed to analyze the auditory processing behavior of children and adolescents diagnosed with stroke and compare it with that of typically developing individuals. METHODS: This was an analytical cross-sectional study involving 48 participants aged between 7 and 17 years with adequate schooling for age and grade, allocated equally to two groups: Stroke (SG) and Control Groups (CG). For the SG, cases identified between 2003 and 2018 were considered. In the CG, school-aged participants with typical development were randomized. After screening for differential audiological assessment and confirmation of auditory pathway integrity at the brainstem level, binaural analyses of the auditory processing behavior were conducted using the Dichotic Digit Test (DDT), Frequency Pattern Test (FPT), and electrophysiological assessment (P300). The Shapiro-Wilk test for normality was conducted, followed by the T and Mann-Whitney tests, with a 95 % confidence level and significance offset at p < 0.05, using the SPSS software (IBM®, v. 22.) RESULTS: The CG performed better in terms of auditory processing. These differences were significant (p < 0.0001) for the binaural integration of DDT, FPT humming and Labeling, and P300 latency. The P300 results were similar; however, with a greater amplitude in the SG. CONCLUSION: This study showed that children and adolescents with stroke performed worse in electrophysiological and behavioral tests of auditory processing assessed using the auditory evoked potentials. These data reinforce the hypothesis that stroke-related lesions compromise the neural mechanisms underlying auditory processing.

HLA-G*14 bp indel variant in autism spectrum disorder in a population from southern Brazil.

Altered immune response during pregnancy has been associated with ASD susceptibility. HLA-G is expressed by the trophoblast at the maternal/fetal interface and induces allogenic tolerance toward the fetus. A 14-bp insertion in the HLA-G 3'UTR (rs371194629) was associated with reduced levels of HLA-G. We aimed to assess the influence of the HLA-G*14 bp indel variant in ASD susceptibility and symptomatology in a Brazilian admixed sample. The insertion genotype (14 bp+/14 bp+) was firstly associated with hetero aggression, but statistical significance was lost after correction (p = 0.035, pcorrected = 0.35). No association between the HLA-G variant and susceptibility to ASD or differential clinical manifestations were observed.

Exploring potential impacts of pregnancy-related maternal immune activation and extracellular vesicles on immune alterations observed in autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders usually observed in early life, with impacts on behavioral and social skills. Incidence of ASD has been dramatically increasing worldwide, possibly due to increase in awareness/diagnosis as well as to genetic and environmental triggers. Currently, it is estimated that ∼1% of the world population presents ASD symptoms. In addition to its genetic background, environmental and immune-related factors also influence the ASD etiology. In this context, maternal immune activation (MIA) has recently been suggested as a component potentially involved in ASD development. In addition, extracellular vesicles (EVs) are abundant at the maternal-fetal interface and are actively involved in the immunoregulation required for a healthy pregnancy. Considering that alterations in concentration and content of EVs have also been associated with ASD, this article raises a debate about the potential roles of EVs in the processes surrounding MIA. This represents the major differential of the present review compared to other ASD studies. To support the suggested correlations and hypotheses, findings regarding the roles of EVs during pregnancy and potential influences on ASD are discussed, along with a review and update concerning the participation of infections, cytokine unbalances, overweight and obesity, maternal anti-fetal brain antibodies, maternal fever, gestational diabetes, preeclampsia, labor type and microbiota unbalances in MIA and ASD.

