Executive Functions Rehabilitation in Premature Children Using an Adaptive Motion-Interaction Videogame Platform: A Randomized Controlled Trial.

Background: Premature children are at increased risk of executive functions (EF) deficits and these difficulties persist into adolescence and adulthood, potentially undermining their development and academic achievements. The aim of the present randomized controlled trial (RCT) is to evaluate the efficacy of the Intendu trainer, an adaptive virtual reality platform, at ameliorating EF in preterm children. Methods: A single-center, RCT was conducted. The intervention group was exposed to game session with the Intendu software in addition to the standard of care in use in our center. The main outcome was the proportion of children with a 10-point increase in the processing speed quotient as measured by WPPSI-III after 4 weeks from the baseline assessment. Results: Forty-seven children born before 36 + 5 weeks were randomized to the experimental (n = 24) or control arm (n = 23). Five children were lost to follow-up. Thirteen of 23 children (56%) reached the main outcome in the experimental group and 5 of 19 (26%) in the control group (P = 0.049, per-protocol analysis) with an absolute benefit increase (ABI) of 30% reconfirmed by the intention-to-treat analysis (P = 0.022, ABI of 32%). Conclusion: Intendu brain-trainer showed promising short-term results on EF in pre-term children, however, larger studies with longer periods of follow-up are warranted to better investigate the role of this or similar technology in promoting better EF in preterm children.

Celiac disease in autism spectrum disorder: data from an Italian child cohort.

BACKGROUND: In recent decades some studies described the frequent co-occurrence of celiac disease autoimmunity and overt celiac disease in patients with autism. Therefore, it was suggested that celiac disease could play a possible role in the etiopathogenesis of autism spectrum disorder. However, several other studies have not confirmed this association. The aim of the present study was to elucidate the potential association between autism spectrum disorder and celiac disease. METHODS: We prospectively collected data from an Italian cohort of 223 children at the time of their clinical diagnosis of autism spectrum disorder in the 2019-2020 period. A serological celiac disease screening was performed and data were available for 196 patients; male (M):female (F) ratio = 4.4:1; median age = 3.6 years; age range = 1.6-12.8 years. Full-blown celiac disease was established according to the diagnostic algorithm of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) 2012 or 2019 guidelines. Fisher's exact test was used to compare the celiac disease seroprevalence and prevalence in our autism spectrum disorder cohort and in the Italian healthy pediatric population studied by Gatti et al. to highlight the possible differences between the two groups. RESULTS: A not statistically significant difference between the celiac disease seroprevalence in our autism spectrum disorder cohort (4.08%) and Gatti's Italian healthy group (2.22%) was found, p = 0.0810; OR = 1.871. A similar result emerged for overt celiac disease prevalences (2.24% versus 1.58%, respectively), p = 0.2862; OR = 1.431. CONCLUSIONS: Our data validates a weakness of association between autism spectrum disorder and celiac disease. On the basis of our results, a regular screening for CD in patients with ASD is not recommended to a greater extent than in the general population.

EEG Features in Autism Spectrum Disorder: A Retrospective Analysis in a Cohort of Preschool Children.

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that can be associated with intellectual disability (ID) and epilepsy (E). The etiology and the pathogenesis of this disorder is in most cases still to be clarified. Several studies have underlined that the EEG recordings in children with these clinical pictures are abnormal, however the precise frequency of these abnormalities and their relationship with the pathogenic mechanisms and in particular with epileptic seizures are still unknown. We retrospectively reviewed 292 routine polysomnographic EEG tracings of preschool children (age < 6 years) who had received a first multidisciplinary diagnosis of ASD according to DSM-5 clinical criteria. Children (mean age: 34.6 months) were diagnosed at IRCCS E. Medea (Bosisio Parini, Italy). We evaluated: the background activity during wakefulness and sleep, the presence and the characteristics (focal or diffuse) of the slow-waves abnormalities and the interictal epileptiform discharges. In 78.0% of cases the EEG recordings were found to be abnormal, particularly during sleep. Paroxysmal slowing and epileptiform abnormalities were found in the 28.4% of the subjects, confirming the high percentage of abnormal polysomnographic EEG recordings in children with ASD. These alterations seem to be more correlated with the characteristics of the underlying pathology than with intellectual disability and epilepsy. In particular, we underline the possible significance of the prevalence of EEG abnormalities during sleep. Moreover, we analyzed the possibility that EEG data reduces the ASD clinical heterogeneity and suggests the exams to be carried out to clarify the etiology of the disorder.

