Enfermedades sin diagnostico y enfermedades raras: avances en neurodesarrollo / Rare diseases and undiagnosed diseases: advances in neurodevelopment

Resumen Las enfermedades raras y enfermedades sin diag nóstico se han posicionado en los últimos años como condiciones clínicas que han permitido avanzar el en tendimiento de las funciones de los genes y el im pacto en el desarrollo del individuo. En esta revisión, presentamos como los esfuerzos individuales hechos por muchos años para entender la fisiopatología de en fermedades comunes, enfermedades raras y otras aún más raras, como las enfermedades sin diagnóstico, que se unen hoy para, de manera cooperativa, avanzar en el conocimiento científico. Estos avances en el conoci miento permiten aplicar los avances obtenidos en un grupo de condiciones clínicas a otras con características fenotípicas similares o viceversa. El trabajo conjunto de equipos multidisciplinarios y la comunicación entre clínicos e investigadores proporcionarán oportunidades para proveer mejores oportunidades de tratamiento para pacientes y familias a lo largo de múltiples diagnósticos comunes o raros.

Abstract Rare diseases and undiagnosed diseases have re cently positioned themselves as clinical entities that provide important opportunities to advance our under standing of gene functions and the impact of them in the individual development. In this review, we present how efforts made over years to understand common diseases, rare diseases and even undiagnosed diseases come together today to cooperatively advances scientific knowledge. These advance in science and new acquired knowledge, make possible to apply the advances ob tained in a group of clinical conditions to others with similar phenotypic characteristics or vice versa. The cooperative work of multidisciplinary teams and the communication between clinicians and researchers have and will provide opportunities for better treatments for patients and families across multiple common and rare diseases.

Corioamnionitis histológica y neurodesarrollo en niños prematuros menores de 34 semanas, Lima-Perú

Para determinar los efectos de la corioamnionitis histológica en el neurodesarrollo de los prematuros menores de 34 semanas evaluados a los 2 años de edad corregida se realizó un estudio secundario de casos y controles. Fueron analizados los datos clínicos, hallazgos histológicos de la placenta e índices del desarrollo medidos por la Escala Bayley III de 38 niños expuestos y 53 niños no expuestos. Las infecciones genitourinarias de la madre y la sepsis precoz fueron más frecuentes en el grupo expuesto (p<0,005). Las dimensiones del desarrollo cognitivo, motor y lenguaje fueron normales en ambos grupos. Los expuestos al subtipo subcorionitis obtuvieron menor desempeño en las tres dimensiones. La corioamnionitis histológica no mostró influencia sobre el neurodesarrollo en prematuros menores de 34 semanas a los 2 años de edad. Se recomienda estudios longitudinales y multicéntricos para definir los efectos a largo plazo.

SUMMARY The objective of this study was to determine the effects of histologically diagnosed chorioamnionitis on neurodevelopment of premature babies born with less than 34-week gestational age who were assessed at two-year corrected age. A secondary case-control study was carried out. Clinical data, placental histological findings, and development indexes assessed using the Bayley III scale were analyzed in 38 exposed children and 53 non-exposed children. Genitourinary infections in mothers and early sepsis were more frequent in the exposed group (p<0.005). Cognitive development, motor development and language were normal in both groups. Those children exposed to the chorionitis subtype had lower scores in the aforementioned variables. Histologically diagnosed chorioamnionitis did not show any influence on neurodevelopment in premature babies born with less than 34-week gestational age when they were assessed at two years. Longitudinal and multicenter studies are advised in order to define the long-term effects.

Translating advances in developmental social neuroscience into greater access to early diagnosis in autism spectrum disorder / Repercusión de los avances en la neurociencia social del desarrollo en un mayor acceso al diagnóstico temprano en el trastorno del espectro autista

Abstract Early identification and diagnosis of autism spectrum disorder (ASD) is necessary to promote access to early treatment, a critical factor in optimizing children's lifetime outcomes. And yet, diagno sis is often late, delaying interventions to a time in which symptoms have aggravated and communication skills already show impairing differences. This review illustrates progress in developmental social neuroscience that shows promise in generating novel tools for objective and cost-effective early diagnosis of ASD. We focus on research of social visual engagement, which is the way infants and toddlers look at and learn from their social environment. Moment-by-moment quantification of social visual engagement is yielding measures that are begin ning to approximate best-practice procedures used by experienced clinicians in the assessment of young children. This progress and potential solutions have public health import ance because experienced clinicians are limited in number, and specialized clinical assessment services tend to be lengthy, costly, and plagued by extended wait time, all of which contributing to limited access, particularly in the case of low-resource families. The research reviewed here illustrates a wider effort to advance biomarker-based measurements intended to develop better and more efficient tools and procedures for screening, diagnosing and monitoring treatment response in children with ASD. The advent of such tools could increase access to early diagnostic services and promote efficiencies in early treatment delivery, with the ultimate goal of ensuring that children with ASD are afforded the services they need to thrive.