Association between NKG2/KLR gene variants and epilepsy in Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is a set of neurodevelopmental disorders mainly characterized by repetitive, restrictive and stereotypical behaviors, and impaired communication skills. Several lines of evidence indicate that alterations of the immune system account for ASD development, including the presence of brain-reactive antibodies, abnormal T cell activation, altered cytokine levels in brain, cerebrospinal fluid and peripheral blood circulation, increased levels of circulating monocytes, and dysregulation in Natural Killer (NK) cells activity. Regarding NK cells, a lower cytotoxic activity, a higher level of activation and an increased number of these cells in individuals with ASD have been described. In 2019, a study showed that NK cells derived from patients with ASD show a characteristic pattern of NKG2C overexpression, highlighting the importance of the NK cell pathway in ASD. In fact, the study of genes related to NK cell activity has proven to be an excellent research target, both in terms of susceptibility as well as a marker for the different clinical manifestations observed in ASD individuals. Here, we evaluated the influence of KLRC2 gene deletion as well as KLRK1 rs1049174 and rs2255336 variants in a cohort of 185 children diagnosed with ASD and their respective biological parents in southern Brazil. Of note, this is the first study concerning genetic variants of the KLRC2 and KLRK1 genes in an ASD sample. The KLRC2 gene deletion (p = 0.001; pc = 0.009), KLRK1 rs1049174 (p = 0.005; pc = 0.045) and KLRK1 rs2255336 (p = 0.001; pc = 0.009) were associated with epilepsy in ASD patients. The results indicate that KLRC2 deletion, KLRK1 rs2255336, and KLRK1 rs1049174 could be involved in epilepsy manifestation in ASD patients, possibly impacting the NK dysregulation already described in ASD and epileptic patients.

Mismatch Negativity in Children and Adolescents with Autism Spectrum Disorder

Abstract Introduction Individuals with autism spectrum disorder (ASD) have abnormalities in auditory perception and sensitivity. The mismatch negativity (MMN) component of the evoked potential demonstrates a brain detection response to an auditory change due to memory, and enables the identification of changes in the auditory system. Objectives To analyze MMN responses in children and adolescents with ASD and compare them with those of a control group. Methods Cross-sectional and comparative study. The sample was composed of 68 children and adolescents, divided into study group (SG), which contained those diagnosed with ASD, and the control group (CG), which contained those with typical development, normal hearing thresholds, and without hearing complaints. All participants were submitted to peripheral and central electrophysiological auditory evaluations. For the electrophysiological auditory evaluation and MMN recording, the electrodes were fixed in the following positions: Fz (active electrode), M1 and M2 (reference electrodes), and on the forehead (ground electrode). Auditory stimuli were presented in both ears simultaneously, with a frequency of 1,000 Hz for the frequent stimulus, and of 2,000 Hz for the rare stimulus, in an intensity of 80 dBNA. Results Latency and amplitude values were increased in the SG, with a statistically significant difference in comparison with the CG. In the MMN analysis, there was no statistically significant difference in the comparison between right and left ears and between genders. Conclusions Children and adolescents with ASD had higher latency and amplitude values in the MMN component than the individuals in the CG.

Mismatch Negativity in Children and Adolescents with Autism Spectrum Disorder.

Introduction Individuals with autism spectrum disorder (ASD) have abnormalities in auditory perception and sensitivity. The mismatch negativity (MMN) component of the evoked potential demonstrates a brain detection response to an auditory change due to memory, and enables the identification of changes in the auditory system. Objective To analyze MMN responses in children and adolescents with ASD and compare them with those of a control group. Methods Cross-sectional and comparative study. The sample was composed of 68 children and adolescents, divided into study group (SG), which contained those diagnosed with ASD, and the control group (CG), which contained those with typical development, normal hearing thresholds, and without hearing complaints. All participants were submitted to peripheral and central electrophysiological auditory evaluations. For the electrophysiological auditory evaluation and MMN recording, the electrodes were fixed in the following positions: Fz (active electrode), M1 and M2 (reference electrodes), and on the forehead (ground electrode). Auditory stimuli were presented in both ears simultaneously, with a frequency of 1,000 Hz for the frequent stimulus, and of 2,000 Hz for the rare stimulus, in an intensity of 80 dBNA. Results Latency and amplitude values were increased in the SG, with a statistically significant difference in comparison with the CG. In the MMN analysis, there was no statistically significant difference in the comparison between right and left ears and between genders. Conclusion Children and adolescents with ASD had higher latency and amplitude values in the MMN component than the individuals in the CG.

