Telerrehabilitación de sujetos con trastornos del neurodesarrollo durante el confinamiento por COVID-19 / Telerehabilitation of Subjects with Neurodevelopmental Disorders During Confinement due to COVID-19

RESUMEN Introducción: Las medidas de distanciamiento social debidas a la pandemia por COVID-19 impidieron que muchos chicos con trastornos del neurodesarrollo pudieran acceder a tratamientos presenciales. La telerrehabilitación creció en este tiempo como una herramienta terapéutica alternativa. El objetivo es analizar la telerrehXbilitación cognitiva en trastornos del neurodesarrollo. Métodos: En este estudio prospectivo, cuasi-experimental (antes-después), se incluyó a 22 pacientes (media de edad, 9,41 arios) con trastornos del neurodesarrollo que realizaron telerrehabilitación con el programa Rehametrics por más de 6 meses. Resultados: Luego de 6 meses de telerrahabilitación, se constató una mejoría estadísticamente significativa con un gran tamaño del efecto en áreas de: atención (sostenida, selectiva y dividida), funciones ejecutivas (memoria de trabajo verbal y visual, categorización, velocidad de procesamiento), habilidades visuoespaciales (orientación espacial, integración perceptiva, percepción, simultagnosia) y lenguaje (comprensivo y expresivo). En la Escala de Impedimento Funcional de Weiss mejoraron con significancia estadística todas las áreas (familia, aprendizaje y escuela, autoconcepto, actividades de la vida diaria, actividades de riesgo). Se constata una correlación positiva entre la cantidad de sesiones y la mejoría observada en funciones ejecutivas (memoria de trabajo visual, velocidad de procesamiento), atencionales (atención sostenida, atención dividida) y habilidades visuoespaciales (orientación espacial, integración perceptiva, percepción, simultagnosia). No encontramos significancia estadística entre la estructura familiar y la cantidad de sesiones realizadas. Se observó un alto grado de percepción de mejora y satisfacción en los padres. Conclusiones: La telerrehabilitación puede ser una herramienta alternativa segura que, sin reemplazar la presencialidad, puede lograr mejoras cognitivas y funcionales significativas en niños con trastornos del neurodesarrollo.

ABSTRACT Introduction: Social distancing measures due to the COVID-19 pandemic prevented many children with neurodevelopmental disorders from accessing face-to-face treatments. Tele-rehabilitation grew at this time as an alternative therapeutic tool. In this study we analyzed remote cognitive rehabilitation in neurodevelopmental disorders. Methods: This was a prospective, quasi-experimental (before-after) study that included 22 patients (mean age 9.41 years) with neurodevelopmental disorders who had telerehabilitation for over six months. Results: After six months of telerehabilitation, a statistically significant improvement was found with a large effect size in these areas: attention (sustained, selective and divided), executive functions (verbal and visual working memory, categorization, processing speed), visuospatial skills (spatial orientation, perceptual integration, perception, simultanagnosia) and language (comprehensive and expressive). On the Weiss Functional Impairment Scale, all areas (family, learning and school, self-concept, activities of daily living, risk activities) improved with statistical significance. We found a positive correlation between the number of sessions and the improvement observed in executive functions (visual working memory, processing speed), attention (sustained attention, divided attention) and visuospatial skills (spatial orientation, perceptual integration, perception, simultanagnosia). We did not find statistical significance between the family structure and the number of sessions carried out. A high degree of perception of improvement and satisfaction was observed in the parents. Conclusions: Telerehabilitation is a safe alternative tool which, although it does not replace face-to-face therapy, can achieve significant cognitive and functional improvements in children with neurodevelopmental disorders.

Programa de Acompañamiento del Sueño en la Infancia con Terapia Ocupacional durante la pandemia por COVID-19 / Program to Support Child Sleep from the Occupational Therapy Perspective during the COVID-19 pandemic

Introducción. Se describen los resultados preliminares del Programa de Acompañamiento al Sueño en la Infancia desde Terapia Ocupacional (PASITO) en niños y niñas con trastornos del neurodesarrollo (NN-TND), de 3 a 10 años, y con insomnio; realizado entre junio de 2020 y septiembre de 2021. Población y métodos. Estudio cuasiexperimental de preintervención y posintervención con un grupo de intervención y otro grupo de control, medido por el Cuestionario de Hábitos de Sueño (CHS) y el Diario de Sueño (DS). Resultados. Participaron 22 NN-TND, 8 en el grupo control. El puntaje total del CHS del grupo de intervención mejoró (p <0,001) de 54,9 (DE 5,5) a 48,4 (DE 4,5) y se acercó al rango de referencia 42,6 (DE 4,9). El DS evidenció aumento en duración, adelanto de fase de sueño y reducción en cantidad de despertares. Conclusión. Estos resultados provisorios y favorables muestran que PASITO podría ser una intervención posible para dificultades del sueño en NN-TND

Introduction. Here we describe the interim results of the Program to Support Child Sleep from the Occupational Therapy Perspective (Programa de Acompañamiento al Sueño en la Infancia desde Terapia Ocupacional, PASITO) for children with neurodevelopmental disorders (NDDs) aged 3­10 years with insomnia, conducted between June 2020 and September 2021. Population and methods. Pre- and post-intervention quasi-experiment in an intervention group and a control group using the Sleep Habits Questionnaire (SHQ) and the Consensus Sleep Diary (CSD). Results. A total of 22 children with NDDs participated, 8 in the control group. The overall SHQ score for the intervention group improved (p < 0.001) from 54.9 (SD: 5.5) to 48.4 (SD: 4.5) and moved closer to the reference range of 42.6 (SD: 4.9). The CSD showed an increased sleep duration, earlier sleep onset, and fewer night wakings. Conclusion. These interim favorable results demonstrate that the PASITO may be a possible intervention to manage sleep problems in children with NDDs.