Resumen La identificación y el diagnóstico temprano del trastorno del espectro autista (TEA) son necesarios para promover el acceso al tratamiento temprano, un factor crítico para optimizar los resultados de por vida de los niños. Y, sin embargo, el diagnóstico suele llegar tarde, lo que retrasa las intervenciones hasta un momento en el que los síntomas se han agravado y las habilidades de comunicación ya muestran diferencias perjudiciales. Esta revisión ilustra el progreso en la neurociencia social del desarrollo que se muestra prometedora en la generación de herramientas novedosas para el diagnóstico temprano objetivo y rentable de los TEA. Hacemos énfasis en la investigación del compromiso visual social, que es la forma en que los bebés y los niños pequeños miran y aprenden de su entorno social. La cuantificación momento a momento del compromiso visual social está gene rando medidas que comienzan a aproximarse a los procedimientos de mejores prácticas utilizados por médicos experimentados en la evaluación de niños pequeños. Este progreso y las posibles soluciones tienen importancia para la salud pública porque los médicos con experiencia son limitados en número y los servicios de evaluación clínica especializados tienden a ser largos, costosos y están plagados de tiempo de espera prolongado, todo lo cual contribuye a un acceso limitado, particularmente en el caso de familias con bajos recursos. La investigación revisada aquí ilustra un esfuerzo más amplio para avanzar en las mediciones basadas en biomarcadores desti nadas a desarrollar herramientas y procedimientos mejores y más eficientes para la detección, el diagnóstico y el seguimiento de la respuesta al tratamiento en niños con TEA. El advenimiento de tales herramientas podría aumentar el acceso a los servicios de diagnóstico temprano y promover la eficiencia en la entrega del trata miento temprano, con el objetivo final de garantizar que los niños con TEA reciban los servicios que necesitan para prosperar.

Trastorno del espectro autista en mujeres: A propósito de un caso clínico / Autism spectrum disorder in women: About a clinical case

El diagnóstico de trastorno del espectro autista (TEA) en mujeres presenta importantes complejidades, desafíos y particularidades. Históricamente se ha planteado que este trastorno es más frecuente en hombres, existiendo, además, un sesgo hacia el género masculino en el screening y criterios diagnósticos. Objetivo: Presentar un caso clínico a fin de revisar las dificultades y particularidades asociadas al proceso diagnóstico de TEA en mujeres. Discusión: Las investigaciones a la fecha han planteado que muchas niñas no encajan en el perfil tradicional de TEA. Se han descrito características específicas del cuadro clínico en el sexo femenino, varias de las cuales se evidencian en el caso clínico presentado. Por otro lado, existen altas tasas de comorbilidades, tanto con patologías médicas como psiquiátricas, las cuales son siempre relevantes de evaluar. Conclusiones: Como en muchos otros aspectos, las mujeres también han sido invisibilizadas en lo que respecta al TEA. Es relevante que se continúe estudiando el tema para lograr un diagnóstico e intervención precoces en esta población.

The diagnosis of autism spectrum disorder (ASD) in women presents with significant complexities and challenges. It has been mentioned that the disorder is more prevalent in males, and there is also a bias towards the male gender in screening and diagnostic criteria. Objectives: To present a clinical case in order to review difficulties and peculiarities associated with the diagnostic process of ASD in women. Discussion: It has been suggested that many girls do not fit the traditional profile of ASD. Specific characteristics of the female gender phenotype have been described, several of which are illustrated in the clinical case presented. On the other hand, there are high rates of comorbidities, both with medical and psychiatric conditions, which are always relevant to assess and recognize. Conclusions: As in various other aspects, women have also been unrecognized and misdiagnosed when it comes to ASD. It is relevant that we keep understanding this issue, in order to achieve an early diagnosis and provide proper interventions to this population.