Stroke in children and adolescents: Analysis of electrophysiological and behavioral assessment findings of auditory processing

Abstract Purpose: This study aimed to analyze the auditory processing behavior of children and adolescents diagnosed with stroke and compare it with that of typically developing individuals. Methods: This was an analytical cross-sectional study involving 48 participants aged between 7 and 17 years with adequate schooling for age and grade, allocated equally to two groups: Stroke (SG) and Control Groups (CG). For the SG, cases identified between 2003 and 2018 were considered. In the CG, school-aged participants with typical development were randomized. After screening for differential audiological assessment and confirmation of auditory pathway integrity at the brainstem level, binaural analyses of the auditory processing behavior were conducted using the Dichotic Digit Test (DDT), Frequency Pattern Test (FPT), and electrophysiological assessment (P300). The Shapiro-Wilk test for normality was conducted, followed by the T and Mann-Whitney tests, with a 95 % confidence level and significance offset at p < 0.05, using the SPSS software (IBM®, v. 22.) Results: The CG performed better in terms of auditory processing. These differences were significant (p < 0.0001) for the binaural integration of DDT, FPT humming and Labeling, and P300 latency. The P300 results were similar; however, with a greater amplitude in the SG. Conclusion: This study showed that children and adolescents with stroke performed worse in electrophysiological and behavioral tests of auditory processing assessed using the auditory evoked potentials. These data reinforce the hypothesis that stroke-related lesions compromise the neural mechanisms underlying auditory processing.

The effect of the "K" technique on levels of anxiety and salivar cortisol in adolescents / O efeito da técnica "K" nos níveis de ansiedade e cortisol salivar em adolescentes / El efecto de la técnica "K" sobre la ansiedad y los niveles de cortisol salivales en adolescentes

This research presents theoretical arguments of a new approach called Technique "K," which aims to reduce student's anxiety before a cognitive challenge. Through a randomized, controlled clinical trial, we evaluate the Beck Anxiety Inventory and salivary cortisol. We compared the results in the last year of high school, who were facing school tests, before and after the application of the "K" technique (intervention group) and placebo (control group). Statistical analyses consisted of using the Chisquare, Spearman and the Wilcoxon test. The principal component analysis observed in the case group, - 10.50 (-18.25; -4.75), was statistically higher than the control group, -6.00 (-8.75; -1.25). It is not possible to identify statistical significance (p = 0.462) in the variation of salivary cortisol concentration. The results suggest the effectiveness of the "K" technique in managing anxiety in high school students. Although, future research is needed to extend the preliminary data obtained in this study

Esta pesquisa apresenta argumentos teóricos de uma nova abordagem denominada Técnica "K", visando reduzir a ansiedade do aluno diante de um desafio cognitivo. Por meio de um ensaio clínico randomizado e controlado, avaliamos o Inventário de Ansiedade de Beck e o cortisol salivar. Comparamos os resultados dos alunos, que estavam enfrentando provas escolares, antes e após a aplicação da técnica "K" (grupo intervenção) e placebo (grupo controle). As análises estatísticas consistiram na utilização do Qui-quadrado, Spearman e teste de Wilcoxon. A análise de componentes principais observada no grupo caso, -10,50 (-18,25; -4,75), foi estatisticamente superior ao grupo controle, -6,00 (-8,75; -1,25). Não é possível identificar significância estatística (p = 0,462) na variação da concentração de cortisol salivar. Os resultados sugerem a eficácia da técnica "K" no manejo da ansiedade em estudantes do ensino médio. No entanto, pesquisas futuras são necessárias para estender os dados preliminares obtidos neste estudo

Esta investigación presenta argumentos teóricos para un nuevo enfoque denominado Técnica "K", con el objetivo de reducir la ansiedad de los estudiantes frente a un desafío cognitivo. A través de un ensayo clínico aleatorizado y controlado, evaluamos el Inventario de Ansiedad de Beck y el cortisol salival. Comparamos los resultados de los estudiantes, que se enfrentaban a pruebas escolares, antes y después de la aplicación de la técnica "K" (grupo de intervención) y placebo (grupo control). Los análisis estadísticos consistieron en utilizar la prueba de Chicuadrado, Spearman y Wilcoxon. El análisis de componentes principales observado en el grupo de casos, -10,50 (-18,25; -4,75), fue estadísticamente superior al grupo control, -6,00 (-8,75; -1,25). No es posible identificar significación estadística (p = 0,462) en la variación de la concentración de cortisol salival. Los resultados sugieren la efectividad de la técnica "K" en el manejo de la ansiedad en estudiantes de secundaria. Sin embargo, se necesitan futuras investigaciones para ampliar los datos preliminares obtenidos en este estudio