Perfil clínico ­ epidemiológico de sepsis temprana en recién nacidos. Estudio observacional de centro único / Clinical-epidemiological profile of early sepsis in newborns. A single-center observational study

Introducción: La sepsis neonatal temprana se describe como un síndrome clínico que se caracteriza por signos y síntomas asociados a infección sistémica, se presenta en las primeras 72 horas posterior al nacimiento. El objetivo del presente estudio fue determinar el perfil clínico ­ epidemiológico de la sepsis neonatal temprana en una unidad de cuidados intensivos neonatales de un centro de referencia regional en Guayaquil-Ecuador. Métodos: El presente estudio observacional, realizado en el Hospital "Teodoro Maldonado Carbo" de enero del 2017 al diciembre del 2020 incluyó neonatos con sepsis neonatal temprana con muestra no probabilística. Las variables: edad, edad gestacional, sexo, vía de infección, presencia de infecciones de del tracto urinario, peso, genopatías, Apgar al 1er minuto, escala de Silverman, etapas clínicas, llenado capilar, gasto urinario, variables clínicas, de laboratorio, hemocultivo, organismo casal. El análisis es univariado, descriptivo con frecuencias y porcentajes. Resultados: Se incluyeron 278 pacientes con edad gestacio-nal promedio de 33 semanas, fueron 59.4% hombres. Los factores de riesgo materno fueron a IVU en el embarazo e infección transplacentaria. Entre los factores asociados al neonato son el bajo peso (56%), prematuridad (67%). La clínica más frecuente fue eutermia y taquipnea (54%). En el perfil de laboratorio la neu-tropenia predominó (49%), mientras que los agentes causales identificados Staphylococcus hominis 7%, Escherichia coli 4.3% y Klebsiella pneumoniae 4%. Conclusión: Se determinó la relación directa entre las características epidemiológicas y las etapas clínicas de la sepsis neonatal.

Introduction: Early neonatal sepsis is a clinical syndrome characterized by signs and symptoms associated with systemic infection; it occurs in the first 72 hours after birth. This study aimed to determine the clinical-epidemiological profile of early neonatal sepsis in a neonatal intensive care unit of a regional reference center in Guayaquil, Ecuador. Methods: The present observational study, carried out at the "Teodoro Maldonado Carbo" Hospital from January 2017 to December 2020, included neonates with early neonatal sepsis with a nonprobabilistic sample. The variables were age, gestational age, sex, route of infection, presence of urinary tract infections, weight, genopathies, Apgar at 1 minute, Silverman scale, clinical stages, capillary refill, urinary output, clinical and laboratory variables, haem culture, and causative organism. The analysis is univariate and descriptive with frequencies and percentages. Results: A total of 278 patients with a mean gestational age of 33 weeks were included, and 59.4% were men. Maternal risk factors were UTI in pregnancy and transplacental infection. Among the factors associated with the newborn were low weight (56%) and prematurity (67%). The most frequent symptoms were euthermia and tachypnea (54%). In the laboratory profile, neutropenia predominated (49%), while the causative agents were Staphylococcus hominis (7%), Escherichia coli (4.3%), and Klebsiella pneumoniae (4%). Conclusion: The direct relationship between the epidemiological characteristics and the clinical stages of neonatal sepsis was determined.

Factores asociados al síndrome de dificultad respiratoria neonatal severa / Factors associated with severe neonatal respiratory distress syndrome

Introducción: El síndrome de dificultad respiratoria neonatal es una patología asociada a neonatos de sexo masculino prematuros. Á nivel regional no se dispone de datos asociados al síndrome de dificultad respiratoria neonatal (SDR) severo, por lo que se desarrolló in estudio observacional para medir los factores de riesgo. Metodología: El presente estudio transversal ­ retrospectivo, fue realizado en el servicio de neonatología del Hospital "Teodoro Maldonado Carbo", de Guayaquil, Ecuador, de enero 2017 a diciembre 2020. Ingresaron al estudio, neonatos, con SDR con una muestra probabilística. Las variables fueron maternas, neonatales, escala de Silverman, valoración de Downes. En base a la escala de Silverman se analizan 2 grupos: SDR leve y moderado, versus SDR Severo, se presenta Odds Ratio, e intervalo de confianza del 95% con valor P. Resultados: Se analizan 302 casos, con edad gestacional de 33 ± 4.2 semanas. Puntaje de Silverman 5.07 ±2.06. Los factores de riesgos identificados fueron la cesárea OR 3.92 (IC 95% 2.13-7.21) P<0.0001, pre-eclampsia OR 1.73 (1.05-2.87) P=0.033. Edad gestacional <28 Semanas 7.626 (2.657-21.89) P=0.0002. Edad Gestacional >36 semanas OR 0.4 (0.273-0.782) P=0.004. Sexo hombre OR 2.19 (1.32-3.63) P=0.002. Conclusión: Se constituyeron los factores de riesgo la cesárea, la pre-eclampsia, la edad gestacional menor a 28 semanas y el sexo hombre. Un factor de protección fue la edad gestacional mayor a 36 semanas.