Early motor development in small for gestational age infants at high risk of brain injury / 中华围产医学杂志

Objective:To investigate the characteristics of early motor development in small for gestational age (SGA) infants at high risk of brain injury.Methods:This study retrospectively enrolled a total of 81 SGA infants and appropriate for gestational age (AGA) infants who were at high risk of brain injury and attended outpatient follow-up visits in Xi'an Children's Hospital from February to October 2022. Seventeen SGA infants (SGA group) and 24 AGA infants (AGA group) were assessed for motor development using the Test of Infant Motor Performance (TIMP) at 2-5 weeks of corrected age (CA) and 20 SGA infants (SGA group) and 20 AGA infants (AGA group) were assessed at 14-17 weeks of CA. Independent samples t-test, rank-sum test, and Chi-square test were used to compare the demographic characteristics, high-risk factors of brain injury, and TIMP scores between the two groups. Results:At 2-5 weeks and 14-17 weeks of CA, the birth weights of SGA group were both less than those of AGA group [(1 817.1±440.3) vs. (2 630.0±560.9) g, t=－4.98; (1 752.0±434.4) vs. (2 226.3±699.8) g, t=－2.58; both P<0.05], but there were no significant differences in gestational age at birth or high-risk factors of brain injury between the two groups (all P>0.05). (1) At 2-5 weeks of CA: SGA group had lower total TIMP score [(71.6±13.7) vs. (80.5±11.5) scores, t=－2.26, P=0.029], elicited item score [61.0 scores (41.0-85.0 scores) vs. 69.1 scores (49.0-96.0 scores), Z=－2.15, P=0.037], sitting position score [8.8 scores (3.0-19.0 scores) vs. 11.2 scores (5.0-22.0 scores), Z=－2.07, P=0.038], and prone position score [(9.8±3.1) vs. (12.3±3.1) scores, t=－2.19, P=0.034] when compared with AGA group. (2) At 14-17 weeks of CA: The standing position score of the SGA group was lower than that of the AGA group [6.5 scores (4.0-11.0 scores) vs. 7.7 scores (2.0-11.0 scores), Z=－2.05, P=0.040], but no statistical difference was observed in the total TIMP score or the scores of sitting, supine, prone, turning, and lateral positions between the two groups (all P>0.05). Conclusion:Early motor performance of SGA infants is inferior to AGA infants before five months of age, which is embodied in the poor head control at 2-5 weeks of CA that further affects the stability of standing posture in them at 14-17 weeks of CA.

Recent research advancements in mechanisms underlying intrauterine brain injury in fetuses with fetal growth restriction / 中华围产医学杂志

The pathogenesis of brain injury in fetal growth restriction (FGR) fetuses is likely associated with oxidative stress and neuroinflammation, although the exact mechanisms are not fully understood. This article mainly reviews the anatomical alterations, potential pathophysiological processes, and the specific molecular mechanisms involving various types of brain cells in FGR.

Multiple copy number variation in a patient with Kleefstra syndrome / Múltiplas variações de número de cópias em paciente com síndrome de Kleefstra

ABSTRACT Objective: To report a rare case of a patient with a molecular diagnosis of Kleefstra syndrome (KS) who has four other chromosomal alterations involving pathogenic variants. Case description: Male patient, two years old, with global delay, including in neuropsychomotor development, ocular hypertelorism, broad forehead, brachycephaly, hypotonia, ligament laxity, unilateral single palmar crease and arachnoid cyst. The microarray-based comparative genomic hybridization (a-CGH) identified copy number variations (CNVs) in five regions: 9q34.3, 6p22.1, Yq11.223, Yp11.23, and 2q24.1. The heterozygous microdeletion in 9q34.3 involving the EHMT1 gene confirms the diagnosis of KS. Comments: The presence of pathogenic CNVs and/or those of uncertain significance, located on chromosomes 2, 6 and Y, may be contributing to a variability in the patient's clinical condition (arachnoid cyst, single palmar fold and ligament laxity), compared to other individuals with only KS genetic alteration, making the dignosis of the disease harder.

RESUMO Objetivo: Relatar um caso raro de paciente com diagnóstico molecular de síndrome de Kleefstra (SK) que apresenta quatro outras alterações cromossômicas envolvendo variantes patogênicas. Descrição do caso: Paciente masculino, dois anos de idade, com atraso global de desenvolvimento neuropsicomotor, hipertelorismo ocular, fronte ampla, braquicefalia, hipotonia, frouxidão ligamentar, prega palmar única unilateral e cisto aracnoide. Exame de hibridização genômica comparativa (a-CGH) identificou variações de número de cópias (CNV) em cinco regiões: 9q34.3, 6p22.1, Yq11.223, Yp11.23 e 2q24.1. A microdeleção heterozigótica em 9q34.3 confirma o diagnóstico de síndrome de Kleefstra. Comentários: A presença das CNV patogênicas e/ou de significado incerto, localizadas nos cromossomos 2, 6 e Y, pode estar contribuindo para uma variabilidade no quadro clínico do paciente (cisto aracnoide, prega palmar única e frouxidão ligamentar) em relação a outros indivíduos somente com alteração genética da SK, dificultando o diagnóstico da doença.