Resveratrol Treatment of Autism Spectrum Disorder-A Pilot Study.

OBJECTIVES: Considering autism spectrum disorder (ASD) as a neurodevelopmental condition associated with immune system impairments, we aimed to evaluate the potential benefits, efficacy, tolerability, and safety of the anti-inflammatory, antioxidant, and neuroprotective trans -resveratrol (RSV) in behavioral impairments and in a set of 8 microRNAs (miR) related to the immune system in pediatric subjects with ASD. METHODS: This is an open-label pilot trial over a 3 months (90 days) study follow-up period designed to assess the effect of 200 mg/d RSV on 5 boys aged 10 to 13 (11.8 ± 1.1) years diagnosed with ASD according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition . RESULTS: The RSV treatment significantly reduced the Aberrant Behavior Checklist total score ( P = 0.042) and Irritability ( P = 0.041), with no alteration in Stereotypical Behavior ( P = 0.066), Hyperactivity ( P = 0.068), and Lethargy/Social Withdrawal ( P = 0.078) subscales. On the Clinical Global Impression scale, 3 individuals showed marked improvement in behavior; one showed mild improvement, and the other had no changes. The RSV treatment increased the miR-195-5p ( P = 0.043), an important modulator of targets related to inflammatory and immunological pathways. RSV administration did not present adverse effects and did not alter clinical laboratory results. CONCLUSIONS: RSV is a safe molecule for administrating in the pediatric population, able to modulate behavior alterations and molecules associated with the immune system, becoming a promising therapeutic strategy for large-scale studies in ASD, to investigate both behavioral and molecular approaches.

Resveratrol Prevents Cytoarchitectural and Interneuronal Alterations in the Valproic Acid Rat Model of Autism.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by several alterations, including disorganized brain cytoarchitecture and excitatory/inhibitory (E/I) imbalance. We aimed to analyze aspects associated with the inhibitory components in ASD, using bioinformatics to develop notions about embryonic life and tissue analysis for postnatal life. We analyzed microarray and RNAseq datasets of embryos from different ASD models, demonstrating that regions involved in neuronal development are affected. We evaluated the effect of prenatal treatment with resveratrol (RSV) on the neuronal organization and quantity of parvalbumin-positive (PV+), somatostatin-positive (SOM+), and calbindin-positive (CB+) GABAergic interneurons, besides the levels of synaptic proteins and GABA receptors in the medial prefrontal cortex (mPFC) and hippocampus (HC) of the ASD model induced by valproic acid (VPA). VPA increased the total number of neurons in the mPFC, while it reduced the number of SOM+ neurons, as well as the proportion of SOM+, PV+, and CB+ neurons (subregion-specific manner), with preventive effects of RSV. In summary, metabolic alterations or gene expression impairments could be induced by VPA, leading to extensive damage in the late developmental stages. By contrast, due to its antioxidant, neuroprotective, and opposite action on histone properties, RSV may avoid damages induced by VPA.

The role of T-cells in neurobehavioural development: Insights from the immunodeficient nude mice.