A preliminary study on the relationship between neural development and gut microbiota in preterm infants / 中国医师杂志

Objective:To explore the relationship between the neural development of preterm infants and gut microbiota.Methods:66 premature infants who were hospitalized in the Neonatology Department of Hunan Children′s Hospital from September 2018 to September 2019 were included in the study. Their fecal samples and clinical data from the first admission were collected. According to the neurodevelopment, the patients were divided into normal neurodevelopment group and neurodysplasia group. The bacterial DNA of fecal samples was extracted by 16S rDNA high-throughput sequencing technology and bioinformatics analysis was conducted to compare the composition and diversity of gut microbiota between the two groups.Results:(1) The Shannon index of gut microbiota in normal neurodevelopmental group and neurodysplastic group was 0.89(0.41, 1.51) and 1.01(0.47, 1.31), respectively. There was no significant difference in diversity index between the two groups ( P>0.05). (2) Bifidobacterium, veronica and negativites in the gut microbiota of the normal neurodevelopmental group were significantly higher (all P<0.05), and streptococcus in the gut microbiota of the dysplastic group were significantly higher ( P<0.05). The gut microbiota of the two groups were mainly enterococcus and escherichia shigella. Conclusions:At the genus level, enterococcus and escherichia are the dominant flora of early gut microbiota in preterm infants. Gut microbiota is related to the neural development of preterm infants. The increased abundance of streptococcus, and the decreased abundance of bifidobacterium, veronicus, and negativites may be risk factors for neurodysplasia of preterm infants. The diversity of gut microbiota in early preterm infants may not be significantly related to neural development.

Effects of lead and manganese combined exposure on neurodevelopmental toxicity and JNK expression in zebrafish / 环境与职业医学

Background Lead and manganese are heavy metal pollutants widely existing in the environment, which can accumulate in the human body through the food chain, exert neurotoxicity, and cause neurodegenerative disorders. Especially in early childhood, the developing blood-brain barrier and nervous system are highly susceptible to environmental chemical pollutants. Most of the previous studies focused on the toxic effects of single heavy metal such as lead or manganese, while the studies on combined toxic effect are still scarce, and involved mechanisms are still unclear. c-Jun N-terminal kinase (JNK) is involved in neuronal development and regeneration, and some studies have found that JNK is involved in lead or manganese induced neurotoxicity. Its role in the toxicity of combined lead and manganese is unknown. Objective To understand the neurodevelopmental toxicity mechanism and to observe changes of JNK expression in zebrafish induced by combined lead and manganese exposure at environmentlly low concentrations. Methods Zebrafish embryos within 2 h post fertilization (hpf) were divided into four groups: control group, lead exposure group (0.1 mg·L−1 lead acetate), manganese exposure group (0.3 mg·L−1 manganous chloride), and lead-manganese combined exposure group (0.1 mg·L−1 lead acetate +0.3 mg·L−1 manganous chloride) and exposed to lead or/and manganese at designed levels for 7 d. Spontaneous movements and motor locomotion were observed, and mortality rate were calculated. The changes of JNK mRNA expression in zebrafish were evaluated. Results The experimental results showed that no significant effect of lead or/and manganese on spontaneous movements and mortality rate was found in zebrafish compared with the control group (P＞0.05). The results of locomotion analysis showed that compared with the control group, the activity counts and activity distance of zebrafish in the manganese exposure group were slightly increased (P＜0.01); the activity counts and activity distance of zebrafish in the lead exposure group were reduced by 50% and those in the lead-manganese exposure group were reduced by 80% (P＜0.01). Compared with the lead exposure group, the activity counts and activity distance of zebrafish in the lead-manganese combined exposure group decreased significantly by 60% (P＜0.05). The real-time quantitative PCR results showed that the JNK mRNA expression level was significantly increased in the lead-manganese combined exposure group compared with the control group(P＜0.01). Conclusion Lead exposure combined with manganese exposure at environmentlly low concentration can induce neurodevelopmental toxicity to zebrafish. JNK may be involved in neurodevelopmental toxicity induced by the combined exposure to lead and manganese.

Physical growth and neurodevelopment of preterm infants at the corrected age of 18-24 months / 中国当代儿科杂志

OBJECTIVES@#To investigate the levels of physical growth and neurodevelopment in preterm infants at the corrected age of 18-24 months.@*METHODS@#The physical growth data and neurodevelopment data of 484 preterm infants at corrected age of 18-24 months were prospectively collected by a post-discharge follow-up system for preterm infants. The infants were regularly followed up in Shenzhen Bao'an Maternal and Child Health Hospital Affiliated to Jinan University from April 2018 to December 2021. The neurodevelopment was evaluated by the Children Neuropsychological and Behavioral Scale-Revision 2016. A total of 219 full-term infants served as controls. The infants were divided into groups (extremely preterm, very preterm, moderate late preterm, and full-term) based on gestational age, and the groups were compared in the levels of physical growth and neurodevelopment.@*RESULTS@#Except that the moderate preterm group had a higher length-for-age Z-score than the full-term group (P=0.038), there was no significant difference in physical growth indicators between the preterm groups and the full-term group (P>0.05). Each preterm group had a significantly lower total developmental quotient (DQ) than the full-term group (P<0.05). Except for the social behavior domain, the DQ of other domains in the extremely preterm and very preterm groups was significantly lower than that in the full-term group (P<0.05). The <32 weeks preterm group had a significantly higher incidence rate of global developmental delay than the full-term group (16.7% vs 6.4%, P=0.012), and the incidence rate of global developmental delay tended to increase with the reduction in gestational age (P=0.026).@*CONCLUSIONS@#Preterm infants can catch up with full-term infants in terms of physical growth at the corrected age of 18-24 months, but with a lower neurodevelopmental level than full-term infants. Neurodevelopment monitoring and early intervention should be taken seriously for preterm infants with a gestational age of <32 weeks.