Effects of maternal hyperthermia on neurodevelopment: a literature review

Maternal hyperthermia, defined as a body temperature above 38°C (100.4°F) is due to various etiologies during pregnancy, and has been a subject of growing research interest. This phenomenon is considered a potential environmental teratogen contributing to the development of neural tube defects (NTDs) and other neurodevelopmental disorders. NTDs such as anencephaly and spina bifida, are known to be multifactorial in origin, resulting from a complex interplay between genetic and environmental factors. In this review, we aim to comprehensively analyze the effect of maternal hyperthermia on neurodevelopmental disorders and associated congenital anomalies. In addition, we will highlight both the infectious and noninfectious causes of maternal hyperthermia, as well as any risks and potential preventive measures. The literature search identified studies reporting associations between maternal hyperthermia and adverse fetal outcomes. We have evaluated the link between maternal fever due to infections during pregnancy and the increased likelihood of NTDs, particularly anencephaly and spina bifida, as well as Neurodevelopmental disorders. ??In addition, the effects of non-infectious causes of maternal hyperthermia, including exercise and exposure to heat sources like saunas and hot tubs, on neurodevelopment have also been studied with varying degrees of evidence. Maternal hyperthermia elevates the risk of NTDs and neurodevelopmental disorders in infants, with folic acid offering partial protection, while other factors elevate this risk. However, further research is needed to define the precious association of these factors.

Mercurio y trastornos del neurodesarrollo en niños: una revisión sistemática / Mercury and neurodevelopmental disorders in children: A systematic review

El mercurio es un metal tóxico que puede atravesar la placenta y la barrera hematoencefálica, y causar la interrupción de varios procesos celulares. Estudios han investigado la exposición al mercurio y trastornos en el neurodesarrollo, por lo que se requiere un análisis crítico y riguroso de esta evidencia. El objetivo de esta revisión fue evaluar la evidencia científica disponible sobre los efectos de la exposición al mercurio durante las etapas prenatal y posnatal, y su relación con el desarrollo de trastornos neuroconductuales. Se realizó una búsqueda sistemática en las bases de datos MEDLINE y ScienceDirect; los resultados se presentaron a través de tablas y síntesis narrativa. Solo 31 estudios cumplieron los criterios de elegibilidad. En general, la evidencia es limitada sobre los efectos de la exposición al mercurio y trastornos del neurodesarrollo en niños. Entre los posibles efectos reportados, se hallan problemas en el aprendizaje, autismo y trastorno por déficit de atención e hiperactividad.

Mercury is a toxic metal which can cross the placenta and the blood-brain barrier and cause the disruption of various cellular processes. Studies have investigated mercury exposure and neurodevelopmental disorders; therefore, a critical and rigorous analysis of this evidence is required. The objective of this review was to evaluate the available scientific evidence on the effects of mercury exposure during the prenatal and postnatal periods and its relationship with the development of neurobehavioral disorders. A systematic search of the MEDLINE and ScienceDirect databases was conducted; the results were presented in tables and narrative synthesis. Only 31 studies met the eligibility criteria. Overall, the evidence on the effects of mercury exposure and neurodevelopmental disorders in children is limited. Learning disabilities, autism, and attention deficit hyperactivity disorder were some of the reported potential effects.

Complicaciones neurológicas de la prematuridad / Neurological consequences of prematurity

Resumen Los nacimientos prematuros representan un in dicador importante de salud de un país. Estos niños tienen un mayor riesgo de mortalidad y morbilidad. Las principales lesiones encefálicas en los prematuros incluyen lesiones de la sustancia blanca, hemorragias intracraneanas y lesiones cerebelosas, que pueden ser detectadas mediante ecografía encefálica y resonancia magnética, siendo esta última la técnica más sensible. Estas lesiones pueden tener repercusión a largo plazo en el neurodesarrollo de los prematuros, con un mayor riesgo de parálisis cerebral, trastornos cognitivos, con ductuales, sensoriales y del aprendizaje, entre otros. Es fundamental aplicar estrategias de prevención y aten ción temprana para reducir las consecuencias negativas de las lesiones encefálicas asociadas a la prematuridad.

Abstract Premature births are an important health indicator for a country. These children have a higher risk of mor tality and morbidity. The main brain injuries in preterm infants include white matter injuries, intracranial hem orrhages, and cerebellar injuries. These injuries can be detected through brain ultrasound and magnetic reso nance imaging (MRI), with MRI being the most sensitive technique. Perinatal brain injuries may have long-term consequences on the neurodevelopment of preterm infants, with an increased risk of cerebral palsy, cogni tive, behavioral, sensory, and learning disorders, among others. It is key to implement prevention strategies and early intervention to reduce the negative consequences of brain injuries associated with prematurity.