Mice homozygous for the nude mutation (Foxn1nu) are hairless and exhibit congenital dysgenesis of the thymic epithelium, resulting in a primary immunodeficiency of mature T-cells, and have been used for decades in research with tumour grafts. Early studies have already demonstrated social behaviour impairments and central nervous system (CNS) alterations in these animals, but did not address the complex interplay between CNS, immune system and behavioural alterations. Here we investigate the impact of T-cell immunodeficiency on behaviours relevant to the study of neurodevelopmental and neuropsychiatric disorders. Moreover, we aimed to characterise in a multidisciplinary manner the alterations related to those findings, through evaluation of the excitatory/inhibitory synaptic proteins, cytokines expression and biological spectrum signature of different biomolecules in nude mice CNS. We demonstrate that BALB/c nude mice display sociability impairments, a complex pattern of repetitive behaviours and higher sensitivity to thermal nociception. These animals also have a reduced IFN-γ gene expression in the prefrontal cortex and an absence of T-cells in meningeal tissue, both known modulators of social behaviour. Furthermore, excitatory synaptic protein PSD-95 immunoreactivity was also reduced in the prefrontal cortex, suggesting an intricate involvement of social behaviour related mechanisms. Lastly, employing biospectroscopy analysis, we have demonstrated that BALB/c nude mice have a different CNS spectrochemical signature compared to their heterozygous littermates. Altogether, our results show a comprehensive behavioural analysis of BALB/c nude mice and potential neuroimmunological influences involved with the observed alterations.

Cortical auditory-evoked potential as a biomarker of central auditory maturation in term and preterm infants during the first 3 months.

OBJECTIVES: To analyze central auditory maturation in term and preterm infants during the first 3 months of life by comparing the latency and amplitude of cortical auditory-evoked potential at different frequencies. METHODS: In this study, 17 term and 18 preterm infants were examined; all had tested positive on the neonatal hearing screening test. Cortical auditory potential was investigated during the first and third months of life. The response of the cortical auditory-evoked potential was investigated at frequencies of 500, 1000, 2000, and 4000 Hz. The latency and amplitude of the cortical response were automatically detected and manually analyzed by three researchers with experience in electrophysiology. The results were compared using analysis of variance and the Bonferroni test. A significance level of 5% was used for all analyses. RESULTS: Latency values of cortical auditory-evoked potential in the first month of birth were significantly higher than those in the third month, and latency values of the preterm group were higher than those of the term group, regardless of the frequency and time of evaluation. In general, the latency of the cortical auditory-evoked potential was higher at high frequencies. Amplitude values in the third month of life were significantly higher than those in the first month for term and preterm infants. CONCLUSION: Central auditory maturation was observed in both groups but with different results between those born at term and preterm, with latencies of cortical auditory-evoked potential higher for the preterm group and at high frequencies.

Resveratrol prevents brain edema, blood-brain barrier permeability, and altered aquaporin profile in autism animal model.

Autism spectrum disorder can present a plethora of clinical conditions associated with the disorder, such as greater brain volume in the first years of life in a significant percentage of patients. We aimed to evaluate the brain water content, the blood-brain barrier permeability, and the expression of aquaporin 1 and 4, and GFAP in a valproic acid-animal model, assessing the effect of resveratrol. On postnatal day 30, Wistar rats of the valproic acid group showed greater permeability of the blood-brain barrier to the Evans blue dye and a higher proportion of brain water volume, prevented both by resveratrol. Prenatal exposition to valproic acid diminished aquaporin 1 in the choroid plexus, in the primary somatosensory area, in the amygdala region, and in the medial prefrontal cortex, reduced aquaporin 4 in medial prefrontal cortex and increased aquaporin 4 levels in primary somatosensory area (with resveratrol prevention). Valproic acid exposition also increased the number of astrocytes and GFAP fluorescence in both primary somatosensory area and medial prefrontal cortex. In medial prefrontal cortex, resveratrol prevented the increased fluorescence. Finally, there was an effect of resveratrol per se on the number of astrocytes and GFAP fluorescence in the amygdala region and in the hippocampus. Thus, this work demonstrates significant changes in blood-brain barrier permeability, edema formation, distribution of aquaporin 1 and 4, in addition to astrocytes profile in the animal model of autism, as well as the use of resveratrol as a tool to investigate the mechanisms involved in the pathophysiology of autism spectrum disorder.

Zika Virus Infection Associated with Autism Spectrum Disorder: A Case Report.