Role of N6-methyladenosine RNA methylation in central nervous system: a review / 生物工程学报

There are a variety of post-transcriptional modifications in mRNA, which regulate the stability, splicing, translation, transport and other processes of mRNA, followed by affecting cell development, body immunity, learning and cognition and other important physiological functions. m6A modification is one of the most abundant post-transcriptional modifications widely existing in mRNA, regulating the metabolic activities of RNA and affecting gene expression. m6A modified homeostasis is critical for the development and maintenance of the nervous system. In recent years, m6A modification has been found in neurodegenerative diseases, mental diseases and brain tumors. This review summarizes the role of m6A methylation modification in the development, function and related diseases of the central nervous system in recent years, providing potential clinical therapeutic targets for neurological diseases.

Baicalin Ameliorates Corticosterone-Induced Depression by Promoting Neurodevelopment of Hippocampal via mTOR/GSK3β Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the role of hippocampal neurodevelopment in the antidepressant effect of baicalin.@*METHODS@#Forty male Institute of Cancer Research mice were divided into control, corticosterone (CORT, 40 mg/kg), CORT+baicalin-L (25 mg/kg), CORT+baicalin-H (50 mg/kg), and CORT+fluoxetine (10 mg/kg) groups according to a random number table. An animal model of depression was established by chronic CORT exposure. Behavioral tests were used to assess the reliability of depression model and the antidepressant effect of baicalin. In addition, Nissl staining and immunofluorescence were used to evaluate the effect of baicalin on hippocampal neurodevelopment in mice. The protein and mRNA expression levels of neurodevelopment-related factors were detected by Western blot analysis and real-time polymerase chain reaction, respectively.@*RESULTS@#Baicalin significantly ameliorated the depressive-like behavior of mice resulting from CORT exposure and promoted the development of dentate gyrus in hippocampus, thereby reversing the depressive-like pathological changes in hippocampal neurons caused by CORT neurotoxicity. Moreover, baicalin significantly decreased the protein and mRNA expression levels of glycogen synthase kinase 3β (GSK3β), and upregulated the expression levels of cell cycle protein D1, p-mammalian target of rapamycin (mTOR), doublecortin, and brain-derived neurotrophic factor (all P<0.01). There were no significant differences between baicalin and fluoxetine groups (P>0.05).@*CONCLUSION@#Baicalin can promote the development of hippocampal neurons via mTOR/GSK3β signaling pathway, thus protect mice against CORT-induced neurotoxicity and play an antidepressant role.

Research hotspots in post-discharge follow-up management of preterm infants / 中国当代儿科杂志

Preterm infants, especially those born extremely or very prematurely, are at high risk for growth retardation and neurodevelopmental disorders. Regular follow-up after discharge, early intervention, and timely catch-up growth are important guarantees for improving the quality of life of preterm infants and improving the quality of the population. This article provides an overview of the research hotspots in follow-up management of preterm infants after discharge over the past two years, including follow-up modes, nutritional metabolism and body composition follow-up, growth pattern follow-up, neurodevelopmental follow-up, early intervention, etc., in order to provide clinical guidance and research ideas for domestic peers.

Follow-up and prognostic study of infants with positional plagiocephaly / 中国当代儿科杂志

OBJECTIVES@#To study the effects of infantile positional plagiocephaly on the growth and neural development.@*METHODS@#A retrospective study was conducted on the medical data of 467 children who underwent craniographic examination and were followed up to 3 years of age in Peking University Third Hospital from June 2018 to May 2022. They were divided into four groups: mild positional plagiocephaly (n=108), moderate positional plagiocephaly (n=49), severe positional plagiocephaly (n=12), and normal cranial shape (n=298). The general information of the four groups and the weight, length, head circumference, visual acuity screening results, hearing test results, and the scores of Pediatric Neuropsychological Developmental Scales/Gesell Developmental Schedules of the four groups from 6 to 36 months old were compared.@*RESULTS@#The rates of adverse perinatal factors, congenital muscular torticollis, and supine fixed sleeping posture in the mild, moderate, and severe positional plagiocephaly groups were higher than the normal cranial group (P<0.05). There was no significant difference in weight, length, and head circumference among the four groups at 6, 12, 24 and 36 months of age (P>0.05). The incidence rate of abnormal vision in the severe positional plagiocephaly group was higher than that in the mild positional plagiocephaly, moderate positional plagiocephaly and normal cranial shape groups at 24 and 36 months of age (P<0.05). The scores of the Pediatric Neuropsychological Developmental Scales at 12 and 24 months of age and the scores of the Gesell Developmental Schedules at 36 months of age in the severe positional plagiocephaly group were lower than those in the mild positional plagiocephaly, moderate positional plagiocephaly and normal cranial shape groups, but the difference was not statistically significant (P>0.05).@*CONCLUSIONS@#Adverse perinatal factors, congenital muscular torticollis, and supine fixed sleeping position may be associated with infantile positional plagiocephaly. Mild or moderate positional plagiocephaly has no significant impact on the growth and neural development of children. Severe positional plagiocephaly have adverse effects on the visual acuity. However, it is not considered that severe positional plagiocephaly can affect the neurological development.