Déficit de atención con hiperactividad: farmacoterapia a través de la vida / Attention deficit hyperactivity: pharmacotherapy through life

Resumen El Trastorno por déficit de atención con hiperactivi dad (TDAH) es un trastorno del neurodesarrollo de ori gen biológico con una base genética del 70 al 80%, que afecta al 5% de niños y adolescentes y a un 2.5% de los adultos, cuyos síntomas principales son la inatención, hiperactividad e impulsividad. Por muchos años se pensó que afectaba solo a los niños; actualmente en el DSM 5 se acepta que se puede diagnosticar en adolescentes y adultos. El tratamiento debe ser individualizado, los objetivos principales son mejorar los síntomas centrales de las personas con TDAH, y su calidad de vida. El abordaje terapéutico es psicológico, conductual y farmacológico. Los medicamentos se clasifican en estimulantes y no estimulantes, siendo los de primera línea los estimu lantes tales como el metilfenidato, lisdexanfetamina y dexanfetamina. Entre los no estimulantes se cuentan a la guanfacina y atomoxetina. El tratamiento es funda mental porque mejora la calidad de vida de la persona a nivel familiar, educativo, laboral y social.

Abstract Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder of biological origin with a 70 to 80% genetic basis, which affects 5% of children and adolescents and 2.5% of adults, whose main symptoms are inattention, hyperactivity, and impulsivity. For many years it was thought that it only affected children; currently in the DSM 5 it is accepted that it can be diagnosed in adolescents and adults. Treatment must be individualized, the main objec tives are to improve the core symptoms of people with ADHD, and their quality of life. The therapeutic approach is psychological, behavioral, and pharmacological. Medications are classified as stimulants and non-stimulants, with stimulants such as methylphenidate, lisdexamfetamine, and dexamphetamine being the first line. Non-stimulants include guanfacine and atomox etine. Treatment is essential because it improves the qual ity of life of the person at the family, educational, work, and social levels.

Salud y discapacidad en niñas y niños argentinos con cardiopatías congénitas complejas operadas. Resultados a los dos años de vida / Health and disability in Argentine children with complex congenital heart disease undergoing surgery. Outcomes at 2 years of life

Introducción. Las cardiopatías congénitas complejas son las malformaciones más frecuentes con una importante carga de morbimortalidad. Se busca conocer el estado de salud y discapacidad de niños operados en un hospital de tercer nivel. Población y métodos. Fueron evaluados en las áreas de crecimiento, neurodesarrollo y discapacidad 84 pacientes entre 21 y 39 meses de edad operados con circulación extracorpórea durante el primer año de vida. Resultados. La mayoría de los niños crece por debajo del percentil 50 en los tres parámetros, con mayor compromiso en aquellos con síndrome genético asociado. La frecuencia de discapacidad fue del 55 %. En el grupo con CC aislada, la gravedad de la cardiopatía y el examen neurológico patológico al alta se asociaron con discapacidad (p = 0,047 y p = 0,03). Contar solo con cobertura de salud pública se asocia a un menor acceso a intervenciones oportunas (p = 0,02). Conclusiones. Cerca de la mitad de los pacientes evoluciona con discapacidad moderada-grave. Es competencia del equipo de salud conocer las morbilidades más allá del aspecto cardiovascular y los factores de riesgo. Las barreras en el acceso a las intervenciones adecuadas advierten a los profesionales sobre la relevancia de buscar estrategias para vencerlas y lograr el máximo potencial de desarrollo de los pacientes.

Introduction. Complex congenital heart defects are the most frequent malformations and entail a significant burden of disease. The objective of this study was to determine the health status and disability of children who underwent surgery at a tertiary care hospital. Population and methods. A total of 84 patients aged 21 to 39 months who had a surgery with extracorporeal circulation during their first year of life were assessed in terms of growth, neurodevelopment, and disability. Results. In most children, growth was below the 50th percentile in all 3 parameters, and greater involvement was observed in those with an associated genetic disorder. The frequency of disability was 55%. In the group with isolated congenital heart disease, the severity of disease and a pathological neurological examination at discharge were associated with disability (p = 0.047 and p = 0.03). Having only public health coverage was associated with less access to timely interventions (p = 0.02). Conclusions. Nearly half of the patients develop moderate-severe disability. Being aware of morbidities beyond the cardiovascular aspect and risk factors is part of the health care team's scope. Barriers in access to appropriate interventions caution health care providers of the relevance of seeking strategies to overcome them and achieve the maximum development potential of patients.

Mecanismos moleculares de la esquizofrenia / Molecular mechanisms of schizophrenia / Mecanismos moleculares da esquizofrenia

La etiología de la esquizofrenia no está totalmente dilucidada. Se conocen más de 100 diferentes loci de genes relacionados con esquizofrenia, la mayoría de los cuales codifican moléculas asociados a los sistemas de neurotransmisores o al neurodesarrollo. Las primeras abarcan receptores de los neurotransmisores como dopamina, GABA o glutamato y de otros neurotransmisores con menor relación, como la serotonina y la acetilcolina. También están implicadas diversas enzimas relacionadas con el metabolismo, cotransportadores y algunas proteínas intracelulares involucradas en la degradación o síntesis de dichos neurotransmisores. Entre las moléculas que intervienen en el neurodesarrollo están los factores neurotróficos (BDNF, DISC1, NRG1) y las proteínas del complemento C3 y C4, que median la respuesta inflamatoria y la poda sináptica durante el desarrollo temprano. Los productos de la producción genética involucrados en la etiología de la esquizofrenia aportan a la vulnerabilidad selectiva o al proceso de lesión que se instaura o progresa en el paciente, por tanto, su estudio es de relevancia para la comprensión de los fenómenos clínicos propios de la enfermedad.