INTRODUCTION: The aim of this case was to investigate the association of the Zika virus infection in utero with the autism spectrum disorder (ASD) as clinical outcome that presented no congenital anomalies. METHODS: ASD was diagnosed in the second year of life by different child neurologists and confirmed by DSM-5 and ASQ. After that, an extensive clinical, epidemiological, and genetic evaluations were performed, with main known ASD causes ruled out. RESULTS: An extensive laboratorial search was done, with normal findings. SNP array identified no pathogenic variants. Normal neuroimaging and EEG findings were also obtained. ZIKV (Zika virus) IgG was positive, while IgM was negative. Other congenital infections were negative. The exome sequencing did not reveal any pathogenic variant in genes related to ASD. CONCLUSION: Accordingly, this report firstly associates ZIKV exposure to ASD.

Central auditory processing: behavioral and electrophysiological assessment of children and adolescents diagnosed with stroke.

INTRODUCTION: Central auditory processing refers to the efficiency and effectiveness with which the central nervous system uses auditory information: it may be altered in neurological disorders and brain injuries, such as strokes. However, despite evidence of probable alterations in the pediatric population, functional abilities and post-stroke limitations are still not well documented in the literature. OBJECTIVE: To analyze the findings of the electrophysiological and behavioral evaluations of central auditory processing of children and adolescents diagnosed with stroke from a reference outpatient clinic, as well as to investigate possible associations with the variables: type and location of the stroke and age group. METHODS: The present study is characterized as comparative cross-sectional. The sample, for convenience, included individuals aged 7-18 years divided into two groups: study group, composed of individuals with a diagnosis of stroke, and control group, composed of individuals with typical development. The evaluation consisted of the following procedures: anamnesis, basic audiological evaluation, behavioral evaluation of the auditory processing disorder (dichotic digit test, dichotic consonant-vowel, synthetic sentence identification/pediatric speech intelligibility, gaps in noise, pitch pattern sequence, masking level difference), and electrophysiological evaluation (P300 and mismatch negativity). RESULTS: Nineteen children and adolescents were included in the study group. The control group was composed of 19 children and adolescents with typical development. In the comparison between the groups, a worse performance is observed for the study group in all the evaluated tests, behavioral and electrophysiological. In the behavioral evaluation of central auditory processing, there was a statistical difference for all tests, except for masking level difference and dichotic digit test, binaural separation step on the left. In the electrophysiological evaluation, there was a statistical difference in the latency of mismatch negativity and P300. No associations were found between the behavioral and electrophysiological findings and the location of the stroke and age group variables. CONCLUSION: Children and adolescents diagnosed with stroke present a worse performance in the electrophysiological and behavioral evaluations of central auditory processing when compared to a control group.

Cortical auditory-evoked potential as a biomarker of central auditory maturation in term and preterm infants during the first 3 months

OBJECTIVES: To analyze central auditory maturation in term and preterm infants during the first 3 months of life by comparing the latency and amplitude of cortical auditory-evoked potential at different frequencies. METHODS: In this study, 17 term and 18 preterm infants were examined; all had tested positive on the neonatal hearing screening test. Cortical auditory potential was investigated during the first and third months of life. The response of the cortical auditory-evoked potential was investigated at frequencies of 500, 1000, 2000, and 4000 Hz. The latency and amplitude of the cortical response were automatically detected and manually analyzed by three researchers with experience in electrophysiology. The results were compared using analysis of variance and the Bonferroni test. A significance level of 5% was used for all analyses. RESULTS: Latency values of cortical auditory-evoked potential in the first month of birth were significantly higher than those in the third month, and latency values of the preterm group were higher than those of the term group, regardless of the frequency and time of evaluation. In general, the latency of the cortical auditory-evoked potential was higher at high frequencies. Amplitude values in the third month of life were significantly higher than those in the first month for term and preterm infants. CONCLUSION: Central auditory maturation was observed in both groups but with different results between those born at term and preterm, with latencies of cortical auditory-evoked potential higher for the preterm group and at high frequencies.