Resultados en el neurodesarrollo en la edad preescolar y escolar de los recién nacidos pretérminos asistidos en el CTI neonatal de la Asociación Médica de San José / Neurodevelopmental preschool and school results of preterm newborns assisted at the neonatal ICU of the San José department medical provider in Uruguay / Resultados neuro desenvolvimento em idade pré-escolar e escolar de recém-nascidos pré-termos atendidos na UTI neonatal da assistência médica do departamento do São José no Uruguai

Uruguay acompaña la tendencia mundial al descenso de la natalidad con un descenso de la mortalidad concomitante, siendo la primera causa de mortalidad infantil la prematurez. Enfocados en la prematurez, es de nuestro interés conocer qué ocurre con estos niños luego del alta de la unidad neonatal. Se realizó el estudio de una cohorte de niños entre 4 y 8 años, nacidos con 32 semanas o menos de edad gestacional y/o con pesos al nacer de 1.500 g o menos, asistidos en su período neonatal en la Asociación Médica de San José, a quienes se les realizó el test de Battelle. Se logró identificar las áreas con mayor dificultad en el desarrollo para cada grupo de edad, concluyendo que se pueden realizar planes específicos de acción para promover el desarrollo de estos niños en la edad preescolar y escolar.

Uruguay follows the global declining trend in birth rates along with decreasing mortality, being prematurity the main cause of infant mortality. We studied premature children who had undergone the Battelle Test and had been discharged from the neonatal unit, a cohort of children between 4 and 8 years of age, born at 32 weeks or less of gestational age and/or having a birth weight of 1500g or less, assisted in their neonatal period at the San José Department Medical Center. We could identify the main areas affecting development for each age group, and concluded that specific action plans can be carried out to promote the development of these children at preschool and school age.

O Uruguai acompanha a tendência mundial de declínio das taxas de natalidade com uma concomitante diminuição da mortalidade, sendo a prematuridade a principal causa de mortalidade infantil. Nos focamos na prematuridade e no estudo do que acontece com essas crianças após a alta da unidade neonatal. Realizamos um estudo de uma coorte de crianças entre 4 e 8 anos que tinham sido submetidas ao Teste de Battelle, nascidas com 32 semanas ou menos de idade gestacional e/ou com peso de nascimento igual ou inferior a 1500g, atendidas no período neonatal na Assistência Médica do Departamento de São José no Uruguai. Foi possível identificar as áreas de maior dificuldade de desenvolvimento para cada faixa etária, e concluir que podem se realizar planos de ação específicos para promover o desenvolvimento dessas crianças em idade pré-escolar e escolar.

Genética de los trastornos del neurodesarrollo. Aspectos prácticos / Genetics of neurodevelopmental disorders. Practical aspects

Resumen Los trastornos del neurodesarrollo (TND) constituyen un grupo relevante de enfermedades, con base biológica y etiología total o parcialmente genética. El reconocimiento de los factores causales cons tituye un reto cuyos resultados se han perfeccionado a lo largo de las últimas décadas, hasta obtener un rédito diagnóstico cada vez mayor. La implementación de estos avances tecnológicos solo puede lograrse mediante la conformación de equipos de trabajo interdisciplinarios, que siguiendo un proceso ordenado, logran un diag nóstico de presunción, que luego es certificado mediante las técnicas que, para cada uno de los casos, resulta más redituable en calidad y costo. En este trabajo, enumeramos estos procedimientos a partir de diferentes escenarios que ponen de relieve el extenso menú de posibilidades y la necesidad de administrar los mismos de un modo racional, sobre bases científicas debidamente fundadas.