The etiology of schizophrenia is not fully elucidated. More than 100 different gene loci related to schizophrenia are known, most of which encode molecules associated with neurotransmitter systems or neurodevelopment. These include receptors for neurotransmitters such as dopamine, GABA, or glutamate, as well as other neurotransmitters with less direct relevance, such as serotonin and acetylcholine. Various enzymes involved in metabolism, cotransporters, and intracellular proteins involved in the degradation or synthesis of said neurotransmitters are also implicated. Among the molecules involved in neurodevelopment are neurotrophic factors (BDNF, DISC1, NRG1) and complement proteins C3 and C4, which mediate the inflammatory response and synaptic pruning during early development. The genetic products involved in the etiology of schizophrenia contribute to selective vulnerability or the process of injury that is established or progresses in the patient. Therefore, their study is relevant to the understanding of the clinical phenomena associated with the disease.

A etiologia da esquizofrenia não está totalmente elucidada. Mais de 100 diferentes loci de genes relacionados à esquizofrenia são conhecidos, a maioria dos quais codifica moléculas associadas a sistemas de neurotransmissores ou neurodesenvolvimento. O primeiro inclui receptores para neurotransmissores como dopamina, GABA ou glutamato e outros neurotransmissores menos relacionados, como serotonina e acetilcolina. Também estão envolvidas várias enzimas relacionadas com o metabolismo, cotransportadores e algumas proteínas intracelulares envolvidas na degradação ou síntese dos referidos neurotransmissores. Entre as moléculas envolvidas no neurodesenvolvimento estão os fatores neurotróficos (BDNF, DISC1, NRG1) e as proteínas do complemento C3 e C4, que medeiam a resposta inflamatória e a poda sináptica durante o desenvolvimento inicial. Os produtos da produção genética envolvidos na etiologia da esquizofrenia contribuem para a vulnerabilidade seletiva ou para o processo de lesão que se instala ou progride no paciente, portanto, seu estudo é relevante para a compreensão dos fenômenos clínicos da esquizofrenia

Evaluación de los movimientos generales en niños prematuros para predicción de parálisis cerebral / Assessment of general movements in preterm infants as a predictor of cerebral palsy

La identificación temprana de la parálisis cerebral es aún en la actualidad un gran desafío para el sistema de salud en el mundo. Hubo grandes avances de la neonatología en disminuir la mortalidad, pero no así la morbimortalidad; la parálisis cerebral continúa siendo la secuela más común de todos los trastornos del desarrollo, especialmente entre quienes nacen prematuramente. La posibilidad de realizar detección precoz antes de los 5 meses de edad conlleva múltiples beneficios para el niño y su familia, ya que permite su incorporación muy temprana a tratamiento. En este trabajo describimos una herramienta con gran sensibilidad y especificidad conocida como evaluación de los movimientos generales de Prechtl y su posible complementación con aplicaciones tecnológicas para la detección temprana.

At present, the early identification of cerebral palsy still poses a major challenge for the health system worldwide. Great advances have been made in neonatology in reducing mortality, but not morbimortality. Cerebral palsy remains the most common sequela of all developmental disorders, especially among those born prematurely. The possibility of early detection before 5 months of age has many benefits for the child and their family, since it allows very early initiation of treatment. In this study, we describe a highly sensitive and specific tool known as Prechtl's assessment of general movements and its potential complementation with technological apps for early detection.

Consanguinidad no declarada en pacientes peruanos con trastorno del neurodesarrollo detectada a través de micromatrices

Introducción. La consanguinidad es la unión entre personas que comparten un ancestro en común, y cuya descendencia presenta un mayor riesgo de aparición de enfermedades autosómicas recesivas, manifestándose en algunos pacientes como trastornos del neurodesarrollo. Objetivos. Describir la consanguinidad parental no declarada en pacientes menores de 18 años con trastornos del neurodesarrollo, descubierta mediante el análisis cromosómico por micromatrices. Métodos. Se realizó el análisis cromosómico por micromatrices a 967 pacientes con trastorno del neurodesarrollo entre 2016 y 2021. Fueron seleccionados los pacientes con regiones de homocigosidad (ROH) con un valor superior a 0,5%. Resultados. Se evaluó a 288 pacientes, el 58,3% fueron varones y el 29,8% presentó una ROH mayor o igual a 0,5%. Se encontró que el 25,9% y el 0,83% de los pacientes tenían padres con un quinto y primer grado de consanguinidad no declarada, respectivamente. Los departamentos con mayor frecuencia relativa de consanguinidad no declarada por cada 10 000 habitantes fueron Huancavelica, Cajamarca y Apurímac. Conclusión. En Perú, existen regiones donde se evidencia uniones parentales consanguíneas, el cual es un factor de riesgo alto para la aparición de enfermedades recesivas autosómicas en su descendencia, como los trastornos del neurodesarrollo.