Vitamin D deficiency in pediatric patients using antiepileptic drugs: systematic review with meta-analysis / Deficiência de vitamina D em pacientes pediátricos que fazem uso de fármacos antiepilépticos - revisão sistemática com metanálise

Abstract Objectives: To measure the prevalence of vitamin D deficiency (through the 25-hydroxyvitamin D metabolite) in pediatric patients using antiepileptic drugs. Source of data: Meta-analysis of studies identified through search in the PubMed, Embase, LILACS, and Cochrane Library databases, on February 19, 2019. Summary of data: A total of 748 articles were identified, 29 of which were relevant to the objectives of this study. The prevalence of vitamin D deficiency found was 0.32 (95% CI = 0.25-0.41; I 2 = 92%, p < 0.01). In the subgroup analyses, the most significant results were observed in the group of patients using cytochrome P450-inducing antiepileptic drugs, with a prevalence of 0.33 (95% CI = 0.21-0.47; I 2 = 86%, p < 0.01) and, considering the study design, in the subgroup of cohort studies, with a prevalence of 0.52 (95% CI = 0.40-0.64; I 2 = 76%, p < 0.01). Conclusions: Taking into account the deleterious effects of vitamin D deficiency on the bone health of individuals using antiepileptic drugs, it is suggested to include in their care 25-hydroxyvitamin D monitoring, cholecalciferol supplementation, and treatment of the deficiency, when present.

Resumo Objetivos: Mensurar a prevalência de deficiência de vitamina D (através do metabólito 25-hidroxivitamina D) em pacientes pediátricos em uso de fármacos antiepilépticos. Fonte dos dados: Metanálise de estudos identificados por meio de pesquisa nas bases de dados Pubmed, Embase, LILACS e Cochrane em 19 de fevereiro de 2019. Síntese dos dados: Foram identificados 748 artigos, dos quais 29 mostraram-se relevantes aos objetivos deste estudo. A prevalência de deficiência de vitamina D encontrada foi de 0,32 (IC 95% = 0,25-0,41) (I2 = 92%, p < 0,01). Nas análises por subgrupos, os resultados mais expressivos foram observados no grupo de pacientes em uso de fármacos antiepilépticos indutores do citocromo P450, que apresentou prevalência de 0,33 (IC 95% = 0,21-0,47) (I2 = 86%, p < 0,01). Considerou-se o delineamento dos estudos, no subgrupo de estudos de coorte, com prevalência de 0,52 (IC 95% = 0,40-0,64) (I2 = 76%, p < 0,01). Conclusões: Levando-se em consideração os efeitos deletérios da deficiência de vitamina D na saúde óssea dos sujeitos em uso de fármacos antiepilépticos, sugere-se incluir em seu atendimento, o monitoramento de 25-hidroxivitamina D, suplementação com colecalciferol e tratamento de deficiência quando existente.

Cortical auditory evoked potential in assessment of neonates: a study about minimum level of responses in term and preterm newborns / Potencial evocado auditivo cortical na avaliac¸ão de neonatos: um estudo sobre o nível mínimo de respostas em nascidos a termo e pré-termos

Abstract Introduction: The study of the threshold level of cortical auditory response in adults has been investigated in previous studies. Due to maturational issues, little is known about these responses in neonates. Technological advances with automatic analysis devices now allow investigation in specific populations. Thus, new studies are needed to establish the feasibility of using this auditory potential to identify the lowest levels of responses in children. Objective: Verify and compare latency and amplitude in 80 dBnNA and the minimum level of cortical auditory response in term and preterm neonates. Methods: A cross-sectional, comparative study involving 59 neonates, 35 full-term births and 24 preterm births, with positive results in the Neonatal Hearing Screening. The Hearlab system was used to investigate the P1i auditory potential with tone burst stimulus at frequencies of 500, 1000, 2000 and 4000 Hz. The minimum response level search ranged from 80 to 0 dBNA and was detected automatically. The results were compared between groups, evaluating the latency and amplitude in 80 dBNA and the minimum level of cortical auditory response. Results: The mean values obtained for the minimum level of cortical auditory response in term group were 26 ± 8.81; 26.14 ± 6.97; 29 ± 7.65 and 29.43 ± 7.04 dBNA and for preterm neonates of 31.96 ± 10.41; 34.13 ± 11.34; 33.64 ± 11.03 and 37.73 ± 11.92 dBNA, for the frequencies of 500, 1000, 2000 and 4000 Hz, respectively. There was a difference between groups for the latency of P1i at 4000 Hz and the minimum response levels at 500, 1000 and 4000 Hz, with higher values for preterm infants. Conclusion: It was possible to obtain latency and amplitude values at 80 dBnNA and the minimum level of cortical response in term and preterm newborns, with different results between groups, with higher values in those born preterm.