Abstract Neurodevelopmental disorders (NDD) constitute a relevant group of pathologies, of childhood, with a biological basis and totally or partially genetic etiology. The recognition of the causal factors constitutes a challenge that has been perfected over the last decades, until obtaining an increasing diagnostic yield. The implementation of these technological advances can only be achieved through the formation of interdisciplinary work teams, which, following an or derly process, achieve a presumptive diagnosis, which is then certified using the techniques that for each of the cases are more profitable in terms of quality and cost. In this paper we list these procedures, based on different scenarios that highlight the extensive menu of possibilities and the need to manage them in a rational way, on well-founded scientific bases.

Evaluación neurológica durante el primer año en niños muy bajo peso al nacer con infección por citomegalovirus / Neurological evaluation during the first year in very low birth weight children with cytomegalovirus infection

Introducción: La infección congénita por citomegalovirus es causa de pérdida auditiva y alteraciones cognitivas. La infección perinatal por este virus es más frecuente en neonatos< 1500 g y produce menos secuelas neurológicas. Objetivo: Describir la evaluación neurológica en el primer año de vida en niños muy bajo peso al nacer con infección por citomegalovirus. Métodos: Estudio descriptivo y longitudinal en el que se incuyeron 14 neonatos< 1500 g, con diagnóstico de infección congénita o perinatal por citomegalovirus; a los cuales se les realizó evaluación del neurodesarrollo, ultrasonido craneal, potenciales evocados auditivos de tallo cerebral y potenciales visuales a las 40 semanas, a los seis meses y al año de edad gestacional corregida. En la primera evaluación se realizó además, electroencefalograma. Resultados: El 43 por ciento tuvo infección congénita y 57 por ciento infección perinatal. A las 40 semanas se evaluaron completamente 79 % de los casos, a los seis meses 64 por ciento y al año 36 por ciento. No se observaron anormalidades en el ultrasonido craneal, ni en el electroencefalograma. Al año de edad corregida, se detectaron alteraciones ligeras del neurodesarrolo en 33,3 por ciento del total de casos (2/6) y con igual porcentaje en los niños con infección congénita (1/3) y perinatal (1/3). En ningún paciente evaluado se detectó sordera neurosensorial, ni daño del nervio visual. Conclusiones: Las alteraciones del neurodesarrollo encontradas al año de edad corregida pueden estar relacionadas con la prematuridad o la infección por citomegalovirus. El seguimiento a mediano y largo plazo es necesario para detectar otras secuelas neurológicas de debut tardío(AU)

Introduction: Congenital cytomegalovirus infection is a cause of hearing loss and cognitive impairments. Perinatal infection by this virus is more frequent in neonates< 1500 g and produces fewer neurological sequelae. Objective: To describe neurological evaluation in the first year of life in very low birth weight children with cytomegalovirus infection. Methods: A descriptive and longitudinal study involving 14 neonates< 1500 g, with a diagnosis of congenital or perinatal cytomegalovirus infection; to which neurodevelopmental evaluation, cranial ultrasound, auditory brain stem evoked potentials and visual potentials were performed at 40 weeks, six months and one year of corrected gestational age. In the first evaluation, electroencephalogram was also performed. Results: 43 percent had congenital infection and 57 percent perinatal infection. At 40 weeks, 79 percent of cases were fully evaluated, at six months 64 percent and at one year 36 percent. No abnormalities were observed on the cranial ultrasound or electroencephalogram. At one year of corrected age, slight alterations in neurodevelopment were detected in 33.3 percent of all cases (2/6) and with the same percentage in children with congenital (1/3) and perinatal (1/3) infection. In no patient evaluated, sensorineural deafness or visual nerve damage was detected. Conclusions: The neurodevelopmental alterations found at one year of corrected age may be related to prematurity or cytomegalovirus infection. Medium- and long-term follow-up is necessary to detect other late-onset neurological sequelae(AU)

Study of Neuro-developmental Outcome of Preterm Babies Using Risk Stratification Score at a Tertiary Care Hospital

Introduction : Recent advances and improvements in technology in Neonatal Intensive Care Unit (NICU) over the past few decades have increased th survival of preterm infants. India ranks first amongst the number of preterm birth. Though the survival of preterm babies have increased Neuro-developmental morbidity amongst such babies still persist. Through this study we aim to establish a risk stratification tool and predict neurodevelopmental delay at 1 year of age. Materials and Methods : A total number of 77 babies were enrolled in the study after fulfilment of inclusion and exclusion criteria. Follow up till 1 year of age of corrected gestational age was done. Development assessment was done through Child Development Centre (CDC) grading, Amile-Tison Angle, Developmental Observation Card, Trivandrum Developmental Screening Chart and development quotient. Vision and Hearing Assessment was also done. Conclusion : Neuro-developmental outcome prediction at 1 year of age is inadequate and proper long term follow p is needed. Overall preterm babies needing extensive resuscitation and 5 minute APGAR <6 had much poor neurological outcome.