Introduction. Consanguinity is the union between people who share a common ancestor, and whose offspring have a higher risk of autosomal recessive diseases, manifesting in some patients as neurodevelopmental disorders. Objectives. To describe non-declared parental consanguinity of patients under 18 years of age with neurodevelopmental disorders, discovered by chromosomal microarray analysis. Methods. Chromosomal microarray analysis was performed on 967 patients with neurodevelopmental disorders between the years 2016-2021 and were selected to patients with regions of homozygosity (ROH) with a value greater than 0.5%. Results. 288 patients were evaluated, 58.3% of the patients were male and 29,8% presented an ROH greater than or equal to 0.5%. We found 25.9% and 0.83% of the patients had their parents of a fifth and first degree of consanguinity not previously declared, respectively. The most frequent neurodevelopmental disorder was delayed psychomotor development with 38.2%. The departments with the highest frequency relative of non declared consanguinity were Huancavelica, Cajamarca y Apurimac. Conclusions. In Peru, non-declared parental consanguinity is frequent, which is a high-risk factor for the appearance of autosomal recessive diseases in their offspring, how neurodevelopment disorders.

Prediction of Perinatal and Neurodevelopmental Outcomes in Newborns with a Birth Weight below the 3rd Percentile: Performance of Two International Curves - Prospective Cohort from a Brazilian City / Predição de resultados perinatais e de neurodesenvolvimento em recém-nascidos com peso ao nascer abaixo do percentil 3: Desempenho de duas curvas internacionais - coorte prospectiva de uma cidade brasileira

Abstract Objectives To evaluate the performance of Intergrowth-21 st (INT) and Fetal Medicine Foundation (FMF) curves in predicting perinatal and neurodevelopmental outcomes in newborns weighing below the 3rd percentile. Methods Pregnant women with a single fetus aged less than 20 weeks from a general population in non-hospital health units were included. Their children were evaluated at birth and in the second or third years of life. Newborns (NB) had their weight percentiles calculated for both curves. Sensitivity, specificity, positive (PPV) and negative predictive value (NPV), and area under the ROC curve (ROC-AUC) for perinatal outcomes and neurodevelopmental delay were calculated using birth weight < 3rd percentile as the cutoff. Results A total of 967 children were evaluated. Gestational age at birth was 39.3 (± 3.6) weeks and birth weight was 3,215.0 (± 588.0) g. INT and FMF classified 19 (2.4%) and 49 (5.7%) newborns below the 3rd percentile, respectively. The prevalence of preterm birth, tracheal intubation >24 hours in the first three months of life, 5th minute Apgar <7, admission to a neonatal care unit (NICU admission), cesarean section rate, and the neurodevelopmental delay was 9.3%, 3.3%, 1.3%, 5.9%, 38.9%, and 7.3% respectively. In general, the 3rd percentile of both curves showed low sensitivity and PPV and high specificity and NPV. The 3rd percentile of FMF showed superior sensitivity for preterm birth, NICU admission, and cesarean section rate. INT was more specific for all outcomes and presented a higher PPV for the neurodevelopmental delay. However, except for a slight difference in the prediction of preterm birth in favor of INT, the ROC curves showed no differences in the prediction of perinatal and neurodevelopmental outcomes. Conclusion Birth weight below the 3rd percentile according to INT or FMF alone was insufficient for a good diagnostic performance of perinatal and neurodevelopmental outcomes. The analyzes performed could not show that one curve is better than the other in our population. INT may have an advantage in resource contingency scenarios as it discriminates fewer NB below the 3rd percentile without increasing adverse outcomes.

Resumo Objetivos Avaliar o desempenho das curvas de Intergrowth-21 st (INT) e Fetal Medicine Foundation (FMF) na predição de resultados perinatais e de neurodesenvolvimento de recém-nascidos com peso abaixo do percentil 3. Métodos Foram incluídas gestantes de feto único com idade inferior a 20 semanas de uma população geral em unidades de saúde não hospitalares. Seus filhos foram avaliados ao nascimento e no segundo ou terceiro anos de vida. Os recém-nascidos tiveram seus percentis de peso calculados para ambas as curvas. Sensibilidade, especificidade, valor preditivo positivo (VPP) e negativo (VPN) e área sob a curva ROC (ROC-AUC) foram calculados para desfechos perinatais e atraso de neurodesenvolvimento considerando o peso ao nascimento menor que o percentil 3 como ponto de corte. Resultados Um total de 967 crianças foram avaliadas ao nascimento e no segundo ou terceiro anos de vida. A idade gestacional ao nascer foi de 39,3 (±3,6) semanas e o peso ao nascimento foi de 3.215,0 (±588,0) g. INT e FMF classificaram 19 (2,4%) e49 (5,7%) recém-nascidos abaixo do percentil 3, respectivamente. A prevalência de parto prétermo, intubação traqueal > 24 horas nos primeiros três meses de vida, Apgar de 5° minuto < 7, internação em unidade de terapia intensiva neonatal (internação em UTIN), taxa de cesariana e atraso de neurodesenvolvimento foi 9,3%, 3,3%, 1,3%, 5,9%, 38,9% e 7,3% respectivamente. Em geral, o percentil 3 de ambas as curvas apresentou baixa sensibilidade e VPP e alta especificidade e VPN. O percentil 3 de FMF mostrou sensibilidade superior para parto prematuro, internação em UTIN e taxa de cesariana. INT foi mais específico para todos os desfechos e apresentou maior VPP para o atraso do neurodesenvolvimento. Entretanto, exceto por uma pequena diferença na predição de parto pré-termo em favor de INT, as curvas ROC não mostraram diferenças na predição de resultados perinatais e de desenvolvimento neurológico. Conclusão O peso ao nascer abaixo do percentil 3 segundo INT ou FMF isoladamente foi insuficiente para um bom desempenho diagnóstico de desfechos perinatais e de neurodesenvolvimento. As análises realizadas não puderam mostrar que uma curva é melhor que a outra em nossa população. INT pode ter vantagem em cenários de contingência de recursos, pois discrimina menos recém-nascidos abaixo do percentil 3 sem aumentar os desfechos adversos.