Resumo Introdução: A investigação do nível mínimo de resposta auditiva cortical tem sido alvo de diferentes estudos em adultos. Devido a questões de maturação, pouco se sabe sobre essas respostas em recém-nascidos. Com o avanço tecnológico, dispositivos de análise automática surgiram com o objetivo de retomar essa avaliação em populações específicas. Assim, novos estudos são necessários para verificar a viabilidade do uso desse potencial auditivo na obtenção de níveis mínimos de respostas na criança. Objetivo: Verificar e comparar latência e amplitude em 80 dBnNA e o nível mínimo de resposta auditiva cortical em recém-nascidos a termo e pré-termo. Método: Estudo transversal, comparativo, envolvendo 59 neonatos, 35 nascidos a termo e 24 pré-termos, com resultados positivos na triagem auditiva neonatal. O sistema Hearlab foi utilizado para investigar o potencial auditivo P1i com estímulo tone burst nas frequências de 500, 1000, 2000 e 4000 Hz. A busca do nível mínimo de resposta variou de 80 a 0 dBNA e foi detectado automaticamente. Os resultados foram comparados entre os grupos, avaliando a latência e amplitude em 80 dBNA e o nível mínimo de resposta auditiva cortical. Resultados: Os valores médios obtidos para o nível mínimo de resposta auditiva cortical no grupo nascido a termo foram 26 ± 8,81; 26,14 ± 6,97; 29 ± 7,65 e 29,43 ± 7,04 dBNA e para recém-nascidos pré-termos foram de 31,96 ± 10,41; 34,13 ± 11,34; 33,64 ± 11,03 e 37,73 ± 11,92 dBNA, para as frequências de 500, 1000, 2000 e 4000 Hz, respectivamente. Houve diferenc¸a entre os grupos para a latência de P1i em 4000 Hz e os níveis mínimos de resposta em 500, 1000 e 4000 Hz, com valores maiores em Pré-termos. Conclusão: Foi possível obter valores de latência e amplitude em 80 dBnNA e o nível mínimo de resposta cortical em recém-nascidos a termo e Pré-termos, com resultados diferentes entre osgrupos, com valores maiores em pré-termos.

Hyperbilirubinemia impact on newborn hearing: a literature review.

The increase in bilirubin levels in newborns can cause toxic effects on the auditory system, which can lead to hearing loss. This review aimed to verify the impact of hyperbilirubinemia in the hearing of newborns, relating audiological findings to serum levels of bilirubin. A literature review was conducted during October 2017, using the terms "hyperbilirubinemia", "jaundice", "infant", "newborn" and "hearing loss", on databases CAPES journals, MEDLINE and BIREME (SciELO, BBO). 827 studies were identified and 59 were selected for full-text reading, resulting in the selection of seven articles that met the inclusion criteria and were considered relevant to the sample of this study. All the reviewed studies performed brainstem auditory evoked potential as the main test for audiological evaluation. Changes in the audiological findings of neonates with hyperbilirubinemia were observed in all studies. There was no consensus on the serum bilirubin levels that may cause auditory changes; however, the relationship between hearing disorders and blood levels of bilirubin was positive. We identify the need to establish reference values for bilirubin levels considered critical for the occurrence of hearing disorders as well as the audiological follow-up of neonates with hyperbilirubinemia.