El desafío para el desarrollo del sistema nervioso central en la reproducción humana asociada con la diabetes / The challenge for the development of the central nervous system in human reproduction associated with diabetes

Introducción: Los hijos de madres con diabetes presentan una mayor incidencia de trastornos del neurodesarrollo como autismo, actividad cognitiva baja, déficit de atención, esquizofrenia y otras enfermedades del espectro autista. Objetivo: Explicar los mecanismos moleculares que subyacen en la aparición de los trastornos del neurodesarrollo en hijos de gestantes con diabetes. Métodos: Se llevó a cabo una revisión de la literatura que aparece en las bases de datos electrónicas Google, MEDLINE/PubMed y SciELO. Se revisaron artículos publicados entre los años 2000 y 2020. Las palabras clave utilizadas fueron: hiperglucemia, neurodesarrollo, malformaciones congénitas y epigenética. Resultados: Se pone de manifiesto el alto riesgo que representa la hiperglucemia durante el desarrollo intrauterino. El riesgo relativo que tienen los hijos de madres con diabetes pregestacional de presentar malformaciones del sistema nerviosos central es 15,5 veces mayor que en gestantes sin diabetes. El hipocampo es especialmente sensible a cambios en los niveles de glucosa. La diabetes materna puede dejar una impronta negativa para la capacidad de procesar información, adquirir habilidades y poseer un comportamiento social adecuado en la descendencia. Conclusiones: Las alteraciones en el metabolismo condicionadas por la hiperglucemia, el estrés oxidativo, la inflamación de bajo grado y las modificaciones epigenéticas crean un fatal engranaje que sustenta el desarrollo anómalo en hijos de gestantes con diabetes(AU)

Introduction: Children, whose mothers suffer from diabetes, have higher incidence of neurodevelopmental disorders such as autism, low cognitive activity, attention deficit, schizophrenia and other autism spectrum diseases. Objective: To explain the molecular mechanisms that underlie the appearance of neurodevelopmental disorders in children of pregnant women with diabetes. Methods: A review of the literature that appears in Google, MEDLINE/PubMed and SciELO electronic databases, was carried out. Articles published from 2000 to 2020 were reviewed. The keywords used were hyperglycemia, neurodevelopment, congenital malformations, and epigenetics. Results: The high risk that hyperglycemia represents during intrauterine development is highlighted. The relative risk that children of mothers with pregestational diabetes have of presenting malformations of the central nervous system is 15.5 times higher than in pregnant women without diabetes. The hippocampus is especially sensitive to changes in glucose levels. Maternal diabetes can leave negative print on the ability to process information, acquire skills and have appropriate social behavior in their children. Conclusions: Alterations in metabolism conditioned by hyperglycemia, oxidative stress, low-grade inflammation and epigenetic modifications create a fatal mechanism that supports abnormal development in children of pregnant women with diabetes(AU)

Frontiers in the research of autism pathogenesis / Fronteras en la investigación de la patogenia del autismo

Abstract This review focuses on four interrelated teams and research lines that form the basis for new research on the pathogenesis of autism spectrum disorder (ASD) at the Marcus Autism Center, in Atlanta (US). These themes probe typical social behavior and brain development from birth, and disruptions thereof in babies later diagnosed with ASD. These four themes are: to leverage lifetime maximal neuroplasticity; to test the hypothesis that developmental disruption of early-emerging mechanisms of socialization drives pathogenesis and results in autistic social disability; the focus on the infant-caregiver dyad, and the iterative context associated with mutually reinforcing and adapted social and communitive inter-action, or emerging cycles of social contingency, from the first days and weeks of life; and the study of time-varying neurodevelopmental transitions in social behavior from experience-expectant (reflexive, endogenous) and subcortically-guided to experience-dependent (caregiver- and reward-driven) and cortically-guided, a transition that our work suggests is uniquely disrupted in babies later diagnosed with ASD. This science is opening a world of opportunities to optimize children's outcomes despite the genetic liabilities that they are born with. It provides the scientific grounding for new community-viable solutions for increasing access to early interventions using treatments that scaffold and strengthen infant-caregiver interactions, which is the platform for early brain development.