Exposição ao praguicida glifosato e a ocorrência do transtorno do espectro autista: existe associação? / Exposure to the pesticide glyphosate and the occurrence of autistic spectrum disorder: is there an association?

O presente estudo teve como objetivo estudar a associação entre a exposição ao glifosato e a ocorrência do Transtorno do Espectro Autista (TEA). Trata-se de um estudo documental com busca de dados acerca da prevalência do TEA (Centers of Disease Control and Prevention) e de um levantamento para verificar o princípio ativo do praguicida mais usado no Brasil (Instituto Brasileiro do Meio Ambiente e dos Recursos Naturais Renováveis) e no mundo (United States Evironmental Prevention Agency). Os resultados mostraram que a prevalência do TEA aumentou ao longo dos anos. Do mesmo modo, o uso e a compra de praguicidas também aumentaram, sendo o glifosato o princípio ativo mais usado. Ainda que os resultados apontem a existência de uma relação entre a exposição ao glifosato e a ocorrência de autismo, são necessários mais estudos para afirmar o potencial neurotóxico do glifosato e sua associação com o nascimento de crianças autistas.

The present study aimed to study the association between exposure to glyphosate and the occurrence of Autistic Spectrum Disorder (ASD). This is a documental study with search for data about the prevalence of ASD (Centers of Disease Control and Prevention) and a survey to verify the active principle of the most used pesticide in Brazil (Brazilian Institute of Environment and Renewable Natural Resources) and worldwide (United States Environmental Prevention Agency). The results showed that the prevalence of ASD increased over the years. Likewise, the use and purchase of pesticides have also increased, with glyphosate being the most widely used active ingredient in the world. Although the results point to the existence of a relationship between exposure to glyphosate and the occurrence of autism, further studies are needed to confirm the neurotoxic potential of glyphosate and its association with the birth of autistic children.

Comparación del desempeño de dos pruebas para la evaluación del neurodesarrollo infantil en un hospital pediátrico de la Ciudad Autónoma de Buenos Aires / Comparison of the performance of two tests for the assessment of child neurodevelopment in a children's hospital in the City of Buenos Aires

Introducción. La detección precoz de los trastornos del desarrollo permite aplicar acciones que mejoren su evolución y pronóstico. En nuestro país, la Prueba Nacional de Pesquisa (PRUNAPE) requiere de un profesional certificado. El Instrumento de Observación del Desarrollo Infantil (IODI) es una herramienta de vigilancia sistematizada del desarrollo que no requiere especialización para su aplicación. La utilización del IODI como herramienta de evaluación del neurodesarrollo sería de utilidad por su fácil aplicabilidad. Objetivo. Evaluar el desempeño del IODI como prueba de vigilancia de trastornos del desarrollo utilizando la PRUNAPE como patrón de oro. Población y métodos. Estudio prospectivo analítico de prueba diagnóstica. Se incluyeron de forma aleatoria pacientes de 1 mes a 4 años, cuyos padres dieron el consentimiento para participar. Se evaluó el desempeño del IODI usando la PRUNAPE como patrón de oro. Se estimaron los valores de clivaje de sensibilidad (S), especificidad (E), valores predictivos positivo y negativo (VPP y VPN), y las razones de verosimilitud positiva y negativa (RVP y RVN, respectivamente). Resultados. Se evaluaron 91 pacientes; 24 no pasaron la PRUNAPE, de los cuales 21 tampoco pasaron el IODI (sensibilidad: 87,5 %; especificidad: 79,1 %; valor predictivo positivo: 60,1 %; valor predictivo negativo: 94,6 %). Razón de verosimilitud positiva: 4,2; negativa: 0,2. Conclusión. El IODI mostró un desempeño aceptable como prueba de vigilancia de trastornos del desarrollo en comparación con la PRUNAPE.

Introduction. An early detection of developmental disorders allows to implement actions to improve their course and prognosis. In Argentina, the administration of the National Screening Test (Prueba Nacional de Pesquisa, PRUNAPE) requires a certified professional. The Child Development Observation Instrument (Instrumento de Observación del Desarrollo Infantil, IODI) is a systematized developmental surveillance tool that does not require specialization for its administration. The use of the IODI as a neurodevelopmental assessment tool would be useful because of its easy applicability. Objective. To assess the performance of the IODI as a surveillance test for developmental disorders using the PRUNAPE as a gold standard. Population and methods. Analytical, prospective study with a diagnostic test. Patients aged 1 month to 4 years, whose parents gave consent to participate, were included randomly. The IODI performance was assessed using the PRUNAPE as the gold standard. Sensitivity (S), specificity (Sp), positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (PLR and NLR) were estimated. Results. Ninety-one patients were assessed; 24 failed the PRUNAPE, of these, 21 also failed the IODI (S: 87.5%, Sp: 79.1%, PPV: 60.1%, NPV: 94.6%). PLR: 4.2, NLR: 0.2. Conclusion. The IODI showed an acceptable performance as a developmental disorders surveillance test compared to the PRUNAPE.