Introduction: Neonatal respiratory distress syndrome is a pathology associated with premature male neo-nates. At the regional level, no data is associated with severe neonatal respiratory distress syndrome (RDS), so an observational study was developed to measure risk factors. Methodology: The present cross-sectional - retrospective study was carried out in the neonatology service of the "Teodoro Maldonado Carbo" Hospital, in Guayaquil, Ecuador, from January 2017 to December 2020. Neonates with RDS entered the study with a probabilistic sample. The variables were maternal, neonatal, Silverman scale, and Downes assessment. Based on the Silverman scale, two groups are analyzed: mild and moderate RDS versus Severe RDS; Odds Ratio is presented, and a 95% confidence interval with a P value. Results: 302 cases were analyzed, with a gestational age of 33 ± 4.2 weeks. Silverman scores 5.07 ±2.06. The identified risk factors were cesarean section OR 3.92 (95% CI 2.13-7.21) P<0.0001, pre-eclampsia OR 1.73 (1.05-2.87) P=0.033. Gestational age <28 Weeks 7.626 (2.657-21.89) P=0.0002. Gestational age >36 weeks OR 0.4 (0.273-0.782) P=0.004. Sex male OR 2.19 (1.32-3.63) P=0.002. Conclusión: The risk factors were cesarean section, pre-eclampsia, gestational age les tan 28 weeks, and male sex. A protective factor was gestational age greater than 36 weeks.

Prenatal Diagnosis and Neurodevelopmental Outcome in Isolated Cerebellar Hypoplasia of Suspected Hemorrhagic Etiology: a Retrospective Cohort Study.

Data about the neurological prognosis of isolated cerebellar hypoplasia in utero are scant and inconsistent. In this monocentric retrospective study, we describe the neurodevelopmental outcomes in a series of children with isolated cerebellar hypoplasia of presumably hemorrhagic origin prenatally detected with fetal magnetic resonance imaging (fMRI). We retrospectively reviewed the charts of all the pregnant women who were referred for a neurological consultation, diagnosed with fetal encephalic malformation/disruption between 2010 and 2020 in the Fetal Therapy Unit of our institution. Fetal MRI (fMRI) was performed in all the pregnancies. Fetuses with cerebellar hypoplasia presumably of hemorrhagic origin were selected for the study. Fetuses exposed to alcohol or with additional malformations in other cerebral or body areas were excluded. All the infants received the postpartum follow-up care adopted in our center, including post-natal MRI, serial neurological examinations, standardized neurodevelopmental tests, and regular parental interviews. Cognitive functions were tested with GRIFFITHS II, WPPSI-III, and WISC-IV according to the child's age. A total of 14 pregnant women out of 479 fetal consultations were eligible and included in the study group. In 57% of cases, the etiology of the hemorrhage was unknown. In 21% of cases, it was attributed to a blood transfusion, while in the remaining ones, it was attributed to maternal predisposing factors. Among the survivors, two infants were excluded for prematurity, and two were lost to follow-up. Ten patients were thus included in the study. Six patients had normal neurodevelopment and cognition, and three presented mild-moderate neurological signs, i.e., mild dyspraxia and visuoperceptual impairment. Only one child had a severe outcome, i.e., autism spectrum disorder. The cerebellum is particularly vulnerable to disruptions throughout its prolonged development. Extreme caution must be used in prenatal counseling considering that in the acute phase, lesion extension and vermis involvement can be overestimated with fMRI. In cases of uncertainty, performing an additional fMRI could be advisable after 4-8 weeks. However, in our series, infants with isolated cerebellar hypoplasia tended to have a favorable prognosis. Nevertheless, a long-term follow-up is needed and should include a postnatal brain MRI, serial neurological examinations, and neurodevelopmental tests at least up to school age.

Emerging drugs for the treatment of attention-deficit hyperactivity disorder (ADHD).

INTRODUCTION: Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder affecting up to 5.3% of children and 2.5% of adults depending on the country considered. Current pharmacological treatments for ADHD are based on stimulant or non-stimulant medications, targeting dopaminergic and noradrenergic systems in the frontal cortex and dopaminergic system in the basal ganglia. These drugs are effective and safe for the majority of patients, whereas about 20% of treated patients do not tolerate current therapies or experience insufficient efficacy. The adequate treatment of ADHD is necessary to allow a proper social placement and prevent the acquisition of additional, more severe, comorbidities. AREAS COVERED: We conducted a review of the scientific literature and of unpublished/ongoing clinical trials to summarize the advances made in the last 10 years (2010-2020) for the pharmacological treatment of ADHD. We found many pharmacological mechanisms beyond dopaminergic and noradrenergic ones have been investigated in patients. EXPERT OPINION: Some emerging drugs for ADHD may be promising as add-on treatment especially in children, amantadine to enhance cognitive functions and tipepidine for hyperactivity/impulsivity. Stand-alone emerging treatments for ADHD include viloxazine and dasotraline, which will soon have more clinical data available to support market access requests.