Resumen Esta revisión se centra en cuatro equipos y líneas de investigación interrelacionados que forman la b ase de nuevas investigaciones sobre la patogenia del Trastorno del Espectro Autista (TEA) en el Marcus Autism Center, en Atlanta (EE.UU.). Estos temas investigan el comportamiento social típico y el desarrollo del cerebro desde el nacimiento, y las altera ciones del mismo en los bebés a los que luego se les diagnostica TEA. Estos cuatro temas son: aprovechar la neuroplasticidad máxima en la vida; probar la hipótesis de que la interrupción del desarrollo de los mecanismos de socialización emergentes impulsa la patogénesis y da como resultado una discapacidad social autista; el enfoque en la díada bebé-cuidador, y el contexto iterativo asoc iado con la mutua interacción de refuerzo social y comunitario, o ciclos emergentes de contingencia social, desde los primeros días y semanas de vida; y el estudio de las transiciones del comportamiento social variable en el tiempo del neurodesarrollo desde la experiencia-expectante (reflexiva, endógena) y guiada subcorticalmente, a la experiencia-dependiente (cuidador e impulsado por la recompensa) y guiada corticalmente, una transición que nuestro trabajo sugiere que se interrumpe única mente en bebés diagnosticados posteriormente con TEA.

Heterogeneous trajectories in schizophrenia: insights from neurodevelopment and neuroprogression models

The notion that schizophrenia is a neuroprogressive disorder is based on clinical perception of cumulative impairments over time and is supported by neuroimaging and biomarker research. Nevertheless, increasing evidence has indicated that schizophrenia first emerges as a neurodevelopmental disorder that could follow various pathways, some of them neuroprogressive. The objective of this review is to revisit basic research on cognitive processes and neuroimaging findings in a search for candidate keys to the intricate connections between neurodevelopment and neuroprogression in schizophrenia. In the complete panorama, schizophrenia is a neurodevelopmental disorder, possibly associated with an additional burden over the course of the disease through pathologically accelerated aging, and cognitive heterogeneity may explain the different trajectories of each patient.

Relationship between interpregnancy interval and neurodevelopment among 6-month-old infants / 预防医学

Objective@#To examine the relationship between interpregnancy interval (IPI) and neurodevelopment among 6-month-old infants, so as to provide insights into the prevention of neurodevelopmental abnormalities among infants.@*Methods@#Puerparas with full-term delivery at Anhui Province Maternity and Child Health Hospital from April 2017 to July 2018 and their babies were recruited. The demographic features, behaviors during pregnancy, IPI and birth outcomes were collected through questionnaires and medical records. The neurodevelopment was evaluated using the Ages and Stages Questionnaire (third edition) among infants at 6 months of age. The association between IPI and neurodevelopment was examined using multivariable logistic regression analysis.@*Results @#Totally 485 maternal-newborn pairs were investigated, and the puerparas had a mean age of ( 29.43±4.40 ) years. There were 330 puerparas ( 68.04% ) with normal pre-pregnancy body mass index, 325 puerparas ( 67.01% ) with eutocia, 233 puerparas (48.04%) with the first delivery, 44 puerparas ( 9.07% ) with IPI of less than one year and 208 puerparas ( 42.89% ) with IPI of one year and greater. There were 246 male babies ( 50.72% ) and 437 babies ( 90.10% ) with normal birth weight. A total of 148 newborns were diagnosed with neurodevelopmental abnormalities, with a detection rate of 30.52%. Of all newborns with neurodevelopmental abnormalities, there were 45 babies with communication abnormalities ( 9.28% ), 87 babies with gross motor abnormalities ( 17.94% ), 73 babies with fine motor abnormalities ( 15.05% ), 68 babies with abnormalities of solving problems ( 14.02% ) and 60 babies with personal-social abnormalities ( 12.37% ). Multivariable logistic regression analysis showed a reduced risk of infant's communication abnormalities ( OR=0.273, 95%CI: 0.090-0.833 ), gross motor abnormalities ( OR=0.340, 95%CI: 0.150-0.770 ), fine motor abnormalities ( OR=0.266, 95%CI: 0.106-0.670 ), personal-social abnormalities ( OR=0.321, 95%CI: 0.121-0.851 ) and neurodevelopmental abnormalities ( OR=0.353, 95%CI: 0.171-0.730 ) among puerparas with IPI of one year and greater as compared to those with IPI of less than one year, and no significant difference was seen in infant's neurodevelopmental abnormalities between puerparas with the first delivery and with IPI of less than one year.@*Conclusion@#IPI is associated with neurodevelopmental abnormalities among 6-month-old infants.

Recent research on the effect of common treatments given in the perinatal period on neurodevelopment in offspring / 中国当代儿科杂志

The perinatal period is the key period for the development of brain and central nervous system, and different events in this period will have a profound influence on brain development. Glucocorticoids, antibiotics, magnesium sulfate, caffeine, pulmonary surfactant, and mild hypothermia treatment are commonly used drugs or treatment methods in the perinatal period and are closely associated with the prognosis of neonatal neurodevelopment. This article reviews the latest research on the effect of perinatal treatments on neonatal neurodevelopment, so as to provide a reference for clinical decision making.