Manejo neurocognitivo en cardiopatía congénita: revisión sistemática de recomendaciones de práctica clínica / Neurocognitive management in congenital heart disease: a systematic review of clinical practice recommendations

Resumen Objetivo: Sintetizar y valorar críticamente las recomendaciones sobre manejo neurocognitivo del paciente con cardiopatía congénita presentadas en guías de práctica clínica y declaraciones científicas. Método: Revisión sistemática de recomendaciones de práctica (PROSPERO CRD42020205202). Se realizó una búsqueda en PubMed, SCOPUS, Ovid/Cochrane, y LILACS y se revisaron repositorios de sociedades científicas y referencias de los documentos incluidos. La valoración crítica se hizo mediante el AGREE-II (escenario ideal) para las guías y declaraciones, y mediante el AGREE-REX para las recomendaciones (escenarios ideal y local). Se presentan la matriz de recomendaciones y el análisis de barreras potenciales para su implementación en Colombia. Resultados: Se incluyeron 18 recomendaciones relacionadas. La media en el AGREE-II fue 89.6. La media en el AGREE-REX fue 90.1 en el escenario ideal y 69.9 en el escenario local. Las recomendaciones incluidas se centran en vigilancia, tamizaje, evaluación y consejería; no se identificaron recomendaciones sobre intervención neurocognitiva. Las principales barreras de implementación en Colombia son la no disposición a pagar por parte del sistema de salud y la ausencia de oferta integral de atención para el manejo neurocognitivo en cardiopatía congénita. Conclusión: Las recomendaciones identificadas podrían ser adaptadas en una guía de práctica colombiana, realizando modificaciones en reconocimiento del contexto local.

Abstract Objective: To synthesize and critically assess the recommendations on neurocognitive management of patients with congenital heart disease presented in clinical practice guidelines and scientific statements. Method: A systematic review of practice recommendations (PROSPERO CRD42020205202). PubMed, SCOPUS, Ovid/Cochrane, and LILACS were searched, and repositories of scientific societies and references of included documents were reviewed. Critical appraisal was performed using the AGREE-II (ideal scenario) for the guidelines and statements, and recommendations were assessed using the AGREE-REX (ideal and local scenarios). A matrix of recommendations and analysis of potential barriers for its implementation in Colombia is presented. Results: Eighteen related recommendations were included. The average AGREE-II was 89.6. The average AGREE-REX was 90.1 in the ideal setting and 69.9 in the local setting. The included recommendations focus on surveillance, screening, evaluation, and counseling; no recommendations on neurocognitive intervention were identified. The main implementation barriers in Colombia are the unwillingness to pay on the part of the health system and the absence of a comprehensive health care offer for neurocognitive management in congenital heart disease. Conclusion: The identified recommendations could be adapted into a Colombian practice guideline, making modifications that recognize the local context.

Nonsense variation of OTUD5 gene in a fetus with X-linked multiple congenital anomalies- neurodevelopmental syndrome / 中华围产医学杂志

We report a fetus presented with complex cardiac malformations, pulmonary atresia with ventricular septal defect, detected by fetal echocardiography at 17 +4 weeks. The pregnancy was terminated after routine counseling and genetic tests were performed on umbilical cord of the induced fetus and peripheral blood samples of the parents. Whole-exome sequencing identified a novel maternally-inherited and likely pathogenic variation hemizygous nonsense variant, c.1651C>T (p.Gln551*) in the OTUD5 gene (NM_017602.3), which was confirmed by subsequent Sanger sequencing. The fetus was finally diagnosed as X-linked multiple congenital anomalies-neurodevelopmental syndrome.

The microbiota-gut-brain axis and neurodevelopmental disorders

The gut microbiota has been found to interact with the brain through the microbiota-gut-brain axis, regulating various physiological processes. In recent years, the impacts of the gut microbiota on neurodevelopment through this axis have been increasingly appreciated. The gut microbiota is commonly considered to regulate neurodevelopment through three pathways, the immune pathway, the neuronal pathway, and the endocrine/systemic pathway, with overlaps and crosstalks in between. Accumulating studies have identified the role of the microbiota-gut-brain axis in neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, and Rett Syndrome. Numerous researchers have examined the physiological and pathophysiological mechanisms influenced by the gut microbiota in neurodevelopmental disorders (NDDs). This review aims to provide a comprehensive overview of advancements in research pertaining to the microbiota-gut-brain axis in NDDs. Furthermore, we analyzed both the current state of research progress and discuss future perspectives in this field.

Polymeric nanocarriers for nose-to-brain drug delivery in neurodegenerative diseases and neurodevelopmental disorders

Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system (CNS) and result in their damage and death. Neurodevelopmental disorders include intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes. The treatment of neurodegenerative and neurodevelopmental conditions, together affecting ∼120 million people worldwide, is challenged by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS. The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions. This pathway is more efficient for nanoparticles than for solutions, hence, the research on intranasal nano-drug delivery systems has grown exponentially over the last decade. Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility. This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions, the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them. Then, a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.